The present disclosure relates to novel compounds for use in therapeutic treatment of a disease associated with peptidylarginine deiminases (PADs), such as peptidylarginine deiminase type 4 (PAD4). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.

Description

291 parts

›CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No. 63/018,411, filed Apr. 30, 2020, and U.S. Provisional Application No. 63/129,430, filed Dec. 22, 2020, both of which are incorporated herein in their entireties for all purposes.

›SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Apr. 8, 2021, is named 1304-US-NP_SL.txt and is 740 bytes in size.

›FIELD

The present disclosure relates to novel compounds for use in therapeutic treatment of a disease associated with peptidylarginine deiminases (PADs). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.

›BACKGROUND

Peptidylarginine deiminases catalyze the posttranslational modification of peptidyl arginine to peptidyl citrulline. There are five known PAD isozymes with 45% to 58% amino acid sequence identity between human isozymes and at least 70% identity across each vertebrate orthologue. PADs have diverse tissue distribution, different putative physiological functions, and reported associations with various disease states. PAD6 is thought to be the only catalytically inactive PAD and is expressed mainly in oocyte, ovary and early embryo; it is proposed to be involved in oocyte cytoskeletal sheet formation and female fertility. PAD1 and PAD3 are expressed in epidermis and hair follicles and are proposed to be involved in cornification of epidermal tissues, hair growth and maintenance of the stratum corneum. PAD2 is expressed more broadly and can be found in multiple tissues and cell types including brain, spinal cord, skeletal muscles, pituitary glands, spleen, neutrophils and macrophages. It is proposed to be involved in plasticity of CNS, transcription regulation, chemokine signaling, and female reproduction. Expression of PAD4 is restricted to cells of the myeloid lineage, in particular: neutrophils, eosinophils and monocyte/macrophages. PAD4 is hypothesized to be involved in an array of functions, including regulation of transcription, cell cycle, apoptosis, formation of neutrophil extracellular traps (NETs), and tumorgenesis. Accordingly, there is a need for inhibitors of PADs that have therapeutic potential in treatment of disease linked to pathological consequences of citrullination and NETosis including, for example, rheumatoid arthritis, systemic lupus erythematous, antiphospholipid antibody syndrome, small vessels vasculitis, colitis, thrombosis, atherosclerosis, sepsis, diabetes and certain types of cancer.

›SUMMARY · 1 of 3

Provided herein are macrocyclic compounds for inhibiting peptidylarginine deiminase type 4 (PAD4). The present disclosure provides a compound of Formula (I):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

X 1 and X 2 are C or N;

X 3 is N—R 3 or C—R 3 ; provided that two of X 1 , X 2 , and X 3 are C; where each dashed line represents an optional bond to complete valency requirements of each X 1 , X 2 and X 3 ;

X 4 is N or C—R 2 ;

X 5 is N or CR 6 ;

X 7 is N or CR 7 ;

R 1 is hydrogen, halo, —CN, —OR 12 , —N(R 12 ) 2 , —SR 12 , —C 1-8 alkyl optionally substituted with 1 to 3 Z 1 , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1 , or 4-6 membered heterocyclyl optionally substituted with 1 to 3 Z 1 ;

R 2 is hydrogen, halo, —CN, —OR 12 , —N(R 12 ) 2 , —SR 12 , —C 1-8 alkyl optionally substituted with 1 to 3 Z 2 , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 2 , or 4-6 membered heterocyclyl optionally substituted with 1 to 3 Z 2 ;

when X 3 is N—R 3 , R 3 is hydrogen, C 1-8 alkyl optionally substituted with 1 to 3 Z 3 , C 3-10 alkenyl optionally substituted with 1 to 3 Z 3 , C 3-10 alkynyl optionally substituted with 1 to 3 Z 3 , C 3-10 cycloalkyl optionally substituted with 1 to 3 Z 3 , or 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z 3 ; and

when X 3 is C—R 3 ; R 3 is hydrogen, halo, —CN, —OR 12 , —N(R 12 ) 2 , —SR 12 , C 1-8 alkyl optionally substituted with 1 to 3 Z 3 , C 2-10 alkenyl optionally substituted with 1 to 3 Z 3 , C 2-10 alkynyl optionally substituted with 1 to 3 Z 3 , C 3-10 cycloalkyl optionally substituted with 1 to 3 Z 3 , or 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z 3 ; or

when R 2 is —C 1-8 alkyl, —OR 12 , or —N(R 12 ) 2 , and R 3 is C 1-8 alkyl, then R 2 and R 3 may be taken together with the atoms to which they are attached to form an optionally substituted 6 to 8 membered ring;

R 6 is hydrogen, halo, —CN, —OR 12 , —C 1-8 alkyl optionally substituted with 1 to 3 Z 6 , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 6 , or 4-6 membered heterocyclyl optionally substituted with 1 to 3 Z 6 ;

R 7 is hydrogen, halo, —CN, —OR 12 , —C 1-8 alkyl optionally substituted with 1 to 3 Z 7 , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 7 , or 4-6 membered heterocyclyl optionally substituted with 1 to 3 Z 7 ;

L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are each independently:

C 1-10 alkylene, optionally substituted with 1 to 3 Z 8 ;

C 2-10 alkenylene, optionally substituted with 1 to 3 Z 8 ;

C 2-10 alkynylene, optionally substituted with 1 to 3 Z 8 ;

2-6 membered heteroalkylene, optionally substituted with 1 to 3 Z 8 ;

C 3 -C 10 cycloalkylene, optionally substituted with 1 to 3 Z 8 ;

4-10 membered heterocyclene, optionally substituted with 1 to 3 Z 8 ;

C 6-10 arylene, optionally substituted with 1 to 3 Z 8 ;

5-10 membered heteroarylene, optionally substituted with 1 to 3 Z 8 ; or

—O—, —N(R 8 )—, —S—, —C(O)—, —C(O)O—, —C(O)N(R 8 )—, —SO—, —SO 2 —, —SO 2 N(R 8 )—, —N(R 8 )C(O)O—, —OC(O)O—, —N(R 8 )C(O)N(R 8 )—, —N(R 8 )S(O) 2 N(R 8 )—, —N(R 8 )C(N—CN)—S(O)(NR 8 )—, or —S(O)(NR 8 )N(R 8 )—; and

m1, m2, m3, m4, m5, and m6 are each independently 0 or 1;

provided that L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 11 to 20 membered macrocyclic ring;

each R 8 and R 9 are each independently hydrogen, C 1-8 alkyl optionally substituted with 1 to 3 Z 1b , C 2-8 alkenyl optionally substituted with 1 to 3 Z 1b , C 2-8 alkynyl optionally substituted with 1 to 3 Z 1b , C 3-10 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z 1b , C 6-10 aryl optionally substituted with 1 to 3 Z 1b , or 5-10 membered heteroaryl optionally substituted with 1 to 3 Z 1b ;

R 10 is hydrogen, —C 1-8 alkyl optionally substituted with 1 to 3 Z 10 , or C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 10 ;

R 11 is hydrogen, —C 1-8 alkyl optionally substituted with 1 to 4 Z 11 , —C 3-8 cycloalkyl optionally substituted with 1 to 4 Z 11 , or 4-12-membered heterocyclyl optionally substituted with 1 to 4 Z 11 ; or

R 10 and R 11 are taken together to form a 4-12-membered heterocyclyl optionally substituted with 1 to 4 Z 11 ;

each R 12 and R 13 are independently hydrogen, C 1-8 alkyl optionally substituted with 1 to 3 Z 1b , C 2-8 alkenyl optionally substituted with 1 to 3 Z 1b , C 2-8 alkynyl optionally substituted with 1 to 3 Z 1b , C 3-10 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z 1b , C 6-10 aryl optionally substituted with 1 to 3 Z 1b , or 5-10 membered heteroaryl optionally substituted with 1 to 3 Z 1b ;

each Z 1 , Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 is independently oxo, halo, —NO 2 , —N 3 , —CN, C 1-8 alkyl optionally substituted by 1 to 3 Z 1a , C 2-8 alkenyl optionally substituted by 1 to 3 Z 1a , C 2-8 alkynyl optionally substituted by 1 to 3 Z 1a , C 3-8 cycloalkyl optionally substituted by 1 to 3 Z 1a , 6-10 membered aryl optionally substituted by 1 to 3 Z 1a , 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z 1a , 5-10 membered heteroaryl optionally substituted with 1 to 3 Z 1a , —OR 9 , —C(O)R 9 , —C(O)OR 9 , —C(O)N(R 9 ) 2 , —N(R 9 ) 2 , —N(R 9 ) 3 + , —N(R 9 )C(O)R 9 , —N(R 9 )C(O)OR 9 , —N(R 9 )C(O)N(R 9 ) 2 , —N(R 9 )S(O) 2 (R 9 ), —NR 9 S(O) 2 N(R 9 ) 2 , —NR 9 S(O) 2 O(R 9 ), —NS(O)(R 9 ) 2 , —OC(O)R 9 , —OC(O)OR 9 , —OC(O)N(R 9 ) 2 , —Si(R 9 ) 3 , —SR 9 , —S(O)R 9 , —SF 5 , —S(O)(NR 9 )R 9 , —S(NR 9 )(NR 9 )R 9 , —S(O)(NR 9 )N(R 9 ) 2 , —S(O)(NCN)R 9 , —S(O) 2 R 9 , —S(O) 2 N(R 9 ) 2 , —C(O)N(R 9 )S(O) 2 R 9 , or —S(O) 2 N(R 9 )C(O)R 9 , wherein each Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 is independently optionally substituted with 1 to 3 Z 1a ;

each Z 1a is independently oxo, halo, —NO 2 , —N 3 , —CN, C 1-8 alkyl optionally substituted by 1 to 3 Z 1b , C 2-8 alkenyl optionally substituted by 1 to 3 Z 1b , C 2-8 alkynyl optionally substituted by 1 to 3 Z 1b , C 3-8 cycloalkyl optionally substituted by 1 to 3 Z 1b , 6-10 membered aryl optionally substituted by 1 to 3 Z 1b , 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z 1b , 5-10 membered heteroaryl optionally substituted with 1 to 3 Z 1b , —OR 13 , —C(O)R 13 , —C(O)OR 13 , —C(O)N(R 13 ) 2 , —N(R 13 ) 2 , —N(R 13 ) 3 + , —N(R 13 )C(O)R 13 , —N(R 13 )C(O)OR 13 , —N(R 13 )C(O)N(R 13 ) 2 , —N(R 13 )S(O) 2 (R 13 ), —NR 13 S(O) 2 N(R 13 ) 2 , —NR 13 S(O) 2 O(R 13 ), —NS(O)(R 13 ) 2 , —OC(O)R 13 , —OC(O)OR 13 , —OC(O)N(R 13 ) 2 , —Si(R 13 ) 3 , —SR 13 , —S(O)R 13 , —SF 5 , —S(O)(NR 13 )R 13 , —S(NR 13 )(NR 13 )R 13 , —S(O)(NR 13 )N(R 13 ) 2 , —S(O)(NCN)R 13 , —S(O) 2 R 13 , —S(O) 2 N(R 13 ) 2 , —C(O)N(R 13 )S(O) 2 R 13 , or —S(O) 2 N(R 13 )C(O)R 13 ;

›SUMMARY · 2 of 3

each Z 10 and Z 11 is independently selected from oxo, halo, —CN, C 1-8 alkyl optionally substituted by 1 to 3 Z 1b , C 3-8 cycloalkyl optionally substituted by 1 to 3 Z 1b , aryl optionally substituted by 1 to 3 Z 1b , 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z 1b , 5-10 membered heteroaryl optionally substituted with 1 to 3 Z 1b , —OR 13 , —C(O)R 13 , —C(O)OR 13 , —C(O)N(R 13 ) 2 , —N(R 13 ) 2 , —N(R 13 ) 3 + , —N(R 13 )C(O)R 13 , —N(R 13 )C(O)OR 13 , —N(R 13 )C(O)N(R 13 ) 2 , —OC(O)R 13 , —OC(O)OR 13 , —OC(O)—N(R 13 ) 2 , and —S—R 13 ; and

each Z 1b is independently oxo, hydroxy, halo, —NO 2 , —N 3 , —CN, C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, C 1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, —O(C 1-9 alkyl), —O(C 2-6 alkenyl), —O(C 2-6 alkynyl), —O(C 3-15 cycloalkyl), —O(C 1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), —OC(O) (C 1-9 alkyl), —OC(O)(C 2-6 alkenyl), —OC(O)(C 2-6 alkenyl), —OC(O)(C 2-6 alkynyl), —OC(O)(C 3-15 cycloalkyl), —OC(O)(C 1-8 haloalkyl), —OC(O)(aryl), —OC(O)(heteroaryl), —OC(O)(heterocyclyl), —NH 2 , —NH(C 1-9 alkyl), —NH(C 2-6 alkenyl), —NH(C 2-6 alkynyl), —NH(C 3-15 cycloalkyl), —NH(C 1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C 1-9 alkyl) 2 , —N(C 3-15 cycloalkyl) 2 , —N(C 2-6 alkenyl) 2 , —N(C 2-6 alkynyl) 2 , —N(C 3-15 cycloalkyl) 2 , —N(C 1-8 haloalkyl) 2 , —N(aryl) 2 , —N(heteroaryl) 2 , —N(heterocyclyl) 2 , —N(C 1-9 alkyl)(C 3-15 cycloalkyl), —N(C 1-9 alkyl)(C 2-6 alkenyl), —N(C 1-9 alkyl)(C 2-6 alkynyl), —N(C 1-9 alkyl)(C 3-15 cycloalkyl), —N(C 1-9 alkyl)(C 1-8 haloalkyl), —N(C 1-9 alkyl)(aryl), —N(C 1-9 alkyl)(heteroaryl), —N(C 1-9 alkyl)(heterocyclyl), —C(O)(C 1-9 alkyl), —C(O)(C 2-6 alkenyl), —C(O)(C 2-6 alkynyl), —C(O)(C 3-15 cycloalkyl), —C(O)(C 1-8 haloalkyl), —C(O)(aryl), —C(O)(heteroaryl), —C(O)(heterocyclyl), —C(O)O(C 1-9 alkyl), —C(O)O(C 2-6 alkenyl), —C(O)O(C 2-6 alkynyl), —C(O)O(C 3-15 cycloalkyl), —C(O)O(C 1-8 haloalkyl), —C(O)O(aryl), —C(O)O(heteroaryl), —C(O)O(heterocyclyl), —C(O)NH 2 , —C(O)NH(C 1-9 alkyl), —C(O)NH(C 2-6 alkenyl), —C(O)NH(C 2-6 alkynyl), —C(O)NH(C 3-15 cycloalkyl), —C(O)NH(C 1-8 haloalkyl), —C(O)NH(aryl), —C(O)NH(heteroaryl), —C(O)NH(heterocyclyl), —C(O)N(C 1-9 alkyl) 2 , —C(O)N(C 3-15 cycloalkyl) 2 , —C(O)N(C 2-6 alkenyl) 2 , —C(O)N(C 2-6 alkynyl) 2 , —C(O)N(C 1-8 haloalkyl) 2 , —C(O)N(aryl) 2 , —C(O)N(heteroaryl) 2 , —C(O)N(heterocyclyl) 2 , —NHC(O)(C 1-9 alkyl), —NHC(O)(C 2-6 alkenyl), —NHC(O)(C 2-6 alkynyl), —NHC(O)(C 3-15 cycloalkyl), —NHC(O)(C 1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C 1-9 alkyl), —NHC(O)O(C 2-6 alkenyl), —NHC(O)O(C 2-6 alkynyl), —NHC(O)O(C 3-15 cycloalkyl), —NHC(O)O(C 1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C 1-9 alkyl), —NHC(O)NH(C 2-6 alkenyl), —NHC(O)NH(C 2-6 alkynyl), —NHC(O)NH(C 3-15 cycloalkyl), —NHC(O)NH(C 1-8 haloalkyl), —NHC(O)NH(aryl), —NHC(O)NH(heteroaryl), —NHC(O)NH(heterocyclyl), —SH, —S(C 1-9 alkyl), —S(C 2-6 alkenyl), —S(C 2-6 alkynyl), —S(C 3-15 cycloalkyl), —S(C 1-8 haloalkyl), —S(aryl), —S(heteroaryl), —S(heterocyclyl), —NHS(O)(C 1-9 alkyl), —N(C 1-9 alkyl)(S(O)(C 1-9 alkyl), —S(O)N(C 1-9 alkyl) 2 , —S(O)(C 1-9 alkyl), —S(O)(NH)(C 1-9 alkyl), —S(O)(C 2-6 alkenyl), —S(O)(C 2-6 alkynyl), —S(O)(C 3-15 cycloalkyl), —S(O)(C 1-8 haloalkyl), —S(O)(aryl), —S(O)(heteroaryl), —S(O)(heterocyclyl), —S(O) 2 (C 1-9 alkyl), —S(O) 2 (C 2-6 alkenyl), —S(O) 2 (C 2-6 alkynyl), —S(O) 2 (C 3-15 cycloalkyl), —S(O) 2 (C 1-8 haloalkyl), —S(O) 2 (aryl), —S(O) 2 (heteroaryl), —S(O) 2 (heterocyclyl), —S(O) 2 NH(C 1-9 alkyl), or —S(O) 2 N(C 1-9 alkyl) 2 ;

wherein any alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl of Z 1b is optionally substituted with one or more halo, C 1-9 alkyl, C 1-8 haloalkyl, —OH, —NH 2 , —NH(C 1-9 alkyl), —NH(C 3-15 cycloalkyl), —NH(C 1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C 1-9 alkyl) 2 , —N(C 3-15 cycloalkyl) 2 , —NHC(O)(C 3-15 cycloalkyl), —NHC(O)(C 1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C 1-9 alkyl), —NHC(O)O(C 2-6 alkynyl), —NHC(O)O(C 3-15 cycloalkyl), —NHC(O)O(C 1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C 1-9 alkyl), —S(O)(NH)(C 1-9 alkyl), —S(O) 2 (C 1-9 alkyl), —S(O) 2 (C 3-15 cycloalkyl), —S(O) 2 (C 1-8 haloalkyl), —S(O) 2 (aryl), —S(O) 2 (heteroaryl), —S(O) 2 (heterocyclyl), —S(O) 2 NH(C 1-9 alkyl), —S(O) 2 N(C 1-9 alkyl) 2 , —O(C 3-15 cycloalkyl), —O(C 1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), or —O(C 1-9 alkyl).

Also provided herein are compounds of Tables 1 and 1A or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof.

The present disclosure provides a method of inhibiting peptidylarginine deiminase type 4 (PAD4) comprising contacting an effective amount of a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, with a cell.

The present disclosure provides a method of inhibiting peptidylarginine deiminase type 4 (PAD4) comprising administering an effective amount of a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, to a patient in need thereof.

The present disclosure provides a method for treating a disease or disorder mediated by peptidylarginine deiminase type 4 (PAD4), comprising administering an effective amount of a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, to a patient in need thereof.

The present disclosure provides a method for treating acute lymphocytic leukemia, ankylosing spondylitis, cancer, chronic lymphocytic leukemia, colitis, lupus, systemic lupus erythematosus, cutaneous lupus erythematosus, rheumatoid arthritis, multiple sclerosis, or ulcerative colitis, comprising administering an effective amount of a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, to a patient in need thereof.

›SUMMARY · 3 of 3

In one embodiment, the present disclosure provides a pharmaceutical composition comprising a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

In one embodiment, the present disclosure provides a pharmaceutical composition comprising a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, at least one additional therapeutic agent suitable for treating rheumatoid arthritis, and at least one pharmaceutically acceptable carrier or excipient.

In one embodiment, the present disclosure provides a kit that includes a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, a label and/or instructions for use of the compound in the treatment of rheumatoid arthritis or a disease or condition mediated by peptidylarginine deiminase type 4 (PAD4).

In one embodiment, the present disclosure provides a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, for use in therapy.

In another embodiment, the present disclosure provides a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, for use in the manufacture of a medicament for treating rheumatoid arthritis or a disease or condition mediated by peptidylarginine deiminase type 4 (PAD4).

›DETAILED DESCRIPTION · 1 of 31

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. It must be noted that as used herein and in the appended claims, the singular forms “a”, “and”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, e.g., reference to “the compound” includes a plurality of such compounds and reference to “the assay” includes reference to one or more assays and equivalents thereof known to those skilled in the art, and so forth.

A dash (“—”) that is not between two letters or symbols is used to indicate a point of attachment for a substituent. For example, —C(O)NH 2 is attached through the carbon atom. A dash at the front or end of a chemical group is a matter of convenience; chemical groups may be depicted with or without one or more dashes without losing their ordinary meaning. Unless chemically or structurally required, no directionality is indicated or implied by the order in which a chemical group is written or named.

A wavy line on a chemical group as shown below, for example,

indicates a point of attachment, i.e., it shows the broken bond by which the group is connected to another described group.

The prefix “C u-v ” indicates that the following group has from u to v carbon atoms. For example, “C 1-6 alkyl” indicates that the alkyl group has from 1 to 6 carbon atoms.

Reference to “about” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se. In certain embodiments, the term “about” includes the indicated amount ±10%. In other embodiments, the term “about” includes the indicated amount ±5%. In certain other embodiments, the term “about” includes the indicated amount ±1%. Also, to the term “about X” includes description of “X”. Also, the singular forms “a” and “the “include plural references unless the context clearly dictates otherwise. Thus, e.g., reference to “the compound” includes a plurality of such compounds and reference to “the assay” includes reference to one or more assays and equivalents thereof known to those skilled in the art.

“Alkyl” refers to an unbranched or branched saturated hydrocarbon chain. As used herein, alkyl has 1 to 20 carbon atoms (i.e., C 1-20 alkyl), 1 to 12 carbon atoms (i.e., C 1-12 alkyl), 1 to 10 carbon atoms (i.e., C 1-10 alkyl), 1 to 8 carbon atoms (i.e., C 1-8 alkyl), 1 to 6 carbon atoms (i.e., C 1-6 alkyl), or 1 to 4 carbon atoms (i.e., C 1-4 alkyl). Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue having a specific number of carbons is named by chemical name or identified by molecular formula, all positional isomers having that number of carbons may be encompassed; thus, for example, “butyl” includes n-butyl (i.e., —(CH 2 ) 3 CH 3 ), sec-butyl (i.e., —CH(CH 3 )CH 2 CH 3 ), isobutyl (i.e., —CH 2 CH(CH 3 ) 2 ) and tert-butyl (i.e., —C(CH 3 ) 3 ); and “propyl” includes n-propyl (i.e., —(CH 2 ) 2 CH 3 ) and isopropyl (i.e., —CH(CH 3 ) 2 ).

“Alkenyl” refers to any group derived from a straight or branched hydrocarbon with at least one carbon-carbon double bond. Unless otherwise specified, alkenyl groups have from 2 to 20 carbon atoms (i.e., C 2-20 alkenyl), 2 to 12 carbon atoms (i.e., C 2-12 alkenyl), 2 to 10 carbon atoms (i.e., C 2-10 alkenyl), 2 to 8 carbon atoms (i.e., C 2-8 alkenyl), 2 to 6 carbon atoms (i.e., C 2-6 alkenyl), or 2 to 4 carbon atoms (i.e., C 2-4 alkenyl). Examples of alkenyl groups include ethenyl, propenyl, butadienyl (including 1,2-butadienyl, and 1,3-butadienyl).

“Alkynyl” refers to any group derived from a straight or branched hydrocarbon with at least one carbon-carbon triple bond. Unless otherwise specified, alkynyl groups have from 2 to 20 carbon atoms (i.e., C 2-20 alkynyl), 2 to 12 carbon atoms (i.e., C 2-12 alkynyl), 2 to 10 carbon atoms (i.e., C 2-10 alkynyl), 2 to 8 carbon atoms (i.e., C 2-8 alkynyl), 2 to 6 carbon atoms (i.e., C 2-6 alkynyl), or 2 to 4 carbon atoms (i.e., C 2-4 alkynyl). The term “alkynyl” also includes those groups having one triple bond and one double bond. Examples of alkynyl groups include, but are not limited to, ethynyl (—C≡C—), propargyl (—CH 2 C≡C—), (E)-pent-3-en-1-ynyl, and the like.

The term “aryl” as used herein refers to a single all carbon aromatic ring or a multiple condensed all carbon ring system wherein at least one of the rings is aromatic. For example, in certain embodiments, an aryl group 6 to 20 ring carbon atoms (i.e., C 6-20 aryl), 6 to 14 carbon ring atoms (i.e., C 6-14 aryl), 6 to 12 carbon ring atoms (i.e., C 6-12 aryl), or 6 to 10 carbon ring atoms (i.e., C 6-10 aryl). Aryl also includes multiple condensed ring systems (e.g., ring systems comprising 2, 3 or 4 rings) having about 9 to 20 carbon atoms in which at least one ring is aromatic and wherein the other rings may be aromatic or not aromatic (i.e., carbocycle). Such multiple condensed ring systems are optionally substituted with one or more (e.g., 1, 2 or 3) oxo groups on any carbocycle portion of the multiple condensed ring system. Aryl, however, does not encompass or overlap in any way with heteroaryl defined below. If one or more aryl groups are fused with a heteroaryl ring, the resulting ring system is heteroaryl. It is also to be understood that when reference is made to a certain atom-range membered aryl (e.g., C 6-10 aryl), the atom range is for the total ring atoms of the aryl. For example, a 6-membered aryl would include phenyl and a 10-membered aryl would include naphthyl and 1,2,3,4-tetrahydronaphthyl. Aryl groups include, but are not limited to, those groups derived from acenaphthylene, anthracene, azulene, benzene, chrysene, a cyclopentadienyl anion, naphthalene, fluoranthene, fluorene, indane, perylene, phenalene, phenanthrene, pyrene, and the like. Non-limiting examples of aryl groups include, but are not limited to, phenyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, anthracenyl, and the like.

›DETAILED DESCRIPTION · 2 of 31

The term “cycloalkyl” refers to a single saturated or partially unsaturated all carbon ring having 3 to 20 annular carbon atoms (i.e., C 3-20 cycloalkyl), 3 to 14 ring carbon atoms (i.e., C 3-14 cycloalkyl), 3 to 12 ring carbon atoms (i.e., C 3-12 cycloalkyl), 3 to 10 ring carbon atoms (i.e., C 3-10 cycloalkyl), 3 to 8 ring carbon atoms (i.e., C 3-8 cycloalkyl), or 3 to 6 ring carbon atoms (i.e., C 3-6 cycloalkyl). As used herein the term “cycloalkenyl” refers to the non-aromatic carbocyclic (partially saturated cyclic alkyl) group having at least one double bond. Accordingly, cycloalkyl includes multicyclic carbocycles such as a bicyclic carbocycles (e.g., bicyclic carbocycles having about 6 to 12 annular carbon atoms such as bicyclo[3.1.0]hexane, bicyclo[2.1.1]hexane), bicyclo[1.1.1]pentane, and polycyclic carbocycles (e.g., tricyclic and tetracyclic carbocycles with up to about 20 annular carbon atoms). The rings of a multiple condensed ring system can be connected to each other via fused, spiro and bridged bonds when allowed by valency requirements. Non-limiting examples of monocyclic cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, spiro[3.3]heptane, and 1-cyclohex-3-enyl.

“Halo” and “halogen” refer to fluoro, chloro, bromo and iodo.

“Haloalkyl” refers to an alkyl group as defined herein, wherein one or more hydrogen atoms (e.g., 1-5, or 1-3) are replaced by a halogen. Examples include, but are not limited to, —CH 2 Cl, —CH 2 F, —CH 2 Br, —CFClBr, —CH 2 CH 2 Cl, —CH 2 CH 2 F, —CF 3 , —CH 2 CF 3 , —CH 2 CCl 3 , and the like, as well as alkyl groups such as perfluoroalkyl in which all hydrogen atoms are replaced by fluorine atoms.

“Heteroalkyl” refers to an alkyl in which one or more of the carbon atoms (and any associated hydrogen atoms) are each independently replaced with the same or different heteroatom or heteroatomic group. Heteroatoms include, but are not limited to, N, P, O, S, etc. Heteroatomic groups include, but are not limited to, —NR—, —O—, —S—, —PH—, —P(O) 2 —, —S(O)—, —S(O) 2 —, and the like, where R is H, alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl or cycloheteroalkyl. Heteroalkyl groups include, but are not limited to, —OCH 3 , —CH 2 OCH 3 , —SCH 3 , —CH 2 SCH 3 , —NRCH 3 , —CH 2 NRCH 3 , —CH 2 OH and the like, where R is hydrogen, alkyl, aryl, arylalkyl, heteroalkyl, or heteroaryl. As used herein, heteroalkyl includes 1 to 10 carbon atoms, 1 to 8 carbon atoms, or 1 to 4 carbon atoms; and 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom.

“Heteroaryl” refers to a monoradical or diradical aromatic group having a single ring, multiple rings, or multiple fused rings, with one or more ring heteroatoms independently selected from nitrogen, oxygen, and sulfur. The term includes fused ring systems wherein one or more (e.g., one, two, or three) fused rings is/are fully or partially unsaturated. As used herein, heteroaryl include 1 to 20 ring carbon atoms (i.e., C 1-20 heteroaryl), 3 to 12 ring carbon atoms (i.e., C 3-12 heteroaryl), or 3 to 8 carbon ring atoms (i.e., C 3-8 heteroaryl); and 1 to 5 heteroatoms, 1 to 4 heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, oxygen, and sulfur. Non-limiting examples of heteroaryl groups include, but are not limited to, groups derived from acridine, benzimidazole, benzothiophene, benzofuran, benzoxazole, benzothiazole, carbazole, carboline, cinnoline, furan, imidazole, imidazopyridine, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyridone, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like.

“Heterocyclyl” refers to a saturated or unsaturated cyclic alkyl group, with one or more ring heteroatoms independently selected from nitrogen, oxygen and sulfur. The term “heterocyclyl” includes heterocycloalkenyl groups (i.e. the heterocyclyl group having at least one double bond), bridged-heterocyclyl groups, fused-heterocyclyl groups, and spiro-heterocyclyl groups. A heterocyclyl may be a single ring or multiple rings wherein the multiple rings may be fused, bridged, or spiro. Any non-aromatic ring containing at least one heteroatom is considered a heterocyclyl, regardless of the attachment (i.e., can be bound through a carbon atom or a heteroatom). Further, the term heterocyclyl is intended to encompass any non-aromatic ring containing at least one heteroatom, which ring may be fused to an aryl or heteroaryl ring, regardless of the attachment to the remainder of the molecule. As used herein, heterocyclyl has 2 to 20 ring carbon atoms, 2 to 12 ring carbon atoms, 2 to 10 ring carbon atoms, 2 to 8 ring carbon atoms, 3 to 12 ring carbon atoms, 3 to 8 ring carbon atoms, or 3 to 6 ring carbon atoms; and having 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, sulfur or oxygen. A heterocyclyl may contain one or more oxo and/or thioxo groups. Examples of heterocyclyl groups include, but are not limited to, groups derived from azetidine, aziridine, imidazolidine, morpholine, oxirane (epoxide), oxetane, piperazine, piperidine, pyrazolidine, piperidine, pyrrolidine, pyrrolidinone, tetrahydrofuran, tetrahydrothiophene, dihydropyridine, tetrahydropyridine, tetrahydro-2H-thiopyran 1,1-dioxide, quinuclidine, N-bromopyrrolidine, N-chloropiperidine, and the like. Heterocycles include spirocycles, such as, for example, aza or oxo-spiroheptanes. As used herein, the term “bridged-heterocyclyl” refers to a four- to ten-membered cyclic moiety connected at two non-adjacent atoms of the heterocyclyl with one or more (e.g., 1 or 2) four- to ten-membered cyclic moiety having at least one heteroatom where each heteroatom is independently selected from nitrogen, oxygen, and sulfur. As used herein, bridged-heterocyclyl includes bicyclic and tricyclic ring systems. Non-limiting examples of bridged-heterocyclyl include 8-azabicyclo[3.2.1]octan-8-yl, 2-azabicyclo[3.2.1]octan-2-yl, 2-azabicyclo[2.2.1]heptan-2-yl, and 7-azabicyclo[2.2.1]heptan-7-yl. Also used herein, the term “spiro-heterocyclyl” refers to a ring system in which a three- to ten-membered heterocyclyl has one or more additional ring, wherein the one or more additional ring is three- to ten-membered cycloalkyl or three- to ten-membered heterocyclyl, where a single atom of the one or more additional ring is also an atom of the three- to ten-membered heterocyclyl. Examples of the spiro-heterocyclyl rings include bicyclic and tricyclic ring systems, such as 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, 5-azaspiro[2.4]heptanyl, and 6-oxa-1-azaspiro[3.3]heptanyl. Examples of the fused-heterocyclyl rings include, but are not limited to, 3-azabicyclo[3.1.0]hexanyl, 1,2,3,4-tetrahydroisoquinolinyl, 1-oxo-1,2,3,4-tetrahydroisoquinolinyl, 1-oxo-1,2-dihydroisoquinolinyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridinyl, indolinyl, and isoindolinyl, where the heterocyclyl can be bound via either ring of the fused system. Additional examples include dihydroquinolines, e.g., 3,4-dihydroquinoline, dihydroisoquinolines, e.g., 1,2-dihydroisoquinoline, dihydroimidazole, tetrahydroimidazole, etc., indoline, isoindoline, isoindolones (e.g., isoindolin-1-one), isatin, dihydrophthalazine, quinolinone, spiro[cyclopropane-1,1′-isoindolin]-3′-one, and the like. Additional examples of heterocycles include 2-azabicyclo[2.2.1]heptane, 8-azabicyclo[3.2.1]octane, 3-azabicyclo[4.1.0]heptane, octahydro-2H-pyrido[4,3-b][1,4]oxazine, hexahydropyridazine, 3,8-diazabicyclo[3.2.1]octanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3-oxa-7,9-diazabicyclo[3.3.1]nonanyl, 7-azabicyclo[2.2.1]heptane, 2-azabicyclo[2.2.2]octane, 6-oxa-2-azabicyclo[3.2.1]octane, and hexahydropyrazino[2,1-c][1,4]oxazinyl, for example, where the heterocyclyl can be bound via either ring of the fused system.

›DETAILED DESCRIPTION · 3 of 31

The term “macrocyclic ring” as used herein refers to a ring having at least 11 annular atoms within a single mono-cyclic ring. The macrocyclic ring may be monocyclic or polycyclic, including but not limited to bridged, fused and spiro rings, provided that the ring system comprises at least one mono-cyclic ring having at least 11 annular atoms. The number of members or atoms in a macrocyclic ring is determined by counting total ring members in the shortest path around the macrocycle. In certain embodiments, the macrocyclic ring is a 12 to 20 membered ring, a 12 to 19 membered ring, a 13 to 19 membered ring, a 12 to 18 membered ring, a 12 to 16 membered ring, a 14 to 20 membered ring, a 14 to 19 membered ring, a 14 to 18 membered ring, a 14 to 16 membered ring, a 20 membered ring, a 19 membered ring, a 18 membered ring, a 17 membered ring, a 16 membered ring, a 15 membered ring, a 14 membered ring, a 13 membered ring, or a 12 membered ring. Examples of a 14-membered macrocyclic ring include, e.g.:

Examples of a 12-membered macrocyclic ring include, e.g.:

“Bridged” refers to a ring fusion wherein non-adjacent atoms on a ring are joined by a divalent substituent, such as an alkylene or heteroalkylene group or a single heteroatom. Quinuclidinyl and adamantyl are examples of bridged ring systems.

“Spiro” refers to a ring substituent which is joined by two bonds at the same carbon atom. Examples of spiro groups include 1,1-diethylcyclopentane, dimethyl-dioxolane, and 4-benzyl-4-methylpiperidine, wherein the cyclopentane and piperidine, respectively, are the spiro substituents. When substituents bound to the same atom join together (e.g., two Z 8 groups join together) they may be taken from the same point of attachment to form a spiro ring.

The term “fused” refers to a ring which is bound to an adjacent ring.

“Oxo” refers to ═O or —O − . “Hydroxyl” and “hydroxy” are used interchangeably and refer to —OH. Where tautomeric forms of the compound exist, hydroxyl and oxo groups are interchangeable.

It is understood that combinations of chemical groups may be used and will be recognized by persons of ordinary skill in the art. For instance, the group “hydroxyalkyl” would refer to a hydroxyl group attached to an alkyl group. A great number of such combinations may be readily envisaged. Additional examples of substituent combinations used herein include: C 1-6 alkylamiocarbonyl (e.g., CH 3 CH 2 NHC(O)—), C 1-6 alkoxycarbonyl (e.g., CH 3 O—C(O)—), 5-7 membered heterocyclyl-C 1-6 alkyl (e.g., piperazinyl-CH 2 —), C 1-6 alkylsulfonyl-5-7 membered heterocyclyl (e.g., CH 3 S(O) 2 -morpholinyl-), 5-7 membered heterocyclyl C 1-6 alkoxy, 5-7 membered heterocyclyloxy, (4-7 membered heterocyclyl)-4-7 membered heterocyclyl (e.g., oxetanyl-pyrrolidinyl-), C 3-6 cycloalkylaminocarbonyl (e.g., cyclopropyl-NH—C(O)—), 5-7 membered heterocyclyl-C 2-6 alkynyl (e.g., N-piperazinyl-CH 2 C≡CCH 2 —), and C 6-10 arylaminocarbonyl (e.g., phenyl-NH—C(O)—).

Certain commonly used alternative chemical names may be used. For example, a divalent group such as a divalent “alkyl” group, a divalent “aryl” group, etc., may also be referred to as an “alkylene” group or an “alkylenyl” group, an “arylene” group or an “arylenyl” group, respectively. The suffix “ene” is often used to refer to a group that has two single bond points of attachments to other groups. For example, methylene refers to —CH 2 —. Similarly, alkylene, alkenylene, alkynylene, cycloalkylene, heterocyclene, arylene, and heteroarylene refer to respective alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups as defined herein having two single bond points of attachments to other groups. Also, unless indicated explicitly otherwise, where combinations of groups are referred to herein as one moiety, e.g., arylalkyl, the last-mentioned group contains the atom by which the moiety is attached to the rest of the molecule.

The compounds described herein include isomers, stereoisomers and the like. As used herein, the term “isomers” refers to different compounds that have the same molecular formula but differ in arrangement and configuration of the atoms. Also as used herein, the term “a stereoisomer” refers to any of the various stereo isomeric configurations which may exist for a given compound disclosed herein and includes geometric isomers. It is understood that a substituent may be attached at a chiral center of a carbon atom. Therefore, the compound disclosed herein includes enantiomers, diastereomers or racemates of the compound.

“Enantiomers” are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a “racemic” mixture.

The term is used to designate a racemic mixture where appropriate. “Diastereoisomers” are stereoisomers that have at least two stereocenters, but which are not mirror-images of each other.

The absolute stereochemistry is specified according to the Cahn-Ingold-Prelog R—S system. When a compound is a pure enantiomer the stereochemistry at each chiral carbon may be specified by either R or S. Resolved compounds whose absolute configuration is unknown can be designated (+) or (−) depending on the direction (dextro- or levorotatory) which they rotate plane polarized light at the wavelength of the sodium D line. Certain of the compounds described herein contain one or more asymmetric centers and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)-. The present disclosure is meant to include all such possible isomers, including racemic mixtures, optically pure forms and intermediate mixtures. Optically active (R)- and (S)-isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be E or Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis- or trans-configuration. All tautomeric forms are also intended to be included. To the extent that compounds depicted herein are represented as having a particular stereochemistry, it is understood by one of skill in the art that such compounds may contain some detectable or undetectable levels of compounds sharing the same structure, but having different stereochemistry.

›DETAILED DESCRIPTION · 4 of 31

“IC 95 ” or “EC 95 ” refers to the inhibitory concentration required to achieve 95% of the maximum desired effect, which in many cases herein is the inhibition of the PAD4 enzyme.

“IC 50 ” or “EC 50 ” refers to the inhibitory concentration required to achieve 50% of the maximum desired effect, which in many cases herein is the inhibition of the PAD4 enzyme.

“Pharmaceutically acceptable” refers to compounds, salts, compositions, dosage forms and other materials which are useful in preparing a pharmaceutical composition that is suitable for veterinary or human pharmaceutical use.

“Pharmaceutically acceptable excipient” includes without limitation any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye/colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier which has been approved by the United States Food and Drug Administration as being acceptable for use in humans or domestic animals.

“Pharmaceutically acceptable salt” refers to a salt of a compound that is pharmaceutically acceptable and that possesses (or can be converted to a form that possesses) the desired pharmacological activity of the parent compound. Such salts include acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, lactic acid, maleic acid, malonic acid, mandelic acid, methanesulfonic acid, 2-napththalenesulfonic acid, oleic acid, palmitic acid, propionic acid, stearic acid, succinic acid, tartaric acid, p-toluenesulfonic acid, trimethylacetic acid, and the like, and salts formed when an acidic proton present in the parent compound is replaced by either a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as diethanolamine, triethanolamine, N-methylglucamine and the like. Also included in this definition are ammonium and substituted or quaternized ammonium salts. Representative non-limiting lists of pharmaceutically acceptable salts can be found in S. M. Berge et al., J. Pharma Sci., 66(1), 1-19 (1977), and Remington: The Science and Practice of Pharmacy, R. Hendrickson, ed., 21st edition, Lippincott, Williams & Wilkins, Philadelphia, PA, (2005), at p. 732, Table 38-5, both of which are hereby incorporated by reference herein.

Compounds disclosed herein include isotopically labeled, solvates, hydrates, tautomers, stereoisomers and salt forms thereof.

Provided are also compounds in which from 1 to n hydrogen atoms attached to a carbon atom may be replaced by deuterium atom or D, in which n is the number of hydrogen atoms in the molecule. As known in the art, the deuterium atom is a non-radioactive isotope of the hydrogen atom. Such compounds exhibit may increase resistance to metabolism, and thus may be useful for increasing the half-life of the compounds when administered to a mammal. See, e.g., Foster, “Deuterium Isotope Effects in Studies of Drug Metabolism,” Trends Pharmacol. Sci., 5(12):524-527 (1984). Such compounds are synthesized by means well known in the art, for example by employing starting materials in which one or more hydrogen atoms have been replaced by deuterium.

Any formula or structure given herein, including Formula (I), or any formula disclosed herein, is intended to represent unlabeled forms as well as isotopically labeled forms of the compounds. Isotopically labeled compounds have structures depicted by the formulas given herein except that one or more (e.g., one to three, or one to five) atoms are replaced by an isotope having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into compounds of the disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as, but not limited to 2 H (deuterium, D), 3 H (tritium), 11 C, 13 C, 14 C, 15 N, 18 F, 31 P, 32 P, 35 S, 36 Cl, and 125 I. Various isotopically labeled compounds of the present disclosure, for example those into which radioactive isotopes such as 3 H and 14 C are incorporated, are within the ambit of the present disclosure. Such isotopically labelled compounds may be useful in metabolic studies, reaction kinetic studies, detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays or in treatment of patients. Such isotopically labeled analogs of compounds of the present disclosure may also be useful for treatment of diseases disclosed herein because they may provide improved pharmacokinetic and/or pharmacodynamic properties over the unlabeled forms of the same compounds. Such isotopically leveled forms of or analogs of compounds herein are within the ambit of the present disclosure. One of skill in the art is able to prepare and use such isotopically labeled forms following procedures for isotopically labeling compounds or aspects of compounds to arrive at isotopic or radiolabeled analogs of compounds disclosed herein.

The present disclosure also provides for prodrugs of the compounds disclosed herein. A “prodrug” is defined in the pharmaceutical field as a biologically inactive derivative of a drug that upon administration to the human body is converted to the biologically active parent drug according to some chemical or enzymatic pathway.

Compounds

Provided herein are compounds that function as inhibitors of peptidylarginine deiminase type 4 (PAD4), methods of using such compounds and compositions comprising such compounds optionally in combination with one or more additional agents or therapies. In all embodiments discussed herein where there is more than one occurrence of a group or variable, it is intended that the group or variable is independently selected the list that follows. All embodiments directed to compounds also include any salt, stereoisomer, mixture of stereoisomers, prodrug, isotopically labeled, solvate, hydrate, or tautomer thereof. It is further contemplated that the macrocycle moiety of the compounds disclosed herein confers enhanced potency as inhibitors of peptidylarginine deiminase type 4 (PAD4).

›DETAILED DESCRIPTION · 5 of 31

Provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

X 1 and X 2 are C or N;

X 3 is N—R 3 or C—R 3 ; provided that two of X 1 , X 2 , and X 3 are C; where each dashed line represents an optional bond to complete valency requirements of each X 1 , X 2 and X 3 ;

X 4 is N or C—R 2 ;

X 5 is N or CR 6 ;

X 7 is N or CR 7 ;

L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are each independently:

C 1-10 alkylene, optionally substituted with 1 to 3 Z 8 ;

C 2-10 alkenylene, optionally substituted with 1 to 3 Z 8 ;

C 2-10 alkynylene, optionally substituted with 1 to 3 Z 8 ;

2-6 membered heteroalkylene, optionally substituted with 1 to 3 Z 8 ;

C 3 -C 10 cycloalkylene, optionally substituted with 1 to 3 Z 8 ;

4-10 membered heterocyclene, optionally substituted with 1 to 3 Z 8 ;

C 6-10 arylene, optionally substituted with 1 to 3 Z 8 ;

5-10 membered heteroarylene, optionally substituted with 1 to 3 Z 8 ; or

—O—, —N(R 8 )—, —S—, —C(O)—, —C(O)O—, —C(O)N(R 8 )—, —SO—, —SO 2 —, —SO 2 N(R 8 )—, —N(R 8 )C(O)O—, —OC(O)O—, —N(R 8 )C(O)N(R 8 )—, —N(R 8 )S(O) 2 N(R 8 )—, —N(R 8 )C(N—CN)—, —S(O)(NR 8 )—, or —S(O)(NR 8 )N(R 8 )—; each of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 may be the same or different; and

m1, m2, m3, m4, m5, and m6 are each independently 0 or 1; each of m1, m2, m3, m4, m5, and m6 may be the same or different;

R 10 is hydrogen, —C 1-8 alkyl optionally substituted with 1 to 3 Z 10 , or C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 10 ;

R 10 and R 11 are taken together to form a 4-12-membered heterocyclyl optionally substituted with 1 to 4 Z 11 ;

each Z 1 , Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 is independently oxo, halo, —NO 2 , —N 3 , —CN, C 1-8 alkyl optionally substituted by 1 to 3 Z 1a , C 2-8 alkenyl optionally substituted by 1 to 3 Z 1a , C 2-8 alkynyl optionally substituted by 1 to 3 Z 1a , C 3-8 cycloalkyl optionally substituted by 1 to 3 Z 1a , 6-10 membered aryl optionally substituted by 1 to 3 Z 1a , 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z 1a , 5-10 membered heteroaryl optionally substituted with 1 to 3 Z 1a , —OR 9 , —C(O)R 9 , —C(O)OR 9 , —C(O)N(R 9 ) 2 , —N(R 9 ) 2 , —N(R 9 ) 3 + , —N(R 9 )C(O)R 9 , —N(R 9 )C(O)OR 9 , —N(R 9 )C(O)N(R 9 ) 2 , —N(R 9 )S(O) 2 (R 9 ), —NR 9 S(O) 2 N(R 9 ) 2 , —NR 9 S(O) 2 O(R 9 ), —NS(O)(R 9 ) 2 , —OC(O)R 9 , —OC(O)OR 9 , —OC(O)N(R 9 ) 2 , —Si(R 9 ) 3 , —SR 9 , —S(O)R 9 , —SF 5 , —S(O)(NR 9 )R 9 , —S(NR 9 )(NR 9 )R 9 , —S(O)(NR 9 )N(R 9 ) 2 , —S(O)(NCN)R 9 , —S(O) 2 R 9 , —S(O) 2 N(R 9 ) 2 , —C(O)N(R 9 )S(O) 2 R 9 , or —S(O) 2 N(R 9 )C(O)R 9 , wherein each Z 1 , Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 is independently optionally substituted with 1 to 3 Z 1a ; each Z 1 , Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 may be the same or different;

›DETAILED DESCRIPTION · 6 of 31

Also provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

X 1 and X 2 are C or N;

X 3 is N—R 3 or C—R 3 ; provided that two of X 1 , X 2 , and X 3 are C; where each dashed line represents an optional bond to complete valency requirements of each X 1 , X 2 and X 3 ;

›DETAILED DESCRIPTION · 7 of 31

X 4 is N or C—R 2 ;

X 5 is N or CR 6 ;

X 7 is N or CR 7 ;

R 2 is hydrogen, halo, —CN, —OR 12 , —N(R 12 ) 2 , —SR 12 , —C 1-8 alkyl optionally substituted with 1 to 3 Z 1 , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 2 , or 4-6 membered heterocyclyl optionally substituted with 1 to 3 Z 2 ;

L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are each independently:

C 1-10 alkylene, optionally substituted with 1 to 3 Z 8 ;

C 2-10 alkenylene, optionally substituted with 1 to 3 Z 8 ;

C 2-10 alkynylene, optionally substituted with 1 to 3 Z 8 ;

2-6 membered heteroalkylene, optionally substituted with 1 to 3 Z 8 ;

C 3 -C 10 cycloalkylene, optionally substituted with 1 to 3 Z 8 ;

4-10 membered heterocyclene, optionally substituted with 1 to 3 Z 8 ;

C 6-10 arylene, optionally substituted with 1 to 3 Z 8 ;

5-10 membered heteroarylene, optionally substituted with 1 to 3 Z 8 ; or

m1, m2, m3, m4, m5, and m6 are each independently 0 or 1;

R 10 is hydrogen, —C 1-8 alkyl optionally substituted with 1 to 3 Z 10 , or C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 10 ;

R 10 and R 11 are taken together to form a 4-12-membered heterocyclyl optionally substituted with 1 to 4 Z 11 ;

›DETAILED DESCRIPTION · 8 of 31

Provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

X 1 and X 2 are C or N;

X 3 is N—R 3 or C—R 3 ; provided that two of X 1 , X 2 , and X 3 are C; where each dashed line represents an optional bond to complete valency requirements of each X 1 , X 2 and X 3 ;

X 4 is N or C—R 2 ;

X 5 is N or CR 6 ;

X 7 is N or CR 7 ;

›DETAILED DESCRIPTION · 9 of 31

L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are each independently:

C 1-10 alkylene, optionally substituted with 1 to 3 Z 8 ;

C 2-10 alkenylene, optionally substituted with 1 to 3 Z 8 ;

C 2-10 alkynylene, optionally substituted with 1 to 3 Z 8 ;

2-6 membered heteroalkylene, optionally substituted with 1 to 3 Z 8 ;

C 3 -C 10 cycloalkylene, optionally substituted with 1 to 3 Z 8 ;

4-10 membered heterocyclene, optionally substituted with 1 to 3 Z 8 ;

C 6-10 arylene, optionally substituted with 1 to 3 Z 8 ;

5-10 membered heteroarylene, optionally substituted with 1 to 3 Z 8 ; or

m1, m2, m3, m4, m5, and m6 are each independently 0 or 1;

R 10 is hydrogen, —C 1-8 alkyl optionally substituted with 1 to 3 Z 10 , or C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 10 ;

R 10 and R 11 are taken together to form a 4-12-membered heterocyclyl optionally substituted with 1 to 4 Z 11 ;

each Z 1 , Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 is independently oxo, halo, —NO 2 , —N 3 , —CN, C 1-8 alkyl optionally substituted by 1 to 3 Z 1b , C 2-8 alkenyl optionally substituted by 1 to 3 Z 1b , C 2-8 alkynyl optionally substituted by 1 to 3 Z 1b , C 3-8 cycloalkyl optionally substituted by 1 to 3 Z 1b , 6-10 membered aryl optionally substituted by 1 to 3 Z 1b , 4-10 membered heterocyclyl optionally substituted by 1 to 3 Z 1b , 5-10 membered heteroaryl optionally substituted with 1 to 3 Z 1a , —OR 9 , —C(O)R 9 , —C(O)OR 9 , —C(O)N(R 9 ) 2 , —N(R 9 ) 2 , —N(R 9 ) 3 + , —N(R 9 )C(O)R 9 , —N(R 9 )C(O)OR 9 , —N(R 9 )C(O)N(R 9 ) 2 , —N(R 9 )S(O) 2 (R 9 ), —NR 9 S(O) 2 N(R 9 ) 2 , —NR 9 S(O) 2 O(R 9 ), —NS(O)(R 9 ) 2 , —OC(O)R 9 , —OC(O)OR 9 , —OC(O)N(R 9 ) 2 , —Si(R 9 ) 3 , —SR 9 , —S(O)R 9 , —SF 5 , —S(O)(NR 9 )R 9 , —S(NR 9 )(NR 9 )R 9 , —S(O)(NR 9 )N(R 9 ) 2 , —S(O)(NCN)R 9 , —S(O) 2 R 9 , —S(O) 2 N(R 9 ) 2 , —C(O)N(R 9 )S(O) 2 R 9 , or —S(O) 2 N(R 9 )C(O)R 9 ,

›DETAILED DESCRIPTION · 10 of 31

In certain embodiments, each Z 1 , Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 , Z 10 , and Z 11 are independently oxo, hydroxy, halo, —NO 2 , —N 3 , —CN, C 1-9 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, C 1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, —O(C 1-9 alkyl), —O(C 2-6 alkenyl), —O(C 2-6 alkynyl), —O(C 3-15 cycloalkyl), —O(C 1-8 haloalkyl), —O(aryl), —O(heteroaryl), —O(heterocyclyl), —OC(O) (C 1-9 alkyl), —OC(O)(C 2-6 alkenyl), —OC(O)(C 2-6 alkenyl), —OC(O)(C 2-6 alkynyl), —OC(O)(C 3-15 cycloalkyl), —OC(O)(C 1-8 haloalkyl), —OC(O)(aryl), —OC(O)(heteroaryl), —OC(O)(heterocyclyl), —NH 2 , —NH(C 1-9 alkyl), —NH(C 2-6 alkenyl), —NH(C 2-6 alkynyl), —NH(C 3-15 cycloalkyl), —NH(C 1-8 haloalkyl), —NH(aryl), —NH(heteroaryl), —NH(heterocyclyl), —N(C 1-9 alkyl) 2 , —N(C 3-15 cycloalkyl) 2 , —N(C 2-6 alkenyl) 2 , —N(C 2-6 alkynyl) 2 , —N(C 3-15 cycloalkyl) 2 , —N(C 1-8 haloalkyl) 2 , —N(aryl) 2 , —N(heteroaryl) 2 , —N(heterocyclyl) 2 , —N(C 1-9 alkyl)(C 3-15 cycloalkyl), —N(C 1-9 alkyl)(C 2-6 alkenyl), —N(C 1-9 alkyl)(C 2-6 alkynyl), —N(C 1-9 alkyl)(C 3-15 cycloalkyl), —N(C 1-9 alkyl)(C 1-8 haloalkyl), —N(C 1-9 alkyl)(aryl), —N(C 1-9 alkyl)(heteroaryl), —N(C 1-9 alkyl)(heterocyclyl), —C(O)(C 1-9 alkyl), —C(O)(C 2-6 alkenyl), —C(O)(C 2-6 alkynyl), —C(O)(C 3-15 cycloalkyl), —C(O)(C 1-8 haloalkyl), —C(O)(aryl), —C(O)(heteroaryl), —C(O)(heterocyclyl), —C(O)O(C 1-9 alkyl), —C(O)O(C 2-6 alkenyl), —C(O)O(C 2-6 alkynyl), —C(O)O(C 3-15 cycloalkyl), —C(O)O(C 1-8 haloalkyl), —C(O)O(aryl), —C(O)O(heteroaryl), —C(O)O(heterocyclyl), —C(O)NH 2 , —C(O)NH(C 1-9 alkyl), —C(O)NH(C 2-6 alkenyl), —C(O)NH(C 2-6 alkynyl), —C(O)NH(C 3-15 cycloalkyl), —C(O)NH(C 1-8 haloalkyl), —C(O)NH(aryl), —C(O)NH(heteroaryl), —C(O)NH(heterocyclyl), —C(O)N(C 1-9 alkyl) 2 , —C(O)N(C 3-15 cycloalkyl) 2 , —C(O)N(C 2-6 alkenyl) 2 , —C(O)N(C 2-6 alkynyl) 2 , —C(O)N(C 1-8 haloalkyl) 2 , —C(O)N(aryl) 2 , —C(O)N(heteroaryl) 2 , —C(O)N(heterocyclyl) 2 , —NHC(O)(C 1-9 alkyl), —NHC(O)(C 2-6 alkenyl), —NHC(O)(C 2-6 alkynyl), —NHC(O)(C 3-15 cycloalkyl), —NHC(O)(C 1-8 haloalkyl), —NHC(O)(aryl), —NHC(O)(heteroaryl), —NHC(O)(heterocyclyl), —NHC(O)O(C 1-9 alkyl), —NHC(O)O(C 2-6 alkenyl), —NHC(O)O(C 2-6 alkynyl), —NHC(O)O(C 3-15 cycloalkyl), —NHC(O)O(C 1-8 haloalkyl), —NHC(O)O(aryl), —NHC(O)O(heteroaryl), —NHC(O)O(heterocyclyl), —NHC(O)NH(C 1-9 alkyl), —NHC(O)NH(C 2-6 alkenyl), —NHC(O)NH(C 2-6 alkynyl), —NHC(O)NH(C 3-15 cycloalkyl), —NHC(O)NH(C 1-8 haloalkyl), —NHC(O)NH(aryl), —NHC(O)NH(heteroaryl), —NHC(O)NH(heterocyclyl), —SH, —S(C 1-9 alkyl), —S(C 2-6 alkenyl), —S(C 2-6 alkynyl), —S(C 3-15 cycloalkyl), —S(C 1-8 haloalkyl), —S(aryl), —S(heteroaryl), —S(heterocyclyl), —NHS(O)(C 1-9 alkyl), —N(C 1-9 alkyl)(S(O)(C 1-9 alkyl), —S(O)N(C 1-9 alkyl) 2 , —S(O)(C 1-9 alkyl), —S(O)(NH)(C 1-9 alkyl), —S(O)(C 2-6 alkenyl), —S(O)(C 2-6 alkynyl), —S(O)(C 3-15 cycloalkyl), —S(O)(C 1-8 haloalkyl), —S(O)(aryl), —S(O)(heteroaryl), —S(O)(heterocyclyl), —S(O) 2 (C 1-9 alkyl), —S(O) 2 (C 2-6 alkenyl), —S(O) 2 (C 2-6 alkynyl), —S(O) 2 (C 3-15 cycloalkyl), —S(O) 2 (C 1-8 haloalkyl), —S(O) 2 (aryl), —S(O) 2 (heteroaryl), —S(O) 2 (heterocyclyl), —S(O) 2 NH(C 1-9 alkyl), or —S(O) 2 N(C 1-9 alkyl) 2 ;

In certain embodiments, R 1 is hydrogen, fluoro, chloro, —CN, —OR 12 , C 1-6 alkyl optionally substituted with 1 to 3 Z 1 , or C 3-5 cycloalkyl optionally substituted with 1 to 3 Z 1 . In certain embodiments, R 1 is hydrogen, fluoro, chloro, —CN, —OR 12 , —C 1-6 alkyl, or C 3-5 cycloalkyl. In certain embodiments, R 1 is hydrogen, fluoro, chloro, —CH 3 , or —OCH 3 . In certain embodiments, R 1 is hydrogen. In certain embodiments, R 1 is fluoro.

In certain embodiments, R 2 is hydrogen, fluoro, chloro, —OR 12 , —N(R 12 ) 2 , C 1-5 alkyl optionally substituted with 1 to 3 Z 2 , or C 3-5 cycloalkyl optionally substituted with 1 to 3 Z 2 . In certain embodiments, R 2 is hydrogen, fluoro, chloro, —OR 12 , —N(R 12 ) 2 , C 1-5 alkyl optionally substituted with 1 to 3 halo, or C 3-5 cycloalkyl optionally substituted with 1 to 3 halo.

In certain embodiments, R 2 is hydrogen, —F, —Cl—CH 3 , —CF 3 , —CHF 2 , cyclopropyl, —OCH 3 , —O-ethyl, —O-propyl, —O-isopropyl, —O-cyclopropyl, —OCF 3 , or —OCHF 2 . In certain embodiments, R 2 is fluoro. In certain embodiments, R 2 is —OCH 3 .

›DETAILED DESCRIPTION · 11 of 31

In certain embodiments, R 3 is hydrogen, C 1-6 alkyl optionally substituted with 1 to 3 Z 3 , C 2-6 alkenyl optionally substituted with 1 to 3 Z 3 , C 2-6 alkynyl optionally substituted with 1 to 3 Z 3 , or C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 3 .

In certain embodiments, X 3 is C—R 3 and R 3 is hydrogen, fluoro, chloro, —CN, —OR 12 , —N(R 12 ) 2 , C 1-6 alkyl optionally substituted with 1 to 3 Z 3 , C 2-6 alkenyl optionally substituted with 1 to 3 Z 3 , C 2-6 alkynyl optionally substituted with 1 to 3 Z 3 , or C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 3 .

In certain embodiments, X 3 is N—R 3 and R 3 is hydrogen, C 1-6 alkyl optionally substituted with 1 to 3 Z 3 , C 3-6 alkenyl optionally substituted with 1 to 3 Z 3 , C 3-6 alkynyl optionally substituted with 1 to 3 Z 3 , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 3 , or 4-6 membered heterocyclyl optionally substituted with 1 to 3 Z 3 .

In certain embodiments, X 3 is N—R 3 and R 3 is —CH 3 , —C 2 H 5 , —CH 2 CHF 2 , —CH 2 CF 3 , —CH 2 CH 2 OCH 3 , —CH 2 CH(CH 3 )OCH 3 , —CH 2 CH 2 OCH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , —CH 2 CH 2 OCH 2 CH 3 , —CH 2 CH 2 CN, —CH 2 CH 2 CONH 2 , —CH 2 CH(CH 3 )OCH 3 , cyclopropyl, cyclobutyl,

In certain embodiments, X is N—R and R is C 1-6 alkyl optionally substituted with 1 to 3 Z 3 or C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 3 . In certain embodiments, X 3 is N and N—R 3 is methyl, (1-fluorocyclopropyl)methyl, (1-cyanocyclopropyl)methyl, 2-(difluoromethyl)cyclopropyl, 2-methylcyclopropyl, (1-methoxycyclopropyl)methyl. 2-methoxyethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, cyclobutyl, isopropyl, ethyl, 2-isopropoxyethyl, 2-ethoxyethyl, 2-cyanoethyl, 2-(2-methoxyethoxy)ethyl, 3-amino-3-oxopropyl, 2-phenoxyethyl, 2-methoxypropyl, 2-(pyridin-2-yloxy)ethyl, 2-fluorocyclopropyl, or 2-methoxy cyclopropyl.

In certain embodiments, X 3 is N—R 3 . In certain embodiments, X 3 is N—R 3 and R 3 is alkyl or cycloalkyl. In certain embodiments, X 3 is N—R 3 and R 3 is methyl or cyclopropyl. In certain embodiments, X 3 is N—R 3 and R 3 is alkyl. In certain embodiments, X 3 is N—R 3 and R 3 is methyl. In certain embodiments, X 3 is N—R 3 and R 3 is cycloalkyl. In certain embodiments, X 3 is N—R 3 and R 3 is cyclopropyl.

In certain embodiments, X 3 is C—R 3 . In certain embodiments, X 3 is C—R 3 and R 3 is alkyl or cycloalkyl. In certain embodiments, X 3 is C—R 3 and R 3 is methyl or cyclopropyl. In certain embodiments, X 3 is C—R 3 and R 3 is alkyl. In certain embodiments, X 3 is C—R 3 and R 3 is methyl. In certain embodiments, X 3 is C—R 3 and R 3 is cycloalkyl. In certain embodiments, X 3 is C—R 3 and R 3 is cyclopropyl.

In certain embodiments, X 4 is N. In certain embodiments, X 4 is C—R 2 . In certain embodiments, X 4 is C—R 2 and R 2 is hydrogen, halo, or —OR 12 . In certain embodiments, X 4 is C—R 2 and R 2 is hydrogen, fluoro, or —O—CH 3 . In certain embodiments, X 4 is C—R 2 and R 2 is hydrogen, fluoro, chloro, or —O—CH 3 . In certain embodiments, X 4 is C—H. In certain embodiments, X 4 is C—F. In certain embodiments, X 4 is C—Cl. In certain embodiments, X 4 is C—CH 3 .

In certain embodiments, X 5 is N. In certain embodiments, X 5 is C—R 6 . In certain embodiments, R 6 is hydrogen, fluoro, chloro, —CN, —CF 3 , —CHF 2 , —OR 12 , —C 1-5 alkyl, or C 3-5 cycloalkyl. In certain embodiments, R 6 is hydrogen, fluoro, chloro, —CH 3 , —OCH 3 , or cyclopropyl. In certain embodiments, R 6 is hydrogen, fluoro, or chloro. In certain embodiments, R 6 is hydrogen or fluoro. In certain embodiments, R 6 is hydrogen. In certain embodiments, R 6 is fluoro.

In certain embodiments, X 7 is N. In certain embodiments, X 7 is C—R 7 . In certain embodiments, R 7 is hydrogen, fluoro, chloro, —CN, —CF 3 , —CHF 2 , —OR 12 , —C 1-3 alkyl, or C 3-5 cycloalkyl. In certain embodiments, R 7 is hydrogen, fluoro, chloro, —CH 3 , —OCH 3 , or cyclopropyl. In certain embodiments, X 7 is C—H. In certain embodiments, R 7 is hydrogen, fluoro, or chloro. In certain embodiments, R 7 is hydrogen or fluoro. In certain embodiments, R 7 is hydrogen. In certain embodiments, R 7 is fluoro.

In certain embodiments, X 5 is N and X 7 is C—R 7 . In certain embodiments, X 5 is N and X 7 is C—H.

In certain embodiments, R 10 is hydrogen or —CH 3 , and R 11 is hydrogen, C 1-6 alkyl optionally substituted with 1 to 3 Z 11 , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 11 , or 4-12-membered heterocyclyl optionally substituted with 1 to 3 Z 11 ; or R 10 and R 11 taken together form a 4-10-membered heterocyclyl optionally substituted with 1 to 3 Z 11 .

In certain embodiments, R 10 is hydrogen or —CH 3 , and R 11 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, or 4-12-membered heterocyclyl optionally substituted with 1 to 3 Z 11 ; or R 10 and R 11 taken together with the nitrogen to which they are attached to form a 4-10-membered heterocyclyl optionally substituted with 1 to 3 Z 11 .

In certain embodiments, R 10 is hydrogen or —CH 3 , and R 11 is 4-12 membered heterocyclyl optionally substituted with 1 to 3 Z 11 .

In certain embodiments, R 10 is hydrogen, and R 11 is 5-10 membered heterocyclyl optionally substituted with 1 to 3 substituents selected from the group consisting of —CH 3 , —CF 3 , fluoro, —OH, —NH 2 , —COOH, and —OCH 3 . In certain embodiments, R 10 is hydrogen, and R 11 is pyrrolidinyl or piperidinyl, wherein pyrrolidinyl or piperidinyl may be monocyclic or part of a bicyclic system, and may be optionally substituted with 1 to 3 substituents selected from the group consisting of —CH 3 , —CF 3 , fluoro, —OH, —COOH, and —OCH 3 .

In certain embodiments, R 10 and R 11 taken together with the nitrogen to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with 1 to 3 Z 11 .

In certain embodiments of Formula (I), the moiety

is:

In certain embodiments of Formula (I), the moiety

is:

In certain embodiments of Formula (I), the moiety

is:

In certain embodiments of Formula (I), the moiety

is:

In certain embodiments of Formula (I), the moiety

›DETAILED DESCRIPTION · 12 of 31

is:

In certain embodiments of Formula (I), the moiety

is:

In certain embodiments, L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are each independently:

C 1-10 alkylene optionally substituted with 1 to 2 Z 8 ; C 2-10 alkenylene optionally substituted with 1 to 2 Z 8 ; C 2-10 alkynylene optionally substituted with 1 to 2 Z 8 ; 2 to 6 membered heteroalkylene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 3 -C 10 cycloalkylene optionally substituted with 1 to 2 Z 8 ; 4-8 membered heterocyclene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 6-10 arylene optionally substituted with 1 to 3 Z 8 ; 5-10 membered heteroarylene having 1 to 3 heteroatoms selected from O, N, and S and optionally substituted with 1 to 3 Z 8 ; or —O—, —N(R 8 )—, —C(O)—, —C(O)O—, —C(O)N(R 8 )—, —SO 2 N(R 8 )—, —SO 2 —, —N(R 8 )C(O)O—, —OC(O)O—, or —N(R 8 )C(O)N(R 8 ); and m1, m2, m3, m4, m5, and m6 are each independently 0 or 1; provided that L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 11 to 20 membered macrocyclic ring.

It is to be understood that the directionality of the L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 moieties recited above is not intended to be limiting. For example, —C(O)O— also encompasses —OC(O)—, —C(O)N(R 8 )— also encompasses —N(R 8 )C(O)—, —SO 2 N(R 8 )— also encompasses —N(R 8 )SO 2 —, and —N(R 8 )C(O)O— also encompasses —OC(O)N(R 8 )—.

In certain embodiments, L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 12 to 18 membered macrocyclic ring. In certain embodiments, L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 12 to 16 membered macrocyclic ring. In certain embodiments, L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 12 to 14 membered macrocyclic ring. In certain embodiments, L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 14 to 16 membered macrocyclic ring. In certain embodiments, L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 14 membered macrocyclic ring.

In certain embodiments, L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are each independently:

C 1-10 alkylene optionally substituted with 1 to 2 Z 8 ; C 2-10 alkenylene optionally substituted with 1 to 2 Z 8 ; 2 to 6 membered heteroalkylene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 3 -C 10 cycloalkylene optionally substituted with 1 to 2 Z 8 ; 4-8 membered heterocyclene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 6-10 arylene optionally substituted with 1 to 3 Z 8 ; 5-10 membered heteroarylene having 1 to 3 heteroatoms selected from O, N, and S and optionally substituted with 1 to 3 Z 8 ; or —O—, —N(R 8 )—, —C(O)—, —C(O)N(R 8 )—, —SO 2 N(R 8 )—, or —N(R 8 )C(O)N(R 8 ); and m1, m2, m3, m4, m5, and m6 are each independently 0 or 1; provided that L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 11 to 20 membered macrocyclic ring, or an optionally substituted 12 to 18 membered macrocyclic ring, or an optionally substituted 12 to 16 membered macrocyclic ring, or an optionally substituted 14 membered macrocyclic ring.

In certain embodiments, L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are each independently:

C 1-3 alkylene optionally substituted with 1 to 2 Z 8 ; C 2-3 alkenylene optionally substituted with 1 to 2 Z 8 ; 2 to 5 membered heteroalkylene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 3 -C 10 cycloalkylene optionally substituted with 1 to 2 Z 8 ; 4-8 membered heterocyclene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 6 arylene optionally substituted with 1 to 3 Z 8 ; 5-10 membered heteroarylene having 1 to 3 heteroatoms selected from O, N, and S and optionally substituted with 1 to 3 Z 8 ; or —O—, —N(R 8 )—, —C(O)—, —C(O)N(R 8 )—, —SO 2 N(R 8 )—, or —N(R 8 )C(O)N(R 8 ); and m1, m2, m3, m4, m5, and m6 are each independently 0 or 1; provided that L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 11 to 20 membered macrocyclic ring, or an optionally substituted 12 to 18 membered macrocyclic ring, or an optionally substituted 12 to 16 membered macrocyclic ring, or an optionally substituted 14 membered macrocyclic ring.

In certain embodiments, the macrocyclic ring moiety

is an optionally substituted 12 to 18 membered macrocyclic ring, or an optionally substituted 12 to 16 membered macrocyclic ring, or an optionally substituted 14 membered macrocyclic ring.

In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is C 1-3 alkylene optionally substituted with 1 to 2 Z 8 .

In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is C 3 -C 10 cycloalkylene optionally substituted with 1 to 2 Z 8 .

In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is —O—, —N(R 8 )—, —C(O)—, —C(O)N(R 8 )—, —SO 2 N(R 8 )—, or —N(R 8 )C(O)N(R 8 ). In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is —O—. In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is —N(R 8 )—. In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is —C(O)—. In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is —C(O)N(R 8 )—. In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is —SO 2 N(R 8 )—. In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is —N(R 8 )C(O)N(R 12 ). In certain embodiments, at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is —CONH—.

›DETAILED DESCRIPTION · 13 of 31

In certain embodiments, at least one of m1, m2, m3, m4, m5, and m6 is 0. In certain embodiments, one of m1, m2, m3, m4, m5, and m6 is 0. In certain embodiments, two of m1, m2, m3, m4, m5, and m6 are 0. In certain embodiments, three of m1, m2, m3, m4, m5, and m6 are 0. In certain embodiments, four of m1, m2, m3, m4, m5, and m6 are 0. In certain embodiments, each of m1, m2, m3, m4, m5, and m6 are 1. In certain embodiments, m1 is 0. In certain embodiments, m1 is 1. In certain embodiments, m2 is 0. In certain embodiments, m2 is 1. In certain embodiments, m3 is 0. In certain embodiments, m3 is 1. In certain embodiments, m4 is 0. In certain embodiments, m4 is 1. In certain embodiments, m5 is 0. In certain embodiments, m5 is 1. In certain embodiments, m6 is 0. In certain embodiments, m6 is 1. In certain embodiments, m1 is 0, and each of m2, m3, m4, m5, and m6 are 1.

In certain embodiments, L 1 , L 2 , and L 3 are each independently:

C 1-10 alkylene optionally substituted with 1 to 2 Z 8 ; C 2-10 alkenylene optionally substituted with 1 to 2 Z 8 ; 2 to 6 membered heteroalkylene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 3 -C 10 cycloalkylene optionally substituted with 1 to 2 Z 8 ; and L 4 , L 5 , and L 6 are each independently: C 1-10 alkylene optionally substituted with 1 to 2 Z 8 ; 4-8 membered heterocyclene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 6-10 arylene optionally substituted with 1 to 3 Z 8 ; 5-10 membered heteroarylene having 1 to 3 heteroatoms selected from O, N, and S and optionally substituted with 1 to 3 Z 8 ; or —O—, —N(R 8 )—, —C(O)—, —C(O)N(R 8 )—, —SO 2 N(R 8 )—, or —N(R 8 )C(O)N(R 8 ); and m1, m2, m3, m4, m5, and m6 are each independently 0 or 1; provided that L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 11 to 20 membered macrocyclic ring, or an optionally substituted 12 to 18 membered macrocyclic ring, or an optionally substituted 12 to 16 membered macrocyclic ring, or an optionally substituted 14 membered macrocyclic ring.

In certain embodiments, L 1 , L 2 , and L 3 are each independently:

C 1-10 alkylene optionally substituted with 1 to 2 Z 8 ; C 2-10 alkenylene optionally substituted with 1 to 2 Z 8 ; 2 to 6 membered heteroalkylene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 3 -C 10 cycloalkylene optionally substituted with 1 to 2 Z 8 ; and L 4 and L 5 are each independently: 4-8 membered heterocyclene having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 2 Z 8 ; C 6-10 arylene optionally substituted with 1 to 3 Z 8 ; 5-10 membered heteroarylene having 1 to 3 heteroatoms selected from O, N, and S and optionally substituted with 1 to 3 Z 8 ; or —O—, —N(R 8 )—, —C(O)—, —C(O)N(R 8 )—, —SO 2 N(R 8 )—, or —N(R 8 )C(O)N(R 8 ); L 6 is: C 1-10 alkylene optionally substituted with 1 to 2 Z 8 ; and m1, m2, m3, m4, m5, and m6 are each independently 0 or 1; provided that L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 taken together with the four consecutive atoms between which they are attached form an optionally substituted 11 to 20 membered macrocyclic ring, or an optionally substituted 12 to 18 membered macrocyclic ring, or an optionally substituted 12 to 16 membered macrocyclic ring, or an optionally substituted 14 membered macrocyclic ring.

In certain embodiments, L 1 is C 1-10 alkylene, optionally substituted with 1 to 3 substituents selected from the group consisting of halo, —OCH 3 , and 5-6 membered heteroaryl optionally substituted with halo; L 2 is C 3 -C 10 cycloalkylene or C 2-10 alkenylene, wherein C 3 -C 10 cycloalkylene or C 2-10 alkenylene is optionally substituted with 1 to 3 substituents selected from the group consisting of halo, and C 1-5 alkyl optionally substituted with halo; L 3 is —O— or —O—C 1-6 alkylene; L 4 is C 1-10 alkylene optionally substituted with 1 to 3 Z 8 , 4-10 membered heterocyclene optionally substituted with 1 to 3 Z 8 , C 3 -C 10 cycloalkylene optionally substituted with 1 to 3 Z 8 , 5-10 membered heteroarylene optionally substituted with 1 to 3 Z 8 , or C 6-10 arylene optionally substituted with 1 to 3 Z 8 ; and m1 is 1.

In certain embodiments, X 5 is N and X 7 is C—H. In certain embodiments, X 5 and X 7 are C—H.

In certain embodiments, the macrocyclic ring moiety

is:

wherein each macrocyclic ring is further optionally substituted with 1-8 Z 8 .

In certain embodiments, the macrocyclic ring moiety

is:

wherein each macrocyclic ring is further optionally substituted with 1-8 Z 8 .

In certain embodiments, the macrocyclic ring moiety

is:

wherein each macrocyclic ring is further optionally substituted with 1-8 Z 8 .

In certain embodiments of any one of Formulas (I), (Ia)-(Id), and (Ip)-(It), the macrocyclic ring moiety

In certain embodiments, each R 8 is hydrogen. In certain embodiments, each R 8 is C 1-6 alkyl optionally substituted with 1 to 3 Z 1b . In certain embodiments, each R 8 is hydrogen or C 1-6 alkyl optionally substituted with 1 to 3 Z 1b . In certain embodiments, each R 8 is C 1-6 alkyl.

In certain embodiments, each R 8 is C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b . In certain embodiments, each R 8 is hydrogen, C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , or C 1-6 alkyl optionally substituted with 1 to 3 Z 1b . In certain embodiments, each R 8 is hydrogen, C 3-6 cycloalkyl optionally substituted with 1 to 3 halo, or C 1-6 alkyl optionally substituted with 1 to 3 halo.

In certain embodiments, each R 8 is a 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N optionally substituted with 1 to 3 Z 1b , C 6-10 aryl optionally substituted with 1 to 3 Z 1b , or 5-6 membered heteroaryl optionally substituted with 1 to 3 Z 1b . In certain embodiments, each R 8 is independently hydrogen, C 1-6 alkyl optionally substituted with 1 to 3 Z 1b , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N optionally substituted with 1 to 3 Z 1b , C 6-10 aryl optionally substituted with 1 to 3 Z 1b , or 5-6 membered heteroaryl optionally substituted with 1 to 3 Z 1b .

›DETAILED DESCRIPTION · 14 of 31

In certain embodiments, each R 8 is independently hydrogen, —CH 3 , ethyl, isopropyl, cyclopropyl, cyclobutyl, tert-butyl, CH 2 -cyclopropyl, fluorocyclopropyl, —CHF 2 , —CF 3 , —CH 2 CF 3 , or —CH 2 CHF 2 .

In certain embodiments, each R 12 and R 13 is independently hydrogen, C 1-6 alkyl optionally substituted with Z 1b , C 3-6 cycloalkyl optionally substituted with Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N optionally substituted with 1 to 3 Z 1b , C 6-10 aryl optionally substituted with 1 to 3 Z 1b , or 5-6 membered heteroaryl optionally substituted with 1 to 3 Z 1b .

In certain embodiments, each R 12 and R 13 is independently hydrogen, —CH 3 , ethyl, isopropyl, cyclopropyl, cyclobutyl, tert-butyl, CH 2 -cyclopropyl, fluorocyclopropyl, —CHF 2 , —CF 3 , —CH 2 CF 3 , or —CH 2 CHF 2 .

In certain embodiments, each R 12 is independently hydrogen, C 1-6 alkyl optionally substituted with 1 to 3 Z 1b , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N optionally substituted with 1 to 3 Z 1b , C 6-10 aryl optionally substituted with 1 to 3 Z 1b , or 5-6 membered heteroaryl optionally substituted with 1 to 3 Z 1b .

In certain embodiments, each R 12 is independently hydrogen, —CH 3 , ethyl, isopropyl, cyclopropyl, cyclobutyl, tert-butyl, CH 2 -cyclopropyl, fluorocyclopropyl, —CHF 2 , —CF 3 , —CH 2 CF 3 , or —CH 2 CHF 2 .

In certain embodiments, each Z 1 , Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 is independently halo, oxo, —CN, C 1-6 alkyl optionally substituted by 1 to 3 Z 1a , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N that is optionally substituted by 1 to 3 Z 1a , 5-6 membered heteroaryl having 1 to 4 heteroatoms selected from O and N and optionally substituted with 1 to 3 Z 1a , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

In certain embodiments, each Z 1 , Z 2 , Z 3 , Z 6 , Z 7 , and Z 8 is independently oxo, hydroxy, fluoro, chloro, —CN, —CH 3 , ethyl, isopropyl, tert-butyl, —CF 3 , —CHF 2 , cyclopropyl, cyclobutyl, —OCH 3 , —O-ethyl, —O-isopropyl, —O-cyclopropyl, —OCF 3 , —OCF 2 H, —C(O)-alkyl, —C(O)-cycloalkyl, —C(O)-aryl, —C(O)-heteroaryl, or —NH 2 .

In certain embodiments, each Z 1 is independently halo, oxo, —CN, C 1-6 alkyl optionally substituted by 1 to 3 Z 1a , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N that is optionally substituted by 1 to 3 Z 1a , 5-6 membered heteroaryl having 1 to 4 heteroatoms selected from O and N and optionally substituted with 1 to 3 Z 1a , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

In certain embodiments, each Z 1 is independently oxo, hydroxy, fluoro, chloro, —CN, —CH 3 , ethyl, isopropyl, tert-butyl, —CF 3 , —CHF 2 , cyclopropyl, cyclobutyl, —OCH 3 , —O-ethyl, —O— isopropyl, —O-cyclopropyl, —OCF 3 , —OCF 2 H, —C(O)-alkyl, —C(O)-cycloalkyl, —C(O)-aryl, —C(O)— heteroaryl, or —NH 2 .

In certain embodiments, each Z 2 is independently halo, oxo, —CN, C 1-6 alkyl optionally substituted by 1 to 3 Z 1a , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N that is optionally substituted by 1 to 3 Z 1a , 5-6 membered heteroaryl having 1 to 4 heteroatoms selected from O and N and optionally substituted with 1 to 3 Z 1a , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

In certain embodiments, each Z 2 is independently fluoro, chloro, —CN, C 1-6 alkyl optionally substituted with 1 to 3 Z 1b , C 3-6 cycloalkyl optionally substituted by 1 to 3 Z 1b , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

In certain embodiments, each Z 2 is independently oxo, hydroxy, fluoro, chloro, —CN, —CH 3 , ethyl, isopropyl, tert-butyl, —CF 3 , —CHF 2 , cyclopropyl, cyclobutyl, —OCH 3 , —O-ethyl, —O— isopropyl, —O-cyclopropyl, —OCF 3 , —OCF 2 H, —C(O)-alkyl, —C(O)-cycloalkyl, —C(O)-aryl, —C(O)— heteroaryl, or —NH 2 .

In certain embodiments, each Z 2 is independently fluoro, chloro, —CN, —OH, —OCH 3 , —OCHF 2 , —OCF 3 , —CH 3 , —CHF 2 , —CF 3 , —CH 2 OH, —CH 2 OCH 3 , or —NH 2 .

In certain embodiments, each Z 3 is independently halo, oxo, —CN, C 1-6 alkyl optionally substituted by 1 to 3 Z 1a , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N that is optionally substituted by 1 to 3 Z 1a , 5-6 membered heteroaryl having 1 to 4 heteroatoms selected from O and N and optionally substituted with 1 to 3 Z 1a , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

In certain embodiments, each Z 3 is independently oxo, hydroxy, fluoro, chloro, —CN, —CH 3 , ethyl, isopropyl, tert-butyl, —CF 3 , —CHF 2 , cyclopropyl, cyclobutyl, —OCH 3 , —O-ethyl, —O— isopropyl, —O-cyclopropyl, —OCF 3 , —OCF 2 H, —C(O)-alkyl, —C(O)-cycloalkyl, —C(O)-aryl, —C(O)— heteroaryl, or —NH 2 .

In certain embodiments, each Z 6 is independently halo, oxo, —CN, C 1-6 alkyl optionally substituted by 1 to 3 Z 1a , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N that is optionally substituted by 1 to 3 Z 1a , 5-6 membered heteroaryl having 1 to 4 heteroatoms selected from O and N and optionally substituted with 1 to 3 Z 1a , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

›DETAILED DESCRIPTION · 15 of 31

In certain embodiments, each Z 6 is independently oxo, hydroxy, fluoro, chloro, —CN, —CH 3 , ethyl, isopropyl, tert-butyl, —CF 3 , —CHF 2 , cyclopropyl, cyclobutyl, —OCH 3 , —O-ethyl, —O— isopropyl, —O-cyclopropyl, —OCF 3 , —OCF 2 H, —C(O)-alkyl, —C(O)-cycloalkyl, —C(O)-aryl, —C(O)— heteroaryl, or —NH 2 .

In certain embodiments, each Z 7 is independently halo, oxo, —CN, C 1-6 alkyl optionally substituted by 1 to 3 Z 1a , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N that is optionally substituted by 1 to 3 Z 1a , 5-6 membered heteroaryl having 1 to 4 heteroatoms selected from O and N and optionally substituted with 1 to 3 Z 1a , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

In certain embodiments, each Z 7 is independently oxo, hydroxy, fluoro, chloro, —CN, —CH 3 , ethyl, isopropyl, tert-butyl, —CF 3 , —CHF 2 , cyclopropyl, cyclobutyl, —OCH 3 , —O-ethyl, —O— isopropyl, —O-cyclopropyl, —OCF 3 , —OCF 2 H, —C(O)-alkyl, —C(O)-cycloalkyl, —C(O)-aryl, —C(O)— heteroaryl, or —NH 2 .

In certain embodiments, each Z 8 is independently halo, oxo, —CN, C 1-6 alkyl optionally substituted by 1 to 3 Z 1a , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O and N that is optionally substituted by 1 to 3 Z 1a , 5-6 membered heteroaryl having 1 to 4 heteroatoms selected from O and N and optionally substituted with 1 to 3 Z 1a , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

In certain embodiments, each Z 8 is independently oxo, hydroxy, fluoro, chloro, —CN, —CH 3 , ethyl, isopropyl, tert-butyl, —CF 3 , —CHF 2 , cyclopropyl, cyclobutyl, —OCH 3 , —O-ethyl, —O— isopropyl, —O-cyclopropyl, —OCF 3 , —OCF 2 H, —C(O)-alkyl, —C(O)-cycloalkyl, —C(O)-aryl, —C(O)— heteroaryl, or —NH 2 .

In certain embodiments, each Z 8 is independently halo, C 1-8 alkyl optionally substituted by 1 to 3 Z 1a , or —OR 9 . In certain embodiments, each Z 8 is independently halo, C 1-8 alkyl, C 1-8 haloalkyl, or —O—C 1-8 alkyl. In certain embodiments, each Z 8 is independently fluoro, methyl, —CF 3 , or —O—CH 3 .

In certain embodiments of any one of Formulas (I), (Ia)-(It), (Iv), and (Iv-1), each Z 8 is independently halo, C 1-5 alkyl, —O(C 1-5 alkyl), C 3-6 cycloalkyl, 6-10 membered aryl, or 5-10 membered heteroaryl, wherein C 1-5 alkyl, —O(C 1-5 alkyl), C 3-6 cycloalkyl, 6-10 membered aryl, or 5-10 membered heteroaryl, is optionally substituted with 1 to 2 halo or —O(C 1-5 alkyl).

In certain embodiments, each Z 8 is independently —CF 3 , —CHF 2 , —OCH 3 , —OCHF 2 , —OCF 3 , fluoro, chloro, cyclopropyl, or —CH 3 optionally substituted with —OCH 3 .

In certain embodiments, each Z 8 is independently fluoro, chloro, cyclopropyl, or —CH 3 . In certain embodiments, Z 8 is fluoro. In certain embodiments, Z 8 is absent.

In certain embodiments, each Z 1a is independently halo, —CN, C 1-6 alkyl optionally substituted by 1 to 3 Z 1b , C 3-6 cycloalkyl optionally substituted by 1 to 3 Z 1b , 6 membered aryl optionally substituted by 1 to 3 Z 1b , 4-6 membered heterocyclyl having 1 to 2 heteroatoms selected from O or N that is optionally substituted by 1 to 3 Z 1b , 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from O and N and optionally substituted with 1 to 3 Z 1b , —OR 12 , —N(R 12 ) 2 , —C(O)R 12 , N(R 12 )C(O)R 12 , —N(R 12 )C(O)OR 12 , —N(R 12 )S(O) 2 R 12 , —OC(O)R 12 , —OC(O)OR 12 , —OC(O)N(R 12 ) 2 , or —S(O) 2 R 12 .

In certain embodiments, each Z 1a is independently halo, —CH 3 , cyclopropyl, or —OCH 3 .

In certain embodiments, each Z 1b is independently hydroxy, halo, —CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 1-6 haloalkyl, aryl, heteroaryl, heterocyclyl, or —O(C 1-6 alkyl).

In certain embodiments, each Z 10 and Z 11 is independently fluoro, chloro, —CN, C 1-6 alkyl optionally substituted with 1 to 3 Z 1b , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , —OR 13 , —C(O)R 13 , —OC(O)R 13 , —OC(O)OR 13 , —OC(O)N(R 13 ) 2 , —N(R 13 )C(O)R 13 , —N(R 13 )C(O)OR 13 , or —N(R 13 ) 2 .

In certain embodiments, each Z 10 and Z 11 is independently fluoro, chloro, —CN, —OH, —OCH 3 , —OCHF 2 , —OCF 3 , —CH 3 , —CHF 2 , —CF 3 , —CH 2 OH, —CH 2 OCH 3 , or —NH 2 .

In certain embodiments, each Z 10 is independently fluoro, chloro, —CN, C 1-6 alkyl optionally substituted with 1 to 3 Z 1b , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , —OR 13 , —C(O)R 13 , —OC(O)R 13 , —OC(O)OR 13 , —OC(O)N(R 13 ) 2 , —N(R 13 )C(O)R 13 , —N(R 13 )C(O)OR 13 , or —N(R 13 ) 2 .

In certain embodiments, each Z 10 is independently fluoro, chloro, —CN, —OH, —OCH 3 , —OCHF 2 , —OCF 3 , —CH 3 , —CHF 2 , —CF 3 , —CH 2 OH, —CH 2 OCH 3 , or —NH 2 .

In certain embodiments, each Z 11 is independently fluoro, chloro, —CN, C 1-6 alkyl optionally substituted with 1 to 3 Z 1b , C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 1b , —OR 13 , —C(O)R 13 , —OC(O)R 13 , —OC(O)OR 13 , —OC(O)N(R 13 ) 2 , —N(R 13 )C(O)R 13 , —N(R 13 )C(O)OR 13 , or —N(R 13 ) 2 .

In certain embodiments, each Z 11 is independently fluoro, chloro, —CN, —OH, —OCH 3 , —OCHF 2 , —OCF 3 , —CH 3 , —CHF 2 , —CF 3 , —CH 2 OH, —CH 2 OCH 3 , or —NH 2 .

In certain embodiments, provided is a compound of Formula (Ia):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

R 1 , R 3 , R 10 , R 11 , L 1 , L 2 , L 3 , L 4 , L 5 , L 6 , X 4 , X 5 , m1, m2, m3, m4, m5, and m6 are as disclosed herein.

In certain embodiments of Formula (I) or (Ia), the moiety

is:

In certain embodiments of Formula (I) or (Ia), the moiety

is:

In certain embodiments of any one of Formulas (I), (Ia)-(Io), (Iv), and (Iv-1), the moiety

is a 5-10 membered heterocyclyl optionally substituted with 1 to 3 substituents selected from the group consisting of oxo, —OR 13 , —N(R 13 ) 2 , fluoro, chloro, and —C 1-5 alkyl optionally substituted with 1 to 3 Z 1b . In certain embodiments, the moiety

›DETAILED DESCRIPTION · 16 of 31

is a 5-8 membered heterocyclyl optionally substituted with 1 to 3 substituents selected from the group consisting of —NH 2 , —NH(C 1-5 alkyl), —OH, fluoro, C 1-5 alkyl, and —O(C 1-5 alkyl), wherein C 1-5 alkyl or —O(C 1-5 alkyl) may be optionally substituted with fluoro, —O(C 1-5 alkyl), or —OH. In certain embodiments, the moiety

is a 5-8 membered monocyclic heterocyclyl. In certain embodiments, the moiety

is a 5-8 membered bridged bicyclic heterocyclyl. In certain embodiments, the moiety

is a 5-8 membered fused bicyclic heterocyclyl. In certain embodiments, the moiety

is a 5-8 membered spiro bicyclic heterocyclyl. In certain embodiments, the moiety

is a bridged bicyclic piperidyl or pyrrolidinyl, wherein piperidyl or pyrrolidinyl is optionally substituted with one to three substituents selected from the group consisting of —NH 2 , —NH(C 1-5 alkyl), —OH, fluoro, and C 1-5 alkyl or —O(C 1-5 alkyl) optionally substituted with fluoro, —O(C 1-5 alkyl), or —OH.

In certain embodiments, the moiety

wherein each Z 12 is independently —NH 2 , fluoro, —OH, C 1-6 alkyl, or —OCH 3 optionally substituted with F; a is 1, 2, or 3. In certain embodiments, the moiety

wherein each Z 12 is independently —F, —OH, C 1-6 alkyl, or —OCH 3 optionally substituted with F; a is 0, 1, or 2. In certain embodiments, the moiety

In certain embodiments, the moiety

wherein each Z 12 is independently —NH 2 , F, or —OCH 3 optionally substituted with F; a is 1, 2, or 3. In certain embodiments, at least one Z 12 is —NH 2 . In certain embodiments, the moiety

In certain embodiments, the moiety

wherein each Z 12 is independently —NH 2 , fluoro, —OH, or —OCH 3 optionally substituted with F; and a is 1, 2, or 3. In certain embodiments, the moiety

wherein each Z 12 is independently fluoro, —OH, or —OCH 3 optionally substituted with F; and a is 0, 1, or 2. In certain embodiments, the moiety

In certain embodiments, the moiety

wherein each Z 12 is independently fluoro, —CH 3 , —CF 3 , —CHF 2 , or —OCH 3 optionally substituted with fluoro; and a is 0, 1, or 2.

In certain embodiments of any one of Formulas (I), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Iv), (Ip), (Iq), (Ir), (Is), and (It), the moiety

wherein R 1 , R 2 , and R 3 are as disclosed herein. In certain embodiments, the moiety

In certain embodiments, the moiety

In certain embodiments, R 1 is hydrogen or fluoro; R 2 is hydrogen, fluoro, or —OCH 3 ; and R 3 is methyl or cyclopropyl.

In certain embodiments of Formula (Ia), R 1 is hydrogen or halo. In certain embodiments of Formula (Ia), R 1 is hydrogen or fluoro. In certain embodiments of Formula (Ia), R 1 is hydrogen. In certain embodiments of Formula (Ia), R 1 is halo. In certain embodiments of Formula (Ia), R 1 is fluoro.

In certain embodiments of Formula (Ia), X 3 is N—R 3 and R 3 is C 1-6 alkyl optionally substituted with 1 to 3 Z 3 or C 3-6 cycloalkyl optionally substituted with 1 to 3 Z 3 . In certain embodiments of Formula (Ia), X 3 is N and N—R 3 is methyl, (1-fluorocyclopropyl)methyl, (1-cyanocyclopropyl)methyl, 2-(difluoromethyl)cyclopropyl, 2-methylcyclopropyl, (1-methoxycyclopropyl)methyl. 2-methoxyethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, cyclobutyl, isopropyl, ethyl, 2-isopropoxyethyl, 2-ethoxyethyl, 2-cyanoethyl, 2-(2-methoxyethoxy)ethyl, 3-amino-3-oxopropyl, 2-phenoxyethyl, 2-methoxypropyl, 2-(pyridin-2-yloxy)ethyl, 2-fluorocyclopropyl, or 2-methoxycyclopropyl.

In certain embodiments of Formula (Ia), R 3 is alkyl or cycloalkyl. In certain embodiments of Formula (Ia), R 3 is methyl or cyclopropyl. In certain embodiments of Formula (Ia), R 3 is alkyl. In certain embodiments of Formula (Ia), R 3 is methyl. In certain embodiments of Formula (Ia), R 3 is cycloalkyl. In certain embodiments of Formula (Ia), R 3 is cyclopropyl.

In certain embodiments of Formula (Ia), X 4 is N. In certain embodiments of Formula (Ia), X 4 is C—R 2 . In certain embodiments of Formula (Ia), X 4 is C—R 2 and R 2 is hydrogen, halo, or —O-alkyl. In certain embodiments of Formula (Ia), X 4 is C—R 2 and R 2 is hydrogen, fluoro, or methoxy. In certain embodiments of Formula (Ia), X 4 is C—R 2 and R 2 is hydrogen, fluoro, chloro, or —O—CH 3 . In certain embodiments of Formula (Ia), X 4 is C—R 2 and R 2 is hydrogen. In certain embodiments of Formula (Ia), X 4 is C—R 2 and R 2 is halo. In certain embodiments of Formula (Ia), X 4 is C—R 2 and R 2 is fluoro. In certain embodiments of Formula (Ia), X 4 is C—R 2 and R 2 is —O-alkyl. In certain embodiments of Formula (Ia), X 4 is C—R 2 and R 2 is methoxy.

In certain embodiments, provided is a compound of Formula (Ib):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

R 1 , R 2 , R 3 , R 10 , R 11 , L 1 , L 2 , L 3 , L 4 , L 5 , L 6 , X 5 , m1, m2, m3, m4, m5, and m6 are as disclosed herein.

In certain embodiments of Formula (Ib), the moiety

In certain embodiments of Formula (Ib), R 1 is hydrogen.

In certain embodiments of Formula (Ib), R 2 is hydrogen or —O-alkyl. In certain embodiments of Formula (Ib), R 2 is hydrogen or methoxy. In certain embodiments of Formula (Ib), R 2 is hydrogen. In certain embodiments of Formula (Ib), R 2 is —O-alkyl. In certain embodiments of Formula (Ib), R 2 is methoxy.

In certain embodiments of Formula (Ib), R 3 is alkyl or cycloalkyl. In certain embodiments of Formula (Ib), R 3 is methyl or cyclopropyl. In certain embodiments of Formula (Ib), R 3 is alkyl. In certain embodiments of Formula (Ib), R 3 is methyl. In certain embodiments of Formula (Ib), R 3 is cycloalkyl. In certain embodiments of Formula (Ib), R 3 is cyclopropyl.

In certain embodiments, provided is a compound of Formula (Ic):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

R 1 , R 2 , R 3 , R 10 , R 11 , L 1 , L 2 , L 3 , L 4 , L 5 , L 6 , X 5 , m1, m2, m3, m4, m5, and m6 are as disclosed herein.

›DETAILED DESCRIPTION · 17 of 31

In certain embodiments of Formula (Ic), the moiety

In certain embodiments of Formula (Ic), R 1 is hydrogen.

In certain embodiments of Formula (Ic), R 2 is hydrogen or —O-alkyl. In certain embodiments of Formula (Ic), R 2 is hydrogen or methoxy. In certain embodiments of Formula (Ic), R 2 is hydrogen. In certain embodiments of Formula (Ic), R 2 is —O-alkyl. In certain embodiments of Formula (Ic), R 2 is methoxy.

In certain embodiments of Formula (Ic), R 3 is alkyl. In certain embodiments of Formula (Ic), R 3 is methyl or ethyl. In certain embodiments of Formula (Ic), R 3 is methyl. In certain embodiments of Formula (Ic), R 3 is ethyl.

In certain embodiments, provided is a compound of Formula (Id):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

R 14 is hydrogen, C 1-8 alkyl optionally substituted with 1-3 Z 1a , C 3-8 cycloalkyl optionally substituted with 1-3 Z 1a , C 4-6 heterocyclyl having 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 Z 1a ;

R 15 is hydrogen, C 1-8 alkyl optionally substituted with 1-3 Z 1a , C 3-8 cycloalkyl optionally substituted with 1-3 Z 1a , C 4-6 heterocyclyl having 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 Z 1a ; or

R 14 and R 15 can be taken together to form a 3-6-membered cycloalkyl that is optionally substituted with 1 to 3 Z 1a or 4-6-membered heterocyclyl containing 1-2 heteroatoms independently selected from O, N, and S that is optionally substituted with 1-3 Z 1a ; and

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 8 , R 10 , R 11 , L 1 , L 2 , L 3 , L 4 , m1, m2, m3, and m4 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Ie):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 10 , R 11 , L 1 , L 2 , L 3 , L 4 , L 5 , m1, m2, m3, m4, and m5 are as disclosed herein; and

I, J, K, Q are each independently N, CH or C—Z 8 provided that at least two of I, J, K, Q are CH or C—Z 8 .

In certain embodiments, provided is a compound of Formula (If):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 10 , R 11 , L 1 , L 2 , L 3 , L 4 , Z 8 , m1, m2, m3, and m4 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Ig):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

I, J, K, Q are each independently N, CH or C—Z 8 provided that at least two of I, J, K, Q are CH or C—Z 8 ; and

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 8 , R 10 , R 11 , L 1 , L 2 , L 3 , Z 8 , m1, m2, m3, and m4 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Ih):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

R 14 and R 15 can be taken together to form a 3-6-membered cycloalkyl that is optionally substituted with 1 to 3 Z 1a or 4-6-membered heterocyclyl containing 1-2 heteroatoms independently selected from O, N, or S that is optionally substituted with 1-3 Z 1a ;

t is 1, 2, 3, or 4; and

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 8 , R 10 , R 11 , L 1 , L 2 , L 3 , L 4 , Z 8 , m1, m2, m3, and m4 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Ii):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

R 14 and R 15 can be taken together to form a 3-6-membered cycloalkyl that is optionally substituted with 1 to 3 Z 1a or 4-6-membered heterocyclyl containing 1-2 heteroatoms independently selected from O, N, or S that is optionally substituted with 1-3 Z 1a ;

q is 0, 1 or 2; and

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 8 , R 10 , R 11 , and Z 8 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Ij):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

›DETAILED DESCRIPTION · 18 of 31

t is 1, 2, 3, or 4;

q is 0, 1 or 2; and

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 8 , R 10 , R 11 , and Z 8 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Ij-1):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

R 14 and R 15 are each independently hydrogen, C 1-8 alkyl optionally substituted with 1-3 Z 1a , C 3-8 cycloalkyl optionally substituted with 1-3 Z 1a , C 4-6 heterocyclyl having 1-3 heteroatoms selected from O, N, and S, optionally substituted with 1-3 Z 1a ;

t is 1, 2, 3, or 4;

q is 0, 1 or 2;

n1 is 0, 1, 2, or 3;

n2 is 0, 1, 2, or 3; and

R 1 , R 2 , R 3 , R 8 , R 10 , R 11 , and Z 8 are as described herein.

In certain embodiments, provided is a compound of Formula (Ik):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

I, J, K, Q are each independently N, CH or C—Z 8 provided that at least two of I, J, K, Q are CH or C—Z 8 ;

q is 0, 1 or 2; and

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 8 , R 10 , R 11 , and Z 8 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Iv):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

L 4 is methylene optionally substituted with 1 to 2 Z 13 , C 3-6 cycloalkylene optionally substituted with 1 to 2 Z 8 , 4-10 membered heterocyclene optionally substituted with 1 to 2 Z 8 , 6-10 membered arylene optionally substituted with 1 to 2 Z 8 , or heteroarylene optionally substituted with 1 to 2 Z 8 ;

each Z 13 is independently selected from the group consisting of fluoro, —C 1-6 alkyl, —CF 3 , —O—C 1-5 alkyl, —OCF 3 , —O—C 3-6 cycloalkyl, C 3-6 cycloalkyl, 4-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl, wherein each of —C 1-6 alkyl, —O—C 1-5 alkyl, C 3-6 cycloalkyl, 4-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl is optionally substituted with 1 to 2 Z 8 ;

m4 is 1;

q is 0, 1 or 2;

n is 0, 1, 2, 3, or 4;

X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , R 1 , R 8 , R 10 , R 11 , and Z 8 are as described herein.

In certain embodiments, Formula (Iv) is represented by Formula (Iv-1):

In certain embodiments, L 4 is selected from the group consisting of:

wherein either of the two broken bonds may be attached to —CO— in —CO—NR 8 .

In certain embodiments, L 4 is

wherein the broken bond with * is attached to —CO— of —NR 8 —CO—. In certain embodiments, L 4 is

In certain embodiments, L 4 is

wherein the broken bond with * is attached to —CO— of —NR 8 —CO—. In certain embodiments, L 4 is

In certain embodiments of Formula (Ig), or (Ik), at least two of I, J, K, and Q are C—H, C—Cl, C—F, C—OCH 3 , C—CH 3 , C-cyclopropyl, C—CH 2 F, or C—CF 3 .

In certain embodiments, provided is a compound of Formula (Il):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

X 4 , X 5 , R 1 , R 3 , R 7 , R 8 , R 10 , R 11 , and Z 8 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Im):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

q is 0, 1 or 2; and

X 5 , R 1 , R 2 , R 3 , R 7 , R 10 , R 11 , and Z 8 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (In):

›DETAILED DESCRIPTION · 19 of 31

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

t is 1, 2, 3, or 4;

q is 0, 1 or 2; and

X 5 , R 1 , R 2 , R 3 , R 7 , R 10 , R 11 , and Z 8 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Io):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:

I, J, K, Q are each independently N, CH, or C—Z 8 provided that at least two of I, J, K, Q are CH, or C—Z 8 ;

q is 0, 1 or 2; and

X 5 , R 1 , R 2 , R 3 , R 10 , R 11 , and Z 8 are as disclosed herein.

In certain embodiments of any one of the Formulas disclosed herein (e.g., Formula (Id), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), or (Io)), R 14 is hydrogen, C 1-8 alkyl optionally substituted with 1-3 Z 1a , or C 3-8 cycloalkyl optionally substituted with 1-3 Z 1a ; and

R 15 is hydrogen, C 1-8 alkyl optionally substituted with 1-3 Z 1a , or C 3-8 cycloalkyl optionally substituted with 1-3 Z 1a .

In certain embodiments of any one of the Formulas disclosed herein (e.g., Formula (Id), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), or (Io)), R 14 is hydrogen, C 1-8 alkyl, or C 3-8 cycloalkyl; and

R 15 is hydrogen, C 1-8 alkyl, or C 3-8 cycloalkyl.

In certain embodiments of any one of the Formulas disclosed herein (e.g., Formula (Id), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), or (Io)), R 14 is hydrogen, —C 1-8 alkyl optionally substituted with 1-3 Z 1a , or C 3-8 cycloalkyl optionally substituted with 1-3 Z 1a ;

R 15 is hydrogen, —C 1-8 alkyl optionally substituted with 1-3 Z 1a , or C 3-8 cycloalkyl optionally substituted with 1-3 Z 1a ; X 5 is N, C—H, or C—F; and R 7 is hydrogen or fluoro.

In certain embodiments, provided is a compound of Formula (Ip):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , L 1 -L 6 , m1-m6, and R 1 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Iq):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein Z 11 , X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , L 1 -L 6 , m1-m6, and R 1 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Ir):

In certain embodiments, provided is a compound of Formula (Is):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , L 1 -L 6 , m1-m6, and R 1 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (It):

or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , L 1 -L 6 , m1-m6, and R 1 are as disclosed herein.

In certain embodiments, provided is a compound of Formula (Iu):

In certain embodiments, the compound of formula (Iu) is represented by Formula (Iu-1):

In certain embodiments, the compound of Formula (Iu), or (Iu-1), or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, is a compound wherein

L 1 is C 1-10 alkylene optionally substituted with 1 to 3 halo; L 2 is C 3 -C 6 cycloalkylene optionally substituted with 1 to 3 halo or C 2-6 alkenylene optionally substituted with 1 to 3 halo; L 3 is —O—, —O—C 1-8 alkylene optionally substituted with 1 to 3 halo, or C 1-8 alkylene optionally substituted with 1 to 3 halo; L 4 is C 1-6 alkylene optionally substituted with 1 to 3 Z 8a , 5-10 membered nitrogen-containing heteroarylene optionally substituted with 1 to 3 Z 8b , C 6-10 arylene optionally substituted with 1 to 3 Z 8b , or C 3 -C 6 cycloalkylene optionally substituted with 1 to 3 Z 8b ; each Z 8a is independently halo, or 5-10 membered heteroaryl optionally substituted with 1-2 halo; and each Z 8b is independently halo, C 1-6 alkyl, C 1-6 haloalkyl, —O(C 1-6 alkyl), —O(C 1-6 haloalkyl), —O(C 3-6 cycloalkyl), cyclopropyl, or phenylethynyl.

In certain embodiments, the compound of Formula (Iu), or (Iu-1), is represented by Formula (Iu-2):

wherein

L 3 is —O—;

m3 is 0 or 1;

m4 is 1;

Z 8 is fluoro;

n is 0, 1, 2, or 3; and

q is 0, 1, or 2.

In certain embodiments, the compound of Formula (Iu), (Iu-1), or (Iu-2), or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, is a compound wherein

›DETAILED DESCRIPTION · 20 of 31

L 4 is selected from the group consisting of

either of the two broken bonds may be attached to L 5 or —CO— in —CO—NH—.

In certain embodiments of Formula (Iu-2), m3 is 0; q is 1 or 2; and L 4 is selected from the group consisting of

and when L 4 is

the broken bond with * is attached to —CO— of —NR 8 —CO—. In certain embodiments, L 4 is

In certain embodiments, L 4 is

wherein the broken bond with * is attached to —CO— of —NH—CO—. In certain embodiments, L 4 is

wherein the broken bond with * is attached to —CO— of —NH—CO—.

In certain embodiments of Formula (Iu-2), m3 is 1; n is 0 or 2; q is 1 or 2; and L 4 is

In certain embodiments, L 4 is

In certain embodiments of any one of Formulas (Iu), (Iu-1), or (Iu-2), at least one Z is —NH 2 .

In certain embodiments of any one of Formulas (Iu), (Iu-1), or (Iu-2), R 1 is hydrogen.

In certain embodiments of any one of Formulas (Iu), (Iu-1), or (Iu-2), R 2 is hydrogen. In certain embodiments of any one of Formulas (Iu), (Iu-1), or (Iu-2), R 2 is fluoro. In certain embodiments of any one of Formulas (Iu), (Iu-1), or (Iu-2), R 2 is —OCH 3 .

In certain embodiments of any one of Formulas (Iu), (Iu-1), or (Iu-2), R 3a is —CH 3 . In certain embodiments of any one of Formulas (Iu), (Iu-1), or (Iu-2), wherein R 3a is cyclopropyl.

In certain embodiments of any one of Formulas (Iu), (Iu-1), or (Iu-2), L 4 is C 1-6 alkylene, optionally substituted with 1 to 3 substituents selected from the group consisting of halo, and pyridyl optionally substituted with 1-2 halo.

In certain embodiments, R 16 is

In certain embodiments, provided is a compound as shown in Table 1, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof. In certain embodiments, provided is a compound as shown in Table 1, or a pharmaceutically acceptable salt. In certain embodiments, provided is a compound as shown in Table 1.

In certain embodiments, provided is a compound as shown in Table 1A, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof. In certain embodiments, provided is a compound as shown in Table 1A, or a pharmaceutically acceptable salt. In certain embodiments, provided is a compound as shown in Table 1A.

One of skill in the art is aware that each and every embodiment of a group (e.g., R 1 ) disclosed herein may be combined with any other embodiment of each of the remaining groups (e.g., R 10 , R 11 , Z 1 , Z 8 , etc.) to generate a complete compound of Formula (I), or any Formula described herein or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, each of which is deemed within the ambit of the present disclosure.

Methods and Compositions

Peptidylarginine deiminase type 4 (PAD4) is hypothesized to be involved in an array of functions, including regulation of transcription, cell cycle, apoptosis, formation of neutrophil extracellular traps (NETs), and tumorgenesis. Expression of PAD4 is restricted to cells of the myeloid lineage, in particular: neutrophils, eosinophils and monocyte/macrophages.

The present disclosure provides compounds and compositions capable of inhibiting peptidylarginine deiminase type 4 (PAD4), and thus, the present disclosure provides a method for treating a disease or disorder mediated by peptidylarginine deiminase type 4 (PAD4), comprising administering an effective amount of a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, to a patient in need thereof.

As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results. For purposes of the present disclosure, beneficial or desired results include, but are not limited to, alleviation of a symptom and/or diminishment of the extent of a symptom and/or preventing a worsening of a symptom associated with a disease or condition. In one embodiment, “treatment” or “treating” includes one or more of the following: a) inhibiting the disease or condition (e.g., decreasing one or more symptoms resulting from the disease or condition, and/or diminishing the extent of the disease or condition); b) slowing or arresting the development of one or more symptoms associated with the disease or condition (e.g., stabilizing the disease or condition, delaying the worsening or progression of the disease or condition); and/or c) relieving the disease or condition, e.g., causing the regression of clinical symptoms, ameliorating the disease state, delaying the progression of the disease, increasing the quality of life, and/or prolonging survival.

As used herein, “delaying” development of a disease or condition means to defer, hinder, slow, retard, stabilize and/or postpone development of the disease or condition. This delay can be of varying lengths of time, depending on the history of the disease and/or subject being treated.

As used herein, “prevention” or “preventing” refers to a regimen that protects against the onset of the disease or disorder such that the clinical symptoms of the disease do not develop. Thus, “prevention” relates to administration of a therapy (e.g., administration of a therapeutic substance) to a subject before signs of disease are detectable in the subject.

As used herein, the term “therapeutically effective amount” or “effective amount” refers to an amount that is effective to elicit the desired biological or medical response, including the amount of a compound that, when administered to a subject for treating a disease, is sufficient to effect such treatment for the disease or to an amount that is effective to protect against the contracting or onset of a disease. The effective amount will vary depending on the compound, the disease, and its severity and the age, weight, etc., of the subject to be treated. The effective amount can include a range of amounts. As is understood in the art, an effective amount may be in one or more doses, i.e., a single dose or multiple doses may be required to achieve the desired treatment outcome. An effective amount may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable or beneficial result may be or is achieved. Suitable doses of any co-administered compounds may optionally be lowered due to the combined action (e.g., additive or synergistic effects) of the compounds.

›DETAILED DESCRIPTION · 21 of 31

“Patient” and “subject” refer to humans, domestic animals (e.g., dogs and cats), farm animals (e.g., cattle, horses, sheep, goats and pigs), laboratory animals (e.g., mice, rats, hamsters, guinea pigs, pigs, pocket pets, rabbits, dogs, and monkeys), and the like. In certain embodiments, the patient is a human.

Protein arginine deiminases (PADs) have been contemplated to display some level of substrate specificity possibly related to their tissue specific expression pattern. For example, keratins are physiological substrates of PAD1 and PAD3, myelin basic protein, enolase are citrullinated by PAD2, whereas histones and transcription factors are citrullinated by PAD4. In vitro, PADs are capable of citrullinating various substrates including intracellular and extracellular arginine containing proteins, peptides and peptide mimetics such as benzoyl arginine ethyl ester, used frequently in biochemical assays. Hydrolysis of peptidyl arginine to citrulline removes positive charge, and therefore may affect protein folding, stability, activity, and ability to form hydrogen bonds. Moreover, citrullinated proteins in susceptible individuals such as rheumatoid arthritis (RA) patients become neo-antigens and elicit an autoimmune response leading to the production of anti-citrullinated protein antibodies known as ACPA. The immunogenic property of citrullinated epitopes appears to be specific to RA, with ACPA detectable in 75% of RA patients and displaying 98% specificity for the disease. RA is a disabling autoimmune disease characterized by chronic inflammation of the joints and synovial tissues, pain and progressive bone destruction. ACPA may appear years prior to the onset of clinical RA and their presence correlates with disease prognosis. ACPA are regarded not only as a useful biomarker for RA diagnosis and for predicting a severe disease course, but they have also been postulated to contribute to a disease pathogenesis. Although the antigens recognized by ACPA are diverse and differ between RA patients, a number of common autoantigens have been reported: citrullinated forms of vimentin, enolase, fibrinogen, collagen II, and histones. PAD4 and also PAD2 are contemplated to be responsible for the generation of citrullinated neo-epitopes in RA as their expression is elevated in the inflamed synovium. Neutrophils and macrophages are the main source of these enzymes. Neutrophils are the most abundant white blood cells in circulation. As critical players in the early innate immune response, they hone quickly to sites of inflammation, are abundant in RA synovial fluid and have been shown to be involved in disease pathology. Neutrophils are also short-lived and may undergo inflammatory forms of cell death, including NETosis and necroptosis, which have been implicated in driving inflammation in the RA synovium. Several lines of evidence point to a putative role for citrullination and ACPAs in driving RA. Genetic (HLA-DR-SE risk allele) and environmental (smoking, periodontitis) factors linked to RA are intimately associated with citrullination and ACPAs. Multiple intracellular and extracellular citrullinated proteins (for example enolase, vimentin, fibrinogen, histones, actin, and collagen) are present in RA synovial tissues but absent in healthy or non-RA synovial tissue. Moreover, PADI4 polymorphisms are linked to RA susceptibility and have been identified in large GWAS studies. PAD4 itself is a target of an autoimmune response and 13-18% of RA patients develop anti-PAD4 antibodies; these auto-antibodies have been shown to activate PAD4 by modulating the enzyme's requirement for calcium and are associated with increased risk of progressive joint damage, interstitial lung disease, and poorer response to SOC.

Currently, it is not fully understood what drives excessive citrullination in RA, or even RA “at risk” individuals. It is contemplated that stimulation of synovial protein citrullination might be linked to the neutrophil cell death/lysis that can occur via one of several proinflammatory mechanisms. Moreover, it is hypothesized that citrullinated proteins are not only acting as neo-epitopes, but are involved directly in disease pathology. PAD4 is postulated to contribute to inflammatory processes in RA via the generation of ACPA neo-epitopes and formation of ACPA-immune complexes which could promote further citrullination, inflammation and pathology through engagement of Fc receptors. Aberrant protein citrullination might also modify the function of critical processes in the RA synovium, either independently or upon association of with cognate ACPAs. For example, it was demonstrated that osteoclast differentiation is linked to the citrullination of proteins and that some ACPAs were able to bind to osteoclast precursor cells promoting differentiation and activation in vitro and stimulation of IL-8 production. Moreover, infusion of some ACPAs into mice causes IL-8 dependent bone loss and IL-8 mediated pain behavior and exaggerate bone erosion in a methylate bovine serum albumin induced arthritis.

Therefore, PAD4 inhibitors should be explored as novel therapeutics for treatment of ACPA positive RA (over 75% of all RA patients) where disease could be exaggerated by citrullination and ACPA immune complexes and other types of RA. Animal studies with the use of knockout (KO) animals or PAD inhibitors provided additional rationale for the use of PAD4 inhibitors in treatment of RA. For example, in a chronic joint inflammation models such as collagen induced arthritis (CIA) or glucose-6 phosphate isomerase induced arthritis, PAD4 KO (DBA/1J) mice display improved clinical (around 60% reduction), histological scores, reduced antibody titer, and reduction of some pro inflammatory cytokines. Similarly, prophylactic treatment with pan-PAD covalent inhibitors such as chloroamidine and BB-chloroamidine or reversible PAD4-specific inhibitor GSK199 in a murine CIA model led to improvement of clinical and histological scores, reduction of antibodies titer and epitope spreading, reduction of citrullinated proteins in joints and shift from pro-inflammatory to pro-resolution immunological responses.

›DETAILED DESCRIPTION · 22 of 31

Beyond R A, activated PAD4 was also shown to be necessary and sufficient for citrullination of a histone H3 on neutrophil extracellular traps (NETs). Therefore, it is thought that PAD4 might be involved in a formation of NETs and citrullination of additional proteins associated with these structures. NETs are composed of chromatin and nuclear, cytoplasmic and granules proteins extruded from neutrophils during programmed cell death known as NETosis. NETosis is often regarded as a doubled-edged sword, because although it is a part of a normal antimicrobial defense, excessive NETs formation and/or defective NETs clearance induce inflammatory responses. NETosis results in a release of citrullinated proteins, granules' enzymes, antimicrobial proteins and DNA-protein complexes that can become neo-antigens and fuel autoimmunity in susceptible individuals. Moreover, active PADs are released during NETosis and can citrullinate cellular proteins associated with NETs and extracellular proteins in synovium or vasculature. NETs were also contemplated to serve as scaffolds for thrombosis. For that reason, NETosis has been postulated to exacerbate autoimmune and other inflammatory diseases with neutrophil infiltration. Thus, it was contemplated that targeting PAD4 may have therapeutic potential in diseases associated with sterile inflammation. PAD4 KO mice show improved outcome, protection from tissue and organs injury, deceased disease parameters and attenuation of NETosis markers in several murine models of acute or chronic injury such as stenosis model of deep vein thrombosis, myocardial ischemia/reperfusion, LPS endotoxemic shock and cecal ligation puncture (CLP) sepsis. Moreover, pan-PAD covalent inhibitors such as BB-chloroamidine, chloroamidine, or YW3-56 resulted in reduction of clinical, inflammatory, histopathological and mechanical end points, attenuation of NETosis and improved outcome in various models of chronic and acute inflammatory diseases including MRL/lpr mouse model of lupus, hemorrhagic shock in rats, mouse CLP sepsis model, mouse DSS-colitis, mouse ApoE −/− and high fat diet arteriosclerosis model, mouse streptozotocin induced diabetic wound healing model. Therefore, PAD4 inhibitors may have therapeutic potential in treatment of disease linked to pathological consequences of NETosis beyond RA, such as systemic lupus erythematous, antiphospholipid antibody syndrome, small vessels vasculitis, colitis, thrombosis, atherosclerosis, sepsis, diabetes, among others.

In certain embodiments, the disease or disorder mediated by peptidylarginine deiminase type 4 (PAD4) is acute lymphocytic leukemia, ankylosing spondylitis, cancer, chronic lymphocytic leukemia, colitis, lupus, systemic lupus erythematosus, cutaneous lupus erythematosus, rheumatoid arthritis, multiple sclerosis, or ulcerative colitis. Accordingly, provided is a method for treating acute lymphocytic leukemia, ankylosing spondylitis, cancer, chronic lymphocytic leukemia, colitis, lupus, systemic lupus erythematosus, cutaneous lupus erythematosus, rheumatoid arthritis, multiple sclerosis, or ulcerative colitis, comprising administering an effective amount of a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, to a patient in need thereof.

As PAD4 may contribute to the initiation and propagation of RA, PAD4 inhibitors can be envisioned as a prophylactic treatment for individuals that are at risk of developing clinical RA, as identified by ACPA positivity, family history of RA, exposure to environmental factors, genetic predisposition and presence of arthralgia.

In certain embodiments, the disease or disorder is inflammatory arthritis. In certain embodiments, the disease or disorder is rheumatoid arthritis. In certain embodiments, the disease or disorder is systemic lupus. In certain embodiments, the disease or disorder is vasculitis. In certain embodiments, the disease or disorder is cutaneous lupus erythematosus. In certain embodiments, the disease or disorder is psoriasis. In certain embodiments, the disease or disorder is a fibrotic lung disease, such as idiopathic pulmonary fibrosis (IPF). In certain embodiments, the disease or disorder is fibroproliferative lung disease. In certain embodiments, the disease or disorder is rheumatoid arthritis with joint and/or lung disease. In certain embodiments, the disease or disorder is inflammatory bowel disease.

In certain embodiments, the disease or disorder is acid-induced lung injury, acne (PAPA), acute lymphocytic leukemia, acute, respiratory distress syndrome, Addison's disease, adrenal hyperplasia, adrenocortical insufficiency, ageing, AIDS, alcoholic hepatitis, alcoholic hepatitis, alcoholic liver disease, allergen induced asthma, allergic bronchopulmonary, aspergillosis, allergic conjunctivitis, alopecia, Alzheimer's disease, amyloidosis, amyotrophic lateral sclerosis, and weight loss, angina pectoris, angioedema, anhidrotic ecodermal dysplasia-ID, ankylosing spondylitis, anterior segment, inflammation, antiphospholipid syndrome, aphthous stomatitis, appendicitis, arthritis, asthma, atherosclerosis, atopic dermatitis, autoimmune diseases, autoimmune hepatitis, bee sting-induced inflammation, Behcet's disease, Behcet's syndrome, Bells Palsy, berylliosis, Blau syndrome, bone pain, bronchiolitis, burns, bursitis, cancer, cardiac hypertrophy, carpal tunnel syndrome, catabolic disorders, cataracts, cerebral aneurysm, chemical irritant-induced inflammation, chorioretinitis, chronic heart failure, chronic lung disease of prematurity, chronic lymphocytic leukemia, chronic obstructive pulmonary disease, colitis, complex regional pain syndrome, connective tissue disease, corneal ulcer, Crohn's disease, cryopyrin-associated periodic syndromes, cyrptococcosis, cystic fibrosis, deficiency of the interleukin-1-receptor antagonist (DIRA), dermatitis, dermatitis endotoxemia, dermatomyositis, diffuse intrinsic pontine glioma, endometriosis, endotoxemia, epicondylitis, erythroblastopenia, familial amyloidotic polyneuropathy, familial cold urticarial, familial Mediterranean fever, fetal growth retardation, glaucoma, glomerular disease, glomerular nephritis, gout, gouty arthritis, graft-versus-host disease, gut diseases, head injury, headache, hearing loss, heart disease, hemolytic anemia, Henoch-Scholein purpura, hepatitis, hereditary periodic fever syndrome, herpes zoster and simplex, HIV-1, hypercalcemia, hypercholesterolemia, hyperimmunoglobulinemia D with recurrent fever (HIDS), hypoplastic and other anemias, hypoplastic anemia, idiopathic thrombocytopenic purpura, incontinentia pigmenti, infectious mononucleosis, inflammatory bowel disease, inflammatory lung disease, inflammatory neuropathy, inflammatory pain, insect bite-induced inflammation, iritis, irritant-induced inflammation, ischemia/reperfusion, juvenile rheumatoid arthritis, keratitis, kidney disease, kidney injury caused by parasitic infections, kidney injury caused by parasitic infections, kidney transplant rejection prophylaxis, leptospiriosis, leukemia, Loeffler's syndrome, lung injury, fibrotic lung disease, lupus, lupus nephritis, lymphoma, meningitis, mesothelioma, mixed connective tissue disease, Muckle-Wells syndrome (urticaria deafness amyloidosis), multiple sclerosis, muscle wasting, muscular dystrophy, myasthenia gravis, myocarditis, mycosis fungoides, mycosis fungoides, myelodysplastic syndrome, myositis, nasal sinusitis, necrotizing enterocolitis, neonatal onset multisystem inflammatory disease (NOMID), nephrotic syndrome, neuritis, neuropathological diseases, non-allergen induced asthma, obesity, ocular allergy, optic neuritis, organ transplant, osteoarthritis, otitis media, Paget's disease, pain, pancreatitis, Parkinson's disease, pemphigus, pericarditis, periodic fever, periodontitis, peritoneal endometriosis, pertussis, pharyngitis and adenitis (PFAPA syndrome), plant irritant-induced inflammation, pneumonia, pneumonitis, pneumosysts infection, poison ivy/urushiol oil-induced inflammation, polyarteritis nodosa , polychondritis, polycystic kidney disease, polymyositis, psoriasis, psoriasis, psoriasis, psoriasis, psychosocial stress diseases, pulmonary disease, pulmonary hypertension, pulmonary fibrosis, pyoderma gangrenosum, pyogenic sterile arthritis, renal disease, retinal disease, rheumatic carditis, rheumatic disease, rheumatoid arthritis, sarcoidosis, seborrhea, sepsis, severe pain, sickle cell, sickle cell anemia, silica-induced disease, Sjogren's syndrome, skin diseases, sleep apnea, solid tumors, spinal cord injury, Stevens-Johnson syndrome, stroke, subarachnoid haemorrhage, sunburn, temporal arteritis, tenosynovitis, thrombocytopenia, thyroiditis, tissue transplant, TNF receptor associated periodic syndrome (TRAPS), toxoplasmosis, transplant, traumatic brain injury, tuberculosis, type 1 diabetes, type 2 diabetes, ulcerative colitis, urticarial, uveitis, Wegener's granulomatosis, interstitial lung disease, psoriatic arthritis, juvenile idiopathic arthritis, Sjögren's syndrome, antineutrophil cytoplasmic antibody (ANCA)-associated Alzheimer's, scleroderma or CREST syndrome.

›DETAILED DESCRIPTION · 23 of 31

In certain embodiments, the disease or disorder is one or more of anti-neutrophil cytoplasm antibodies (ANCA) vasculitis, antiphospholipid syndrome, psoriasis, lung inflammatory diseases, interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and COVID 19 ARDS.

In certain embodiments, the disease or disorder is one or more of rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, or cancer.

Also provided is a pharmaceutical composition comprising a compound of Formula (I)-(Iv) or shown in Tables 1 and 1A, or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

The pharmaceutical compositions of compounds of Formula (I)-(Iv) may be administered in either single or multiple doses by any of the accepted modes of administration of agents having similar utilities, for example as described in those patents and patent applications incorporated by reference, including rectal, buccal, intranasal and transdermal routes, by intra-arterial injection, intravenously, intraperitoneally, parenterally, intramuscularly, subcutaneously, orally, topically, as an inhalant, or via an impregnated or coated device such as a stent, for example, or an artery-inserted cylindrical polymer.

In some embodiments, the compounds or pharmaceutical compositions disclosed herein exhibit high inhibitory potency for PAD4 in a whole blood assay.

In one aspect, the compounds described herein may be administered orally. Oral administration may be via, for example, capsule or enteric coated tablets. In making the pharmaceutical compositions that include at least one compound of Formula (I)-(Iv) or shown in Tables 1 and 1A, or a pharmaceutically acceptable salt, is usually diluted by an excipient and/or enclosed within such a carrier that can be in the form of a capsule, sachet, paper or other container. When the excipient serves as a diluent, it can be in the form of a solid, semi-solid, or liquid material (as above), which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments containing, for example, up to 10% by weight of the active compound, soft and hard gelatin capsules, sterile injectable solutions, and sterile packaged powders.

Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, sterile water, syrup, and methyl cellulose. The formulations can additionally include: lubricating agents such as talc, magnesium stearate, and mineral oil; wetting agents; emulsifying and suspending agents; preserving agents such as methyl and propylhydroxy-benzoates; sweetening agents; and flavoring agents.

The compositions may, in some embodiments, be formulated in a unit dosage form. The term “unit dosage forms” refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient (e.g., a tablet, capsule, ampoule). The compounds are generally administered in a pharmaceutically effective amount. In some embodiments, for oral administration, each dosage unit contains from about 10 mg to about 1000 mg of a compound described herein, for example from about 50 mg to about 500 mg, for example about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, or about 500 mg. In other embodiments, for parenteral administration, each dosage unit contains from 0.1 to 700 mg of a compound a compound described herein. It will be understood, however, that the amount of the compound actually administered usually will be determined by a physician, in the light of the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered and its relative activity, the age, weight, and response of the individual subject, and the severity of the subject's symptoms.

In certain embodiments, dosage levels of the compound of Formula (I)-(Iv) or shown in Tables 1 and 1A may be from 0.1 mg to 100 mg per kilogram of body weight per day, for example from about 1 mg to about 50 mg per kilogram, for example from about 5 mg to about 30 mg per kilogram. Such dosage levels may, in certain instances, be useful in the treatment of the above-indicated conditions. In other embodiments, dosage levels may be from about 10 mg to about 2000 mg per subject per day. The amount of active ingredient that may be combined with the vehicle to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. Dosage unit forms may contain from 1 mg to 1000 mg of an active ingredient.

The compounds disclosed herein, or a pharmaceutically acceptable salt thereof, may be administered to a subject in accordance with an effective dosing regimen for a desired period of time or duration, such as at least about one day, at least about one week, at least about one month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 6 months, or at least about 12 months or longer. In one variation, the compound is administered on a daily or intermittent schedule. In one variation, the compound is administered on a monthly schedule. In one variation, the compound is administered every two months. In one variation, the compound is administered every three months. In one variation, the compound is administered every four months. In one variation, the compound is administered every five months. In one variation, the compound is administered every 6 months.

›DETAILED DESCRIPTION · 24 of 31

The dosage or dosing frequency of a compound disclosed herein, or a pharmaceutically acceptable salt thereof, may be adjusted over the course of the treatment, based on the judgment of the administering physician. The compound may be administered to a subject (e.g., a human) in an effective amount. In certain embodiments, the compound is administered once daily.

For preparing solid compositions such as tablets, the principal active ingredient may be mixed with a pharmaceutical excipient to form a solid preformulation composition containing a homogeneous mixture of a compound of Formula (I), or a pharmaceutically acceptable salt, thereof. When referring to these preformulation compositions as homogeneous, the active ingredient may be dispersed evenly throughout the composition so that the composition may be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules.

The tablets or pills of the compounds described herein may be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action, or to protect from the acid conditions of the stomach. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer that serves to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, cetyl alcohol, and cellulose acetate.

In certain embodiments, a method of treating or preventing rheumatoid arthritis (RA) comprising administering a therapeutically effective amount of a compound disclosed herein, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, is provided. In certain embodiments, a method of treating RA comprising administering a therapeutically effective amount of a compound disclosed herein, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, is provided. In certain embodiments, the method comprises administering a compound disclosed herein, or a pharmaceutically acceptable salt thereof, in combination with one, two, three, or four additional therapeutic agents. In certain embodiments, the subject may have not previously received prior treatment (treatment naïve) for RA. In certain embodiments, the subject may have previously received treatment (treatment experienced) for RA.

In certain embodiments, a compound disclosed herein, or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for treating RA in a subject (e.g., a human) is disclosed.

Also disclosed herein is a compound disclosed herein, or a pharmaceutically acceptable salt thereof, for use in the therapeutic treatment or delaying the onset of RA.

Also disclosed herein is a compound disclosed herein, or a pharmaceutically acceptable salt thereof, for use in the therapeutic treatment of RA.

In certain embodiments, a compound disclosed herein, or a pharmaceutically acceptable salt thereof can be used as a research tool (e.g., to study the inhibition of PAD4 in a subject or in vitro).

Kits that include a compound of Formula (I)-(Iv) or shown in Tables 1 and 1A, or a pharmaceutically acceptable salt, thereof, and suitable packaging are provided. In one embodiment, a kit further includes instructions for use. In one aspect, a kit includes a compound of Formula (I)-(Iv) or shown in Tables 1 and 1A, or a pharmaceutically acceptable salt thereof, and instructions for use of the compounds in the treatment of the diseases or conditions described herein.

Articles of manufacture that include a compound of Formula (I)-(Iv), or a pharmaceutically acceptable salt thereof, in a suitable container are provided. The container may be a vial, jar, ampoule, preloaded syringe, and intravenous bag.

Combination Therapy

In certain embodiments, a compound disclosed herein is administered with one or more additional therapeutic agents. In one embodiment, the present disclosure provides a pharmaceutical composition comprising a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, and at least one additional therapeutic agent and at least one pharmaceutically acceptable carrier or excipient.

In one embodiment, the present disclosure provides a pharmaceutical composition comprising a compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, at least one additional therapeutic agent suitable for treating rheumatoid arthritis, and at least one pharmaceutically acceptable carrier or excipient.

Co-administration of a compound disclosed herein with one or more additional therapeutic agents generally refers to simultaneous or sequential administration of a compound disclosed herein and one or more additional therapeutic agents, such that therapeutically effective amounts of the compound disclosed herein and the one or more additional therapeutic agents are both present in the body of the patient. When administered sequentially, the combination may be administered in two or more administrations.

Co-administration includes administration of unit dosages of the compounds disclosed herein before or after administration of unit dosages of one or more additional therapeutic agents. For example, the compound disclosed herein may be administered within seconds, minutes, or hours of the administration of the one or more additional therapeutic agents. In some embodiments, a unit dose of a compound disclosed herein is administered first, followed within seconds or minutes by administration of a unit dose of one or more additional therapeutic agents. Alternatively, a unit dose of one or more additional therapeutic agents is administered first, followed by administration of a unit dose of a compound disclosed herein within seconds or minutes. In other embodiments, a unit dose of a compound disclosed herein is administered first, followed, after a period of hours (e.g., 1-12 hours), by administration of a unit dose of one or more additional therapeutic agents. In yet other embodiments, a unit dose of one or more additional therapeutic agents is administered first, followed, after a period of hours (e.g., 1-12 hours), by administration of a unit dose of a compound disclosed herein.

›DETAILED DESCRIPTION · 25 of 31

In certain embodiments, a compound disclosed herein is combined with one or more additional therapeutic agents in a unitary dosage form for simultaneous administration to a patient, for example as a solid dosage form for oral administration.

In certain embodiments, a compound of Formula (I)-(Iv) or shown in Tables 1 and 1A is formulated as a tablet, which may optionally contain one or more other compounds useful for treating the target indication. In certain embodiments, such tablets are suitable for once daily dosing. In other embodiments, the tablets are suitable for twice a day dosing.

Combination Drugs

In one embodiment, a compound as disclosed herein, such as a compound of Formula (I)-(Iv) or shown in Tables 1 and 1A, may be combined with one or more other active agents.

For example, in certain embodiments, a compound as disclosed herein, such as a compound of Formula (I)-(Iv) or shown in Tables 1 and 1A, may be used in combination with conventional synthetic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) or biological DMARDs due to orthogonal or complementary mechanisms of action.

The one or more active agents may be chosen from 14-3-3 protein eta inhibitors, 5-Lipoxygenase inhibitors, Abl tyrosine kinase inhibitors, ACTH receptor agonists, Adenosine A3 receptor agonists, adenosine deaminase inhibitors, ADP ribosyl cyclase-1 inhibitors, ADP ribosyl cyclase-1 modulators, ADP ribosylation factor 6 inhibitors, Adrenocorticotrophic hormone ligands, Aggrecanase-2 inhibitors, Albumin modulators, API transcription factor inhibitors, Basigin inhibitors, Bcr protein inhibitors, B-lymphocyte antigen CD19 inhibitors, B-lymphocyte antigen CD20 inhibitors, B-lymphocyte antigen CD20 modulators, B-lymphocyte stimulator ligand inhibitors, Bradykinin receptor modulators, BRAF gene inhibitors, branched amino acid aminotransferase 1 inhibitors, Bromodomain containing protein inhibitors, BTK tyrosine kinase inhibitors, Cadherin-11 antagonists, Calcineurin inhibitors, Calcium channel inhibitors, Carbonic anhydrase inhibitors, Cathepsin K inhibitors, Cathepsin S inhibitors, CCR1 chemokine antagonists, CCR2 chemokine antagonists, CCR3 gene modulators, CCR5 chemokine antagonists, CD 126 antagonists, CD29 modulators, CD3 modulators, CD39 agonists, CD4 agonists, CD4 antagonists, CD40 ligand inhibitors, CD40 ligand receptor antagonists, CD40 ligand receptor modulators, CD52 antagonists, CD73 agonists, CD79b modulators, CD80 antagonists, CD86 antagonists, CD95 antagonists, Cell adhesion molecule inhibitors, Choline kinase inhibitors, Clusterin stimulators, Complement C5 factor inhibitors, Complement Factor stimulators, C-reactive protein inhibitors, CSF-1 antagonists, CXC10 chemokine ligand inhibitors, CXCR4 chemokine antagonists, Cyclin-dependent kinase inhibitor 1 inhibitors, Cyclin-dependent kinase-2 inhibitors, Cyclin-dependent kinase-4 inhibitors, Cyclin-dependent kinase-5 inhibitors, Cyclin-dependent kinase-6 inhibitors, Cyclin-dependent kinase-7 inhibitors, Cyclin-dependent kinase-9 inhibitors, Cyclooxygenase 2 inhibitors, Cyclooxygenase 2 modulators, Cyclooxygenase inhibitors, Cytosolic phospholipase A2 inhibitors, Cytotoxic T-lymphocyte protein-4 modulators, Cytotoxic T-lymphocyte protein-4 stimulators, DHFR inhibitors, Diamine acetyltransferase inhibitors, Dihydroorotate dehydrogenase inhibitors, Elongation factor 2 inhibitors, Eotaxin 2 ligand inhibitors, EP4 prostanoid receptor antagonists, Erythropoietin receptor agonists, Fas ligands, FGF-2 ligand inhibitors, FK506 binding protein-12 modulators, Folate antagonists, Folate receptor agonists, Folate receptor beta antagonists, Folate receptor modulators, Fractalkine ligand inhibitors, Fyn tyrosine kinase inhibitors, G protein coupled receptor 15 antagonists, GABA A receptor modulators, glucocorticoid agonists, Glucocorticoid antagonists, Glucocorticoid induced leucine zipper stimulators, GM-CSF ligand inhibitors, GM-CSF receptor antagonists, GM-CSF receptor modulators, growth regulated protein alpha ligand inhibitors, H+ K+ ATPase inhibitors, histamine H4 receptor antagonists, histone deacetylase inhibitors, histone deacetylase-6 inhibitors, HIV-1 gp120 protein inhibitors, HLA class II antigen DQ-2 alpha modulators, HLA class II antigen inhibitors, HLA class II antigen modulators, Hsp 70 family inhibitors, Hypoxia inducible factor-1 inhibitors, IFNB gene stimulators, I-kappa B kinase beta inhibitors, I-kappa B kinase inhibitors, IL-1 antagonists, IL-10 agonists, IL-11 agonists, IL-12 antagonists, IL-15 antagonists, IL-17 antagonists, IL-17 receptor modulators, IL-8 ligand inhibitors, IL-2 agonists, IL-2 antagonists, IL-21 antagonists, IL-23 antagonists, IL-3 antagonists, IL-4 agonists, IL-6 antagonists, IL-6 receptor modulators, IL-6 neutralizing human antibodies, anti-IL6 antibody, immunoglobulin antagonists, immunoglobulin G1 agonists, immunoglobulin G1 antagonists, Immunoglobulin G1 modulators, Immunoglobulin G2 antagonists, immunoglobulin G2 modulators, immunoglobulin gamma Fc receptor II modulators, immunoglobulin gamma Fc receptor IIB antagonists, immunoglobulin kappa modulators, immunoglobulin M antagonists, inducible nitric oxide synthase inhibitors, Inosine monophosphate dehydrogenase inhibitors, insulin sensitizers, integrin alpha-1/beta-1 antagonists, integrin alpha-4/beta-1 antagonists, integrin alpha-9 antagonist, integrin antagonists, interferon beta ligands, interferon gamma ligands, interleukin 17A ligand inhibitors, Interleukin 17F ligand inhibitors, Interleukin 23A inhibitors, Interleukin ligands, Interleukin receptor 17A antagonists, Interleukin-1 beta ligand inhibitors, Interleukin-10 ligands, Interleukin-2 ligands, Interleukin-4 ligands, Interleukin-6 ligand inhibitors, Itk tyrosine kinase inhibitors, JAK tyrosine kinase inhibitors, Jak1 tyrosine kinase inhibitors, Jak2 tyrosine kinase inhibitors, JAK3 gene inhibitors, Jak3 tyrosine kinase inhibitors, Jun N terminal kinase inhibitors, KCNA voltage-gated potassium channel-3 modulators, Kelch like ECH associated protein 1 modulators, Kit tyrosine kinase inhibitors, LanC like protein 2 modulators, Leukotriene BLT receptor antagonist, LITAF gene inhibitors, Lymphocyte function antigen-3 receptor antagonists, Lyn tyrosine kinase inhibitors, Macrophage mannose receptor 1 modulators, MAdCAM inhibitors, MAP kinase modulators, MAP3K2 gene inhibitors, MAPKAPK5 inhibitors, Matrix metalloprotease inhibitors, MCL1 gene inhibitors, MEK protein kinase inhibitors, MEK-1 protein kinase inhibitors, MEK-2 protein kinase inhibitors, Membrane copper amine oxidase inhibitors, Metalloprotease-2 inhibitors, Metalloprotease-9 inhibitors, methylprednisolone, Midkine ligand inhibitors, Mitochondrial 10 kDa heat shock protein stimulators, mTOR complex 1 inhibitors, mTOR inhibitors, NAD ADP ribosyltransferase stimulators, NAMPT gene inhibitors, NF kappa B inhibitor stimulators, NFAT gene inhibitors, NFE2L2 gene stimulators, Nicotinic acetylcholine receptor antagonists, NK cell receptor modulators, NKG2 A B activating NK receptor antagonists, NKG2 D activating NK receptor antagonists, Nuclear erythroid 2-related factor 2 stimulators, Nuclear factor kappa B inhibitors, Nuclear factor kappa B modulators, Nuclear factor kappa B p105 inhibitors, Opioid growth factor receptor agonists, Opioid receptor delta antagonists, Osteoclast differentiation factor antagonists, Osteoclast differentiation factor ligand inhibitors, Oxidoreductase inhibitors, P2X7 purinoceptor agonists, p38 MAP kinase alpha inhibitors, p38 MAP kinase inhibitors, PDE 4 inhibitors, PDE 5 inhibitors, PDGF receptor agonists, PDGF receptor antagonists, PDGF-B ligand inhibitors, PERK gene inhibitors, Phosphoinositide-3 kinase delta inhibitors, Phosphoinositide-3 kinase gamma inhibitors, Phospholipase A2 inhibitors, Platelet activating factor receptor antagonists, PPAR gamma agonists, Programmed cell death protein 1 modulators, Prostaglandin D synthase stimulators, peptidylarginine deiminase inhibitors, Protein tyrosine kinase inhibitors, PurH purine biosynthesis protein inhibitors, Rho associated protein kinase 2 inhibitors, Seprase inhibitors, Signal transducer CD24 modulators, Signal transduction inhibitors, Sodium glucose transporter-2 inhibitors, Sphingosine 1 phosphate phosphatase modulators, STAT3 gene inhibitors, Superoxide dismutase stimulators, SYK family tyrosine kinase inhibitors, Syk tyrosine kinase inhibitors, Syndecan-1 inhibitors, T cell receptor antagonists, T cell receptor modulators, T cell surface glycoprotein CD28 inhibitors, T cell surface glycoprotein CD28 stimulators, TAK1 binding protein modulators, Talin modulators, T-cell differentiation antigen CD6 inhibitors, T-cell surface glycoprotein CD8 inhibitors, Tenascin modulators, TGF beta agonists, Thymulin agonists, TLR-2 antagonists, TLR-4 antagonists, TLR-9 antagonists, TNF alpha ligand inhibitors, TNF alpha ligand modulators, TNF antagonists, TNF gene inhibitors, TNF receptor modulators, TNFSF11 gene inhibitors, Transcription factor p65 inhibitors, Transcription factor RelB inhibitors, Transferrin modulators, Tumor necrosis factor 13C receptor antagonists, Tumor necrosis factor 15 ligand inhibitors, Tumor necrosis factor ligand 13 inhibitors, Tumor necrosis factor ligand inhibitors, Type IIL-1 receptor antagonists, Type I TNF receptor antagonists, Type II TNF receptor modulators, Unspecified GPCR agonists, VEGF receptor antagonists, VEGF-2 receptor antagonists, VEGF-2 receptor modulators, VEGF-B ligand inhibitors, X-linked inhibitor of apoptosis protein inhibitors, or Zap70 tyrosine kinase inhibitors.

›DETAILED DESCRIPTION · 26 of 31

Examples of active agents that may be combined with the compounds described herein include 99mTc labelled annexin V-128, abatacept, abatacept biosimilar, ABBV-257, ABT-122, ABT-494, acalabrutinib, aceclofenac, actarit, AdMSCs, MS-392, adalimumab, adalimumab biosimilar, adalimumab follow-on biologic, AK-106, ALX-0061, aminopterin, anakinra, anakinra biosimilar, anakinra follow-on biologic, ARG-301, ASLAN-003, ASP-5094, AT-132, AZD-9567, baricitinib, BI-655064, bimekizumab, BiP (rheumatoid arthritis), BLHP-006, blisibimod, BMS-986104, BMS-986142, ABBV-105, BTT-1023, canakinumab, Cartistem, CCX-354, CD24-IgFc, celecoxib, cerdulatinib, certolizumab pegol, CF-101, CFZ-533, CHR-5154, cibinetide, ciclosporin, clazakizumab, CNTO-6785, corticotropin, CR-6086, CreaVax-RA, CWG-92, CWG-940, Cx-611, DE-098, DEN-181, deflazacort, Rheumavax, denosumab, diacerein, diclofenac, E-6011, eicosapentaenoic acid monoglycerides, etanercept, etanercept biosimilar, etanercept follow-on biologic, etodolac, etoricoxib, filgotinib, fosdagrocorat, gerilimzumab, ginsenoside C-K, givinostat, goat polyclonal antibodies, golimumab, GS-5745, GS-9876, GSK-3196165, HM-71224, HMPL-523, hyaluronate sodium, IB-RA (injectable, rheumatoid arthritis), IB-RA (oral, rheumatoid arthritis), ICP-022, iguratimod, IMD-2560, imidazole salicylate, infliximab, infliximab biobetter, infliximab biosimilar, CT-P13, INSIX RA, interferon gamma follow-on biologic, interleukin-2 (injectable), interleukin-2 follow-on biologic, INV-103, IR-501, itolizumab, JNJ-40346527, Ka Shu Ning, KD-025, ketoprofen+omeprazole, leflunomide, lenzilumab, LLDT-8, LNP-1955, lumiracoxib, LY-3090106, masitinib, mavrilimumab, MBS-2320, MEDI-5117, meloxicam, methotrexate, MGD-010, misoprostol+diclofenac, MM-A01-01, monalizumab, MORAb-022, MPC-300-IV, MRC-375, nabumetone, namilumab, naproxen+esomeprazole, naproxen+esomeprazole strontium, ocaratuzumab, ofatumumab, OHR-118, olokizumab, OM-89, once-daily naproxen (oral controlled release, pain), ONO-4059, Oralgam, ozoralizumab, peficitinib, pelubiprofen, PF-06687234, piperidone hydrochloridum, piroxicam, prednisolone, prednisone, Procell, Prosorba, PRT-2607, PRTX-100, PRX-167700, QBSAU, rabeximod, RCT-18, recombinant human CD22 monoclonal antibody (iv infusion), Lonn Ryonn Pharma/SinoMab Bioscience (Shenzhen), RA-Curcusome, recombinant human interleukin-1 receptor antagonist (rheumatoid arthritis), recombinant human interleukin-2 recombinant TNF receptor 2-Fc fusion protein mutant, RG-6125, RhuDex, rifabutin+clarithromycin+clofazimine, rituximab, rituximab biosimilar, Toritz, rituximab follow-on biologic, RPI-78, SAN-300, sarilumab, SBI-087, seliciclib, SHR-0302, sirukumab, spebrutinib, SSS-07, KDDF-201110-06, Syn-1002, T-5224, TAB-08, tacrolimus, TAK-020, TAK-079, tarenflurbil (transdermal spraygel, skin disease/rheumatoid arthritis), technetium Tc 99m tilmanocept, technetium[99Tc] methylenediphosphonate, tenoxicam, Debio-0512, tocilizumab, tofacitinib, tofacitinib citrate, Trichuris suis ova, umbilical cord-derived mesenchymal stem cells (iv, RA/liver disease), ustekinumab, VAY-736, VB-201, WF-10, XmAb-5871, YHB-1411-2, or YRA-1909.

In certain embodiments, a compound described herein may be combined with a 14-3-3 protein eta inhibitor, such as anti-AGX-020 mAbs (rheumatoid arthritis) or Augurex; a 5-Lipoxygenase inhibitor, such as darbufelone, tebufelone, ZD-2138, etalocib, PGV-20229, L-708780, T-0757, T-0799, ZM-216800, L-699333, BU-4601A, or SKF-104351; a 5-Lipoxygenase/Cyclooxygenase inhibitor, such as tenoxicam, licofelone, tenidap, tepoxalin, flobufen, SKF-86002, WY-28342, or CI-986; or a 5-Lipoxygenase/PPAR gamma agonist, such as etalocib; a Abl tyrosine kinase inhibitor/Bcr protein inhibitor/Kit tyrosine kinase inhibitor/PDGF receptor antagonist/or Signal transduction inhibitors, such as imatinib; a ACTH receptor agonist/Adrenocorticotrophic hormone ligand/Opioid growth factor receptor agonist, such as FAR-404, or metenkefalin acetate+tridecactide acetate; an adenosine A3 receptor agonist, such as CF-101 (piclidenoson); an adenosine deaminase inhibitor, such as cladribine, pentostatin, or FR-221647; a ADP ribosyl cyclase-1 inhibitor, such as daratumumab; a ADP ribosyl cyclase-1 modulator/Syndecan-1 inhibitor, such as indatuximab ravtansine; a ADP ribosylation factor 6 inhibitor, such as NAV-2729; a adrenocorticotrophic hormone ligand, such as corticotropin or Mallinckrodt; aggrecanase-2/TNF gene inhibitors, such as GIBH-R-001-2; albumin modulators, such as ONS-1210; albumin modulators/IL-6 antagonists, such as ALX-0061 (vobarilizumab); albumin modulators/TNF alpha ligand inhibitors, such as HOT-3010; a API transcription factor/Nuclear factor kappa B inhibitor, such astarenflurbil or SP-100030; anti-TNF steroid antibody-drug conjugates (anti-TNF-GRM), such as ABBV-3373; Basigin inhibitors/Branched amino acid aminotransferase l/Metalloprotease-9 inhibitors/Metalloprotease-2 inhibitors, such as ERG-240; BET inhibitors such as GSK-3358699; Bispecic anti-CD86/IL-10, such as APVO-210; bispecific humanized monoclonal antibody targeted against BAFF and IL-17A, such as tibulizumab; bispecific antibody-peptide conjugate (BAFF/ICOSL), such as AMG-570; B-lymphocyte antigen CD19 inhibitors, such as MDX-1342; B-lymphocyte antigen CD19 inhibitors/Immunoglobulin gamma Fc receptor IIB antagonists, such as XmAb-5871; B-lymphocyte antigen CD20 inhibitors, such as ocrelizumab, ofatumumab, rituximab, ABP-798, Maball, Mabtas, Reditux, Zytux, veltuzumab, ocaratuzumab, BLX-301, IDEC-102, ABP-798, GP-2013, MK-8808, HLX-01, CT-P10, TL-011, PF-05280586, IBPM-001RX, IBI-301, AME-133v, BCD-020, BT-D004, SAIT-101, or JHL-1101; B-lymphocyte antigen CD20 modulators, such as SBI-087, TRU-015, DXL-625, or MabionCD20; B-lymphocyte stimulator ligand inhibitors, such as belimumab, RCT-18, blisibimod, tabalumab, or briobacept; B-lymphocyte stimulator ligand/Tumor necrosis factor ligand 13 inhibitors, such as atacicept; bradykinin receptor modulators/Histone deacetylase inhibitors/P2X7 purinoceptor agonists, such asgivinostat; BRAF gene/MEK protein kinase/PERK gene inhibitors, such as binimetinib; Bromodomain containing protein inhibitors, such as RVX-297 or ZEN-003694; Btk tyrosine kinase inhibitors, such as AC-0058, acalabrutinib, HM-71224, spebrutinib, BMS-986142, TAK-020, tirabrutinib (ONO-4059), TAS-5315, ABBV-105, GDC-0834, EBI-1459, BMS-986195, evobrutinib, or fenebrutinib; Btk tyrosine kinase inhibitors/Syk tyrosine kinase inhibitors/VEGF-2 receptor antagonists, such as CG-026806; Btk tyrosine kinase inhibitors/IL-6 antagonists, such as RN-486; Btk tyrosine kinase/Jak1 tyrosine kinase inhibitors, such as upadacitinib+ABBV-105; Btk tyrosine kinase/Jak3 tyrosine kinase inhibitors, such as AC-0025; cadherin-11 antagonists, such as RG-6125; calcineurin inhibitors, such as ciclosporin; calcineurin inhibitors/opioid receptor delta antagonists, such as HS-378; calcium channel inhibitors, such as RP-3128; carbonic anhydrase/Cyclooxygenase 2 inhibitors, such as polmacoxib; cathepsin K inhibitors, such as CRA-013783 or VEL-0230; cathepsin K/cathepsin S inhibitors, such as AM-3876 or NPI-2019; cathepsin S inhibitors, such as MIV-247 or RWJ-445380; CCR1 chemokine antagonists, such as BX-471, BMS-817399, BI-638683, CCX-354, MLN-3701, MLN-3897, CP-481715 or PS-375179; CCR2 chemokine antagonists, such as MK-0812 or AZD-6942; CCR3 gene modulators/Eotaxin 2 ligand inhibitors, such as CM-102; CCR5 chemokine antagonists, such as OHR-118, NIBR-6465, AZD-5672, or AZD-8566; CD29 modulators/Interleukin-10 ligands, such as PF-06687234; CD3 modulators, such as otelixizumab; CD39/CD73 agonists, such as AAV5-CD39/CD73 (rheumatoid arthritis), or Arthrogen; CCR5 chemokine antagonists/CD4 agonists/HIV-1 gp120 protein inhibitors, such as maraviroc; CD4 antagonists, such as zanolimumab, MTRX-1011A, BW-4162W94, EP-1645, or clenoliximab; CD40 ligand inhibitors, such as dapirolizumab pegol; CD40 ligand receptor antagonists, such as BI-655064, anti-CD40-XTEN, teneliximab, VIB-4920, or iscalimab; CD40 ligand receptor modulators/Immunoglobulin G1 modulators, such as CFZ-533; CD52 antagonists/Clusterin stimulators, such as alemtuzumab; bispecific CD32B/CD79B antibody, such as PRV-3279 (MGD-010); CD80 antagonists, such as abatacept biobetter; CD80 antagonists/T cell surface glycoprotein CD28 inhibitors, such as RhuDex; CD80 antagonists/CD86 antagonists, such as XENP-9523 or ASP-2408; CD86 antagonists, such as abatacept or biosuperior; CD86 antagonists/Cytotoxic T-lymphocyte protein-4 modulators, such as ES-210; CD95 antagonists, such as DE-098 or CS-9507; cell adhesion molecule inhibitors, such as alicaforsen, NPC-17923, TK-280 and PD-144795; chemokine receptor antagonists, such as PF-06835375; complement C5 factor inhibitors, such as eculizumab; complement C5 factor inhibitors/IL-1 antagonists, such as antisense oligonucleotides (rheumatoid arthritis); Leiden University Medical CenterComplement Factor stimulators, such as CM-101; C-reactive protein inhibitors, such as ISIS-353512; C-reactive protein inhibitors/Cyclooxygenase 2 inhibitors/Nuclear factor kappa B inhibitors/Immunoglobulin M antagonists/IL-2 receptor antagonists/PGE2 antagonists, such as IB-RACSF-1 antagonists: masitinib, FPA-008, JNJ-27301937, JNJ-40346527, PLX-5622, CT-1578, PD-360324, or JNJ-28312141; CSF-1 antagonists/Fyn tyrosine kinase inhibitors/Kit tyrosine kinase inhibitors/Lyn tyrosine kinase inhibitors/NK cell receptor modulators/PDGF receptor antagonists, such as masitinib; CXC10 chemokine ligand inhibitors, such as 946414-98-8 or BMS-936557; CXCR4 chemokine antagonists, such as plerixafor; CDK-2/7/9 inhibitors/MCL1 gene inhibitors, such as seliciclib; CDK-1/2/5/7/9 inhibitors, such as BP-14; cyclooxygenase 2 inhibitors, such as celecoxib, etoricoxib, meloxicam, or lumiracoxib; cyclooxygenase 2/Oxidoreductase inhibitors, such as etodolac; cyclooxygenase 2 modulators, such as DRGT-46; cyclooxygenase inhibitors, such as aceclofenac, diclofenac, naproxcinod, naproxen etemesil, nabumetone, Aleve, pelubiprofen, LY-210073, NS-398, bromfenac, L-746483, LY-255283, ibuprofen, flurbiprofen, SC-57666, or bermoprofen; cyclooxygenase inhibitors/H+ K+ ATPase inhibitors, such as naproxen+esomeprazole strontium; cyclooxygenase inhibitors/PGE1 agonists, such as misoprostol+diclofenac; cyclooxygenase inhibitors/Oxidoreductase inhibitors, such as imidazole salicylate; cytosolic phospholipase A2 inhibitors/Phospholipase A2 inhibitors, such as AVX-002; cytotoxic T-lymphocyte protein-4 stimulators/T cell surface glycoprotein CD28 inhibitors, such as abatacept, (BMS-188667) or belatacept; DHFR inhibitors, such as MPI-2505, Jylamvo, or ZeNEO-Methotrexate; DHFR inhibitors/Folate antagonists/Transferrin modulators, such as methotrexate; Diamine acetyltransferase inhibitors, such as diminazene aceturate; dihydroorotate dehydrogenase inhibitors, such as ASLAN-003, HWA-486, or ABR-224050; dihydroorotate dehydrogenase/Protein tyrosine kinase inhibitors, such as leflunomide; elongation factor 2 inhibitors/interleukin-2 ligands/NAD ADP ribosyltransferase stimulators, such as denileukin diftitox; EP4 prostanoid receptor antagonists, such as CR-6086; Erythropoietin receptor agonists, such as cibinetide; Fas ligands, such as AP-300; FGF-2 ligand inhibitors, such as RBM-007; FK506 binding protein-12 modulators/mTOR inhibitors, such as temsirolimus; folate antagonists/Transferrin modulators/DHFR inhibitors, such as MBP-Y003; folate receptor modulators, such as technetium (99mTc) etarfolatide; fractalkine ligand inhibitors, such as E-6011; Fyn tyrosine kinase inhibitors/GABA A receptor modulators/Cyclooxygenase 2 inhibitors/Dihydroorotate dehydrogenase inhibitors, such as laflunimus; Glucocorticoid agonists, such as prednisone, prednisolone, or fosdagrocorat; Glucocorticoid antagonists, such as REC-200; Glucocorticoid induced leucine zipper stimulators, such as ART-G01; GM-CSF ligand inhibitors, such as namilumab, gimsilumab (MORAb-022), or TJM-2; GM-CSF receptor antagonists, such as mavrilimumab; GM-CSF receptor modulators, such as GSK-3196165 or otilimab; growth regulated protein alpha ligand inhibitors/AP1 transcription factor; inhibitors/IF-6 antagonists/Interleukin-1 beta ligand inhibitors/Cathepsin K inhibitors/NFAT gene inhibitors, such as T-5224; H+K+ATPase inhibitors, such as naproxen+esomeprazole, ketoprofen+omeprazole, KEO-25001, HC-1004, or PN-40020; histamine H4 receptor antagonists, such as toreforant or GD-48; histone deacetylase inhibitors, such as CHR-5154 (GSK-3117391); histone deacetylase-6 inhibitors, such as CKD-506; HFA class II antigen DQ-2 alpha modulators, such as NexVax2; HFA class II antigen inhibitors, such as HFA-DR1/DR4 inhibitors (rheumatoid arthritis) or Provid; HFA class II antigen modulators, such as recombinant T-cell receptor ligand (rheumatoid arthritis) or Artielle; Hsp 70 family inhibitors, such as gusperimus trihydrochloride; hypoxia inducible factor-1 inhibitors/VEGF receptor antagonists, such as 2-methoxyestradiol; IFNB gene stimulators, such as ART-102; I-kappa B kinase beta inhibitors, such as IMD-2560; I-kappa B kinase beta inhibitors/Nuclear factor kappa B inhibitors, such as IMD-0560; I-kappa B kinase inhibitors/NFE2F2 gene stimulators/Nuclear factor kappa B inhibitors/STAT3 gene inhibitors, such as bardoxolone methyl; IF-1 antagonists, such as recombinant human interleukin-1 receptor antagonist (rheumatoid arthritis), Shanghai Fudan-Zhangjiang Bio-Pharmaceutical; IF-1 antagonists/Interleukin-1 beta ligand inhibitors, such as rilonacept; IF-10 agonists, such as peg-ilodecakin; IF-11 agonists/PDGF receptor agonists, such as oprelvekin; IF-12 antagonists/IF-23 antagonists, such as ustekinumab or briakinumab; IF-15 antagonists, such as AMG-714; IF-17 antagonists, such as ixekizumab or secukinumab; IF-17 receptor modulators, such as CNTO-6785; IF-2 receptor agonists, such as interleukin-2 follow-on biologic (IF-2), Anteluke or Interking; IF-2/IF-21/IF-15 antagonists, such as BNZ-132-2; IL-21 antagonists, such as NN-8828; IL-4 agonists, such as SER-130-AMI; IL-6 antagonists, such as BCD-089, olokizumab, clazakizumab, sirukumab, SA-237,FB-704A, OP-R003, peptide IL-6 antagonist, MEDI-5117, AMG-220, FM-101, BLX-1025, esonarimod, TA-383, or sarilumab; IL-6 antagonists/Interleukin-1 beta ligand inhibitors/TNF alpha ligand inhibitors, such as K-832; IL-6 antagonists/Insulin sensitizers/Interleukin-1 beta ligand inhibitors, such as BLX-1002; IL-6 receptor antagonists/modulators, such as tocilizumab, HS-628, or LusiNEX; IL-6 receptor modulators, such as BAT-1806 or RO-4877533; immunoglobulin antagonists, such as iguratimod; immunoglobulin G1 agonists, such as BX-2922 and HF-1020; immunoglobulin G1 agonists/Interleukin-1 beta ligand inhibitors, such as canakinumab; immunoglobulin G1 agonists/TNF alpha ligand inhibitors, such as STI-002; immunoglobulin G1 antagonists/TNF alpha ligand inhibitors, such as YHB-1411-2; immunoglobulin G1 modulators/GM-CSF ligand inhibitors/immunoglobulin kappa modulators, such as lenzilumab; immunoglobulin G2 antagonists/NF kappa B inhibitor stimulators/Osteoclast differentiation factor antagonists/Osteoclast differentiation factor ligand inhibitors/TNFSF11 gene inhibitors, such as denosumab; immunoglobulin gamma Fc receptor II modulators, such as MGD-010; inducible nitric oxide synthase inhibitors/Cyclooxygenase 2 inhibitors/MAP kinase modulators/Nuclear factor kappa B inhibitors, such as SKLB-023; inosine monophosphate dehydrogenase inhibitors, such as mizoribine; insulin sensitizers/Nuclear factor kappa B inhibitors/interleukin ligand inhibitors, such as HE-3286; integrin alpha-1/beta-1 antagonists, such as SAN-300; integrin alpha-4/beta-1 antagonists/cell adhesion molecule inhibitors, such as natalizumab; integrin alpha-9 antagonist, such as ASP-5094; integrin antagonists, such as PEG-HM-3 or CY-9652; interferon beta ligands, such as recombinant interferon beta-la; interferon beta ligands/IL-6 antagonists, such as TA-383; interferon gamma ligands, such as Li Zhu Yin De Fu or Clongamma; interleukin 17A ligand inhibitors/Tumor necrosis factor ligand inhibitors, such as ABT-122 or ABBV-257; interleukin 17F ligand inhibitors, such as bimekizumab; interleukin 18 ligand inhibitors, such as tadekinig alfa; interleukin 23A inhibitors, such as guselkumab; interleukin ligands/IL-1 antagonists, such as IBPB-007-IL; interleukin receptor 17A antagonists, such as brodalumab; interleukin-1 beta ligand inhibitors, such as gevokizumab, LY-2189102 or CDP-484; interleukin-1 beta ligand inhibitors/TNF alpha ligand inhibitors, such as PMI-001; interleukin-1 beta ligands/TNF alpha ligand modulators, such as PUR-0110; interleukin-2 ligands, such as recombinant interleukin-2; IL-2 modulators, such as AMG-592; interleukin-4 ligands/Tenascin modulators, such as Tetravil; interleukin-6 ligand inhibitors, such as gerilimzumab or PF-4236921; IRAK-4 protein kinase inhibitor, such as BAY-1830839, BAY-1834845, or PF-06650833; Itk tyrosine kinase inhibitors, such as JTE-051; Itk tyrosine kinase inhibitors/Jak3 tyrosine kinase inhibitors, such as ARN-4079; JAK tyrosine kinase inhibitors, such as deuterated tofacitinib analog or SD-900; JAK tyrosine kinase inhibitors/Syk tyrosine kinase inhibitors, such as cerdulatinib or CVXL-0074; Jak1 tyrosine kinase inhibitors, such as ABT-494 (upadacitinib), ruxolitinib, filgotinib, itacitinib, NIP-585, YJC-50018, GLPG-0555, MRK-12, or SHR-0302; Jak1/3 tyrosine kinase inhibitors, such as tofacitinib, tofacitinib citrate, peficitinib, CKD-374, or CS-944X; Jak1/2 tyrosine kinase inhibitors, such as baricitinib or ruxolitinib; Jak2 tyrosine kinase inhibitors/CSF-1 antagonists, such as CT-1578; JAK3 gene inhibitors, such as PF-06651600; Jak3 tyrosine kinase inhibitors, such as decemotinib, DNX-04042, MTF-003, or PS-020613; Jun N terminal kinase inhibitors, such as IQ-1S; KCNA voltage-gated potassium channel-3 modulators, such as MRAD-P1; Kelch like ECH associated protein 1 modulators/Nuclear erythroid 2-related factor 2 stimulators, such as dimethyl fumarate; FanC like protein 2 modulators, such as BT-11; FDF receptor related protein-1 stimulator, such as SP-16; Feukotriene BET receptor antagonists/complement C5 factor inhibitors, such as nomacopan; FITAF gene inhibitors/JAK3 gene inhibitors/MAP3K2 gene inhibitors/TNF antagonists, such as GBF-5b; Fymphocyte function antigen-3 receptor antagonists, such as alefacept; Macrophage mannose receptor 1 modulators, such as technetium Tc 99m tilmanocept; MAdCAM inhibitors/Immunoglobulin G2 modulators, such as PF-547659; MAPKAPK5 inhibitors/matrix metalloprotease inhibitors, such as GFPG-0259; MEK protein kinase inhibitors, such as AD-GF0001; Membrane copper amine oxidase inhibitors, such as BTT-1023, PRX-167700, or vepalimomab; Metalloprotease-9 inhibitors, such as GS-5745; Microbiome modulator, such as EDP-1815; Midkine ligand inhibitors, such as CAB-102; Mitochondrial 10 kDa heat shock protein stimulators, such as INV-103; mTOR inhibitors, such as everolimus; NAMPT gene inhibitors, such as ART-D01; Nicotinic acetylcholine receptor antagonists, such as RPI-78 or RPI-MN; NKG2 A B activating NK receptor antagonists, such as monalizumab; NKG2 D activating NK receptor antagonists, such as NNC-0142-002; Nuclear factor kappa B inhibitors, such as dehydroxymethylepoxyquinomicin, MP-42, VGX-1027,SP-650003, MG-132, SIM-916, VGX-350, VGX-300, GIT-027, MLN-1145, or NVP-IKK-005; Nuclear factor kappa B modulators/Nuclear factor kappa B p105 inhibitors/Transcription factor RelB inhibitors/Transcription factor p65 inhibitors, such as REM-1086; Osteoclast differentiation factor antagonists, such as cyclic peptidomimetics (rheumatoid arthritis/osteoporosis), University of Michigan; p38 MAP kinase alpha inhibitors, such as VX-745, BMS-582949, or BMS-751324; p38 MAP kinase inhibitors, such as BCT-197, losmapimod, or ARRY-797; PDE 4 inhibitors, such as apremilast; PDE 5 inhibitors, such as PDE5 inhibitors (rheumatoid arthritis), University of Rochester; PDGF-B ligand inhibitors/VEGF receptor antagonists, such as SL-1026; Phosphoinositide-3 kinase delta inhibitors, such as CT-732, INK-007 or GNE-293; Phosphoinositide-3 kinase delta/gamma inhibitors, such as duvelisib or RP-6503; Phospholipase A2 inhibitors, such as AK-106, varespladib methyl, Ro-31-4493, BM-162353, Ro-23-9358, or YM-26734; Platelet activating factor receptor antagonists, such as piperidone hydrochloridum; PPAR gamma agonists, such as rosiglitazone XR; PPAR gamma agonists/Insulin sensitizers, such as rosiglitazone; Programmed cell death protein 1 modulators, such as INSIX RA; Prostaglandin D synthase stimulators, such as HF-0220; Protein tyrosine kinase inhibitors, such as tairuimide; PurH purine biosynthesis protein inhibitors/Inosine monophosphate dehydrogenase inhibitors, such as mycophenolate mofetil; Rev protein modulators, such as ABX-464; RIP-1 kinase inhibitors, such as GSK-2982772; IL-17 antagonist/Rho associated protein kinase 2 inhibitor, such as KD-025; Signal transducer CD24 modulators, such as CD24-IgFc; Sodium glucose transporter-2 inhibitors/PPAR gamma agonists/Insulin sensitizers, such as THR-0921; STAT3 gene inhibitors, such as vidofludimus; STAT-3 inhibitors, such as HL-237; Superoxide dismutase stimulators, such as imisopasem manganese; SYK family tyrosine kinase inhibitors/Zap70 tyrosine kinase inhibitors, such as MK-8457; Syk tyrosine kinase inhibitors, such as fostamatinib, entospletinib, KDDF-201110-06, HMPL-523,AB-8779, GS-9876, PRT-2607, CG-103065, or SKI-O-703; T cell receptor antagonists, such as TCR inhibiting SCHOOL peptides (systemic/topical, rheumatoid arthritis/dermatitis/scleroderma), SignaBlok, CII modified peptide (rheumatoid arthritis), or Peking University; T cell receptor modulators/HLA class II antigen modulators, such as ARG-301; T cell surface glycoprotein CD28 stimulators, such as TAB-08 or theralizumab; TAK1 binding protein modulators, such as epigallocatechin 3-gallate; Talin modulators, such as short-form talin regulators (rheumatoid arthritis) or KayteeBio; T-cell differentiation antigen CD6 inhibitors, such as itolizumab; T-cell surface glycoprotein CD8 inhibitors/TGF beta agonists/CD4 antagonists, such as tregalizumab; Thymulin agonists, such as Syn-1002; TLR-2/TLR-4 antagonists, such as VB-201; TLR-4 antagonists, such as NI-0101; TLR-2/4/9 antagonists, such as P-13; TNF agonists/TNF antagonists/Type II TNF receptor modulators, such as Lifmior; TNF alpha ligand inhibitors, such as Adfrar, FKB-327, Exemptia, Cinnora, Mabura, adalimumab, infliximab, Flixabi, PF-06438179, hadlima, recombinant humanized anti-TNF-alpha monoclonal antibody, CMAB-008, CT-P13, GB-242, golimumab (CNTO-148), ozoralizumab, AT-132, ISIS-104838, ISU-202, CT-P17, MB-612, Debio-0512, anti-TNF alpha human monoclonal antibody, UB-721, KN-002, DA-3113, BX-2922, R-TPR-015, BOW-050, PF-06410293, CKD-760, CHS-1420, GS-071, ABP-710, BOW-015, HLX-03, BI-695501, MYL-1401A, ABP-501, BAX-2923, SCH-215596, ABT-D2E7, BAT-1406, XPro-1595, Atsttrin, SSS-07, golimumab biosimilar, TA-101, BLX-1002, ABX-0401, TAQ-588, TeHL-1, placulumab, CYT-007-TNFQb, SSR-150106, PassTNF, Verigen, DOM-0200, DOM-0215, AME-527, anti-TNF-alpha mAb, GENZ-38167, BEX-1028, CYT-020-TNFQb, CC-1080, CC-1069, LBAL, GP-2017, Idacio, IBI-303, or HS-016; TNF alpha ligand inhibitors/TNF antagonists/Type II TNF receptor modulators, such as BAX-2200; TNF alpha ligand inhibitors/Type II TNF receptor modulators, such as Eucept, TNF alpha ligand modulators, such as MM-A01-01, CDP-571, camobucol, or JNJ-63823539; TNF antagonists, such as DNX-114, TNF antagonist+IF-12 antagonist (rheumatoid arthritis), University of Oxford, BN-006, pegsunercept, ACE-772, onercept, DE-096, PN-0615, lenercept, ITF-1779, MDF-201112,HD-203, Qiangke, or TNF a Fc; TNF antagonists/Type II TNF receptor modulators, such as Altebrel, Intacept, QF-0902, etanercept, Erelzi, opinercept, YISAIPU, Anbainuo, Benepali, YFB-113, SCB-808, DA-3853, or SCB-131; TNF antagonists/TNF alpha ligand inhibitors, such as certolizumab pegol; TNF receptor modulators, such as recombinant TNF receptor 2-Fc fusion protein mutant or T-0001; TNF receptor modulators/TNF alpha ligand inhibitors, such as tgAAV-TNFR:Fc; tumor necrosis factor 13C receptor antagonists, such as VAY-736; tumor necrosis factor 15 ligand inhibitors, such as anti-TF1A antibodies (rheumatoid arthritis/inflammatory bowel disease), or NIAMS; Tumor necrosis factor ligand inhibitors, such as etanercept biosimilar; Type IIF-1 receptor antagonists, such as anakinra, IF-1 Ra, anakinra follow-on biologic or AXXO; Type I TNF receptor antagonists, such as NM-9405; Type II TNF receptor modulators, such as FBEC-0101, DMB-3853, DWP-422, or BT-D001; Unspecified GPCR agonists, such as NCP-70X; VEGF receptor antagonists, such as NSC-650853; VEGF-2 receptor modulators, such as VEGFR2 neutralizing antibody (rheumatoid arthritis), University of Rochester; VEGF-B ligand inhibitors, such as CSF-346; X-linked inhibitor of apoptosis protein inhibitors, such as IAP inhibitors (oral) or Pharmascience; or Zap70 tyrosine kinase inhibitors, such as CT-5332.

›DETAILED DESCRIPTION · 27 of 31

In one embodiment, the compound of Formula (I), or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, is useful for the treatment of cancer in combination with a JAK-1 inhibitor. An example of such JAK-1 inhibitor is a compound disclosed in WO2008/109943. Examples of other JAK inhibitors include, but are not limited to, AT9283, AZD1480, baricitinib, BMS-911543, fedratinib, filgotinib (GFPG0634), gandotinib (FY2784544), INCB039110 (itacitinib), lestaurtinib, momelotinib (CYT0387), NS-018, pacritinib (SB 1518), peficitinib (ASP015K), ruxolitinib, tofacitinib (formerly tasocitinib), INCB052793, and XF019. In one embodiment, a compound as disclosed herein, such as a compound of Formula (I) or any formula described herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, may be combined with filgotinib (GLPG0634).

Synthesis

The compounds of the disclosure may be prepared using methods disclosed herein and routine modifications thereof which will be apparent given the disclosure herein and methods well known in the art. Conventional and well-known synthetic methods may be used in addition to the teachings herein. The synthesis of typical compounds of formula (I), e.g., compounds having structures described by one or more of formula (I), or other formulas or compounds disclosed herein, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, may be accomplished as described in the following examples.

General Syntheses

Typical embodiments of compounds in accordance with the present disclosure may be synthesized using the general reaction schemes and/or examples described below. It will be apparent given the description herein that the general schemes may be altered by substitution of the starting materials with other materials having similar structures to result in products that are correspondingly different. Descriptions of syntheses follow to provide numerous examples of how the starting materials may vary to provide corresponding products. Starting materials are typically obtained from commercial sources or synthesized using published methods for synthesizing compounds which are embodiments of the present disclosure, inspection of the structure of the compound to be synthesized will provide the identity of each substituent group. The identity of the final product will generally render apparent the identity of the necessary starting materials by a simple process of inspection, given the examples herein.

Synthetic Reaction Parameters

The compounds of this disclosure can be prepared from readily available starting materials using, for example, the following general methods and procedures. It will be appreciated that where typical or preferred process conditions (e.g., reaction temperatures, times, mole ratios of reactants, solvents, pressures, etc.) are given; other process conditions can also be used unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvent used, but such conditions can be determined by one skilled in the art by routine optimization procedures.

Additionally, as will be apparent to those skilled in the art, conventional protecting groups may be necessary to prevent certain functional groups from undergoing undesired reactions. Suitable protecting groups for various functional groups as well as suitable conditions for protecting and deprotecting particular functional groups are well known in the art. For example, numerous protecting groups are described in T. W. Greene and G. M. Wuts (1999) Protecting Groups in Organic Synthesis, 3rd Edition, Wiley, New York, and references cited therein. Protective groups can be added or removed at any appropriate stage in order to enable the syntheses described herein.

Furthermore, the compounds of this disclosure may contain one or more chiral centers. Accordingly, if desired, such compounds can be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers or diastereomers or as stereoisomer-enriched mixtures. All such stereoisomers (and enriched mixtures) are included within the scope of this disclosure, unless otherwise indicated. Pure stereoisomers (or enriched mixtures) may be prepared using, for example, optically active starting materials or stereoselective reagents well-known in the art. Alternatively, racemic mixtures of such compounds can be separated using, for example, chiral column chromatography, chiral resolving agents, and the like.

The starting materials for the following reactions are generally known compounds or can be prepared by known procedures or obvious modifications thereof. For example, many of the starting materials are available from commercial suppliers such as Aldrich Chemical Co. (Milwaukee, Wisconsin, USA). Others may be prepared by procedures or obvious modifications thereof, described in standard reference texts such as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-15 (John Wiley, and Sons, 1991), Rodd's Chemistry of Carbon Compounds, Volumes 1-5, and Supplementals (Elsevier Science Publishers, 1989) organic Reactions, Volumes 1-40 (John Wiley, and Sons, 1991), March's Advanced Organic Chemistry, (John Wiley, and Sons, 5 th Edition, 2001), and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989).

The terms “solvent,” “inert organic solvent” or “inert solvent” refer to a solvent inert under the conditions of the reaction being described in conjunction therewith (including, for example, benzene, toluene, acetonitrile, tetrahydrofuran (“THF”), dimethylformamide (“DMF”), chloroform, methylene chloride (or dichloromethane), diethyl ether, methanol, pyridine and the like). Unless specified to the contrary, the solvents used in the reactions of the present disclosure are inert organic solvents, and the reactions are carried out under an inert gas, preferably nitrogen.

›DETAILED DESCRIPTION · 28 of 31

The following is a list of abbreviations and acronyms used throughout the application:

Compounds as provided herein may be synthesized according to the general schemes provided below. In the Schemes below, it should be appreciated that each of the compounds shown therein may have protecting groups as required present at any step. Standard protecting groups are well within the purview of one skilled in the art. Further, unless otherwise defined, the various substituents depicted in the following Schemes (e.g., X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , L 6 m6 , R 1 , R 2 , R 3 , R 10 , R 11 , etc.) are as defined in the embodiments and compounds disclosed herein. In certain Schemes, L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 are generalized using L n and L m . It is to be understood that either of L n and L m can include any combination of L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 , provided that upon closure of the macrocycle ring, the resulting compound can be defined by the L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 provided herein.

Scheme A shows an exemplary synthetic route for the synthesis of compounds provided herein (e.g., compounds of Formula (I)). In Scheme A, X 1 , X 2 , X 3 , X 4 , X 5 , X 7 , L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , L 6 m6 , R 1 , R 10 , and R 11 , are as defined herein, Pi is hydrogen or a suitable protecting group, Z is the moiety —NR 10 R 11 , or a suitable precurser thereto (e.g., —OH or —O-alkyl, and the like), and R 100 and R 101 , X and Y are each, respectively, suitable complimentary functional groups capable of forming a covalent bond therebetween.

In Scheme A, a compound A-100 can first be deprotected as needed and then reacted with a compound of formula Y-L n -L m -LG, where LG is a leaving group (e.g., halo), under suitable conditions to provide compound A-101. Compound A-101 can then be converted to compound A-103 under suitable cyclization conditions. Alternatively, compound A-100 can be deprotected as needed and reacted with a compound of formula R 100 -L m -LG, where LG is a leaving group (e.g., halo), and then, when X comprises a nucleophilic functional group, a compound of formula R 101 -L n -LG, where LG is a leaving group (e.g., halo), or alternatively, when X is a leaving group (e.g., halo), a compound of formula R 101 -L n -M, to provide compound A-102, where M is a suitable cross coupling functional group, such as a boronic ester, acid, or trifluoroborate group, a zinc or magnesium halide species, or a trialkylstannane in the presence of a palladium catalyst. It should also be understood that the order in which the installation of the respective macrocyclic precursers (i.e., R 100 -L m - and R 101 -L n -) can be reversed, and/or the various groups can be further modified after the formation of compound A-102 as desired. Cyclization of compound A-102 provides compound A-103. Exemplary functional groups and methods for achieving cyclization, and well as other functional group modifications, are detailed in the Schemes and Procedures below.

In Scheme A, compound A-103, shown both generalized using L n and L m , and specifically using L 1 m1 , L 2 m2 , L 3 m3 , L 4 m4 , L 5 m5 , and L 6 m6 , can be further modified to install the —NR 10 R 11 moiety and thus provide compounds of Formula (I). In certain embodiments of compound A-100, A-102 or A-103, Z is —NR 10 R 11 . Thus, it can be understood that at any point in the synthesis prior to the formation of the macrocyclic ring, an intermediate can be modified to convert a Z group, where Z is suitable precurser (e.g., —OH or —O-alkyl, and the like), to Z is —NR 10 R 11 .

In certain embodiments, R 10 or R 11 may contain a protected amine substituent (e.g., —NHP 1 , —NP 1 P 2 , or —NR 12 P 1 , where examples of P 1 and P 2 include -Boc, -Cbz, -trityl, or any other group known to be useful as an amine protective group). Additionally, R 11 may be a nitrogen-containing heterocycle wherein the ring nitrogen is protected with P 1 , as defined above. In these cases, removal of P 1 and P 2 can be carried out using standard conditions, including TFA or HCl for -Boc or -trityl, and hydrogenolysis over a suitable catalyst (e.g., Pd/C) for -Cbz to afford amine products.

Where the individual steps do not provide a desired isomer (e.g., stereoisomer), resolution of the isomers of Formula (I), or any intermediate used in the preparation thereof, can be performed as needed using standard chiral separation/resolution conditions (e.g., chromatography, crystallization, etc.).

Suitably substituted compounds A-100, A-101, A-102, and A-103 for use in the methods provided herein can be purchased from commercial sources or synthesized by known methods, or according to methods described in the Schemes and Procedures detailed herein.

For example, Scheme B shows exemplary methods for the synthesis of compound of formula A-100 for use in Scheme A. In Scheme B, compound B-102 (i.e., compound A-100 where X 1 and X 2 are C and X 3 is N—R 3 ) can be prepared by contacting compound B-100 with compound B-101 under conditions sufficient to provide compound B-102. Further, compound B-105 (i.e., compound A-100 where X 3 is C—R 3 ) can be prepared by contacting compound B-103 with compound B-104 under conditions sufficient to provide compound B-105.

Suitably substituted compounds for use in Scheme B (i.e., compounds B-100, B-101, B-103, and B-104) can be purchased from commercial sources, synthesized by known methods, or synthesized according to the general Schemes detailed below, and/or the specific Procedures disclosed herein.

It is understood that the order of events depicted in Scheme C-1 could be rearranged; for example, step 3 could precede steps 1 and 2.

It is understood that fragments containing functional precursors to —CO 2 P 2 (for example —CH 2 OP 4 , where P 4 =H or suitable protective group) may also be used in Step 2, where —CO 2 P 2 may be subsequently accessed by functional group transformation (for example by deprotection/oxidation of —CH 2 OP 4 ).

›DETAILED DESCRIPTION · 29 of 31

It is also understood that that fragments containing functional precursors to —N(R 8 )P 3 may also be used in step 3, where —N(R 8 )P 3 may be subsequently accessed by functional group transformation, for example by Curtius rearrangement of a carboxylic acid, or by reductive amination upon a ketone or aldehyde. Several specific cases are outlined in Scheme C-2, C-3, and C-4.

Scheme C-2 depicts a synthesis of a macrocyclic lactam precursor wherein the amine-containing macrocycle fragment is accessed from an acetyl precursor.

Step 1 and 2 describe installation of an acetyl moiety by cross coupling of a vinyl ether nucleophile mediated by a suitable palladium catalyst followed by acidic hydrolysis. In this sequence, M is often trialkylstannane (for example, as in 1-ethoxyvinyltributylstannane), but other suitable organometallic species for cross-coupling may also be used. Alternatively, a Heck coupling mediated by a suitable palladium catalyst may be used where M=H.

Step 3 describes the installation of a protected or unprotected amino moiety condensation of a suitable amine derivative followed by reduction of the formed imine intermediate. This transformation may be accomplished in several ways, including in situ reductive amination, where the acetyl intermediate is treated with amine and a suitable reducing agent (e.g., NaBH(OAc) 3 , NaBH 3 CN) concurrently. Alternatively, this can be accomplished stepwise, where a suitable amine derivative is condensed in the presence of a Lewis acid dehydrating reagent (e.g., Ti(OiPr) 4 , Ti(OEt) 4 , CuSO 4 ) to provide an imine followed by reduction in a second step with a suitable reducing agent (e.g., NaBH 4 , L-selectride). tert-butyl sulfinamide is an especially useful amine derivative, due to the availability of enantiomeric forms and the known ability of these to exert control over stereoconfiguration in the reduction step. It is understood that protective group/auxiliary manipulation can take after amine installation (e.g., P 3 =S(O)tBu can be removed and/or converted to Boc), or that the amine can be deprotected (to provide P 3 =H) using known conditions.

Steps 4 and 5 are analogous to Steps 1 and 2 in Scheme C-1.

This product can be treated as described in Steps 4 and 5 of Scheme C-1 to deliver macrolactam products. The product of Step 3 can also be derivatized and treated as described in Scheme C-7 to deliver macrolactam products via ring closing metathesis.

It is understood that the order of events depicted in Scheme C-2 could be rearranged; for example, steps 4 and 5 could precede steps 1-3.

Scheme C-3 depicts a synthesis of a macrocyclic lactam precursor similar to that described in Scheme C-2 but with a modified method for carbonyl group installation.

Step 1 and 2 describe the preparation of a ketone (R=Me, alkyl, or other groups) or aldehyde (R=H) intermediate by cross coupling with an olefin-containing partner mediated by a suitable palladium catalyst, where M=boronic ester, acid, trifluoroborate salt, trialkylstannane or organozinc or organomagnesium halide, followed by oxidative cleavage using standard methods (e.g., OsO 4 /NaIO 4 , O 3 /PPh 3 , etc.).

Steps 3 through 5 are analogous to Steps 3 through 5 in Scheme C-2 above.

The product of this sequence can be used as described in Steps 4 and 5 of Scheme C-1. The product of Step 3 can also be derivatized and treated as described in Scheme C-7 to deliver macrolactam products via ring closing metathesis.

It is understood that the order of events depicted in Scheme C-3 could be rearranged; for example, steps 4 and 5 could precede steps 1-3.

Scheme C-4 depicts a synthesis of a macrocyclic lactam precursor that allows for variable substitution (e.g., R 15 ) on the amine-containing fragment.

Step 1 describes the initial condensation of a tert-butyl sulfinamide with an aldehyde (R=H) or ketone (R=Me, alkyl, or other group) in the presence of a Lewis acid dehydrating reagent (e.g., Ti(OiPr) 4 , Ti(OEt) 4 , CuSO 4 ) to provide a sulfinimine product.

Step 2 describes the reaction of the sulfinimine above with a suitable nucleophile (e.g., M=Li, magnesium halide or zinc halide, R=alkyl, aryl, alkenyl, etc.). This reaction can be facilitated by Lewis acid promoters (e.g., BF 3 ·OEt 2 , AlMe 3 , etc.). In certain cases, M-R′ refers to a fluoroalkylsilane, where M=trialkylsilane (e.g., TMS-CF 3 , TMS-CHF 2 ), and in these cases a suitable promoter is used to facilitate the reaction (e.g., tetrabutylammonium difluorotriphenylsilicate, tetraalkylammonium fluoride, etc.)

Steps 3 and 4 describe the optional removal of the tert-butanesulfinyl group and protection of the resulting amine with a suitable P 3 group (e.g., Boc).

Steps 5 and 6 are analogous to Steps 1 and 2 in Scheme C-1.

It is understood that the sulfinamide described in Step 1 could be racemic or enriched to good enantiomeric excess as a either enantiomer, and that enantioenriched forms may allow for control over the stereocenter formed on addition of R 15 .

The product of this sequence can be used as described in Steps 4 and 5 of Scheme C-1. The product of Step 4 can also be derivatized and treated as described in Scheme C-7 to deliver macrolactam products via ring closing metathesis.

It is understood that the order of events depicted in Scheme C-4 could be rearranged; for example, steps 5 and 6 could precede steps 1-4. An example intermediate prepared by this sequence is described in the synthesis of Example 259.

Scheme C-5 depicts the synthesis of an alternate macrocyclic lactam precursor by installation of an amine-containing and carboxylic acid containing fragments.

Steps 1 and 2 describe the installation of a protected amine-containing macrocycle precursor fragment by deprotection of P 1 (for example, using TFA/DCM when P 1 =Boc or SEM; or using TBAF when P 1 =benzenesulfonyl) followed by alkylation with Y-L m -N(R 8 )(P 2 ), where Y=halogen (preferably Br or I) in the presence of a suitable base (e.g., Cs 2 CO 3 , NaH, NaHMDS). When Y=OH, the alkylation described in Step 2 is accomplished using a Mitsunobu protocol (for example, using DIAD and PPh 3 ). In certain cases, P 1 =H, wherein the deprotection step is omitted.

›DETAILED DESCRIPTION · 30 of 31

Step 3 describes the installation of a carboxylic acid-containing macrocycle precursor fragment by coupling M-L n -CO 2 P 3 , where M=boronic ester, acid, or trifluoroborate salt, trialkylstannane, or magnesium or zinc halide, in the presence of a suitable palladium catalyst. One specific example of M-L n -CO 2 P 3 is (2-(tert-butoxycarbonyl)phenyl)boronic acid, where M=B(OH) 2 , L n =Ph, and P 3 =tert-butyl. Another example of M-L n -CO 2 P 3 is the lithium enolate of tert-butyl isobutyrate.

The product of this sequence can be used as described in Steps 4 and 5 of Scheme C-1 to deliver macrocyclic lactam products. An example prepared by this protocol is Example 227.

It is understood that the order of events depicted in Scheme C-5 could be reversed or modified; for example, step 3 could precede steps 1 and 2.

It is understood that fragments containing functional precursors to —CO 2 P 3 (for example —CH 2 OP 4 , where P 4 =H or suitable protective group) may also be used in Step 2, where —CO 2 P 3 may be subsequently accessed by functional group transformation (for example by deprotection/oxidation of —CH 2 OP 4 ).

It is also understood that that fragments containing functional precursors to —N(R 8 )P 2 may also be used in step 3, where —N(R 8 )P 2 may be subsequently accessed by functional group transformation, for example by Curtius rearrangement of a carboxylic acid, or by reductive amination upon a ketone or aldehyde.

Scheme C-6 describes the synthesis of a macrocycle using a ring closing olefin metathesis approach.

Step 1 is carried out as described in Step 1 of Scheme C-1 or is omitted when P 1 =H.

Step 2 describes incorporation of one olefin-containing fragment by alkylation with Y-L m -CHCH 2 where Y=halogen or pseudohalide (e.g., triflate, tosylate, mesylate) in the presence of a suitable base (e.g., Cs 2 CO 3 , NaH, NaHMDS, etc.). This transformation can be accomplished when Y=OH using a Mitsunobu-type protocol (e.g., by treatment with DIAD and PPh 3 ). One example of Y-L m -CHCH 2 is 5-bromopent-1-ene.

Step 3 describes the installation of a second olefin-containing fragment by cross-coupling with M-L n -CHCH 2 , where M=boronic ester, acid, or trifluoroborate salt, trialkylstannane, or magnesium or zinc halide, in the presence of a suitable palladium catalyst. One example of M-L n -CHCH 2 is (2-vinylphenyl)boronic acid.

Step 4 describes ring closing macrocyclization of the bis-olefin intermediate by treatment with a suitable metathesis catalyst, including (1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)mthenium (Grubbs-Hoveyda II), (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium (Grubbs II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][[5-[(dimethylamino)sulfonyl]-2-(1-methylethoxy-0)phenyl]methylene-C]ruthenium(II) (Zhan-1b), and other suitable metal-carbene complexes, under appropriate conditions. The olefin product may be formed as a single geometric isomer or mixtures of isomers.

Step 5 describes the optional reduction of the macrocyclic olefin. This can be accomplished by hydrogenation over a suitable metal catalyst (e.g., Pd/C). Alternatively, this may be accomplished using diimide, which can be generated in situ under a variety of conditions, one preferred method being use of p-toluenesulfonhydrazide and sodium acetate in aqueous/organic solvent mixtures (e.g., water/THF) at elevated temperature (e.g., 90° C.). The latter method is useful to avoid undesired hydrogenation/hydrogenolysis, for example hydrogenolytic ring opening of a vinylcyclopropane motif.

It is understood that the order of events depicted in Scheme C-6 can be modified, e.g., Step 3 may precede steps 1 and 2.

It is also understood that —CHCH 2 fragments are depicted in this sequence for convenience, but that substituted olefins may also be used that productively engage in metathesis chemistry.

It is also understood that the olefin moieties depicted in Scheme C-6 may be accessed from a suitable functional precursor after installation of said precursor-containing fragment according to the sequence depicted. For example, an olefin could be accessed from an alcohol moiety by oxidation to the corresponding aldehyde followed by Wittig-type olefination, among other possibilities. Additionally, olefin moieties could also be incorporated by coupling of an olefin-containing fragment with a suitable partner in L n or L m . For instance, an olefin moiety could be accessed from a corresponding aryl halide (e.g., where L n =phenyl) by cross-coupling of M-CHCH 2 , where M=boronic ester, acid, trifluoroborate salt, trialkylstannane, or magnesium or zinc halide, in the presence of a suitable palladium catalyst. Alternatively, an olefin-containing carboxylic acid fragment could be coupled with an amine moiety in L m or L n to form an amide-containing ring-closing metathesis precursor; a more specific version of this general approach is outlined in Scheme C-7 below.

Scheme C-7 described the synthesis of an amide-containing ring closing metathesis macrocyclization precursor.

Step 1 is as described in Step 1 of Scheme C-1 or is omitted when P 1 =H.

Step 2 describes alkylation with Y-L m -CHCH 2 (where Y=halogen) in the presence of a suitable base (e.g., Cs 2 CO 3 , NaH, NaHMDS). When Y=OH, the alkylation described in this step is accomplished using a Mitsunobu protocol (for example, using DIAD and PPh 3 ).

Steps 3 and 4 describe the installation of a second olefin-containing fragment by removal of the P 3 protective group (for example, using TFA/DCM when P 3 =Boc) followed by amide bond formation with CH 2 CH-L n -CO 2 H. The amide bond forming step is mediated by standard peptide coupling reagents (e.g., DIC, EDC, HATU, etc.) in the presence of a suitable base (e.g., Et 3 N, Hunig's base), or the acid can first be converted to its corresponding acid chloride with oxalyl chloride.

The product of this sequence can be used as described as in Steps 5 and/or 6 in Scheme C-6 to afford macrocyclic products. Examples of compounds prepared by this approach are Examples 1-3 and Example 273.

›DETAILED DESCRIPTION · 31 of 31

It is understood that the order of events depicted in Scheme C-7 can be changed; for example, where Steps 3 and 4 precede Steps 1 and 2.

It is also understood that —CHCH 2 fragments are depicted in this sequence for convenience, but that substituted olefins may also be used that productively engage in metathesis chemistry.

It is also understood that functional precursors to the olefins depicted in Scheme C-7 could be installed using the same fragment coupling approaches, and that the depicted olefins could be subsequently installed using transformations known to those versed in the art to the olefins as depicted. For example, an olefin moiety could be accessed from a corresponding aryl halide (e.g., where L n =phenyl) by cross-coupling of M-CHCH 2 , where M=boronic ester, acid, trifluoroborate salt, trialkylstannane, or magnesium or zinc halide, in the presence of a suitable palladium catalyst.

It is understood that the connectivity of the macrocycle precursor may be reversed (e.g., where Y is bonded to L m and Nu-P 2 is bonded to L n as depicted) but that the same sequence can be employed to effect macrocyclization.

An example of a compound prepared by this approach is Example 96.

It is understood that the sequence described above can be carried out at any appropriate stage prior to elaboration of the macrocyclic intermediate depicted in Scheme D-1.

›PREPARATION EXAMPLES

Methods for preparing the novel compounds described herein will be apparent to those of skill in the art with suitable procedures being described, for example, in the reaction schemes and examples below.

The chemical names of the Examples in Tables 1 and 1A were generated using OpenEye, implemented in Dassault Systemes' Biovia Pipeline Pilot (version 19.1.0.1963). ChemBioDraw Ultra 14.0 or the naming function residing within Biovia Notebook 2019 (version 19.1.0.23) was used to generate names for intermediates reported herein. It should be understood that other names may be used to identify Examples or intermediates of the same structure. Other compounds, such as reactants, reagents and solvents, may be named with common names, or systematic or non-systematic names. The compounds may also be named using other nomenclature systems and symbols that are commonly recognized in the art of chemistry including, for example, Chemical Abstract Service (CAS) and International Union of Pure and Applied Chemistry (IUPAC). The naming and numbering of the compounds of the present disclosure is illustrated with representative compounds of formula (I), or (Ia)-(Iv) shown in Tables 1 and 1A below. The compounds provided in Tables 1 and 1A may be a single enantiomer (e.g., (S)-enantiomer, (R)-enantiomer), or the compounds may be present in a racemic or scalemic composition having one or more diastereomers or enantiomers as mixture.

1. Synthesis of Intermediates I-1 to I-25

Preparation of methyl 5-methoxy-3-methyl-2-(((trifluoromethyl)sulfonyl)oxy)imidazo[1,2-a]pyridine-7-carboxylate (I-1)

›Step 1

Methyl 2-chloro-6-methoxyisonicotinate (10 g, 50 mmol), Pd 2 (dba) 3 (900 mg, 1.0 mmol), Xantphos (1150 mg, 1.99 mmol), and cesium carbonate (33 g, 100 mmol) were taken up in 1,4-dioxane (300 mL) under N 2 . Benzophenone imine (9.6 mL, 57 mmol) was added, and the resulting mixture was stirred at 90° C. for 16 h. The mixture was then cooled and partitioned between EtOAc and water. The phases were separated, and the organic phase was washed with brine, dried over Na 2 SO 4 , filtered, and concentrated. The crude residue was dissolved in THF (300 mL) and water (150 mL). Hydrochloric acid (12 M, 21 mL, 250 mmol) was added, and the resulting mixture was stirred until LC/MS indicated completion (˜1 h). Solid NaHCO 3 (25 g, 300 mmol) was added, and the resulting mixture was diluted with EtOAc and water. The phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na 2 SO 4 , filtered, and concentrated. The resulting residue was purified by silica gel chromatography (0-60% EtOAc in hexanes) to afford methyl 2-amino-6-methoxyisonicotinate. ES/MS: m/z 183.1 [M+H] + .

›Step 2

(R)-2-(benzyloxy)propanoic acid (3.84 g, 21.3 mmol) was dissolved in DCM (64 mL) under N 2 . DMF (100 uL) was added followed by dropwise addition of oxalyl chloride (1.80 mL, 21.3 mmol). The resulting mixture was stirred for 2 h at rt and was then added to a solution of methyl 2-amino-6-methoxyisonicotinate (3 g, 16.5 mmol) and trimethylamine (6.9 mL, 50 mmol) in DCM (40 mL) cooled in an ice water bath. The stirred mixture was let warm to rt. After 90 min, the mixture was diluted with DCM and water. The phases were separated, and the aqueous phase was extracted with DCM. The combined organic phase was dried over Na 2 SO 4 , filtered, and concentrated. The crude residue was purified by silica gel chromatography (10-50% EtOAc in hexanes) to afford methyl (R)-2-(2-(benzyloxy)propanamido)-6-methoxyisonicotinate. ES/MS: m/z 345.1 [M+H] + .

›Step 3

Methyl (R)-2-(2-(benzyloxy)propanamido)-6-methoxyisonicotinate (5.19 g, 15 mmol) was dissolved in THF (100 mL) and EtOH (50 mL). Palladium on carbon (Degussa, 10% dry wt., 50% overall water wt.) (2 g, 0.94 mmol) was added and the reaction vessel was purged with H 2 . The resulting mixture was stirred under 1 atm H 2 for 90 min and was then filtered through a pad of celite with THF. The filtrate was concentrated to afford methyl (R)-2-(2-hydroxypropanamido)-6-methoxyisonicotinate which was used without further purification. ES/MS: m/z 255.1 [M+H] + .

›Step 4

Methyl (R)-2-(2-hydroxypropanamido)-6-methoxyisonicotinate (3.78 g, 14.9 mmol) was dissolved in DCM (150 mL) under N 2 and was cooled in a CO 2 /acetone bath. 2-Methoxypyridine (4.7 mL, 44.7 mmol) was added followed by dropwise trifluoromethanesulfonic anhydride (7.53 mL, 44.6 mmol). The resulting mixture was stirred for 5 min and was then allowed to warm to rt. After 5 h, the reaction mixture was partitioned between DCM and water, and the aqueous phase was acidified with HCl. The phases were separated, and the aqueous phase was extracted with DCM. The combined organic phase was dried over Na 2 SO 4 , filtered, and concentrated to afford a crude residue. Purification by silica gel chromatography (20-100% EtOAc in hexanes) provided methyl 5-methoxy-3-methyl-2-(((trifluoromethyl)sulfonyl)oxy)imidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 368.9 [M+H] + . 1 H NMR (400 MHz, Chloroform-d) δ 7.89 (d, J=1.4 Hz, 1H), 6.64 (d, J=1.4 Hz, 1H), 4.07 (s, 3H), 3.94 (s, 3H), 2.71 (s, 3H).

Preparation of 6-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (I-2)

›Step 1

Under an argon atmosphere, 6-chloro-1H-pyrrolo[2,3-b]pyridine (37.9 g, 248.1 mmol) and dry DMF (800 mL) were added to a 3 L oven-dried round bottom flask containing a magnetic stirring bar. The mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 10.9 g, 273 mmol, 1.1 equiv) was added in portion over 10 minutes. The resulting mixture was vigorously stirred for 1 hour and 2-(trimethylsilyl) ethoxymethyl chloride (45.5 g, 273 mmol, 1.1 equiv) was added. The resulting mixture was warmed to rt and stirred overnight, diluted with dichloromethane (1.5 L), and then quenched with water (100 mL). Additional water (500 mL) was added. The organic layer was washed with water, and brine, and dried over magnesium sulfate, filtered and evaporated to dryness. The residue was purified by chromatography over silica gel (EtOAc in Hexane, 0 to 5%) to afford 6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine. ES/MS: m/z 283.2 [M+H] + . 1 H NMR (300 MHz, Chloroform-d) δ 7.84 (d, J=8.1 Hz, 1H), 7.32 (d, J=3.6 Hz, 1H), 7.10 (d, J=8.1 Hz, 1H), 6.52 (d, J=3.6 Hz, 1H), 5.64 (s, 2H), 3.53 (t, J=7.2 Hz, 1H), 2H), 0.91 (t, J=7.2 Hz, 2H), −0.06 (s, 9H).

›Step 2

A solution of 6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (8.8 g, 31.1 mmol) in THF (100 mL) was cooled to −78° C. and n-BuLi (2.5 M in hexanes, 37.3 mmol, 1.2 equiv.) was added dropwise over 10 minutes. The resulting solution was stirred for an additional 2 h at this temperature. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6.94 g, 37.3 mmol, 1.2 equiv.) was then added and the mixture was warmed to −20° C. over one hour. Then mixture was then stirred for 5 additional minutes at −20° C. before being quenched with HCl (1 M, 60 mL). The mixture was diluted with EtOAc and water. The organic phase was dired and concentrated, and the residual orange oil was purified by chromatography over silica gel (Hexanes:EtOAc 0 to 10%). 6-Chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine was obtained. ES/MS: m/z 409.3 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 7.87 (d, J=8.2 Hz, 1H), 7.13-7.06 (m, 2H), 5.91 (s, 2H), 3.59-3.50 (m, 2H), 1.39 (s, 12H), 0.96-0.85 (m, 2H), −0.07 (s, 9H).

Preparation of methyl 2-(6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (I-3)

›Step 1

A round bottom flask was loaded with 6-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (I-2, 11.5 g, 1.1 equiv.), methyl 5-methoxy-3-methyl-2-(((trifluoromethyl)sulfonyl)oxy)imidazo[1,2-a]pyridine-7-carboxylate (I-1, 9.4 g, 1 equiv.) and potassium phosphate tribasic (16.2 g, 3 equiv.). Dioxane (120 mL) and water (14 mL) were added, and the mixture was degassed with argon for 15 minutes. PdCl 2 (dppf) (1.56 g, 7.5 mol %) was added in one portion and the mixture was heated to 45° C. for 6 hours. The reaction was worked up using EtOAc and water, and the combined organics were dried over sodium sulfate then evaporated to dryness. Purification via silica gel column chromatography using a solid loading over silica (0-45% ether/(hexanes:DCM 1:1)) delivered methyl 2-(6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 501.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.08 (brs, 1H), 7.88 (d, J=8.1 Hz, 1H), 7.16 (d, J=8.1 Hz, 1H), 6.68 (brs, 1H), 6.66 (brs, 1H), 6.08 (s, 2H), 4.13 (s, 3H), 3.99 (s, 3H), 3.48-3.37 (m, 2H), 2.89 (s, 3H), 0.82-0.71 (m, 2H), −0.18 (s, 9H).

Preparation of 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (I-4)

›Step 1

To a solution of 6-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (I-2, 9.6 g, 23.5 mmol) in THF (120 mL) and water (30 mL) was added sodium periodate (14 g, 70.5 mmol). After stirring 20 min at rt, hydrochloric acid (1 M, 18 mL) was added. After an additional 2.5 h, the reaction mixture was partitioned between EtOAc and water. The organic phase was washed with brine, dried over Na 2 SO 4 , filtered, and concentrated under reduced pressure. The resulting residue along with methyliminodiacetic acid (10.4 g, 70 mmol), and 4 A MS (15 g) were taken up in DMF (52 mL), and that mixture was heated to 120° C. under N 2 for 2 h. The mixture was cooled and filtered to remove sieves, washing with DMF. The filtrate was concentrated in vacuo and the resulting residue was partitioned between EtOAc and water (˜100 mL each). The phases were separated, and the organic phase was washed with water and brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure. The resulting crude residue was purified on silica gel (5-25% acetone in hexanes) to yield 2-(6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione. 1 H NMR (400 MHz, Chloroform-d) δ 7.82 (d, J=8.1 Hz, 1H), 7.09 (d, J=8.1 Hz, 1H), 6.84 (s, 1H), 5.76 (s, 2H), 4.09 (d, J=16.5 Hz, 2H), 3.94 (d, J=16.5 Hz, 2H), 3.68-3.59 (m, 2H), 2.75 (s, 3H), 1.00-0.81 (m, 2H), 0.00 (s, 9H).

›Step 2

2-(6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (4.51 g, 10.3 mmol) was taken up in dioxane (100 mL) under N 2 . The reaction mixture was degassed by Ar bubbling for 10 min. 1-ethoxyvinyltributylstannane (7.4 mL, 20.6 mmol) and PdCl 2 (dppf) (750 mg, 1.23 mmol) were added and the resulting mixture was heated to 100° C. After 20 h, LCMS showed complete conversion, and the reaction was cooled to room temperature, filtered over a plug of celite and the plug was rinsed with EtOAc three times. The resulting solution was evaporated to dryness. The resulting residue was dissolved in THF (100 mL) and aqueous 1 M HCl (50 mL, 50 mmol) was added. The resulting mixture was stirred vigorously for 45 minutes and was then diluted with DCM (200 mL) and water (150 mL). The phases were separated, the aqueous layer was extracted with DCM (150 mL) and the organic phase was dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel chromatography (5-70% acetone in hexanes) afforded 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione. 1 H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 6.85 (s, 1H), 5.82 (s, 2H), 4.46 (d, J=17.3 Hz, 2H), 4.17 (d, J=17.2 Hz, 2H), 3.59-3.50 (m, 2H), 3.32 (s, 3H), 2.72 (s, 2H), 2.64 (s, 3H), 1.01-0.92 (m, 2H), −0.03-−0.11 (m, 1H), −0.08 (s, 9H).

Preparation of methyl 2-chloro-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate (I-5a)

›Step 1

Methyl 2-aminoisonicotinate (7 g, 46 mmol) was suspended in ethyl bromoacetate (22 mL) and the reaction mixture was stirred at rt for 96 h. The reaction mixture was diluted with ether, stirred for 1 h, and filtered. The solids were washed with diethyl ether, and then dried in vacuo to provide 2-amino-1-(2-ethoxy-2-oxoethyl)-4-(methoxycarbonyl)pyridin-1-ium bromide. 1 H NMR (400 MHz, DMSO-d6) δ 9.02 (s, 2H), 8.15 (d, J=7.0 Hz, 1H), 7.62 (d, J=1.8 Hz, 1H), 7.25 (dd, J=7.0, 1.8 Hz, 1H), 5.21 (s, 2H), 4.21 (q, J=7.1 Hz, 2H), 3.92 (s, 3H), 1.25 (t, J=7.1 Hz, 3H).

›Step 2

A mixture of 2-amino-1-(2-ethoxy-2-oxoethyl)-4-(methoxycarbonyl)pyridin-1-ium bromide (580 mg, 1.82 mmol) and phosphorus oxychloride (3.4 mL, 36.6 mmol) was heated at 110° C. for 2 h. The reaction mixture was cooled to rt and quenched in portions into room temperature water. The mixture was then diluted with EtOAc and quenched with saturated NaHCO 3 (aq). The layers were separated and the aqueous phase was extracted with EtOAc. The combined organics were dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-50% acetone in hexanes) to yield methyl 2-chloroimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 211.1 [M+H] + .

›Step 3

To a solution of methyl 2-chloroimidazo[1,2-a]pyridine-7-carboxylate (1.04 g, 4.94 mmol) in acetonitrile (50 mL) was added N-iodosuccinimide (1.35 g, 6 mmol). After 90 min, the reaction mixture was quenched with 10% aqueous sodium thiosulfate and diluted with water. The heterogeneous mixture was filtered, and the solids were washed with water and dried in vacuo to yield methyl 2-chloro-3-iodoimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 337.2 [M+H] + .

›Step 4

A mixture of methyl 2-chloro-3-iodoimidazo[1,2-a]pyridine-7-carboxylate (2.09 g, 6.21 mmol), potassium cyclopropyltrifluoroborate (2315 mg, 15.64 mmol), palladium(II) acetate (167 mg, 0.74 mmol), butyldi-1-adamantylphosphine (539 mg, 1.5 mmol) and cesium carbonate (8150 mg, 25.01 mmol) in dioxane (15 mL) and water (1.5 mL) was heated at reflux for 15 h. After cooling to rt, the mixture was partioned between ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics were washed with brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-40% ethyl acetate in hexanes) to yield methyl 2-chloro-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 251.1 [M+H] + .

Preparation of methyl 2-chloro-3-cyclopropyl-5-methoxyimidazo[1,2-a]pyridine-7-carboxylate (I-5b)

›Step 1

A solution of oxalyl chloride (2 M, 10.3 mL, 20.6 mmol) in dichloromethane was added to a solution of 2-cyclopropylacetic acid (1.0 mL, 10.3 mmol) in dichloromethane (17 mL) at room temperature. DMF (4 drops) was added and the reaction mixture was stirred at room temperature. After 4 h, the reaction mixture was concentrated under reduced pressure to yield 2-cyclopropylacetyl chloride, which was used directly in the next step without purification.

›Step 2

To a mixture of 2-cyclopropylacetyl chloride (1.22 g, 10.3 mmol, above) and methyl 2-amino-6-methoxyisonicotinate (intermediate described in the syntheise of I-1, 1.50 g, 8.23 mmol) in chloroform (50 mL) was added triethylamine (2.3 mL, 16.5 mmol) at room temperature. After stirring overnight, the reaction mixture was transferred into 5×10 mL sealed reaction vessels. Triethylamine (0.24 mL, 1.72 mmol) and thionyl chloride (0.26 mL, 3.6 mmol) was added to each vessel. Each vessel was sealed and the reaction mixtures were heated at 70° C. for 90 minutes. After cooling to room temperature, the reaction mixtures were combined, diluted with dichloromethane, and quenched with sat. NaHCO 3 (aq). The organic and aqueous layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-40% ethyl acetate/hexanes) to yield methyl 2-chloro-3-cyclopropyl-5-methoxyimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 281.0 [M+H] + .

methyl 2-chloro-3-cyclopropyl-6-fluoroimidazo[1,2-a]pyridine-7-carboxylate (I-5c)

Prepared following a similar procedure to I-5a using methyl 2-amino-5-fluoroisonicotinate. ES/MS: m/z 269.2 [M+H] + .

Preparation of methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate (I-6a)

›Step 1

A mixture of methyl 2-chloro-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate (I-5a, 800 mg, 3.19 mmol), K 3 PO 4 (5.08 g, 23.9 mmol), 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (I-4, 1.84 g, 4.13 mmol), and XPhos Pd G3 (271 mg, 0.32 mmol) in dioxane (25 mL) and water (5 mL) was heated at 100° C. After 3 h, additional I-4 (923 mg, 2.07 mmol), and XPhos Pd G3 (270 mg, 0.32 mmol) were added and the reaction mixture was heated at 100° C. After 1 h, the reaction mixture was cooled to rt and partitioned between ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics were washed with brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-50% ethyl acetate in hexanes) to yield methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 505.0 [M+H] + .

methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropyl-5-methoxyimidazo[1,2-a]pyridine-7-carboxylate (I-6b)

Prepared following a similar procedure to I-6a starting with I-5b. ES/MS: m/z 535.0 [M+H] + .

Preparation of methyl 2-(6-bromo-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-7a)

›Step 1

A 250 mL round bottom flask was charged with methyl 4-chloro-3-methoxy-5-nitrobenzoate (14.0 g, 57 mmol) and methylamine hydrochloride salt (4.65 g, 69 mmol). The solids were taken in DMF (100 mL) and triethylamine (14.1 g, 143 mmol) was added. The flask was sealed and the reaction mixture was stirred at 75° C. for 16 h. The reaction was partitioned between water and DCM. The aqueous layer was extracted with DCM and the combined organics were washed with water then brine. The combined organic layer was dried over sodium sulfate, filtered, and evaporated to dryness. The crude product was dissolved in hot EtOAc (80 mL) and hexanes (220 mL) were added. The mixture was allowed to cool to room temperature and the crystallization was aged overnight before collecting solids by filtration to afford methyl 2-(6-bromo-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 241.0 [M+H] + .

methyl 4-(cyclopropylamino)-3-methoxy-5-nitrobenzoate (I-7b)

Prepared following a similar procedure to I-7a using cyclopropylamine instead of methylamine. ES/MS: m/z 267.0 [M+H] + .

methyl 2-fluoro-4-(methylamino)-5-nitrobenzoate (I-7c)

Prepared following a similar procedure to I-7a using methyl 2,4-difluoro-5-nitrobenzoate. ES/MS: 227.1 [M−H] + .

methyl 4-(cyclopropylamino)-2-fluoro-5-nitrobenzoate (I-7d)

Prepared following a similar procedure to I-7a using methyl 2,4-difluoro-5-nitrobenzoate and cyclopropylamine instead of methylamine. 1 H NMR (400 MHz, DMSO-d6) δ 8.64 (d, J=7.8 Hz, 1H), 8.45 (s, 1H), 7.16 (d, J=14.0 Hz, 1H), 3.84 (s, 3H), 2.76-2.64 (m, 1H), 0.98-0.87 (m, 2H), 0.76-0.64 (m, 2H).

methyl 4-(cyclopropylamino)-3-nitrobenzoate (I-7e)

Prepared following a similar procedure to I-7a using methyl 4-fluoro-3-nitrobenzoate and cyclopropylamine instead of methylamine. ES/MS: m/z 237.8 [M+H] + .

methyl 6-(methylamino)-5-nitronicotinate (I-7f)

Prepared following a similar procedure to I-7a using methyl 6-fluoro-5-nitronicotinate. 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.97 (q, J=4.8 Hz, 1H), 8.92 (d, J=2.1 Hz, 1H), 8.72 (d, J=2.1 Hz, 1H), 3.86 (s, 3H), 3.10 (d, J=4.8 Hz, 3H).

methyl 2-fluoro-4-[(1-methoxycyclopropyl)methylamino]-5-nitro-benzoate (I-7g)

Prepared following a similar procedure to I-7a using methyl 2,4-difluoro-5-nitrobenzoate and (1-methoxycyclopropyl)methanamine instead of methylamine. 1 H NMR (400 MHz, Chloroform-d) δ 8.95 (d, J=7.7 Hz, 1H), 8.63 (s, 1H), 6.50 (d, J=13.2 Hz, 1H), 3.93 (s, 3H), 3.42 (d, J=4.5 Hz, 2H), 3.35 (d, J=1.0 Hz, 3H), 1.06-1.01 (m, 2H), 0.71-0.65 (m, 2H). 19 F NMR (376 MHz, Chloroform-d) δ −98.29 (d, J=13.5 Hz).

methyl 2-fluoro-4-((2-methoxyethyl)amino)-5-nitrobenzoate (I-7h)

Prepared following a similar procedure to I-7a using methyl 2,4-difluoro-5-nitrobenzoate and 2-methoxyethanamine. ES/MS: m/z 273.0 [M−H] + .

methyl 4-((2,2-difluoroethyl)amino)-2-fluoro-5-nitrobenzoate (I-7i)

Prepared following a similar procedure to I-7a using methyl 2,4-difluoro-5-nitrobenzoate and 2,2-difluoroethane-1-amine. ES/MS: m/z Does not ionize.

methyl 2-fluoro-5-nitro-4-((2,2,2-trifluoroethyl)amino)benzoate (I-7j)

Prepared following a similar procedure to I-7a using methyl 2,4-difluoro-5-nitrobenzoate and 2,2,2-trifluoroethan-1-amine. ES/MS: m/z 297.1 [M−H] + .

methyl 3-methoxy-4-((2-methoxyethyl)amino)-5-nitrobenzoate (I-7k)

Prepared following a similar procedure to I-7a using methyl 3-methoxy-4-((2-methoxyethyl)amino)-5-nitrobenzoate. ES/MS: m/z 285.1 [M−H] + .

methyl 2-fluoro-4-[(1-methoxycyclopropyl)methylamino]-5-nitro-benzoate (I-7l)

methyl 2-methoxy-4-(methylamino)-5-nitrobenzoate (I-7m)

Prepared following a similar procedure to I-7a using methyl 4-fluoro-2-methoxy-5-nitro-benzoate. ES/MS: m/z 241.0 [M−H] + .

methyl 2-methyl-4-(methylamino)-5-nitrobenzoate (I-7n)

Prepared following a similar procedure to I-7a using methyl 4-fluoro-2-methyl-5-nitrobenzoate. ES/MS: m/z 225.2 [M−H] + .

methyl 2,3-difluoro-4-(methylamino)-5-nitrobenzoate (I-7o)

Prepared following a similar procedure to I-7a using methyl 2,3,4-trifluoro-5-nitrobenzoate. ES/MS: m/z does not ionize.

methyl 2,3-difluoro-4-((2-methoxyethyl)amino)-5-nitrobenzoate (I-7p)

Prepared following a similar procedure to I-7a using methyl 2,3,4-trifluoro-5-nitrobenzoate and 2-methoxyethan-1-amine. ES/MS: m/z does not ionize.

methyl 6-(cyclopropylamino)-5-nitronicotinate (I-7q)

Prepared following a similar procedure to I-7a using methyl 6-fluoro-5-nitronicotinate and cyclopropylamine. ES/MS: m/z 238.0 [M−H] + .

methyl 3-chloro-4-(methylamino)-5-nitrobenzoate (I-7r)

Prepared following a similar procedure to I-7a using methyl 3,4-dichloro-5-nitrobenzoate. ES/MS: m/z 246.0 [M+H] + .

methyl 3-fluoro-4-(methylamino)-5-nitrobenzoate (I-7s)

Prepared following a similar procedure to I-7a using methyl 3,4-difluoro-5-nitrobenzoate. ES/MS: m/z 229.2 [M+H] + .

methyl 3-fluoro-4-(isopropylamino)-5-nitrobenzoate (I-107t)

Prepared following a similar procedure to I-140c using isopropylamine. ES/MS: m/z 256.9 [M+H] + .

methyl 4-(2,2-dimethylpropylamino)-3-fluoro-5-nitro-benzoate (I-107u)

Prepared following a similar procedure to I-140c using 2,2-dimethylpropan-1-amine. ES/MS: m/z 285.0 [M+H] + .

Preparation of methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-8a)

›Step 1

To a stirred solution of 6-bromo-1H-pyrrolo[2,3-b]pyridine (10.0 g, 50.8 mmol) in DMF (100 mL) was added NaH (2.43 g, 101.3 mmol) at 0° C. After stirring for 10 minutes, benzenesulfonyl chloride (7.1 mL, 55.9 mmol) was added and the reaction mixture was held for 2 h at 0° C. The reaction mixture was quenched with ice-water, filtered, washed with cold water and the solid was dried under vacuum to afford 6-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine, which was used directly without any further purification. 1 H NMR (400 MHz, Chloroform-d) δ 8.27-8.20 (m, 2H), 7.72-7.65 (m, 2H), 7.65-7.57 (m, 1H), 7.56-7.48 (m, 2H), 7.32 (dd, J=8.1, 0.6 Hz, 1H), 6.56 (d, J=4.0 Hz, 1H).

›Step 2

To a stirred solution of 6-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (5 g, 14.8 mmol) in THF (50 mL) was added 2 M LDA solution in THF (11.5 mL, 16.3 mmol) under argon at −78° C. The reaction mixture was stirred for 30 min at −78° C., then quenched with DMF (1.62 g) and stirred for 1 h at −78° C. The reaction mixture was quenched with sat. aq. NH 4 Cl solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude mixture was purified by silica gel column chromatography, eluting with 30% ethyl acetate in petroleum ether to afford 6-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde. ES/MS: m/z 364.9, 366.9 [M+H] + .

›Step 3

To a stirred solution of 6-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (13.5 g, 37.1 mmol) in methanol (130 mL) under argon was added 1 M NaOH aqueous solution (270 mL) at 0° C., and the reaction was stirred for 6 h at 0° C. The reaction mixture was filtered through a plug of Celite, washed with methanol and the filtrate was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography, eluting with 30% ethyl acetate in petroleum ether to obtain 6-bromo-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde. ES/MS: m/z 225.1, 227.1 [M+H] + .

›Step 4

Methyl 3-methoxy-4-(methylamino)-5-nitrobenzoate (I-7a, 4 g, 16.65 mmol) and 6-bromo-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (3.75 g, 16.65 mmol) were charged in a sealable 500 mL round bottom flask. The mixture was dissolved in 300 mL of EtOH/H 2 O (2:1) and sodium dithionite (8.70 g, 50 mmol) was added in one portion. The flask was immediately sealed and heated to 90° C. A white precipitate quickly forms and the reaction was stirred ˜ 2 h. Water (300 mL) was added to the reaction mixture and it was allowed to cool to room temperature. The white solid was then filtered and washed with water (2×100 mL) followed by diethyl ether (2×75 mL). The solid was dried to afford methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 415.1, 417.1 [M+H] + .

methyl 2-(6-bromo-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-8b)

Prepared following a similar procedure to I-8a using commercially available 6-bromo-1H-indole-2-carbaldehyde instead of 6-bromo-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde. ES/MS: m/z 414.2, 416.2 [M+H] + .

methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-8c)

Prepared following a similar procedure to I-8a using I-7c. ES/MS: m/z 403.2, 405.2 [M+H] + .

Preparation of methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-9a)

›Step 1

10% Pd/C (631 mg, 0.59 mmol) was added to a mixture of methyl 4-(cyclopropylamino)-3-methoxy-5-nitrobenzoate (1580 mg, 5.93 mmol) in ethanol (30 mL) and ethyl acetate (15 mL). The reaction mixture was placed under 1 atm of hydrogen. After 4 h, the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (10-40% ethyl acetate in hexanes) to yield methyl 3-amino-4-(cyclopropylamino)-5-methoxybenzoate. ES/MS: m/z 237.1 [M+H] + .

›Step 2

OXONE®, monopersulfate compound (711 mg, 2.31 mmol) was added to a mixture of methyl 3-amino-4-(cyclopropylamino)-5-methoxybenzoate (455 mg, 1.93 mmol) and 6-bromo-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (intermediate described in the synthesis of I-8a, 477 mg, 2.12 mmol) in DMF (6 mL) and water (2.5 mL). After 2 h, water was added to precipitate solids. The solid was filtered, washed with water, and dried in vacuo to yield methyl methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 441.1, 443.1 [M+H] + .

methyl 2-(6-bromo-1H-indol-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-9b)

Prepared following a similar procedure to I-9a using 6-bromo-1H-indole-2-carbaldehyde (cas 105191-12-6) instead of 6-bromo-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde. ES/MS: m/z 440.1, 442.1 [M+H] + .

methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-9c)

Prepared following a similar procedure to I-9a using I-7d. ES/MS: m/z 429.2, 431.2 [M+H] + .

methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-1H-benzo[d]imidazole-5-carboxylate (I-9d)

Prepared following a similar procedure to I-9a using I-7e. ES/MS: m/z 411.2, 413.1 [M+H] + .

methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-9e)

Prepared following a similar procedure to I-9a using methyl 4-(methylamino)-3-nitrobenzoate. ES/MS: m/z 385.1, 387.1 [M+H] + .

methyl 2-(6-bromo-1H-indol-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-9f)

Prepared following a similar procedure to I-9a using 6-bromo-1H-indole-2-carbaldehyde (cas 105191-12-6) instead of 6-bromo-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde and methyl 2-fluoro-4-(methylamino)-5-nitrobenzoate (I-7c). ES/MS: m/z 403.4 [M+H] + .

Preparation of methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-10a)

›Step 1

A suspension of methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-8a, 10.68 g, 25.7 mmol) in DMF 260 mL was cooled to −15° C. (sodium chloride ice bath) and a solution of NaHMDS (2M in THF, 14.1 mL, 28.3 mmol) was added dropwise over 10 minutes. The resulting mixture was stirred 1 hour at −15° C. and then 4 hours at 0° C. before 2-(chloromethoxy) ethyl-trimethyl-silane (5.14 g, 30.8 mmol) was added. The resulting mixture was stirred at 0° C. until full conversion (about one hour). The mixture was then carefully quenched with saturated aqueous ammonium chloride and after usual work up (EtOAc/water) the residual oil was purified by silica gel column chromatography (0-40% EtOAc in hexanes) to afford methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 544.8, 546.8 [M+H] + .

methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-10b)

Prepared following a similar procedure to I-10a starting with I-9a. ES/MS: m/z 571.2, 573.2 [M+H] + .

methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-10c)

Prepared following a similar procedure to I-10a starting with I-8c. ES/MS: m/z 533.2, 535.2 [M+H] + .

methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-10d)

Prepared following a similar procedure to I-10a starting with I-9c. ES/MS: m/z 558.8, 560.8 [M+H] + .

methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-1H-benzo[d]imidazole-5-carboxylate (I-10e)

Prepared following a similar procedure to I-10a starting with I-9d. ES/MS: m/z 541.2, 543.2 [M+H] + .

methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-10f)

Prepared following a similar procedure to I-10a starting with I-9e. ES/MS: m/z 515.2, 517.2 [M+H] + .

Preparation of methyl 2-(6-bromo-1-(tert-butoxycarbonyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-11a)

›Step 1

Methyl 2-(6-bromo-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (19.9 g, 48 mmol) was suspended in DCM (150 mL). Triethylamine (7 mL, 50 mmol) was added followed by Boc 2 O (11.5 g, 52.8 mmol) and DMAP (4.18 g, 24 mmol). The mixture was stirred until full conversion as judged by LCMS analysis. Silica was added to the reaction mixture and the crude was evaporated to dryness. The residue was then purified by column chromatography (0-35% EtOAc in Heptane) to afford methyl 2-(6-bromo-1-(tert-butoxycarbonyl)-1H-indol-2-yl)-7-methoxy-1-methyl-H-benzo[d]imidazole-5-carboxylate. ES/MS: does not ionize, see I-13b for next intermediate.

methyl 2-(6-bromo-1-(tert-butoxycarbonyl)-1H-indol-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-11b)

Prepared following a similar procedure to I-11a starting with I-9b. ES/MS: does not ionize, see I-13c for next intermediate.

methyl 2-(6-bromo-1-(tert-butoxycarbonyl)-1H-indol-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-11c)

Prepared following a similar procedure to I-11a starting with I-9f. ES/MS: does not ionize, see I-13j for next intermediate.

Preparation of methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-12)

›Step 1

Methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-10b, ca. 2.95 mmol) was dissolved in ethanol (30 mL) and potassium trifluoro(isopropenyl)boronate (1.33 g, 9 mmol), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloromethane (0.24 g, 0.3 mmol) and triethylamine (2.1 mL, 15.1 mmol) were added. The system was evacuated, placed under argon, and the reaction mixture was heated at reflux. After 3 h, the reaction mixture was cooled to rt and filtered through celite. The filtrate was concentrated to yield methyl 1-cyclopropyl-7-methoxy-2-(6-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxylate, which was used below without further purification. ES/MS: m/z 533.0 [M+H] + .

›Step 2

Potassium osmate(VI) dihydrate (54 mg, 0.15 mmol) and sodium periodate (2270 mg, 10.61 mmol) were added to a mixture of methyl 1-cyclopropyl-7-methoxy-2-(6-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxylate (1.57 g, 2.98 mmol) in THF (60 mL) and water (50 mL) at rt. After stirring overnight, the reaction mixture was diluted with water and ethyl acetate. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics were washed with water, brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (5-45% ethyl acetate in hexanes) to yield methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 534.9 [M+H] + .

Preparation of methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-13a)

›Step 1

Methyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-10a, 6.92 g, 12.7 mmol) and PdCl 2 (dppf).CH 2 Cl 2 (600 mg, 0.735 mmol, 6 mol %) were taken up in dioxane (150 mL), and the headspace was flushed with N 2 . 1-Ethoxyvinyltributyltin (7.5 mL, 22.2 mmol, 1.75 equiv.) was added, and the resulting mixture was stirred at 100° C. for 6 h. Upon cooling, the mixture was filtered with EtOAc through Celite and the filtrate was concentrated. The resulting residue was dissolved in DCM and was filtered through a plug of silica gel with 1:1 DCM to remove most of the dark coloration. The filtrate was concentrated and was dissolved in THF (200 mL) and water (50 mL). Hydrochloric acid (3 M, 4.2 mL, 12.6 mmol) was added, and the resulting solution was stirred 20 min. Solid NaHCO 3 (2.5 g, 30 mmol) was added, and the mixture was diluted further with brine and DCM (50 mL). The organic phase was washed with brine, dried over Na 2 SO 4 , filtered, and concentrated. The resulting crude solid was slurried in 10 mL EtOAc and 100 mL hexanes. The product was collected via filtration, and the filter cake was washed with additional 15% EtOAc in hexanes (30 mL) and 100% hexanes to afford methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 509.3 [M+H] + .

methyl 2-(6-acetyl-1-(tert-butoxycarbonyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-13b)

Prepared following a similar procedure to I-13a using I-11a. ES/MS: m/z 478.0 [M+H] + .

methyl 2-(6-acetyl-1-(tert-butoxycarbonyl)-1H-indol-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-13c)

Prepared following a similar procedure to I-13a using I-11b. ES/MS: m/z 504.0 [M+H] + .

methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-13d)

Prepared following a similar procedure to I-13a using I-10c. ES/MS: m/z 497.0 [M+H] + .

methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-13e)

Prepared following a similar procedure to I-13a using I-10d. ES/MS: m/z 550.9 [M+H] + .

methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-1H-benzo[d]imidazole-5-carboxylate (I-13f)

Prepared following a similar procedure to I-13a using I-10e. ES/MS: m/z 505.0 [M+H] + .

1-(5-fluoro-1-(phenylsulfonyl)-1H-indol-6-yl)ethan-1-one (I-13g)

Prepared following a similar procedure to I-13a using 6-bromo-5-fluoro-1-(phenylsulfonyl)-1H-indole (which was obtained from 6-bromo-5-fluoro-1H-indole following step 1 of I-8a). ES/MS: m/z 318.0 [M+H] + . 1 HNMR (400 MHz, DMSO-d6): δ 8.37 (d, J=6.0 Hz, 1H), 8.11 (d, J=3.6 Hz, 1H), 7.96 (dd, J=7.2, 1.2 Hz, 2H), 7.74-7.70 (m, 1H), 7.64-7.56 (m, 3H), 6.92 (d, J=3.6 Hz, 1H), 2.62 (d, J=5.2 Hz, 3H).

1-(1-(phenylsulfonyl)-1H-indol-6-yl)ethan-1-one (I-13h)

Prepared following a similar procedure to I-13a using 6-bromo-1-(phenylsulfonyl)-1H-indole (which was obtained from 6-bromo-1H-indole following step 1 of I-8a). ES/MS: m/z 300.1 [M+H] + . 1 H NMR (400 MHz, CDCl3): δ 8.60 (s, 1H), 7.91 (d, J=5.2 Hz, 2H), 7.88 (dd, J=11.2, 1.2 Hz, 1H), 7.73 (d, J=4.0 Hz, 1H), 7.59-7.54 (m, 2H), 7.48-7.44 (m, 2H), 6.71 (dd, J=3.6, 0.4 Hz, 1H), 2.68 (s, 3H).

methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-13i)

Prepared following a similar procedure to I-13a using I-10f. ES/MS: m/z 479.2 [M+H] + .

methyl 2-(6-acetyl-1-(tert-butoxycarbonyl)-1H-indol-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-13g)

Prepared following a similar procedure to I-13a using I-11c. ES/MS: m/z 466.7 [M+H] + .

Preparation of 6-cyano-3-ethylpyrazolo[1,5-a]pyridin-2-yl trifluoromethanesulfonate (I-14)

›Step 1

A mixture of ethyl 2-(5-bromopyridin-2-yl)acetate (454 mg, 1.86 mmol), zinc cyanide (616 mg, 5.24 mmol), and tetrakis(triphenylphosphine)palladium(0) (322 mg, 0.28 mmol) was taken up in DMF (8 mL) and the resulting reaction mixture was heated at 100° C. under argon for 17 h. After cooling to rt, the reaction mixture was poured into water and extracted with ethyl acetate. The combined organics were washed with water, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-35% ethyl acetate/hexanes) to yield ethyl 2-(5-cyanopyridin-2-yl)acetate. ES/MS: m/z 191.0 [M+H] + .

›Step 2

To a cooled solution of ethyl 2-(5-cyanopyridin-2-yl)acetate (118 mg, 0.62 mmol) in dichloromethane (4 mL) at 0° C. was added portionwise freshly prepared (according to Organic Process Research & Development 2009, 13, 263-267)O-(mesitylsulfonyl)hydroxylamine (˜50% purity with remaining mass H 2 O, 335 mg, 0.78 mmol). The reaction mixture was warmed to rt and stirred for 18 h. The reaction mixture was concentrated under reduced pressure and the resulting solid residue was suspended in water (8 mL) and filtered. The filtered solid was washed with water (3×8 mL) and dried in vacuo to yield 2-hydroxypyrazolo[1,5-a]pyridine-6-carbonitrile. ES/MS: m/z 160.0 [M+H] + .

›Step 3

To a mixture of 2-hydroxypyrazolo[1,5-a]pyridine-6-carbonitrile (1200 mg, 7.54 mmol) in DCM (40 mL) was added a solution of acetaldehyde (0.7 mL, 13 mmol) in 3 mL of DCM. Trifluoroacetic acid (1.4 mL, 18 mmol) was added followed by dropwise addition of triethylsilane (2 mL, 13 mmol). After 72 hours, the reaction mixture was concentrated under reduced pressure and dried in vacuo to afford 3-ethyl-2-hydroxypyrazolo[1,5-a]pyridine-6-carbonitrile.

›Step 4

A mixture of 3-ethyl-2-hydroxypyrazolo[1,5-a]pyridine-6-carbonitrile in 12 mL of THF and 18 mL of DMF was cooled to 0° C. Sodium hydride (60% dispersion, 670 mg, 17 mmol) was added, followed by N-phenyl-bis(trifluoromethanesulfonimide) (3232 mg, 9.05 mmol). After 2 h at 0° C., the reaction mixture was quenched with cold water and extracted with ethyl acetate. The organic phase was washed with water, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-35% ethyl acetate/hexanes) to yield 6-cyano-3-ethylpyrazolo[1,5-a]pyridin-2-yl trifluoromethanesulfonate. 1 H NMR (400 MHz, DMSO-d6) δ 9.58 (s, 1H), 7.98 (dd, J=9.3, 1.0 Hz, 1H), 7.60 (dd, J=9.3, 1.5 Hz, 1H), 2.73 (q, J=7.6 Hz, 2H), 1.19 (t, J=7.6 Hz, 3H).

Preparation of 6-cyano-3-methylpyrazolo[1,5-a]pyridin-2-yl trifluoromethanesulfonate (I-15)

›Step 1

Step 1 of I-14 was followed to produce methyl 2-(5-cyano-3-methoxypyridin-2-yl)acetate from methyl 2-(5-bromo-3-methoxypyridin-2-yl)acetate. ES/MS: m/z 207.0 [M+H] + .

›Step 2

To a solution of methyl 2-(5-cyano-3-methoxypyridin-2-yl)acetate (0.261 g, 1.27 mmol) in THF (6 mL) at 0° C. was added LiHMDS (1.35 mL of 1 M solution in THF, 1.35 mmol). The reaction mixture was stirred at 0° C. for 30 min. Iodomethane (0.14 mL, 2.26 mmol) was added and the reaction mixture was stirred at rt for 16 h. The reaction mixture was diluted with EtOAc/water. The aqueous layer was extracted with EtOAc. The organic layer was washed with water, dried (MgSO 4 ), filtered, and concentrated. The residue was purified via column chromatography on silica gel to afford methyl 2-(5-cyano-3-methoxypyridin-2-yl)propanoate. ES/MS: m/z 221.0 [M+H] + .

›Step 3

Steps 3 and 4 of I-14 were followed to afford 6-cyano-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl trifluoromethanesulfonate. ES/MS: m/z 336.0 [M+H] + .

Preparation of tert-butyl (R)-(1-(2-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocane-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-16)

›Step 1

A mixture tert-butyl (R)-(1-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (2.5 g, 6.23 mmol), 10M NaOH (3 mL), and MeOH (10 mL) was heated in a microwave reactor at 100° C. for 20 min. The methanol was removed and the product was extracted with MeTHF and water. The organic layer was dried with Na 2 SO 4 , filtered, and concentrated. The crude product was taken to next step without further purification. ES/MS: m/z 262.1 [M+H] + .

›Step 2

Step 1 of I-11a was followed to produce tert-butyl (R)-6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate from tert-butyl (R)-(1-(1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate. ES/MS: m/z 362.2 [M+H] + .

›Step 3

To a solution of tert-butyl 6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]pyrrolo[2,3-b]pyridine-1-carboxylate (1 g, 2.77 mmol) in THF (20 mL) was added triisopropyl borate (1.28 mL, 5.53 mmol). The mixture was cooled to −40° C. and a solution of 0.5 M LDA in THF (16.6 mL, 8.4 mmol) was added dropwise maintaining an internal temperature below −10° C. The mixture was stirred for 5 mins after addition of LDA and the mixture was warmed to 0° C. and quenched with NH 4 Cl (aq). The mixture was diluted with ethyl acetate and the layers were separated. The organic layer was dried with Na 2 SO 4 , filtered, and concentrated. The resulting residue was purified by silica chromatography (0-5% MeOH in DCM) to yield (R)-(1-(tert-butoxycarbonyl)-6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic acid. ES/MS: m/z 406.2 [M+H] + .

›Step 4

A mixture of (R)-(1-(tert-butoxycarbonyl)-6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic acid (490 mg, 1.21 mmol) and 2-[carboxymethyl(methyl)amino]acetic acid (0.178 g, 1.21 mmol) in acetonitrile (2 mL) was heated at 130° C. in a microwave reactor. After 6 minutes, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica chromatography (50-100% ethyl acetate in hexanes) to yield tert-butyl (R)-(1-(2-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocane-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-16). ES/MS: m/z 417.1 [M+H] + .

(R)-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic Acid (I-16b)

Prepared following steps 2 and 3 of I-16 using I-25a. ES/MS: m/z 445.9 [M+H] + .

Preparation of rac-((1R,3R)-2,2-difluoro-3-vinylcyclopropyl)methanol (I-17)

(Z)-5-((tert-butyldimethylsilyl)oxy)pent-2-en-1-yl acetate is prepared as described in Z. Al-Shuhaib, H. Böckemeier, L. Coghlan, E. Dörksen, I. V. Jones, P. J. Murphy, R. Nash, J. M. Page, Tetrahedron Letters, 54, 2013, 6716-6718.

›Step 1

To a solution of (Z)-5-((tert-butyldimethylsilyl)oxy)pent-2-en-1-yl acetate (1.5 g, 5.8 mmol) in diglyme (5.8 mL) at 180° C. was added a solution of sodium chlorodifluoroacetate (8.8 g, 58 mmol) in diglyme (12 mL) dropwise over 1 hr. The solution stirred for another 15 min at 180° C. and then, was allowed to cool to room temperature. The mixture was poured onto ice and the aqueous layer was washed with 1:1 EtOAc:hexanes twice. The combined organic layers were washed with water, dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (0-25% EtOAc in hex) to give rac-((1R,3R)-3-(2-((tert-butyldimethylsilyl)oxy)ethyl)-2,2-difluorocyclopropyl)methyl acetate. 1 H NMR (400 MHz, Chloroform-d) δ 4.25-4.09 (m, 2H), 3.68 (t, J=6.1 Hz, 2H), 2.08 (s, 3H), 2.00-1.87 (m, 1H), 1.87-1.75 (m, 1H), 1.74-1.65 (m, 2H), 0.90 (s, 9H), 0.07 (s, 6H).

›Step 2

To a solution of rac-((1R,3R)-3-(2-((tert-butyldimethylsilyl)oxy)ethyl)-2,2-difluorocyclopropyl)methyl acetate (1.5 g, 5.0 mmol) in THF (20 mL) was added a 1M solution of tetrabutylammonium fluoride in THF (7.5 mL, 7.5 mmol). The solution stirred for 2 hr. Saturated sodium bicarbonate was added and the aqueous layer was washed twice with diethylether. The combined organic layers were dried over MgSO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (0-100% diethyl ether in hex) to afford rac-((1R,3R)-2,2-difluoro-3-(2-hydroxyethyl)cyclopropyl)methyl acetate. 1 H NMR (400 MHz, Chloroform-d) δ 4.28-4.11 (m, 2H), 3.74 (t, J=5.9 Hz, 2H), 2.08 (s, 3H), 2.04-1.88 (m, 1H), 1.87-1.72 (m, 3H).

›Step 3

To a solution rac-((1R,3R)-2,2-difluoro-3-(2-hydroxyethyl)cyclopropyl)methyl acetate (480 mg, 2.4 mmol), triethylamine (0.55 mL, 3.9 mmol), imidazole (180 mg, 2.7 mmol), and triphenylphosphine (710 mg, 2.7 mmol) in dichloromethane (4 mL) in an ice bath was added iodine (620 mg, 2.5 mmol). The reaction stirred for 20 min in an ice bath. The ice bath was removed, and the reaction was allowed to warm to room temperature. The reaction stirred for 2 hr. The reaction mixture was diluted with EtOAc and washed with water and diluted NaHSO 3 , dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (0-50% EtOAc in hex) to afford rac-((1R,3R)-2,2-difluoro-3-(2-iodoethyl)cyclopropyl)methyl acetate. 1 H NMR (400 MHz, Chloroform-d) δ 4.30-4.07 (m, 2H), 3.22 (t, J=7.0 Hz, 2H), 2.09 (s, 3H), 2.08-1.68 (m, 3H).

›Step 4

A solution of rac-((1R,3R)-2,2-difluoro-3-(2-iodoethyl)cyclopropyl)methyl acetate (510 mg, 1.7 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.99 mL, 6.6 mmol) in THF (10 mL) was stirred at room temperature for 2 days. The solution was diluted with diethyl ether and washed with 1 N HCl and saturated sodium bicarbonate, dried over MgSO 4 , filtered and concentrated to afford rac-((1R,3R)-2,2-difluoro-3-vinylcyclopropyl)methyl acetate. 1 H NMR (400 MHz, Chloroform-d) δ 5.66-5.51 (m, 1H), 5.36 (d, J=17.2 Hz, 1H), 5.27 (d, J=10.4 Hz, 1H), 4.25-4.13 (m, 2H), 2.47-2.36 (m, 1H), 2.20-2.04 (m, 4H).

›Step 5

To a solution rac-((1R,3R)-2,2-difluoro-3-vinylcyclopropyl)methyl acetate (190 mg, 1.1 mmol) in 1:1 THF/MeOH (4 mL) was added a 1N solution of lithium hydroxide (2.1 mL, 2.1 mmol). The resulting solution stirred for 2 hr. Saturated sodium bicarbonate was added and the aqueous layer was washed three times with diethyl ether. The combined organic layers were dried over MgSO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (0-100% Et 2 O in hex) to afford rac-((1R,3R)-2,2-difluoro-3-vinylcyclopropyl)methanol. 1 H NMR (400 MHz, Chloroform-d) δ 5.65 (dddt, J=17.2, 10.4, 8.9, 1.5 Hz, 1H), 5.38 (d, J=17.3 Hz, 1H), 5.28 (d, J=10.5 Hz, 1H), 3.92-3.68 (m, 3H), 2.46-2.34 (m, 1H), 2.09 (ddtd, J=13.4, 11.6, 7.8, 1.8 Hz, 1H).

Preparation of ((1S,2S)-2-vinylcyclopropyl)methanol (I-18)

›Step 1

((1S,2S)-2-vinylcyclopropyl)methanol was prepared using a similar procedure to step 9 of L45a with tert-butyldiphenyl(((1S,2S)-2-vinylcyclopropyl)methoxy)-silane.

Preparation of rac-((1R,3S)-2,2-difluoro-3-vinylcyclopropyl)methanol (I-19)

Cis-(3,3-difluorocyclopropane-1,2-diyl)dimethanol was prepared as described in T. Itoh, N. Ishida, K. Mitsukura, S. Hayase, K. Ohashi, Journal of Fluorine Chemistry 125 (2004) 775-783.

›Step 1

To a mixture of 60% sodium hydride (810 mg, 21 mmol) in THF (100 mL) in an ice bath was added a solution of (3,3-difluorocyclopropane-1,2-diyl)dimethanol (2.9 g, 21 mmol) in THF (50 mL). The mixture stirred for 5 min, and then, tert-butyldimethylsilyl chloride (3.2 g, 21 mmol) was added. The mixture stirred for 30 min. Water was added to the reaction mixture and the aqueous layer was washed three times with EtOAc. The combined organic layers were dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (0-50% EtOAc in hex) to give rac-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-difluorocyclopropyl)methanol. 1 H NMR (400 MHz, Chloroform-d) δ 4.06 (ddd, J=12.0, 6.3, 3.0 Hz, 1H), 3.96-3.84 (m, 1H), 3.77-3.63 (m, 2H), 3.05 (dd, J=11.1, 2.2 Hz, 1H), 2.18-1.93 (m, 2H), 0.91 (s, 9H), 0.13 (s, 3H), 0.12 (s, 3H).

›Step 2

rac-(1R,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-difluorocyclopropane-1-carbaldehyde was prepared using a similar procedure to step 1 of L30a with rac-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-difluorocyclopropyl)methanol

›Step 3

To a mixture of methyl(triphenyl)phosphonium bromide (8.1 g, 23 mmol) in THF (30 mL) cooled in an ice bath was added a 1 M solution of sodium bis(trimethylsilyl)amide in THF (23 mL, 23 mmol). The reaction mixture stirred at room temperature for 30 min and was placed back in the ice bath. To the cooled mixture was added a solution of rac-(1R,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-difluorocyclopropane-1-carbaldehyde (3.5 g, 14 mmol) in THF (20 mL) over 10 min. The reaction stirred in the ice bath for 2 hr. To the mixture was added saturated ammonium chloride and the aqueous layer was washed with EtOAc three times. The combined organic layers were dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (0-30% EtOAc in hex) to give rac-tert-butyl(((1R,3S)-2,2-difluoro-3-vinylcyclopropyl)methoxy)dimethylsilane. 1 H NMR (400 MHz, Chloroform-d) δ 5.55 (dddd, J=17.1, 10.1, 8.5, 1.7 Hz, 1H), 5.32-5.06 (m, 2H), 3.83-3.66 (m, 2H), 2.38-1.71 (m, 2H), 0.89 (s, 9H), 0.16 (s, 3H), 0.07 (s, 5H).

›Step 4

To a solution of rac-tert-butyl(((1R,3S)-2,2-difluoro-3-vinylcyclopropyl)methoxy)dimethylsilane (3.5 g, 14 mmol) in THF (20 mL) was added a 1M solution of tetrabutylammonium fluoride in THF (21 mL, 21 mmol). The solution stirred for 2 hr. Saturated sodium bicarbonate was added and the aqueous layer was washed twice with diethylether. The combined organic layers were dried over MgSO 4 , filtered and concentrated. The residue was purified by silica gel chromatography (0-100% diethyl ether in hex) to afford rac-((1R,3S)-2,2-difluoro-3-vinylcyclopropyl)methanol. 1 H NMR (400 MHz, Chloroform-d) δ 5.63-5.48 (m, 0H), 5.26 (d, J=17.3 Hz, 0H), 5.18 (d, J=10.5 Hz, 0H), 3.89-3.68 (m, 2H), 2.17-2.05 (m, 1H), 1.87 (dq, J=14.3, 7.1 Hz, 1H).

Preparation of ((1S,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-1-fluorocyclopropyl)methanol (I-20a) and ((1R,2R)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-1-fluorocyclopropyl)methanol (I-20b)

(Z)-4-((tert-butyldiphenylsilyl)oxy)-2-fluorobut-2-en-1-ol was prepared as described in Nucleosides, Nucleotides & Nucleic Acids, 22 (5-8), 659-661; 2003.

›Step 1

Diiodomethane (3.42 g, 1.02 mL, 12.8 mmol) was added to a solution of Et 2 Zn (1.0 M in hexane, 6.96 mmol, 6.96 mL) in CH 2 Cl 2 (20 mL) at 0° C. and stirred for 15 min. The resulting white slurry was cooled to −78° C. and a solution of (Z)-4-((tert-butyldiphenylsilyl)oxy)-2-fluorobut-2-en-1-ol (2.0 g, 5.8 mmol) in CH 2 Cl 2 (10 mL) was added. The reaction was allowed to warm to room temperature by removal of the cooling bath and stirring continued for 17 h. The reaction was cooled to 0° C., saturated aqueous NH 4 Cl was added and the layers were separated. The aqueous phase was extracted with CH 2 Cl 2 (3×6 mL) and the combined organic fractions dried (MgSO 4 ) and concentrated under reduced pressure. The crude residue was purified by flash chromatography eluting with EtOAc/hexane (5-100%) to give rac-((1S,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-1-fluorocyclopropyl)methanol. 1 H NMR: (CDCl 3 400 MHz): δ 7.70-7.68 (m, 4H), 7.43-7.39 (m, 6H), 3.90-3.72 (m, 4H), 1.29-1.27 (m, 1H), 1.06 (s, 9H), 0.89-0.81 (m, 2H).

›Step 2

((1S,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-1-fluorocyclopropyl)methanol (I-20a) and ((1R,2R)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-1-fluorocyclopropyl)methanol (I-20b) were obtained from SFC (column: DAICEL CHIRALCEL OJ (250 mm*50 mm, 10 um); mobile phase: [0.1% NH 3 H 2 O IPA]; B %: 11%-11%, 2.6 min).

((1S,2R)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-1-fluorocyclopropyl)methanol (I-20c) and ((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)-1-fluorocyclopropyl)methanol (I-20d)

Prepared following a similar procedure to I-20a/I-20b using (E)-4-((tert-butyldiphenylsilyl)oxy)-2-fluorobut-2-en-1-ol ((E)-4-((tert-butyldimethylsilyl)oxy)-2-fluorobut-2-en-1-ol is reported in Tetrahedron 2004, 60, 10907-10914). 1 H NMR: (CDCl3 400 MHz): δ7.70-7.66 (m, 4H), 7.52-7.35 (m, 6H), 4.49-4.19 (m, 1H), 4.01-4.10 (m, 1H), 3.78-3.57 (m, 1H), 3.28-3.25 (m, 1H), 3.19-3.14 (m, 1H), 1.75-1.62 (m, 1H), 1.20-1.18 (m, 1H), 1.07 (s, 9H), 0.59-0.56 (m, 1H).

Preparation of methyl 4-(methylamino)-5-nitro-2-(trifluoromethyl)benzoate (I-21)

›Step 1

Methyl 4-fluoro-2-(trifluoromethyl)benzoate (1.4 mL, 6.3 mmol) was dissolved in concentrated sulfuric acid (1.4 mL, 26.3 mmol) and the resulting reaction mixture was cooled to 0° C. Fuming nitric acid (99%) (2.63 mL, 41.1 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 30 min. Then, the mixture was warmed to 45° C. and stirred for 16 h. The reaction mixture was added dropwise into ice-water (9 mL), diluted with ethyl acetate (9 mL) and left to stir for 30 min. The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated sodium bicarbonate solution. The organics were collected, dried over anhydrous magnesium sulfate, filtered and concentrated to produce the crude product, which was purified via silica gel column chromatography (0-30% ethyl acetate in hexanes) to yield methyl 4-fluoro-5-nitro-2-(trifluoromethyl)benzoate. 1 H NMR (400 MHz, Chloroform-d) δ 7.92-7.82 (m, 1H), 7.59 (t, J=8.4 Hz, 1H), 3.99 (s, 3H). 19 F NMR (376 MHz, Chloroform-d) δ−56.16, −117.55 (dd, J=8.1, 5.0 Hz).

›Step 2

Triethylamine (0.26 mL, 1.88 mmol) was added to a solution of methyl 4-fluoro-5-nitro-2-(trifluoromethyl)benzoate (167 mg, 0.63 mmol) in tetrahydrofuran (2 mL) at 0° C., followed by 2 M methylamine in tetrahydrofuran (0.7 mL, 1.37 mmol). The resulting reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with water to crash out the product, filtering and washing the cake with water, repeating twice. The resulting cake was dissolved in dichloromethane, dried over anhydrous magnesium sulfate and concentrated to yield methyl 4-(methylamino)-5-nitro-2-(trifluoromethyl)benzoate, which was carried forward without further purification. 1 H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J=8.9 Hz, 1H), 6.99 (d, J=8.9 Hz, 1H), 3.93 (s, 3H), 2.99 (d, J=4.9 Hz, 3H). 19 F NMR (376 MHz, Chloroform-d) δ −56.16.

Preparation of tert-butyl (3S,4S)-3-(4-(cyclobutylamino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22a)

›Step 1

A mixture of 2,4-difluoro-5-nitro-benzoic acid (512 mg, 2.52 mmol), (1-chloro-2-methyl-propenyl)-dimethylamine (0.371 mL, 2.80 mmol) and DCM (37 mL) is stirred for 30 min, then A1.15 (500 mg, 2.29 mmol) and N,N-diisopropylethylamine (0.650 mL, 3.80 mmol) are added and it is stirred for 2 h. The mixture is concentrated and purified by silica gel chromatography (5-50% EtOAc in hexanes) provided tert-butyl (3S,4S)-3-[(2,4-difluoro-5-nitro-benzoyl)amino]-4-fluoro-piperidine-1-carboxylate. ES/MS: m/z 402.1 [M+H] + .

›Step 2 · 1 of 2

A 50 mL round bottom flask was charged with tert-butyl (3S,4S)-3-[(2,4-difluoro-5-nitro-benzoyl)amino]-4-fluoro-piperidine-1-carboxylate (100 mg, 0.248 mmol) a stir bar and THF (5 mL). The solution was cooled to 0° C. and Hunig's base (42.4 μL, 0.248 mmol) was added followed by dropwise addition of cyclopropylamine (25.4 μL, 0.298 mmol). The remaining mixture was stirred at 0° C. for 2 hr. The mixture is concentrated and purified by silica gel chromatography (5-80% EtOAc in hexanes) provided tert-butyl (3S,4S)-3-[[4-(cyclobutylamino)-2-fluoro-5-nitro-benzoyl]amino]-4-fluoro-piperidine-1-carboxylate. ES/MS: m/z 455.3 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-4-(isopropylamino)-5-nitrobenzamido)piperidine-1-carboxylate (I-22b)

Prepared following a similar procedure to I-22a using isopropylamine. ES/MS: m/z 443.3 [M+H] + .

tert-butyl (3S,4S)-3-(4-(ethylamino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22c)

Prepared following a similar procedure to I-22a using ethylylamine. ES/MS: m/z 429.3 [M+H] + .

tert-butyl (3S,4S)-3-(4-((2-ethoxyethyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22d)

Prepared following a similar procedure to I-22a using 2-ethoxyethane-1-amine. ES/MS: m/z 473.3 [M+H] + .

tert-butyl (3S,4S)-3-(4-((2-cyanoethyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22e)

Prepared following a similar procedure to I-22a using 2-aminoacetonitrile. ES/MS: m/z Does not ionize.

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-4-((2-(2-methoxyethoxy)ethyl)amino)-5-nitrobenzamido)piperidine-1-carboxylate (I-22f)

Prepared following a similar procedure to I-22a using 2-(2-methoxyethoxy)ethan-1-amine. ES/MS: m/z 503.3 [M+H] + .

tert-butyl (3S,4S)-3-(4-((3-amino-3-oxopropyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22g)

Prepared following a similar procedure to I-22a using 3-aminopropanamide. ES/MS: m/z 471.7 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-5-nitro-4-((2-phenoxyethyl)amino)benzamido)piperidine-1-carboxylate (I-22h)

Prepared following a similar procedure to I-22a using 2-phenoxyethan-1-amine. ES/MS: m/z 520.2 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-4-((2-methoxypropyl)amino)-5-nitrobenzamido)piperidine-1-carboxylate (I-22i)

Prepared following a similar procedure to I-22a using 2-methoxypropan-1-amine. ES/MS: m/z Does not ionize.

2-fluoro-N-((3S,4S)-4-fluoropiperidin-3-yl)-5-nitro-4-((2-(pyridin-2-yloxy)ethyl)amino)benzamide (I-22j)

Prepared following a similar procedure to I-22a using 2-(pyridin-2-yloxy)ethan-1-amine. ES/MS: m/z 422.0 [M+H] + .

tert-butyl ((3S,4R)-1-(3-fluoro-4-((2-methoxyethyl)amino)-5-nitrobenzoyl)-4-methoxypiperidin-3-yl)carbamate (I-22k)

Prepared following a similar procedure to I-22a using 3,4-difluoro-5-nitrobenzoic acid, A1.03 and 2-methoxyethan-1-amine. ES/MS: m/z 470.8 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-4-((2-isopropoxyethyl)amino)-5-nitrobenzamido)piperidine-1-carboxylate (I-22l)

Prepared following a similar procedure to I-22a using 2-isopropoxyethan-1-amine. ES/MS: m/z 486.6 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-4-(((1-fluorocyclopropyl)methyl)amino)-5-nitrobenzamido)piperidine-1-carboxylate (I-22m)

Prepared following a similar procedure to I-22a using (1-fluorocyclopropyl)methanamine. ES/MS: m/z 473.73 [M+H] + .

tert-butyl (3S,4S)-3-(4-(((1-cyanocyclopropyl)methyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22n)

Prepared following a similar procedure to I-22a using 1-(aminomethyl)cyclopropanecarbonitrile. ES/MS: m/z 479.94 [M+H] + .

tert-butyl (3S,4S)-3-(4-(((1R,2S)-2-(difluoromethyl)cyclopropyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate and tert-butyl (3S,4S)-3-(4-(((1S,2R)-2-(difluoromethyl)cyclopropyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22p)

Prepared following a similar procedure to I-22a using rac-(1R,2S)-2-(difluoromethyl)cyclopropanamine. ES/MS: m/z 490.8 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-4-(((1S,2S)-2-methylcyclopropyl)amino)-5-nitrobenzamido)piperidine-1-carboxylate (I-22q)

Prepared following a similar procedure to I-22a using (1S,2S)-2-methylcyclopropanamine. ES/MS: m/z 454.3 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-4-(((1R,2R)-2-methylcyclopropyl)amino)-5-nitrobenzamido)piperidine-1-carboxylate (I-22r)

Prepared following a similar procedure to I-22a using (1R,2R)-2-methylcyclopropanamine. ES/MS: m/z 455.6 [M+H] + .

tert-butyl (3S,4S)-3-(4-(((1R,2R)-2-(difluoromethyl)cyclopropyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate and tert-butyl (3S,4S)-3-(4-(((1S,2S)-2-(difluoromethyl)cyclopropyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22s)

Prepared following a similar procedure to I-22a using rac-(1R,2R)-2-(difluoromethyl)cyclopropanamine. ES/MS: m/z 490.6 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-5-nitro-4-((2-(trifluoromethoxy)ethyl)amino)benzamido)piperidine-1-carboxylate (I-22t)

Prepared following a similar procedure to I-22a using 2-(trifluoromethoxy)ethanamine hydrochloride. ES/MS: m/z 512.6 [M+H] + .

tert-butyl (3S,4S)-3-(4-((2-cyclopropoxyethyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22u)

Prepared following a similar procedure to I-22a using 2-(cyclopropoxy)ethanamine hydrochloride. ES/MS: m/z 484.6 [M+H] + .

tert-butyl (3S,4S)-3-(4-((2-(difluoromethoxy)ethyl)amino)-2-fluoro-5-nitrobenzamido)-4-fluoropiperidine-1-carboxylate (I-22v)

Prepared following a similar procedure to I-22a using 2-(difluoromethoxy)ethanamine hydrochloride. ES/MS: m/z 495.2 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(4-(methylamino)-3-nitro-5-(trifluoromethyl)benzamido)piperidine-1-carboxylate (I-22w)

Prepared following a similar procedure to I-22a using 4-fluoro-3-nitro-5-(trifluoromethyl)benzoic acid. ES/MS: m/z 465.6 [M+H] + .

tert-butyl (3S,4S)-4-fluoro-3-(2-fluoro-5-nitro-4-(spiro[2.2]pentan-1-ylamino)benzamido)piperidine-1-carboxylate (I-22x)

Prepared following a similar procedure to I-22a. ES/MS: m/z 466.4 [M+H] + .

›Step 2 · 2 of 2

tert-butyl ((3S,4R)-1-(4-(cyclopropylamino)-3-fluoro-5-nitrobenzoyl)-4-methoxypiperidin-3-yl)carbamate (I-22y)

Prepared following a similar procedure to I-22a using 3,4-difluoro-5-nitrobenzoic acid, A1.03 and cyclopropylamine.

Preparation of tert-butyl (3S,4S)-3-(5-amino-2-fluoro-4-((2-methoxypropyl)amino)benzamido)-4-fluoropiperidine-1-carboxylate (I-23a)

›Step 1

tert-butyl (3S,4S)-3-(5-amino-2-fluoro-4-((2-methoxypropyl)amino)benzamido)-4-fluoropiperidine-1-carboxylate was prepared following a similar procedure to step 2 of I-140a. ES/MS: m/z 442.8 [M+H] + .

5-amino-2-fluoro-N-((3S,4S)-4-fluoropiperidin-3-yl)-4-((2-(pyridin-2-yloxy)ethyl)amino)benzamide (I-23c)

Prepared following a similar procedure to I-23a using I-22j. ES/MS: m/z 491.9 [M+H] + .

tert-butyl ((3S,4R)-1-(3-amino-5-fluoro-4-((2-methoxyethyl)amino)benzoyl)-4-methoxypiperidin-3-yl)carbamate (I-23d)

Prepared following a similar procedure to I-23a using I-22k. ES/MS: m/z 440.9 [M+H] + .

tert-butyl (3S,4S)-3-(5-amino-4-(((1R,2S)-2-(difluoromethyl)cyclopropyl)amino)-2-fluorobenzamido)-4-fluoropiperidine-1-carboxylate and tert-butyl (3S,4S)-3-(5-amino-4-(((1S,2R)-2-(difluoromethyl)cyclopropyl)amino)-2-fluorobenzamido)-4-fluoropiperidine-1-carboxylate (I-23f)

Prepared following a similar procedure to I-23a using I-22p. ES/MS: m/z 460.79 [M+H] + . Note: Dianiline doesn't ionize well.

tert-butyl (3S,4S)-3-(5-amino-2-fluoro-4-(((1S,2S)-2-methylcyclopropyl)amino)benzamido)-4-fluoropiperidine-1-carboxylate (I-23g)

Prepared following a similar procedure to I-23a using I-22q. ES/MS: Dianiline does not ionize well; retention time: 1.65 min.

tert-butyl (3S,4S)-3-(5-amino-2-fluoro-4-(((1R,2R)-2-methylcyclopropyl)amino)benzamido)-4-fluoropiperidine-1-carboxylate (I-23h)

Prepared following a similar procedure to I-23a using I-22r. ES/MS: m/z 424.93 [M+H] + . Note: Dianiline does not ionize well.

tert-butyl (3S,4S)-3-(5-amino-4-(((1R,2R)-2-(difluoromethyl)cyclopropyl)amino)-2-fluorobenzamido)-4-fluoropiperidine-1-carboxylate and tert-butyl (3S,4S)-3-(5-amino-4-(((1S,2S)-2-(difluoromethyl)cyclopropyl)amino)-2-fluorobenzamido)-4-fluoropiperidine-1-carboxylate (I-23i)

Prepared following a similar procedure to I-23a using I-22s. ES/MS: m/z 460.29 [M+H] + .

tert-butyl (3S,4S)-3-(5-amino-2-fluoro-4-(spiro[2.2]pentan-1-ylamino)benzamido)-4-fluoropiperidine-1-carboxylate (I-23k)

Prepared following a similar procedure to I-23a using I-22x. ES/MS: m/z 436.8 [M+H] + .

tert-butyl ((3S,4R)-1-(3-amino-4-(cyclopropylamino)-5-fluorobenzoyl)-4-methoxypiperidin-3-yl)carbamate (I-23m)

Prepared following a similar procedure to I-23a using I-22y.

Preparation of 6-bromo-7-fluoro-1-(phenylsulfonyl)-1H-indole-2-carbaldehyde (I-24a

›Step 1

6-bromo-7-fluoro-1H-indole (14 g, 65 mmol) was dissolved in THF (140 mL) and cooled to 0° C. NaH (60% dispersion, 3.92 g, 98.1 mmol) was added, and the mixture was allowed to warm to r.t. and stirred for 1 h. The mixture was cooled to 0° C., and benzenesulfonyl chloride (13.9 g, 78.5 mmol) was then added, and the mixture was allowed to warm to r.t. and was stirred for 1 h. The mixture was then poured into saturated aqueous NH 4 Cl below 5° C., and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na 2 SO 4 , filtered, and concentrated. The obtained residue was triturated with 2/1 EtOAc/hexanes (90 mL), and the mixture was filtered to collect 6-bromo-7-fluoro-1-(phenylsulfonyl)-1H-indole. 1 H NMR: (CDCl 3 400 MHz): δ 7.96-7.98 (m, 2H), 7.79 (d, J=3.67 Hz, 1H), 7.60-7.64 (m, 1H), 7.51-7.55 (m, 2H), 7.34 (dd, J=8.38, 5.69 Hz, 1H), 7.21 (d, J=8.44 Hz, 1H), 6.67 (dd, J=3.67, 2.20 Hz, 1H).

›Step 2

6-bromo-7-fluoro-1-(phenylsulfonyl)-1H-indole (22.7 g, 63.2 mmol) was dissolved in THF (220 mL) under N 2 and cooled to −65° C. A solution of LDA (2 M, 47.4 mL, 94.8 mmol) was added followed by the dropwise addition of TMEDA (16.7 mL, 111 mmol). The mixture was stirred for 1 h at −65° C. and DMF (24.3 mL, 316 mmol) was added. After an additional 3 h, the mixture was poured into saturated aqueous NH 4 Cl (300 mL) and was extracted with DCM. The combined organic phase was washed with brine, dried over Na 2 SO 4 , filtered, and concentrated. The obtained residue was triturated with EtOAc (60 mL), and solids were collected by filtration. The trituration was repeated to afford 6-bromo-7-fluoro-1-(phenylsulfonyl)-1H-indole-2-carbaldehyde. 1 H NMR: (CDCl3 400 MHz): δ 10.4 (s, 1H), 8.10-8.13 (m, 2H), 7.65-7.70 (m, 1H), 7.56-7.60 (m, 2H), 7.42-7.47 (m, 2H), 7.32 (d, J=8.44 Hz, 1H).

6-bromo-5-fluoro-1-(phenylsulfonyl)-1H-indole-2-carbaldehyde (I-24b)

Prepared following a similar procedure to I-24a from 6-bromo-5-fluoro-1H-indole. 1 H NMR (CDCl 3 400 MHz): δ 10.5 (s, 1H), 8.51 (d, J=5.75 Hz, 1H), 7.78-7.81 (m, 2H), 7.59-7.63 (m, 1H), 7.47-7.50 (m, 2H), 7.39 (d, J=0.490 Hz, 1H), 7.35 (d, J=7.82 Hz, 1H).

Preparation of tert-butyl (R)-(1-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-25a)

›Step 1

Step 1 of I-8a was followed to produce 1-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethan-1-one from 1-(1H-pyrrolo[2,3-b]pyridin-6-yl)ethan-1-one. ES/MS: m/z 301.0 [M+H] + .

›Step 2

Steps 1-4 of I-102 were followed to produce tert-butyl (R)-(1-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate from 1-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethan-1-one. ES/MS: m/z 401.8 [M+H] + .

tert-butyl (R)-(1-(5-fluoro-1-(phenylsulfonyl)-1H-indol-6-yl)ethyl)carbamate (I-25b)

Prepared following a similar procedure to I-25a starting with I-13g. ES/MS: m/z 441.1 [M+Na] + . 1 H NMR (400 MHz, DMSO-d6) δ 8.02-7.97 (m, 3H), 7.81-7.77 (m, 2H), 7.70-7.67 (m, 1H), 7.57-7.53 (m, 2H), 7.35 (d, J=10.4 Hz, 1H), 6.78 (d, J=3.6 Hz, 1H), 4.94-4.91 (m, 1H), 1.40 (s, 9H), 1.31 (d, J=6.8 Hz, 3H).

tert-butyl (R)-(1-(1-(phenylsulfonyl)-1H-indol-6-yl)ethyl)carbamate (I-25c)

Prepared following a similar procedure to I-25a starting with I-13h. ES/MS: m/z 423.0 [M+Na] + . 1 H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.86 (dd, J=7.2, 1.6 Hz, 2H), 7.54-7.50 (m, 2H), 7.48-7.40 (m, 3H), 7.18 (dd, J=8.4, 1.2 Hz, 1H), 6.62 (d, J=3.6 Hz, 1H), 4.89-4.87 (m, 2H), 1.49-1.45 (m, 3H), 1.44 (s, 9H).

Preparation of methyl 2-bromo-4-(methylamino)-5-nitrobenzoate (I-26)

›Step 1

A mixture of methyl 2-bromo-4-(methylamino)-5-nitro-benzoate (0.167 g, 0.578 mmol), zinc cyanide (0.271 g, 2.31 mmol), and tetrakis(triphenylphosphine)-palladium(0) (0.0668 g, 0.058 mmol) in DMF (2 mL) was heated at 90° C. After stirring overnight, the reaction mixture was cooled to rt and poured into water. The resulting solid was filtered, washed with water, and dried in vacuo. Purification via silica gel column chromatography (10-100% ethyl acetate/hexanes) yields methyl 2-cyano-4-(methylamino)-5-nitrobenzoate. 1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J=5.4 Hz, 1H), 8.69 (s, 1H), 7.63 (s, 1H), 3.88 (s, 3H), 3.06 (d, J=5.0 Hz, 3H).

Preparation of methyl 3-(difluoromethoxy)-4-(methylamino)-5-nitrobenzoate (I-27a)

›Step 1

To a solution of methyl 4-chloro-3-methoxy-5-nitrobenzoate (1.0 g, 4.07 mmol) in DCM (10 mL) at −78° C. was added BBr 3 (3.1 g, 12.2 mmol). The reaction was warm to rt and attired o/n. The reaction was cooled to 0° C., MeOH was added and the reaction mixture was stirred at rt for o/n. Concentration and purification via silica gel column chromatography (0-100% ethyl acetate/hexanes) affords methyl 4-chloro-3-hydroxy-5-nitrobenzoate.

›Step 2

To a solution of methyl 4-chloro-3-hydroxy-5-nitrobenzoate (350 mg, 1.51 mmol) was added K 2 CO 3 (3.1 g, 22.7 mmol) and the mixture was heated you 90° C. Chlorodifluoromethane was bubbled for 15 minutes. Upon cooling, the reaction was portioned between water and EtOAc. The organic phase was washed with brine and dried with MgSO 4 . The crude mixture was used as is in the next step.

›Step 3

methyl 3-(difluoromethoxy)-4-(methylamino)-5-nitrobenzoate was prepared following a similar procedure to I-7a from methyl 4-chloro-3-(difluoromethoxy)-5-nitrobenzoate. ES/MS: m/z 277.0 [M+H] + .

methyl 4-(cyclopropylamino)-3-(difluoromethoxy)-5-nitrobenzoate (I-27b)

Prepared following a similar procedure to I-27a using cyclopropylamine. ES/MS: m/z 302.1 [M+H] + .

Preparation of 6-chloro-2-vinyl-pyridine-3-carboxylic Acid (I-29)

›Step 1

A mixture of methyl 2-bromo-6-chloro-pyridine-3-carboxylate (211 mg, 0.842 mmol), Vinylboronic Acid Pinacol Ester (0.163 mL, 0.842 mmol), Bis(triphenylphosphine)palladium Chloride (59.1 mg, 0.0842 mmol), and cesium fluoride (384 mg, 2.53 mmol) in dioxane (1.5 mL) and water (0.75 mL) was heated at 80 degrees under argon overnight. After cooling to rt, the reaction mixture was diluted with ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics were dried, filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-8% ethyl acetate/hexanes) to yield methyl 6-chloro-2-vinyl-pyridine-3-carboxylate. ES/MS: m/z 198.0 [M+H] + .

›Step 2

Lithium hydroxide, monohydrate (40.8 mg, 0.972 mmol) was added to a solution of methyl 6-chloro-2-vinyl-pyridine-3-carboxylate (48.0 mg, 0.243 mmol) in THF (1 mL), MeOH (0.5 mL), and water (0.5 mL) at rt. After 2 hours, an aqueous solution of hydrochloric acid (6N, 0.243 mL, 1.46 mmol) was added and the reaction mixture was diluted with ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics were dried, filtered, and concentrated under reduced pressure to yield 6-chloro-2-vinyl-pyridine-3-carboxylic acid. ES/MS: m/z 183.9 [M+H] + .

Preparation of ethyl rac-(1S,2R)-2-((benzyloxy)methyl)-1-(trifluoromethyl)cyclopropane-1-carboxylate (I-30a) and ethyl rac-(1S,2S)-2-((benzyloxy)methyl)-1-(trifluoromethyl)cyclopropane-1-carboxylate (I-30b)

›Step 1

A solution of allyl benzyl ether (48.8 g, 329 mmol) in DCM (300 mL) was degassed and purged with N 2 ·Rh 2 (OAc) 4 (1.82 g, 8.24 mmol) was added followed by a solution of ethyl 2-diazo-3,3,3-trifluoropropanoate (30 g, 164 mmol) (prepared according to Shi, G. et. al. J. Org. Chem. 1990, 55, 3383-3386) in DCM (300 mL). The reaction mixture was stirred for 8 h at r.t. and was filtered. The filtrate was concentrated in vacuo, and the crude residue was purified by silica gel chromatography (1-5% EtOAc in hexanes) to provide ethyl rac-(1S,2R)-2-((benzyloxy)methyl)-1-(trifluoromethyl)cyclopropane-1-carboxylate and ethyl rac-(1S,2S)-2-((benzyloxy)methyl)-1-(trifluoromethyl)cyclopropane-1-carboxylate. Relative stereochemistry was assigned on the basis of NOEs observed in the hydroxymethyl products following ester reduction using LiAlH 4 .

HNMR data for ethyl rac-(1S,2R)-2-((benzyloxy)methyl)-1-(trifluoromethyl)cyclopropane-1-carboxylate 1 H NMR: (CDCl 3 400 MHz): δ 7.37-7.30 (m, 5H), 4.55 (s, 2H), 4.24-4.20 (m, 2H), 3.71-3.65 (m, 2H), 2.10-2.09 (m, 1H), 1.76-1.75 (m, 1H), 1.38-1.35 (m, 1H), 1.31-1.28 (m, 3H).

HNMR data for ethyl rac-(1S,2S)-2-((benzyloxy)methyl)-1-(trifluoromethyl)cyclopropane-1-carboxylate: 1 H NMR: (CDCl 3 400 MHz): δ 7.36-7.29 (m, 5H), 4.52-4.23 (m, 2H), 4.23-4.18 (m, 2H), 3.77-3.76 (m, 1H), 3.53-3.48 (m, 1H), 2.04-2.02 (m, 1H), 1.59-1.52 (m, 2H), 1.29-1.25 (m, 3H).

Preparation of methyl 4-(methylamino)-3-nitro-5-(trifluoromethoxy)benzoate (I-31)

›Step 1

To a stirring solution of 4-fluoro-3-(trifluoromethoxy)benzoic acid (2.0 g, 8.9 mmol) in MeOH (160 mL) at 0° C. was added acetyl chloride (2.5 mL, 36 mmol) dropwise. The reaction mixture was stirred overnight, and concentrated. The residue was diluted with dichloromethane and a saturated sodium bicarbonate solution. The aqueous layer was washed twice with dichloromethane. The combined organic layers were dried over Na 2 SO 4 , filtered and concentrated. The crude residue was purified by flash chromatography eluting with hexanes/EtOAc to give a colorless oil (1.5 g, 72%). 1H NMR (400 MHz, Chloroform-d) δ 8.05-7.97 (m, 2H), 7.33-7.22 (m, 1H), 3.94 (s, 3H).

›Step 2

A mixture of methyl 4-fluoro-3-(trifluoromethoxy)benzoate (1.5 g, 6.4 mmol), methylamine hydrochloride (520 mg, 7.7 mmol), and potassium carbonate (1.8 g, 13 mmol) in DMF (12 mL) was stirred at 80° C. for 18 hr. The reaction was allowed to cool and water was added. The aqueous layer was washed three time with diethyl ether. The combined organic layers were washed twice with brine, dried over MgSO 4 , filtered and concentrated. The crude residue was purified by flash chromatography eluting with hexanes/EtOAc to give a colorless oil (930 mg, 58%). ES/MS: m/z 250.00 [M+H]+.

›Step 3

To a solution of methyl 4-(methylamino)-3-(trifluoromethoxy)benzoate (808 mg, 3.24 mmol) in sulfuric acid (5 mL) at 0° C. was added nitric acid (0.180 mL, 3.9 mmol). The reaction stirred at 0° C. for 30 min. Ice was added and saturated sodium bicarbonate until basic. The aqueous layer was washed three times with diethyl ether. The combined organic layers were dried over MgSO 4 , filtered and concentrated. The crude residue was purified by flash chromatography eluting with hexanes/EtOAc to give a colorless oil (282 mg, 30%). ES/MS: m/z 294.99 [M+H]+.

Preparation of methyl 5-nitro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carboxylate (I-32)

›Step 1

To a solution of methyl 4-chloro-3-methoxy-5-nitrobenzoate (39.0 g, 0.16 mol) in DCM (500 mL) was added BBr 3 (1M in DCM, 78.6 g, 0.32 mol) at 0° C. dropwise over 30 minutes. The reaction mixture was stirred at room temperature for 5 h. After completion, the mixture was cooled to 0° C., quenched carefully with methanol, combined and concentrated in vacuo to give methyl 4-chloro-3-hydroxy-5-nitrobenzoate as a red solid. 1 H NMR (400 MHz, CDCl 3 ): δ ppm 8.09 (s, 1H), 8.08 (s, 1H), 6.16 (s, 1H), 3.90 (s, 3H).

›Step 2

To a solution of methyl 4-chloro-3-hydroxy-5-nitrobenzoate (43.0 g, 0.19 mmol, 1.0 eq) and tert-butyl (2-bromoethyl)carbamate (104.0 g, 0.46 mol, 2.5 eq) in DMF was added cesium carbonate (60.6 g, 0.19 mol, 1.0 eq) and the reaction mixture was stirred at room temperature for 8 h. After HPLC showed completion, the mixture was poured into ice-water and extracted with EtOAc (200 ml×3). The organic layer was separated, dried over MgSO 4 and solvent removed by evaporation. Purification by silica gel chromatography (EtOAc:petroleum ether=1:10) to give methyl 3-(2-((tert-butoxycarbonyl)amino)ethoxy)-4-chloro-5-nitrobenzoate as a yellow solid. 1 H NMR (400 MHz, CDCl 3 ): δ ppm 7.98 (d, J=1.2 Hz, 1H), 7.68 (d, J=1.6 Hz, 2H), 4.14 (t, J=4.8 Hz, 2H), 3.83 (s, 3H), 3.57 (d, J=5.2 Hz, 2H), 1.38 (s, 9H).

›Step 3

To a solution of methyl 3-(2-((tert-butoxycarbonyl)amino)ethoxy)-4-chloro-5-nitrobenzoate (41.6 g, 0.11 mmol, 1.0 eq) in DCM (400 mL) was added TFA (60 mL) in room temperature. After stirring at room temperature until starting material was consumed, the solution was concentrated in vacuo and use directly without purification for the next step. DMSO (400 mL) and trimethylamine (56.1 g, 0.55 mol, 5.0 eq) was added. The reaction stirred for 14 h before partitioning between water (500.0 mL) and EtOAc (400.0 mL). The organic layer was separated, dried with MgSO 4 and the solvent removed by evaporation. Purification by recrystallization from EtOAc (50 mL) to give methyl 5-nitro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carboxylate as yellow solid. 1 H NMR (400 MHz, CDCl 3 ): δ ppm 8.53 (d, J=2.0 Hz, 1H), 8.27 (s, 1H), 7.62 (dd, J1=0.8 Hz, J1=2.0 Hz, 1H), 4.29 (t, J=4.4 Hz, 2H), 3.91 (s, 3H), 3.74-3.71 (m, 2H).

Preparation of tert-butyl (R)-(1-(5-fluoro-2-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-33)

›Step 1

6-chloro-5-fluoro-pyridine-2-carboxylic acid (7.5 g, 43 mmol) was taken up in t-BuOH (120 mL), and triethylamine (4.8 mL, 34 mmol) was added followed by diphenylphosphoryl azide (7.2 mL, 33 mmol). The mixture was allowed to stir at r.t. overnight and was then heated to 50° C. for 2 h. The reaction mixture was then heated to 85° C. for an additional 6 h and was then partitioned between EtOAc and water, dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-15% EtOAc in hexanes) provided tert-butyl N-(6-chloro-5-fluoro-2-pyridyl)carbamate. 1 H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 7.88 (dd, J=9.0, 8.0 Hz, 1H), 7.80 (dd, J=8.9, 3.2 Hz, 1H), 3.33 (s, 1H), 1.47 (s, 9H).

›Step 2

tert-butyl N-(6-chloro-5-fluoro-2-pyridyl)carbamate (6.78 g, 27.5 mmol) was dissolved in DCM (50 mL), and TFA (25 mL) was added. The mixture was allowed to stir for 1 h and was then concentrated. The mixture was partitioned between EtOAc and sat. NaHCO 3 . The organic phase was cried over Na 2 SO 4 , filtered, and concentrated to afford crude 6-chloro-5-fluoro-pyridin-2-amine was carried on without further purification. ES/MS: m/z 146.93 [M+H] + .

›Step 3

6-chloro-5-fluoro-pyridin-2-amine (27 mmol) was dissolved in DMF. TFA (2.38 mL, 31 mmol) was added followed by N-iodosuccinimide (6.7 g, 30 mmol). After stirring for 2 h, additional N-iodosuccinimide (0.45 g, 2 mmol) was added. After an additional 30 min, the mixture was diluted with EtOAc, saturated aqueous NaHCO 3 , and saturated aqueous sodium thiosulfate. The mixture was stirred for 5 min and the phases were separated. The organic phase was washed twice with 5% aqueous LiCl, dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-20% EtOAc in hexanes) provided 6-chloro-5-fluoro-3-iodo-pyridin-2-amine. ES/MS: m/z 146.93 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J=7.6 Hz, 1H), 6.43 (s, 2H).

›Step 4

6-chloro-5-fluoro-3-iodo-pyridin-2-amine (5.6 g, 21 mmol) and Pd 2 (dba) 3 (565 mg, 0.62 mmol) were taken up in DMA (55 mL) under N 2 . N,N-dicyclohexylmethylamine (15.3 mL, 72 mmol) was added followed by pyruvic acid (4.3 mL, 62 mmol). The reaction was heated to 60° C. for 3 h, at which time it was cooled and diluted with EtOAc and water. 6 M Hydrochloric acid (17 mL, 100 mmol) was added and the phases were separated. The organic phase was washed with 5% aqueous LiCl, dried over Na 2 SO 4 , filtered, and concentrated. The crude product was slurried in 1:1 EtOAc:hexanes and filtered to afford 6-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid. ES/MS: m/z 214.92 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 13.41 (s, 1H), 12.82-12.62 (m, 1H), 8.21 (d, J=9.1 Hz, 1H), 7.13 (d, J=2.1 Hz, 1H).

›Step 5

6-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (2.3 g, 10.7 mmol) was suspended in MeOH (20 mL) under N 2 and concentrated sulfuric acid (1.73 mL, 32 mmol) was added. The mixture was heated to reflux for 18 h. The mixture was then cooled, diluted with DCM, and washed with saturated aqueous NaHCO 3 and water. The organic phase was dried over Na 2 SO 4 , filtered, and concentrated to afford methyl 6-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate which was used without further purification. 1 H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.23 (d, J=9.1 Hz, 1H), 7.20 (d, J=1.9 Hz, 1H), 3.90 (s, 3H).

›Step 6

methyl 6-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (2.29 g, 10 mmol) was dissolved in DMF (45 mL) under N 2 and the solution was cooled in an ice water bath. NaH (60% dispersion) (520 mg, 13.6 mmol) wad added in portions over 1 min. The mixture was stirred for 5 min, and was then removed from the cold bath and allowed to stir an additional 10 min. Benzenesulfonyl chloride (1.6 mL, 12.5 mmol) was then added. The reaction mixture was stirred for 1 h and was then diluted with saturated aqueous NH 4 Cl, EtOAc, and water. The phases were separated, and the organic phase was washed with 10% aqueous LiCl, dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel chromatography provided methyl 1-(benzenesulfonyl)-6-chloro-5-fluoro-pyrrolo[2,3-b]pyridine-2-carboxylate. 1 H NMR (400 MHz, DMSO-d6) δ 8.31 (d, J=8.4 Hz, 1H), 8.24-8.17 (m, 2H), 7.86-7.80 (m, 1H), 7.78-7.71 (m, 2H), 7.38 (s, 1H), 3.95 (s, 3H).

›Step 7

methyl 1-(benzenesulfonyl)-6-chloro-5-fluoro-pyrrolo[2,3-b]pyridine-2-carboxylate (3.1 g, 8.4 mmol) and potassium isopropyltrifluoroborate (2.49 g, 16.8 mmol) and PdCl 2 (dppf).CH 2 Cl 2 were taken up in EtOH (90 mL) under N 2 . Triethylamine (5.9 mL, 42 mmol) was added and the mixture was heated to 80° C. After 3 h, the mixture was concentrated by half in vacuo, and cooled in an ice water bath. The resulting solids were collected by filtration and washed with additional EtOH (15 mL) to provide methyl 1-(benzenesulfonyl)-5-fluoro-6-isopropenyl-pyrrolo[2,3-b]pyridine-2-carboxylate. ES/MS: m/z 374.96 [M+H] + .

›Step 8

methyl 1-(benzenesulfonyl)-5-fluoro-6-isopropenyl-pyrrolo[2,3-b]pyridine-2-carboxylate (2.54 g, 6.78 mmol) was dissolved in THF (70 mL) and water (50 mL). Potassium osmate (VI) dihydrate (75 mg, 0.2 mmol) was added followed by sodium periodate (4.35 g, 20.4 mmol). The mixture was stirred for 18 h and was then partitioned between EtOAc and water. The organic phase was washed with water and brine, dried over Na 2 SO 4 , filtered, and concentrated to afford crude methyl 6-acetyl-1-(benzenesulfonyl)-5-fluoro-pyrrolo[2,3-b]pyridine-2-carboxylate that was used without further purification. ES/MS: m/z 376.99 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 8.30-8.25 (m, 2H), 8.22 (d, J=10.9 Hz, 1H), 7.87-7.79 (m, 1H), 7.79-7.71 (m, 2H), 7.39 (s, 1H), 3.99 (s, 3H), 2.72 (s, 3H).

›Step 9

methyl 6-acetyl-1-(benzenesulfonyl)-5-fluoro-pyrrolo[2,3-b]pyridine-2-carboxylate (1.2 g, 3.2 mmol) and (S)-2-methylpropane-2-sulfinamide were dissolved in THF (30 mL) under N 2 . Titanium (IV) isopropoxide (7.5 mL, 25 mmol) was added, and the resulting mixture was heated to 80° C. After stirring for 20 h, the mixture was diluted with EtOAc, and brine (2.5 mL) was slowly added, resulting in precipitation of solids. Additional water (2.5 mL) was added, and the mixture was filtered through Celite. Purification by silica gel chromatography provided [(E)-1-[1-(benzenesulfonyl)-5-fluoro-2-isopropoxycarbonyl-pyrrolo[2,3-b]pyridin-6-yl]ethylideneamino]-tert-butyl-oxido-sulfonium. ES/MS: m/z 507.78 [M+H] + .

›Step 10

[(E)-1-[1-(benzenesulfonyl)-5-fluoro-2-isopropoxycarbonyl-pyrrolo[2,3-b]pyridin-6-yl]ethylideneamino]-tert-butyl-oxido-sulfonium (1.14 g, 2.25 mmol) was dissolved in THF (25 mL) and a 1 M solution of TBAF in THF (2.7 mL, 2.7 mmol) was added. The reaction was stirred for 3 h, and was then partitioned between EtOAc and water. The organic phase was washed with brine, dried over Na 2 SO 4 , filtered, and concentrated to afford crude tert-butyl-[(E)-1-(5-fluoro-2-isopropoxycarbonyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethylideneamino]-oxido-sulfonium that was used without further purification. ES/MS: m/z 367.89 [M+H] + .

›Step 11

tert-butyl-[(E)-1-(5-fluoro-2-isopropoxycarbonyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethylideneamino]-oxido-sulfonium (2.25 mmol) was dissolved in DMF. Hunig's base (2 mL, 12 mmol) was added, followed by 2-(Trimethylsilyl)ethoxymethyl chloride (0.48 mL, 2.7 mmol). The reaction was stirred until complete by LCMS and was then partitioned between EtOAc and water. The organic phase was washed with 10% aq. LiCl, dried over Na 2 SO 4 , filtered and concentrated. Purification by silica gel chromatography provided tert-butyl-[(E)-1-[5-fluoro-2-isopropoxycarbonyl-1-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyridin-6-yl]ethylideneamino]-oxido-sulfonium. (1.08 g, 96%) ES/MS: m/z 497.86 [M+H] + .

›Step 12

tert-butyl-[(E)-1-[5-fluoro-2-isopropoxycarbonyl-1-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyridin-6-yl]ethylideneamino]-oxido-sulfonium (0.95 g, 1.9 mmol) was dissolved in THF (20 mL) under N 2 . The solution was cooled to −78° C. and a 1 M solution of L-selectride in THF (2.3 mL, 2.3 mmoL) was added. The reaction mixture was allowed to stir 1 h and was removed from the cold bath. Once the temperature approached 0° C., the reaction mixture was placed in an ice water bath and stirred an additional 30 min. The mixture was recooled to −78° C., and additional L-selectride (0.35 mL, 0.35 mmol) was added.

The reaction mixture was stirred 5 min, and was then placed in an ice water bath. After an additional 15 min, the mixture was quenched with saturated aqueous NH 4 Cl and diluted with EtOAc. The phases were separated, and the organic phase was dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel chromatography provided tert-butyl-[[(1R)-1-[5-fluoro-2-isopropoxycarbonyl-1-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyridin-6-yl]ethyl]amino]-oxido-sulfonium. ES/MS: m/z 499.78 [M+H] + .

›Step 13 and 14

tert-butyl-[[(1R)-1-[5-fluoro-2-(hydroxymethyl)-1-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyridin-6-yl]ethyl]amino]-oxido-sulfonium (450 mg, 1.0 mmol) was dissolved in Et 2 O (15 mL). A solution of hydrochloric acid in dioxane (4 M, 0.51 mL) was added dropwise, and the resulting mixture was stirred 30 min and concentrated. The crude residue was triturated twice with hexanes and was dissolved in DCM (15 mL). Triethylamine (0.62 mL, 4.4 mmol) was added followed by di-tert-butyl dicarbonate (205 mg, 0.94 mmol). The mixture was stirred overnight, concentrated directly onto silica gel, and purified by silica gel chromatography (0-60% EtOAc in hexanes) to afford tert-butyl N-[(1R)-1-[5-fluoro-2-(hydroxymethyl)-1-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyridin-6-yl]ethyl]carbamate. ES/MS: m/z 439.86 [M+H] + .

›Step 15

tert-butyl N-[(1R)-1-[5-fluoro-2-(hydroxymethyl)-1-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyridin-6-yl]ethyl]carbamate (300 mg, 0.68 mmol) was dissolved in DCM (6 mL). MnO 2 (330 mg, 3.8 mmol) was added and the reaction mixture was stirred at r.t. for 3 h, at which time additional MnO 2 (150 mg, 1.7 mmol) was added. The mixture was stirred an additional 18 h and was then filtered through a short pad of silica gel with 1:1 EtOAc:DCM. The filtrate was concentrated to provide tert-butyl (R)-(1-(5-fluoro-2-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate. ES/MS: m/z 437.71 [M+H] + .

Preparation of tert-butyl (2-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-y)carbamate (I-34)

›Step 1

A mixture of 1-(benzenesulfonyl)-6-bromo-pyrrolo[2,3-b]pyridine (1.31 g, 3.88 mmol), potassium vinyltrifluoroborate (1.15 g, 7.78 mmol), Dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloromethane (0.222 g, 0.271 mmol) and triethylamine (2.7 mL, 19.4 mmol) in ethanol (60 mL) was heated at 75 degrees under argon overnight. After cooling to rt, the reaction mixture was diluted with ethyl acetate and filtered over celite. The filtrate was concentrated under reduced pressure and the resulting residue was purified via silica gel column chromatography (0-35% ethyl acetate/hexanes) to yield 1-(phenylsulfonyl)-6-(prop-1-en-2-yl)-1H-pyrrolo[2,3-b]pyridine. ES/MS: m/z 300.0 [M+H] + .

›Step 2

Iron(III) oxalate hexahydrate (1.86 g, 0.00385 mol) was stirred in water (30 mL) until completely dissolved (˜3 hours). After cooling to zero degrees, sodium azide (401 mg, 6.17 mmol) and THF (15 mL) was added. To the cooled mixture was added a solution of 1-(benzenesulfonyl)-6-isopropenyl-pyrrolo[2,3-b]pyridine (230 mg, 0.771 mmol) in THF (20 mL) followed by slow addition of sodium borohydride (0.0933 g, 0.00247 mol). After 5 minutes, a second batch of sodium borohydride (0.0933 g, 0.00247 mol) was slowly added. After 30 minutes, the reaction mixture was quenched with 28% aq NH 4 OH (12 mL) and diluted with ethyl acetate and brine. The layers were separated and the aqueous extracted with ethyl acetate. The combined organics were dried, filtered, and concentrated under reduced pressure to yield 6-(2-azidopropan-2-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine, which was used without purification. ES/MS: m/z 341.8 [M+H] + .

›Step 3

A mixture of 6-(1-azido-1-methyl-ethyl)-1-(benzenesulfonyl)pyrrolo[2,3-b]pyridine (263 mg, 0.770 mmol) and palladium on carbon (10%, 82 mg, 0.077 mmol) in ethanol (6 mL) was hydrogenated under an atmosphere of hydrogen. After 2 hours, the reaction mixture was diluted with ethyl acetate and filtered over celite. The filtrate was concentrated to yield 2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-amine. ES/MS: m/z 315.9 [M+H] + .

›Step 4

Di-tert-butyl dicarbonate (0.202 g, 0.000925 mol) was added to a mixture of 2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-amine (243 mg, 0.770 mmol) and triethylamine (0.23 mL, 0.925 mmol) in DCM (4 mL) at rt. After 4 hours, the reaction mixture was concentrated and the resulting residue purified via silica gel column chromatography (0-35% ethyl acetate in hexanes) to yield tert-butyl (2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-yl)carbamate. ES/MS: m/z 415.9 [M+H] + .

›Step 5

To a cooled solution of tert-butyl (2-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-yl)carbamate (196 mg, 0.472 mmol) in THF (4 mL) at −78 degrees was slowly added a solution of BuLi in hexanes (2.5M, 0.57 mL, 1.4 mmoL) dropwise). After 30 min, DMF (0.18 mL, 2.36 mmol) was added dropwise. After 30 min, the reaction mixture was quenched with sat. NH 4 Cl (aq) and diluted with ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate. The combined organics were dried, filtered, and concentrated under reduced pressure to yield tert-butyl (2-(2-formyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-yl)carbamate. ES/MS: m/z 443.9 [M+H] + .

›Step 6

A solution of TBAF in THF (1M, 0.87 mL, 0.87 mmol) was added to solution of crude tert-butyl (2-(2-formyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-yl)carbamate (258 mg, 0.582 mmol) in THF (5 mL) at rt. After one hour, the reaction mixture was concentrated and the resulting residue purified via silica gel column chromatography (0-50% ethyl acetate in hexanes) to yield tert-butyl (2-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-yl)carbamate. ES/MS: m/z 303.8 [M+H] + .

2. Synthesis of Intermediates I-100 to I-157

Preparation of ethyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (I-100)

›Step 1

Methyl 2-(6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (I-3, 2.1 g, 4.17 mmol) and PdCl 2 (dppf).CH 2 Cl 2 (341 mg, 0.42 mmol, 10 mol %) were taken up in dioxane (20 mL) in a pressure flask. The mixture was stirred and degassed with nitrogen for 10 minutes. 1-Ethoxyvinyltributyltin (2.8 ml, 8.34 mmol, 2 equiv.) was added and the resulting mixture was stirred at 100° C. for 3 hours. Upon cooling, the mixture was filtered with EtOAc through Celite and the filtrate was concentrated. The resulting residue was dissolved in THF (30 mL), and 1N HCl (4.0 mL, 4.0 mmol, 0.95 equiv.) was added. The mixture was stirred 30 min, at which time it was diluted with EtOAc and water. Phases were separated, and the aqueous phase was extracted with EtOAc. The organic phase was dried over MgSO 4 , filtered, and concentrated to crude solid. The solid was slurried in 30 mL hexanes for 30 min, and the mixture was filtered to collect solids. The filter cake was slurried in ˜30 mL hexanes for 30 minutes and the mixture was filtered to collect methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate which was used without further purification for the next step. ES/MS: m/z 509.3 [M+H] + .

›Step 2

Methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (4.17 mmol) and (S)-2-methylpropane-2-sulfinamide (2.02 g, 16.7 mmol. 4 equiv.) were suspended in THF (30 mL) under nitrogen. Titanium (IV) ethoxide* (5.2 mL, 25 mmol, 6 equiv.) was added, and the resulting stirred mixture was heated at 60° C. After 18 h, the reaction mixture was poured into a vigorously stirred mixture of brine (150 mL) and EtOAc (100 mL). The heterogeneous mixture was diluted further with EtOAc and the phases were separated. The aqueous phase was diluted with EtOAc, Celite (˜50 g) was added and stirred with the resulting emulsion. The mixture was filtered through a pad of Celite with EtOAc, and the resulting clear biphasic mixture was separated. The combined organic phase was dried over Na 2 SO 4 , filtered and concentrated. Purification by silica gel (10-60% EtOAc in hexanes) provided ethyl (S)-2-(6-(1-((tert-butylsulfinyl)imino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 626.4 [M+H] + . *Titanium (IV) isopropoxide can also be used; in that case, the resulting product of this step would be an isopropyl ester.

›Step 3

Ethyl (S)-2-(6-(1-((tert-butylsulfinyl)imino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (2.6 g, 4.2 mmol) was dissolved in THF (40 mL) under nitrogen. The resulting mixture was cooled in a CO 2 /acetone bath to approximately −78° C. L-Selectride (1 M in THF, 4.6 mL, 4.6 mmol, 1.1 equiv.) was then added dropwise over 30 min, and the resulting mixture was stirred for 20 min at −78° C. The reaction was quenched with sat. aq. NH 4 Cl and diluted with EtOAc and water. The phases were separated, and the organic phase was dried over MgSO 4 , filtered, and concentrated. The obtained residue was purified by silica gel chromatography (5-100% 3:1 EA/EtOH in hexane) to afford ethyl 2-(6-((R)-1-(((S)-tert-butylsulfinyl)amino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 628.4 [M+H] + .

›Step 4

Ethyl 2-(6-((R)-1-(((S)-tert-butylsulfinyl)amino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (675 mg, 1.08 mmol) was dissolved in dioxane (10 mL) at 0° C. 4M HCl in dioxane (1.34 mL, 5.4 mmol, 5 equiv.) was added, resulting in the immediate precipitation of solids. After stirring 15 min, the reaction mixture was concentrated in vacuo to provide crude ethyl (R)-2-(6-(1-aminoethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (putative bis-HCl salt) which was used without further purification. ES/MS: m/z 524.3 [M+H] + .

›Step 5

Ethyl (R)-2-(6-(1-aminoethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (1.08 mmol, putative bis-HCl salt) was dissolved in DCM (10 mL) at room temperature. TFA (1.6 mL, 20 equiv.) was added. After stirring 60 min, the reaction mixture was concentrated in vacuo and dried under vacuum to provide crude mixture of ethyl (R)-2-(6-(1-aminoethyl)-1-(hydroxymethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate and ethyl (R)-2-(6-(1-aminoethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate which was used without further purification. ES/MS: m/z 424.2 [M+H] + , 394.2 [M+H] + .

›Step 6. Part A

The above crude mixture (ca. 1.08 mmol) was dissolved in DCM (5 mL). Di-tert-butyl dicarbonate (235 mg, 1.08 mmol, 1.0 equiv) and diisopropylethylamine (0.94 mL, 5.4 mmol, 5.0 equiv.) were added. The mixture was stirred at room temperature for 2 h. Water and EtOAc were added, phases were separated, and the aqueous phase was extracted with EtOAc. The organic phase was dried over MgSO 4 , filtered, and concentrated. Part B: The resulting residue was dissolved in methanol (5 mL) and ethylenediamine (0.72 mL, 10.8 mmol, 10 equiv.) was added. The mixture was stirred at room temperature for 3.5 h. The mixture was concentrated and purified by silica gel chromatography (5-80% 3:1 EA/EtOH in hexane) to afford ethyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 494.3 [M+H] + .

Preparation of isopropyl (R)-2-(6-(1-(((benzyloxy)carbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate (I-101a)

›Step 1

Isopropyl 2-(6-((R)-1-(((S)-tert-butylsulfinyl)amino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate was prepared following steps 2 and 3 of I-100 using I-6a. ES/MS: m/z 637.9 [M+H] + .

›Step 2

A solution of 4M HCl in Dioxane, (1.1 mL, 4.4 mmol) was added to a solution of isopropyl 2-(6-((R)-1-(((S)-tert-butylsulfinyl)amino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate (562 mg, 0.881 mmol) in dioxane (12 mL). After 4 hours, the reaction mixture was concentrated under reduced pressure. To the resulting residue in DCM (12 mL) was added triethylamine (0.7 mL, 5.0 mmol) and N-carbobenzoxyoxysuccinimide (0.26 g, 1.06 mmol). After stirring 3 days, sat. NaHCO 3 (aq) was added and the reaction mixture was diluted with DCM. The layers were separated and the aqueous was extracted with DCM. The combined organics were washed with brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-85% ethyl acetate in hexanes) to yield isopropyl (R)-2-(6-(1-(((benzyloxy)carbonyl)amino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 666.9 [M+H] + .

›Step 3

Isopropyl (R)-2-(6-(1-(((benzyloxy)carbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropylimidazo[1,2-a]pyridine-7-carboxylate was prepared following step 5 and Part B of step 6 of I-100. ES/MS: m/z 537.9 [M+H] + .

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropyl-5-methoxyimidazo[1,2-a]pyridine-7-carboxylate (I-101b)

Prepared following a similar procedure to I-101a using I-6b. 1 H NMR (400 MHz, Chloroform-d) δ 11.99 (brs, 1H), 8.11 (d, J=8.0 Hz, 1H), 7.99 (s, 1H), 7.46-7.31 (m, 4H), 7.20 (d, J=8.0 Hz, 1H), 7.04 (s, 1H), 6.67 (s, 1H), 6.40 (d, J=7.8 Hz, 1H), 5.36-5.24 (m, 1H), 5.16 (d, J=12.4 Hz, 1H), 5.12 (d, J=7.6 Hs, 1H), 5.08 (d, J=12.3 Hz, 1H), 4.15 (s, 3H), 2.51-2.41 (m, 1H), 1.64 (d, J=7.0 Hz, 3H), 1.62-1.50 (m, 1H), 1.43 (d, J=6.2 Hz, 6H), 1.25-1.19 (m, 2H), 0.76-0.66 (m, 2H).

Preparation of isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-102)

›Step 1

Methyl 2-(6-acetyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-13a, 5.58 g, 11.0 mmol) and (S)-2-methylpropane-2-sulfinamide (5.3 g, 44 mmol. 4 equiv.) were taken up in THF (100 mL) under nitrogen. Titanium(IV) isopropoxide (26 mL, 88 mmol, 8 equiv.) was added, and the resulting stirred mixture was heated at 60° C. After 16 h, brine (7 mL) and EtOAc (200 mL) were added and the reaction mixture was stirred vigorously. The organic phase was decanted off, and EtOAc (150 mL) was added with stirring followed by some DCM to cut the emulsion. The organic layer was decanted, and this process was repeated once more. The aqueous phase was diluted with EtOAc (150 mL), and Celite (40 g) was added. The mixture was filtered through Celite. The combined organic phase was dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel (15-80% EtOAc in hexanes) provided isopropyl (S,E)-2-(6-(1-((tert-butylsulfinyl)imino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1 methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 640.3 [M+H] + .

›Step 2

Isopropyl (S,E)-2-(6-(1-((tert-butylsulfinyl)imino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1 methyl-1H-benzo[d]imidazole-5-carboxylate (5.7 g, 4.2 mmol) was dissolved in THF (120 mL) under nitrogen. The resulting mixture was cooled to −78° C. 1 M L-Selectride in THF (5.1 mL, 5.1 mmol, 1.2 equiv.) was then added dropwise over 5 min, and the resulting mixture was stirred for 6 h at −78° C. The reaction was removed from the cold bath and placed in an ice bath once the internal temperature was −5° C. The reaction was stirred an additional 20 min, whereupon LCMS indicated complete conversion. The reaction was quenched with sat. aq. NH 4 Cl and diluted with EtOAc and water. The phases were separated, and the organic phase was dried over MgSO 4 , filtered, and concentrated. The obtained residue was purified by silica gel chromatography (10-60% acetone in hexanes) to afford product isopropyl 2-(6-((R)-1-(((S)-tert-butylsulfinyl)amino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 642.4 [M+H] + .

›Step 3

Isopropyl (S,E)-2-(6-(1-((tert-butylsulfinyl)imino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1 methyl-1H-benzo[d]imidazole-5-carboxylate (3.48 g, 3.86 mmol) was dissolved in MeCN (50 mL). 4M HCl in dioxane (24 mL, 97 mmol) was added, resulting in an immediate precipitation of solids that re-dissolved on further addition of HCl. The resulting solution was heated to 45° C. and stirred for 6 h, over which time solids precipitated out. The reaction mixture was then concentrated in vacuo, suspended in DCM (20 mL), and diluted with diethyl ether (60 mL). Filtration followed by washing with diethyl ether provided isopropyl (R)-2-(6-(1-aminoethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (putative bis-HCl salt) that was used without further purification. ES/MS: m/z 408.3 [M+H] + . *This procedure was also followed in the case where Boc was used instead of SEM as protecting group (see I-13b and I-13c, used for the synthesis of I-104a and I-104b, respectively). *Alternatively, a Mitsunobu reaction can be performed using the corresponding primary alcohol as electrophile (see step 1 of Procedure 27).

›Step 4

Isopropyl (R)-2-(6-(1-aminoethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (HCl salt) from above was taken up in DCM (50 mL, suspension), and trimethylamine (5.4 mL, 38 mmol, 10 equiv.) was added. The resulting mixture was cooled in an ice water bath, and Boc 2 O (842 mg, 3.85 mmol) was added as a solution in DCM (5 mL). The resulting mixture was removed from the cold bath and stirred an additional 10 min. The mixture was diluted with DCM and washed with a mixture of 5% aq. Na 2 CO 3 and water. DCM was used to extract, and the combined organic phase was dried (Na 2 SO 4 ), filtered, and concentrated. The resulting residue was slurried in 20 mL EtOAc, and 60 mL hexane was added in portions. After stirring an additional 30 min, the mixture was filtered to collect solids. The solids were washed with additional 20% EtOAC in hexanes (20 mL) followed by hexanes. Drying afforded isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 508.3 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 12.33 (d, J=2.1 Hz, 1H), 8.06 (d, J=8.2 Hz, 1H), 7.93 (d, J=1.3 Hz, 1H), 7.38 (d, J=8.1 Hz, 1H), 7.36 (d, J=1.3 Hz, 1H), 7.19 (d, J=8.2 Hz, 1H), 7.13 (d, J=2.0 Hz, 1H), 5.16 (hept, J=6.3 Hz, 1H), 4.77 (p, J=7.2 Hz, 1H), 4.29 (s, 3H), 4.03 (s, 3H), 1.43-1.34 (m, 18H).

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-103a)

Prepared following a similar procedure to I-102 starting with I-12. ES/MS: m/z 534.1 [M+H] + .

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-104a)

Prepared following a similar procedure to I-102 starting with I-13b. ES/MS: m/z 507.3 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 11.92 (d, J=2.2 Hz, 1H), 7.91 (d, J=1.3 Hz, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.46 (d, J=8.3 Hz, 1H), 7.42 (s, 1H), 7.34 (d, J=1.3 Hz, 1H), 7.15 (d, J=2.1 Hz, 1H), 7.06 (d, J=8.3, 1H), 5.22-5.16 (m, 1H), 4.77-4.64 (m, 1H), 4.32 (s, 3H), 4.02 (s, 3H), 1.38 (brs, 9H), 1.37 (s, 6H), 1.36 (s, 3H).

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-indol-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-104b)

Prepared following a similar procedure to I-102 starting with I-13c. ES/MS: m/z 533.3 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 11.86 (brs, 1H), 7.86 (d, J=1.3 Hz, 1H), 7.59 (d, J=8.2 Hz, 1H), 7.46 (d, J=8.2 Hz, 1H), 7.41 (s, 1H), 7.37 (d, J=1.4 Hz, 1H), 7.31-7.28 (m, 1H), 7.05 (dd, J=8.3, 1.5 Hz, 1H), 5.20-5.12 (m, 1H), 4.76-4.63 (m, 1H), 4.02 (s, 3H), 3.95-3.84 (m, 1H), 1.39 (s, 9H), 1.37 (d, J=6.3 Hz, 6H), 1.32-1.23 (m, 2H), 1.25 (brs, 3H), 0.91-0.85 (m, 2H).

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-1H-benzo[d]imidazole-5-carboxylate (I-104c)

Prepared following a similar procedure to I-102 starting with I-13f. ES/MS: m/z 504.1 [M+H] + .

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-104d)

Prepared following a similar procedure to I-102 starting with I-13i. ES/MS: m/z 478.2 [M+H] + .

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-105a)

Prepared following a similar procedure to I-102 starting with I-13d. ES/MS: m/z 496.0 [M+H] + .

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-105b)

Prepared following a similar procedure to I-102 starting with I-13e. ES/MS: m/z 522.1 [M+H] + .

isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-indol-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-105c)

Prepared following a similar procedure to I-102 starting with I-13j. ES/MS: m/z 522.1 [M+H] + .

Preparation of isopropyl 2-(6-(2-((tert-butoxycarbonyl)amino)propan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-106)

›Step 1

To a cooled solution of isopropyl (S,E)-2-(6-(1-((tert-butylsulfinyl)imino)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (54 mg, 0.0844 mmol) in toluene (0.4 mL) at −78° C. was added dropwise a solution of AlMe 3 in toluene (2 M, 0.046 mL, 0.092 mmol). After 5 minutes, a solution of methylmagnesium bromide in ether (3 M, 0.062 mL, 0.186 mmol). After 2 hours, the reaction mixture was warmed to 0° C. and then gradually warmed to room temperature overnight. The reaction mixture was quenched with NH 4 Cl (aq) and extracted with ethyl acetate. The combined organics were dried (MgSO 4 ), filtered, and concentrated under reduced pressure to give isopropyl (S)-2-(6-(2-((tert-butylsulfinyl)amino)propan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 655.9 [M+H] + .

›Step 2

Isopropyl 2-(6-(2-((tert-butoxycarbonyl)amino)propan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was made following steps 3-4 for the preparation of 1-102. ES/MS: m/z 522.0 [M+H] + .

Preparation of isopropyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107a)

Note:

Methyl ester analogs of all intermediates I-107 can also be made from any methyl ester intermediates I-141 or I-143.

›Step 1

Isopropyl 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (500 mg, 0.985 mmol) was dissolved in DMF (8 mL). 5-bromopent-1-ene (0.17 mL, 1.6 mmol) was added followed by Cs 2 CO 3 . The reaction mixture was heated to 60° C. After 1 h, the reaction mixture was filtered to remove solids and partitioned between EtOAc and water. The phases were separated, and the organic phase was washed with water and brine, dried over Na 2 SO 4 , filtered, and concentrated to afford isopropyl 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate. ES/MS: m/z 576.3 [M+H] + . *Alternatively, a Mitsunobu reaction can be performed using the corresponding primary alcohol as electrophile (see step 1 of Procedure 27).

›Step 2 · 1 of 2

Isopropyl 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (509 mg, 0.884 mmol) was dissolved in DCM (15 mL). TFA (7.5 mL) was added and the reaction mixture was stirred for 30 min and then concentrated in vacuo to provide isopropyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate as its TFA salt. ES/MS: m/z 475.9 [M+H] + .

isopropyl (R)-2-(1-(2-allylbenzyl)-6-(1-aminoethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107b)

Prepared following a similar procedure to I-107a using 1-allyl-2-(bromomethyl)benzene instead of 5-bromopent-1-ene. ES/MS: m/z 538.1 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107c)

Prepared following a similar procedure to I-107a using I-104a instead of I-102. ES/MS: m/z 475.2 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(but-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107d)

Prepared following a similar procedure to I-107a using 4-bromobut-1-ene instead of 5-bromopent-1-ene. ES/MS: m/z 461.9 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(but-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-107e)

Prepared using a similar procedure to I-107d using I-141b instead of I-102. ES/MS: m/z 448.6 [M+H] + .

isopropyl (R)-2-(1-allyl-6-(1-aminoethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107f)

Prepared following a similar procedure to I-107a using allyl bromide instead of 5-bromopent-1-ene. ES/MS: m/z 447.9 [M+H] + .

ethyl (R)-2-(1-allyl-6-(1-aminoethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (I-107g)

Prepared following a similar procedure to I-107a using I-100 and allyl bromide instead of 5-bromopent-1-ene. ES/MS: m/z 433.8 [M+H] + .

isopropyl 2-(6-((R)-1-((tert-butoxycarbonyl)amino)ethyl)-1-(((1S,2S)-2-vinylcyclopropyl)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107h)

Prepared following a similar procedure to I-107a using I-18 (Mitsunobu reaction, see step 1 of Procedure 27). ES/MS: m/z 488.3 [M+H] + .

isopropyl 2-(6-((R)-1-aminoethyl)-1-(((trans)-2,2-difluoro-3-vinylcyclopropyl)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107i)

Prepared following a similar procedure to I-107a using I-19 (Mitsunobu reaction, see step 1 of Procedure 27). ES/MS: m/z 524.3 [M+H] + .

methyl 2-(6-((R)-1-aminoethyl)-1-(((1S,2S)-2-vinylcyclopropyl)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107j)

Prepared following a similar procedure to I-107a using I-143b and I-18 (Mitsunobu reaction, see step 1 of Procedure 27). ES/MS: m/z 447.9 [M+H] + .

methyl 2-(6-((R)-1-aminoethyl)-1-(((cis)-2,2-difluoro-3-vinylcyclopropyl)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107k)

Prepared following a similar procedure to I-107a using I-143b and I-17 (Mitsunobu reaction, see step 1 of Procedure 27). ES/MS: m/z 584.2 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107l)

Prepared following a similar procedure to I-107a using I-143b. ES/MS: m/z 436.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-107m)

Prepared following a similar procedure to I-107a using I-141b. ES/MS: m/z 462.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(but-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-(2-methoxyethyl)-1H-benzo[d]imidazole-5-carboxylate (I-107n)

Prepared following a similar procedure to I-107a using I-143e. ES/MS: m/z 466.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-107o)

Prepared following a similar procedure to I-107a using I-141c. ES/MS: m/z 462.0 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl-1,1-d2)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-107p)

Prepared following a similar procedure to I-107a using I-141c and 1,1-dideuteriopent-4-en-1-ol (Mitsunobu reaction, see step 1 of Procedure 27). ES/MS: m/z 464.3 [M+H] + .

methyl (R)-2-(1-allyl-6-(1-aminoethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107q)

Prepared following a similar procedure to I-1071 using allyl bromide. ES/MS: m/z 408.2 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(but-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107r)

Prepared following a similar procedure to I-1071 using 4-bromobut-1-ene. ES/MS: m/z 422.2 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(but-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropyl-6-fluoroimidazo[1,2-a]pyridine-7-carboxylate (I-107s)

Prepared following a similar procedure to I-107a using I-136c. ES/MS: m/z 448.3 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (I-107t)

Prepared following a similar procedure to I-107a using I-100. ES/MS: m/z 476.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-107u)

Prepared following a similar procedure to I-107a using I-101b. ES/MS: m/z 474.3 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(but-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-1H-benzo[d]imidazole-5-carboxylate (I-107v)

Prepared following a similar procedure to I-107d using I-104c. ES/MS: m/z 458.3 [M+H] + .

›Step 2 · 2 of 2

methyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107w)

Prepared following a similar procedure to I-107a using I-143j. ES/MS: m/z 436.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(but-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-107x)

Prepared following a similar procedure to I-107a using I-141i. ES/MS: m/z 460.3 [M+H] + .

methyl 2-(6-((R)-1-aminoethyl)-1-(((1S,2S)-2-vinylcyclopropyl)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-107y)

Prepared following a similar procedure to I-107a using I-143i and I-18 (Mitsunobu reaction, see step 1 of Procedure 27). ES/MS: m/z 486.3 [M+H] + .

methyl (R)-2-(1-allyl-6-(1-aminoethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107z)

Prepared following a similar procedure to I-1071 using allyl bromide. ES/MS: m/z 408.2 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropyl-5-methoxyimidazo[1,2-a]pyridine-7-carboxylate (I-107aa)

Prepared following a similar procedure to I-107a using I-141i. ES/MS: m/z 474.3 [M+H] + .

methyl 2-(6-(2-aminopropan-2-yl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107bb)

Prepared following a similar procedure to I-107a using I-141k. ES/MS: m/z 461.9 [M+H] + .

methyl 2-(6-((R)-1-aminoethyl)-1-(((1S,2S)-2-vinylcyclopropyl)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-107cc)

Prepared following a similar procedure to I-107a using I-141c and I-18 (Mitsunobu reaction, see step 1 of Procedure 27). ES/MS: m/z 474.3 [M+H] + .

Preparation of methyl 2-(1-(6-((tert-butoxycarbonyl)amino)hexyl)-6-(2-(tert-butoxycarbonyl)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-108)

›Step 1

To a mixture of methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-8a, 250 mg, 0.60 mmol), tert-butyl N-(6-bromohexyl)carbamate (202 mg, 0.72 mmol), and cesium carbonate (588 mg, 1.8 mmol) was added 2.5 mL of DMF. The reaction mixture was stirred at ambient temperature overnight, then heated to 60° C. for 1 h. After cooling to ambient temperature, the mixture was poured into EtOAc and washed with water, then brine. The organic phase was concentrated, adsorbed to isolute, and purified by silica gel chromatography (eluent: EtOAc/hexane) to provide methyl 2-(6-bromo-1-(6-((tert-butoxycarbonyl)amino)hexyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 614.2 [M+H] + .

›Step 2

To a solution of methyl 2-(6-bromo-1-(6-((tert-butoxycarbonyl)amino)hexyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (174 mg, 0.28 mmol) in dioxane (2 mL) was added tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate (173 mg, 0.57 mmol), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloromethane (23 mg, 0.03 mmol), and aqueous sodium carbonate (0.28 mL of 2 M solution, 0.57 mmol). N 2 was bubbled through the mixture, and the reaction heated to 100° C. for 2 h. After removing from heat, the reaction was filtered through a celite pad and adsorbed to isolute. Purification by silica gel chromatography (eluent: 3:1 EtOAc/EtOH with 0.25% triethylamine in heptane) provided methyl 2-(1-(6-((tert-butoxycarbonyl)amino)hexyl)-6-(2-(tert-butoxycarbonyl)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 713.4 [M+H] + .

methyl 2-(1-(6-((tert-butoxycarbonyl)amino)hexyl)-6-(2-(tert-butoxycarbonyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-109)

Prepared following a similar procedure to I-108 using tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate instead of tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate. ES/MS: m/z 712.4 [M+H] + .

methyl 2-(1-(6-((tert-butoxycarbonyl)amino)hexyl)-6-(2-(tert-butoxycarbonyl)phenyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-110a)

Prepared following a similar procedure to I-108 using I-8b instead of I-8a, and tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate instead of tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate. ES/MS: m/z 711.4 [M+H] + .

methyl 2-(6-(2-(tert-butoxycarbonyl)phenyl)-1-(3-(1-(tert-butoxycarbonyl)piperidin-4-yl)propyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-110b)

Prepared following a similar procedure to I-110a using tert-butyl 4-(3-bromopropyl)piperidine-1-carboxylate instead of tert-butyl N-(6-bromohexyl)carbamate. ES/MS: m/z 737.4 [M+H] + .

methyl 2-(1-(6-((tert-butoxycarbonyl)amino)hexyl)-6-(2-(tert-butoxycarbonyl)pyridin-3-yl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-111)

Prepared following a similar procedure to I-108 using I-8b instead of I-8a. ES/MS: m/z 712.4 [M+H] + .

methyl 2-(6-(2-(tert-butoxycarbonyl)-6-methylphenyl)-1-(6-((tert-butoxycarbonyl)amino)hexyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-112)

Prepared following a similar procedure to I-108 using tert-butyl 3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (synthesized in one chemical step starting from tert-butyl 2-iodo-3-methylbenzoate) instead of tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate. ES/MS: m/z 726.4 [M+H] + .

methyl 2-(6-(3-(tert-butoxycarbonyl)-2-fluoropyridin-4-yl)-1-(6-((tert-butoxycarbonyl)amino)hexyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-113)

Prepared following a similar procedure to I-108 using tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinate (synthesized in two chemical steps starting from 2-fluoro-4-iodonicotinic acid) instead of tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate. ES/MS: m/z 731.3 [M+H] + .

Preparation of methyl 2-(1-(7-(tert-butoxy)-7-oxoheptyl)-6-(2-((tert-butoxycarbonyl)amino)pyridin-3-yl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-114)

›Step 1

Followed step 1 of I-108 using I-8b (500 mg, 1.2 mmol) and tert-butyl 7-bromoheptanoate (384 mg, 1.45 mmol) and heating to 60° C. for 2 hours. Purification by silica gel column chromatography provided methyl 2-(6-bromo-1-(7-(tert-butoxy)-7-oxoheptyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 598.2 [M+H] + .

›Step 2

Followed step 2 of I-108 using methyl 2-(6-bromo-1-(7-(tert-butoxy)-7-oxoheptyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (120 mg, 0.20 mmol) and tert-butyl N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (84 mg, 0.26 mmol) and stirring at 100° C. for 1.5 hours. The reaction was poured into EtOAc and washed with water, aq. NaHCO 3 , then brine. The organic phase was dried over MgSO 4 , filtered, and concentrated, which was used in the next step (Procedure 15) without purification. ES/MS: m/z 712.3 [M+H] + . Note: Methyl 2-(6-(2-aminopyridin-3-yl)-1-(7-(tert-butoxy)-7-oxoheptyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (ES/MS: m/z 612.3 [M+H] + ) was also observed in the crude mixture.

methyl 2-(1-(7-(tert-butoxy)-7-oxoheptyl)-6-(2-((tert-butoxycarbonyl)amino)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-115)

Prepared following a similar procedure to I-114 using I-8a instead of I-8b. ES/MS: m/z 613.1 [(M-Boc)+H] + .

methyl 2-(1-(7-(tert-butoxy)-7-oxoheptyl)-6-(2-((tert-butoxycarbonyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-116)

Prepared following a similar procedure to I-115 using tert-butyl (2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate instead of tert-butyl N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate. ES/MS: m/z 712.4 [M+H] + .

methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(2-((tert-butoxycarbonyl)amino)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-117)

Prepared following a similar procedure to I-115 using tert-butyl 8-bromooctanoate instead of tert-butyl 7-bromoheptanoate. ES/MS: m/z 627.3 [(M-Boc)+H] + .

methyl 2-(1-(7-(tert-butoxy)-7-oxoheptyl)-6-(4-((tert-butoxycarbonyl)amino)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-118)

Prepared following a similar procedure to I-115 using tert-butyl (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-4-yl)carbamate instead of tert-butyl N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate. ES/MS: m/z 713.4 [M+H] + .

methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(2-((tert-butoxycarbonyl)amino)phenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-119)

Prepared following a similar procedure to I-116 using tert-butyl 8-bromooctanoate instead of tert-butyl 7-bromoheptanoate. ES/MS: m/z 726.4 [M+H] + .

methyl 2-(1-(7-(tert-butoxy)-7-oxoheptyl)-6-(2-((tert-butoxycarbonyl)amino)phenyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-120)

Prepared following a similar procedure to I-114 using tert-butyl (2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate instead of tert-butyl N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate. ES/MS: m/z 711.4 [M+H] + .

methyl 2-(1-(7-(tert-butoxy)-7-oxoheptyl)-6-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-121)

methyl 2-(1-(8-(tert-butoxy)-7,7-dimethyl-8-oxooctyl)-6-(2-((tert-butoxycarbonyl)amino)pyridin-3-yl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-122)

Prepared following a similar procedure to I-114 using tert-butyl 8-bromo-2,2-dimethyloctanoate (L4a) instead of tert-butyl 7-bromoheptanoate. ES/MS: m/z 654.1 [(M-Boc)+H] + .

methyl 2-(1-(8-(tert-butoxy)-7,7-dimethyl-8-oxooctyl)-6-(2-((tert-butoxycarbonyl)amino)phenyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-123)

Prepared following a similar procedure to I-120 using tert-butyl 8-bromo-2,2-dimethyloctanoate (L4a) instead of tert-butyl 7-bromoheptanoate. ES/MS: m/z 753.4 [M+H] + .

methyl 2-(1-(6-(tert-butoxy)-6-oxohexyl)-6-(2-((tert-butoxycarbonyl)amino)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-124)

Prepared following a similar procedure to I-115 using tert-butyl 6-bromohexanoate instead of tert-butyl 7-bromoheptanoate. ES/MS: m/z 599.3 [(M-Boc)+H] + .

Preparation of methyl 2-(6-bromo-1-(7-((3-bromopyridin-2-yl)oxy)heptyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-125)

›Step 1

Followed step 1 of I-108 using 3-bromo-2-(7-bromoheptoxy)pyridine (L24a, 122 mg, 0.35 mmol). Purification by silica gel column chromatography provided methyl 2-(6-bromo-1-(7-(tert-butoxy)-7-oxoheptyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylat. ES/MS: m/z 686.1[M+H] + .

methyl 2-(6-bromo-1-(6-((3-bromopyridin-2-yl)oxy)hexyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-126)

Prepared following a similar procedure to I-125 using L24b instead of L24a. ES/MS: m/z 672.1 [M+H] + .

methyl 2-(6-bromo-1-(8-((3-bromopyridin-2-yl)oxy)octyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-127)

Prepared following a similar procedure to I-125 using L24c instead of L24a. ES/MS: m/z 700.1 [M+H] + .

Preparation of methyl 2-[1-[6-[bis(tert-butoxycarbonyl)amino]hexyl]-6-bromo-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (I-128)

›Step 1

Methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (102 mg, 0.247 mmol) and di(tert-butyl) 6-bromohexylcarbonate (140 mg, 0.37 mmol) were charged in a vial and dissolved in DMF (1 mL) and Cs 2 CO 3 (241 mg, 0.74 mmol) was added. The vial was sealed and the mixture was heated to 60° C. overnight. The mixture was cooled down to room temperature and was worked up with EtOAc and water. The organic layer was dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by column chromatography over silica gel (Hexanes/EtOAc 0-15%) to afford methyl 2-[1-[6-[bis(tert-butoxycarbonyl)amino]hexyl]-6-bromo-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate.

Preparation of methyl 7-methoxy-1-methyl-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-6-vinyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxylate (I-129)

›Step 1

A mixture of methyl 2-[6-bromo-1-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (1000 mg, 1.83 mmol), potassium vinyltrifluoroborate (614 mg, 4.58 mmol), and dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloromethane (75 mg, 0.0917 mmol) in isopropanol (40 mL) was heated at reflux overnight. After cooling to rt, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-35% ethyl acetate in hexanes) to yield methyl 7-methoxy-1-methyl-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-6-vinyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 492.9 [M+H] + .

Preparation of methyl (E)-2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(((tert-butylsulfinyl)imino)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-130)

›Step 1

Methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-vinyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was made following step 3 of Procedure 20. ES/MS: m/z 561.1 [M+H] + .

›Step 2

Methyl (E)-2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(((tert-butylsulfinyl)imino)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was made following step 4 of Procedure 20. ES/MS: m/z 666.0 [M+H] + .

Preparation of methyl (E)-2-(1-(8-(tert-butoxy)-7,7-dimethyl-8-oxooctyl)-6-(((tert-butylsulfinyl)imino)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-130b)

Prepared following a similar procedure to I-130 using L4a instead of L1a. ES/MS: m/z 694.2 [M+H] + .

Preparation of methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(((tert-butylsulfinyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-131)

›Step 1

To a cooled solution of methyl (E)-2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(((tert-butylsulfinyl)imino)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (60 mg, 0.090 mmol) in methanol (1 mL) at −40° C. was added sodium borohyride (4 mg, 0.106 mmol). After 90 minutes, additional sodium borohyride (4 mg, 0.106 mmol) was added. After warming to rt and stirring overnight, sodium borohyride (4 mg, 0.106 mmol) was added. After one hour, the reaction mixture was diluted with ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics were washed with water, brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure to yield methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(((tert-butylsulfinyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate, which was used without purification. ES/MS: m/z 668.0 [M+H] + .

Preparation of methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(1-((tert-butylsulfinyl)amino)-2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-132)

›Step 1

Trimethyl(trifluoromethyl)silane (0.18 mL, 1.22 mmol) was added to a mixture of methyl 2-[1-(8-tert-butoxy-8-oxo-octyl)-6-[(E)-tert-butylsulfinyliminomethyl]pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (450 mg, 0.68 mmol) and tetrabutylammonium difluorotriphenylsilicate (640 mg, 1.19 mmol) in THF (15 mL) at −45° C. After four hours, additional tetrabutylammonium difluorotriphenylsilicate (1277 mg, 2.37 mmol) and trimethyl(trifluoromethyl)silane (0.35 ml, 2.37 mmol) were added at −45° C. After 2 hours, the reaction mixture was quenched with sat. NH 4 Cl(aq), warmed to rt, and diluted with ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics washed with water, brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (5-100% ethyl acetate in hexanes) to yield methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(1-((tert-butylsulfinyl)amino)-2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 736.0 [M+H] + .

methyl 2-(1-(8-(tert-butoxy)-7,7-dimethyl-8-oxooctyl)-6-(1-((tert-butylsulfinyl)amino)-2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-132b)

Prepared following a similar procedure to I-132 using I-130b instead of I-130. ES/MS: m/z 764.0 [M+H] + .

Preparation of methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(1-((tert-butylsulfinyl)amino)-2,2-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-133)

›Step 1

Difluoromethyltrimethylsilane (0.697 mL, 5.11 mmol) was added to a solution of methyl 2-[1-(8-tert-butoxy-8-oxo-octyl)-6-[(E)-tert-butylsulfinyliminomethyl]pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (425 mg, 0.638 mmol) in THF (12 mL). After 72 hours, the reaction mixture was diluted with water and ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate. The combined organics were dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-100% ethyl acetate/hexanes) to yield methyl 2-(1-(8-(tert-butoxy)-8-oxooctyl)-6-(1-((tert-butylsulfinyl)amino)-2,2-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 718.0 [M+H] + .

Preparation of isopropyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135a)

›Step 1

A solution of 2,2-difluoropent-4-en-1-ol (1.0 g, 8.2 mmol) in DCM (16 mL) was cooled to 0° C. and 2,6-lutidine (1.92 mL, 16.4 mmol) was added followed by trifluoromethanesulfonic anhydride (1.51 mL, 9 mmol). The resulting mixture was stirred for 30 minutes at 0° C. then 30 minutes at room temperature. It was cooled back to 0° C. and quenched with a saturated solution of ammonium chloride. After work up, the organics were carefully evaporated and the residue was purified by column chromatography over silica gel (Pentane/diethyl ether 0-5%) to afford 2,2-difluoropent-4-en-1-yl trifluoromethanesulfonate. Analytical data matches the literature: Kendrick, D. A.; Danzin, C.; Kolb, M. J. Med. Chem. 1989, 32, 170-173.

›Step 2

Isopropyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was prepared following a similar procedure to steps 1-2 of I-107a using 2,2-difluoropent-4-en-1-yl trifluoromethanesulfonate (I-134a) instead of 5-bromopent-1-ene. ES/MS: m/z 511.9 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6,7-difluoro-1H-benzo[d]imidazole-5-carboxylate (I-135b)

Prepared following a similar procedure to I-135a using I-141a instead of I-102 and using 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 502.1 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-135c)

Prepared following a similar procedure to I-135a using I-141b instead of I-102. ES/MS: m/z 497.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135d)

Prepared following a similar procedure to I-135a using I-143b instead of I-102. ES/MS: m/z 472.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-135e)

Prepared following a similar procedure to I-135a using I-141c instead of I-102. ES/MS: m/z 498.0 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-7-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135f)

Prepared following a similar procedure to I-135a using I-146a instead of I-102 and using 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 516.15 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135g)

Prepared following a similar procedure to I-135a using 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 498.43 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-135h)

Prepared following a similar procedure to I-135a using 1-141b and 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 483.90 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1-(2,2-difluorobut-3-en-1-yl)-5-fluoro-1H-indol-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-135i)

Prepared following a similar procedure to I-135a using 1-149b and 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 501.03 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1-(2,2-difluorobut-3-en-1-yl)-5-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135j)

Prepared following a similar procedure to I-135a using 1-149a and 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 487.03 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorohept-6-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135k)

Prepared following a similar procedure to I-135a using 2,2-difluorooct-7-en-1-yl trifluoromethanesulfonate. ES/MS: m/z 540.4 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6,7-difluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135l)

Prepared following a similar procedure to I-135a using I-143i instead of I-102 and using 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 476.2 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135m)

Prepared following a similar procedure to I-135a using I-143b instead of I-102 and using 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 458.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1,6-dimethyl-1H-benzo[d]imidazole-5-carboxylate (I-135n)

Prepared following a similar procedure to I-135a using I-143h instead of I-102 and using 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol. ES/MS: m/z 454.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-135o)

Prepared following a similar procedure to I-135a using 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol and I-141c. ES/MS: m/z 484.2 [M+H] + .

isopropyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-1H-benzo[d]imidazole-5-carboxylate (I-135p)

Prepared following a similar procedure to I-135b starting with I-104c. ES/MS: m/z 494.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-135q)

Prepared following a similar procedure to I-135a using 2,2-difluorobut-3-en-1-ol instead of 2,2-difluoropent-4-en-1-ol and I-141j. ES/MS: m/z 458.2 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluorobut-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-135r)

Prepared following a similar procedure to I-141a using I-141i. ES/MS: m/z 496.3 [M+H] + .

methyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-135s)

Prepared following a similar procedure to I-141a using I-141i. ES/MS: m/z 510.3 [M+H] + .

Preparation of tert-butyl (R)-(1-(2-(6-cyano-3-ethylpyrazolo[1,5-a]pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-136a)

›Step 1

A mixture of 6-cyano-3-ethylpyrazolo[1,5-a]pyridin-2-yl trifluoromethanesulfonate (I-14, 85 mg, 0.266 mmol), tert-butyl (R)-(1-(2-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocane-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-16, 221 mg, 0.532 mmol), bis(triphenylphosphine) palladium (II) dichloride 23.1 mg, 0.032 mmol), and sodium carbonate (227 mg, 2.16 mmol) in dioxane (3.9 mL) and water (0.75 mL) was heated at 100° C. under argon. After 2.5 h, the reaction mixture was cooled to rt and diluted with ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics washed with water, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-55% ethyl acetate/hexanes) to yield tert-butyl (R)-(1-(2-(6-cyano-3-ethylpyrazolo[1,5-a]pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate. ES/MS: m/z 431.4 [M+H] + .

tert-butyl (R)-(1-(2-(6-cyano-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-136b)

Prepared following a similar procedure to I-136a using I-15 instead of I-14. ES/MS: m/z 447.2 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-cyclopropyl-6-fluoroimidazo[1,2-a]pyridine-7-carboxylate (I-136c)

Prepared following a similar procedure to I-136a using I-5c instead of I-14. ES/MS: m/z 494.3 [M+H] + .

Preparation of (6-(benzyloxy)-1-(tert-butoxycarbonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic Acid (I-137)

›Step 1

To a solution of 1H-pyrrolo[2,3-b]pyridine (150 g, 1.27 mol) in ethyl acetate (1500 mL) at 0° C. was added a solution of 85% m-CPBA (335 g, 1.65 mol) in ethyl acetate (1500 mL) over 1.5 h. The resulting solution was stirred at room temperature for 4 h. After cooling to 0° C. the resulting slurry was filtered and the solid was washed with ethyl acetate (3×50 mL). The solid was added to 30% potassium carbonate solution (200 mL) and this mixture was stirred for 2 h at 0° C. The solid was collected by filtration, washed with water (2×30 mL) and dried in vacuo to give crude 1H-pyrrolo[2,3-b]pyridine 7-oxide.

›Step 2

Crude 1H-pyrrolo[2,3-b]pyridine 7-oxide (150 g, 670.9 mmol, ca. 60% purity) in acetic anhydride (450 mL) was heated to reflux for 12 h. The mixture was cooled, concentrated to half of its volume, diluted with DCM (500 mL), washed with water (2×100 mL), dried over anhydrous sodium sulfate and concentrated to give crude 1-acetyl-1H-pyrrolo[2,3-b]pyridin-6-yl acetate.

›Step 3

A mixture of crude 1-acetyl-1H-pyrrolo[2,3-b]pyridin-6-yl acetate (150 g, 412 mmol, 60% purity) and potassium carbonate (250 g, 1810 mmol) in methanol/water (1:1, 2600 mL) was stirred at room temperature for 12 h. The reaction mixture was concentrated to half its volume and extracted with chloroform (6×300 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (MeOH/DCM=1:10) to give 1H-pyrrolo[2,3-b]pyridin-6-ol. 1 H NMR (400 MHz, DMSO) δ 11.09 (s, 1H), 10.37 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.18-6.89 (m, 1H), 6.41-6.18 (m, 2H).

›Step 4

A mixture of 1H-pyrrolo[2,3-b]pyridin-6-ol (60 g, 447 mmol), potassium carbonate (250 g, 1809 mmol) and benzyl bromide (76 g, 447 mmol) in acetone (1500 mL) was stirred at 50° C. for 16 h. The reaction mixture was cooled and filtered through Celite. The filtrate was concentrated and the crude product was purified by column chromatography on silica gel (3:1 petroleum ether:ethyl acetate) to give 6-(benzyloxy)-1H-pyrrolo[2,3-b]pyridine. 1 H NMR: (400 MHz, DMSO) δ 11.43 (s, 1H), 7.85 (d, J=8.2 Hz, 0H), 7.45 (d, J=7.3 Hz, 1H), 7.39-7.26 (m, 1H), 7.17 (s, 1H), 6.56 (d, J=8.4 Hz, 1H), 6.33 (s, 1H), 5.34 (s, 2H).

›Step 5

A mixture of 6-(benzyloxy)-1H-pyrrolo[2,3-b]pyridine (70 g, 310 mmol), triethylamine (34.7 g, 343 mmol), DMAP (2.29 g, 18.7 mmol), and di-tert-butyl dicarbonate (74.85 g, 343 mmol) in DCM (1000 mL) was stirred at rt for 2h. The reaction mixture was concentrated and the crude product was purified by column chromatography on silica gel (3:1 petroleum ether:ethyl acetate) to give tert-butyl 6-(benzyloxy)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate. 1 H NMR: 1 H NMR (400 MHz, DMSO) δ 7.90 (t, J=22.5 Hz, 1H), 7.61-7.44 (m, 3H), 7.42-7.20 (m, 3H), 6.75 (d, J=8.4 Hz, 1H), 6.57 (dd, J=21.0, 19.9 Hz, 1H), 5.38 (d, J=37.9 Hz, 2H), 1.60 (s, 9H).

›Step 6

To a solution of tert-butyl 6-(benzyloxy)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (60 g, 185 mmol) and triisopropyl borate (76.5 g, 407 mmol) in THF (600 mL) under N 2 at −78° C. was added LDA (2 M in THF, 123 mL) dropwise. The reaction was stirred at this temperature for 5 h. The reaction mixture was quenched with 600 mL of 1 M pH ˜7 phosphate buffer. The mixture was diluted with EtOAc, and the phases were separated. The organic phase was washed with water and brine, dried over Na 2 SO 4 , filtered and concentrated. The crude product was purified by column chromatography on silica gel (1:1 petroleum ether:ethyl acetate) to give tert-butyl 6-(benzyloxy)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate. ES/MS: m/z 368.9 [M+H] + . 1 H NMR: (400 MHz, DMSO) δ 8.13 (s, 1H), 7.88 (d, J=8.4 Hz, 0H), 7.50 (d, J=7.2 Hz, 1H), 7.34 (d, J=7.4 Hz, 2H), 6.71 (d, J=8.4 Hz, 1H), 6.57 (s, 1H), 5.43 (s, 2H), 1.58 (s, 5H).

Preparation of methyl 2-(6-(benzyloxy)-1-(tert-butoxycarbonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate (I-138)

›Step 1

A solution of methyl 5-methoxy-3-methyl-2-(trifluoromethylsulfonyloxy)imidazo[1,2-a]pyridine-7-carboxylate (I-1, 0.5 g, 1.36 mmol) and (6-benzyloxy-1-tert-butoxycarbonyl-pyrrolo[2,3-b]pyridin-2-yl)boronic acid (I-137, 0.65 g, 1.76 mmol), cesium carbonate (1.11 g, 3.39 mmol), and Jackiephos (0.05 g, 0.04 mmol) in MeTHF (5 mL) and water (0.5 mL) was purged with argon. The mixture was stirred at ambient temperature for 18 h. The aqueous layer was removed and the organic layer washed with water, dried with Na 2 SO 4 , filtered, and concentrated. The product was purified by silica chromatography using EtOAc in hexanes to afford methyl 2-(6-(benzyloxy)-1-(tert-butoxycarbonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-5-methoxy-3-methylimidazo[1,2-a]pyridine-7-carboxylate. ES/MS: m/z 543.2 [M+H] + .

Preparation of tert-butyl (R)-(1-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-139)

›Step 1

A solution of s-BuLi in cyclohexane (1.4 M, 24.9 mL, 34.9 mmol) was added dropwise to cooled solution of tert-butyl N-[(1R)-1-[1-(benzenesulfonyl)pyrrolo[2,3-b]pyridin-6-yl]ethyl]carbamate (intermediate described in the synthesis of I-16) (4.0 g, 10.0 mmol) in THF (100 mL) at −78° C. After 2 h, N,N-dimethylformamide (5.3 mL, 7.1 mmol) was added dropwise. The reaction mixture was stirred at −78° C. After two hours, the reaction mixture was quenched with aqueous ammonium chloride and extracted with ethyl acetate. The combined organics were washed with water, brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-35% ethyl acetate/hexanes) to yield tert-butyl (R)-(1-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate. 1 H NMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 9.85 (s, 1H), 8.17 (d, J=8.3 Hz, 1H), 7.40 (d, J=8.3 Hz, 1H), 7.37 (s, 1H), 7.21 (d, J=8.3 Hz, 1H), 4.83-4.61 (m, 1H), 1.38 (d, J=4.8 Hz, 3H), 1.37 (s, 9H).

Preparation of methyl 5-amino-4-(cyclopropylamino)-2,3-difluorobenzoate (I-140a)

›Step 1

A 100 mL round bottom flask was charged with methyl 2,3,4-trifluoro-5-nitrobenzoate (1.18 g, 5 mmol) a stir bar and THF (20 mL). The solution was cooled to −78° C. and Hunig's base (1.3 mL, 7.5 mmol) was added followed by dropwise addition of cyclopropylamine (346 μL, 5 mmol). The remaining mixture was stirred at −78° C. (acetone dry ice bath) for 30 minutes then at −46° C. (acetonitrile dry ice bath) for 1 h. It was then slowly warmed up to 0° C. over 1 h and quenched with water. After usual work up (EtOAc, water) the residue was purified by flash chromatography over silica gel (Hexanes/EtOAc 0-10%) to afford methyl 4-(cyclopropylamino)-2,3-difluoro-5-nitrobenzoate. ES/MS: m/z 270.8 [M+H] + .

›Step 2 · 1 of 2

Methyl 4-(cyclopropylamino)-2,3-difluoro-5-nitrobenzoate (272 mg, 1 mmol) was charged in a vial and (1% Pt)/(2% V) on carbon (Strem Chemical 78-1536) (55 mg) was added followed by ethyl acetate (3 mL). The mixture was degassed with nitrogen for 5 minutes and then placed under an atmosphere of hydrogen for 12 hours at which point the LCMS analysis showed full conversion of the starting material. Filtration and evaporation yielded the crude methyl 5-amino-4-(cyclopropylamino)-2,3-difluorobenzoate which was used in the next step without further purification. ES/MS: m/z 243.1 [M+H] + .

methyl 5-amino-4-(cyclopropylamino)-2-fluorobenzoate (I-140b)

Prepared following a similar procedure to I-140a using methyl 2,4-difluoro-5-nitrobenzoate. ES/MS: m/z 225.1 [M+H] + .

methyl 3-amino-4-(cyclopropylamino)-5-fluorobenzoate (I-140c)

Intermediate I-140c (ES/MS: m/z 225.05 [M+H] + ) prepared following a similar procedure to I-140a starting with methyl 3,4-difluoro-5-nitrobenzoate prepared as described here: 3,4-difluoro-5-nitro-benzoic acid (8.26 g, 40.7 mmol) was dissolved in DCM under N 2 . Oxalyl chloride (3.7 mL, 43.1 mmol) was added over 2 min. After 3 h, the mixture was cooled to −20° C., and methanol (2.1 mL) was added slowly followed by Et 3 N (11.3 mL, 81.3 mmol). The mixture was stirred 15 min and was then allowed to warm to r.t. After an additional 90 min, the mixture was partitioned between DCM and water. Phases were separated, and the organic phase was dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel (5-15% EtOAc in hexanes) provided methyl 3,4-difluoro-5-nitro-benzoate.

methyl 3-amino-5-fluoro-4-(((1R,2R)-2-fluorocyclopropyl)amino)benzoate (I-140d)

Prepared following a similar procedure to I-140c using (1R,2R)-2-fluorocyclopropane-1-amine. ES/MS: m/z 242.96 [M+H] + .

methyl 3-amino-5-fluoro-4-(((1S,2S)-2-fluorocyclopropyl)amino)benzoate (I-140e)

Prepared following a similar procedure to I-140c using (1S,2S)-2-fluorocyclopropane-1-amine. ES/MS: m/z 242.96 [M+H] + .

methyl 3-amino-5-fluoro-4-(((1R,2S)-2-fluorocyclopropyl)amino)benzoate (I-140f)

Prepared following a similar procedure to I-140c using (1R,2S)-2-fluorocyclopropane-1-amine. ES/MS: m/z 242.96 [M+H] + .

methyl (rac)-3-amino-4-(((1S,2S)-2-(difluoromethyl)cyclopropyl)amino)-5-fluorobenzoate (I-140g)

Prepared following a similar procedure to I-140c using trans-2-(difluoromethyl)cyclopropane-1-amine. ES/MS: m/z 274.98 [M+H] + .

methyl 5-amino-6-(cyclopropylamino)nicotinate (I-140h)

Prepared following a similar procedure to I-140a using methyl 6-fluoro-5-nitro-pyridine-3-carboxylate. ES/MS: m/z 208.05 [M+H] + .

methyl 3-amino-5-fluoro-4-(((1S,2R)-2-fluorocyclopropyl)amino)benzoate (I-140i)

Prepared following a similar procedure to I-140c using (1S,2R)-2-fluorocyclopropane-1-amine. ES/MS: m/z 242.96 [M+H] + .

methyl 3-amino-5-fluoro-4-(methylamino)benzoate (I-140j)

Prepared following a similar procedure to I-140c using methylamine instead of cyclopropylamine. ES/MS: m/z 199.0 [M+H] + .

methyl 3-amino-5-chloro-4-(cyclopropylamino)benzoate (I-140k)

Prepared following a similar procedure to I-140a using methyl 3-chloro-4-fluoro-5-nitrobenzoate. ES/MS: m/z 241.1 [M+H] + .

methyl 3-amino-5-fluoro-4-(((1S,2S)-2-methoxycyclopropyl)amino)benzoate (I-140l)

Prepared following a similar procedure to I-140c using (1S,2S)-2-methoxycyclopropane-1-amine instead of cyclopropylamine. ES/MS: m/z 254.7 [M+H] + .

methyl 5-amino-2-fluoro-4-(((1R,2S)-2-fluorocyclopropyl)amino)benzoate (I-140m)

Prepared following a similar procedure to I-140f using methyl 2,4-difluoro-5-nitrobenzoate and (1R,2S)-2-fluorocyclopropane-1-amine. ES/MS: m/z 243.1 [M+H] + .

methyl 5-amino-2-fluoro-4-(((1R,2S)-2-fluorocyclopropyl)amino)benzoate (I-140n)

Prepared following a similar procedure to I-140f using methyl 2,4-difluoro-5-nitrobenzoate and 2-methoxycyclopropanamine hydrochloride. ES/MS: m/z 254.8 [M+H] + .

methyl 5-amino-2-chloro-4-(methylamino)benzoate (I-140o)

Prepared following a similar procedure to I-140j using methyl 2-chloro-4-fluoro-5-nitrobenzoate. ES/MS: m/z 215.0 [M+H] + .

methyl 3-amino-5-methoxy-4-((2-methoxyethyl)amino)benzoate (I-140p)

Prepared following a similar procedure to I-140a using I-7k. ES/MS: m/z 255.0 [M+H] + .

methyl 3-amino-5-methoxy-4-(methylamino)benzoate (I-140q)

Prepared following a similar procedure to I-140a using I-7a. ES/MS: m/z 211.04 [M+H] + .

methyl 3-amino-4-(cyclopropylamino)-5-methoxybenzoate (I-140r)

Prepared following a similar procedure to I-140a using I-7b. ES/MS: m/z 237.2 [M+H] + .

methyl 5-amino-2-fluoro-4-(((1S,2R)-2-fluorocyclopropyl)amino)benzoate (I-140s)

Prepared following a similar procedure to I-140a using methyl 2,4-difluoro-5-nitrobenzoate and (1S,2R)-2-fluorocyclopropanamine. ES/MS: m/z 243.1 [M+H] + .

methyl 3-amino-5-fluoro-4-[[(1S,2S)-2-fluorocyclopropyl]amino]benzoate (I-140t)

Prepared following a similar procedure to I-140a using methyl 3,4-difluoro-5-nitro-benzoate and (1S,2S)-2-fluorocyclopropanamine. ES/MS: m/z 243.0 [M+H] + .

methyl 3-amino-5-fluoro-4-[[(1R,2R)-2-fluorocyclopropyl]amino]benzoate (I-140u)

Prepared following a similar procedure to I-140a using methyl 3,4-difluoro-5-nitro-benzoate and (1R,2R)-2-fluorocyclopropanamine. ES/MS: m/z 243.0 [M+H] + .

methyl 3-amino-5-fluoro-4-(((1S,2R)-2-fluorocyclopropyl)amino)benzoate (I-140v)

Prepared following a similar procedure to I-140a using methyl 3,4-difluoro-5-nitro-benzoate and (1S,2R)-2-fluorocyclopropanamine. ES/MS: m/z 243.0 [M+H] + .

methyl 3-amino-4-(cyclopropylamino)-2-fluorobenzoate (I-140w)

Prepared following a similar procedure to I-140a using methyl 2,4-difluoro-3-nitrobenzoate. ES/MS: m/z 225.0 [M+H] + .

methyl 3-amino-4-(((1S,2R)-2-(difluoromethyl)cyclopropyl)amino)-5-fluorobenzoate (I-140x)

Prepared following a similar procedure to I-140c using cis-2-(difluoromethyl)cyclopropane-1-amine. ES/MS: m/z 274.98 [M+H] + .

methyl 3-amino-4-(cyclopropylamino)-5-(difluoromethoxy)benzoate (I-140y)

Prepared following a similar procedure to I-140a using I-27b. ES/MS: m/z 273.9 [M+H] + .

›Step 2 · 2 of 2

methyl 3-amino-5-(difluoromethoxy)-4-(methylamino)benzoate (I-140z)

Prepared following a similar procedure to I-140a using I-27a. ES/MS: m/z 246.9 [M+H] + .

methyl 5-amino-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carboxylate (I-140aa)

Prepared following a similar procedure to I-140a using I-32. ES/MS: m/z 209.1 [M+H] + .

methyl 3-amino-4-(ethylamino)-5-fluorobenzoate (I-140dd)

Prepared following a similar procedure to I-140a using methyl 3,4-difluoro-5-nitro-benzoate and ethylamine. ES/MS: m/z 213.98 [M+H] + .

methyl 3-amino-4-((2,2-difluoroethyl)amino)-5-fluorobenzoate (I-140ee)

Prepared following a similar procedure to I-140a using methyl 2,4-difluoro-5-nitrobenzoate and 2,2-difluoroethane-1-amine. ES/MS: m/z 250.0 [M+H] + .

methyl 3-amino-4-((cyclopropylmethyl)amino)-5-fluorobenzoate (I-140ff)

Prepared following a similar procedure to I-140a using methyl 2,4-difluoro-5-nitrobenzoate and cyclopropylmethanamine. ES/MS: m/z 239.9 [M+H] + .

methyl 3-amino-4-(cyclopropylamino)benzoate (I-140gg)

Prepared following a similar procedure to I-140a using methyl 4-fluoro-3-nitrobenzoate and cyclopropylamine. ES/MS: m/z 208.0 [M+H] + .

Preparation of methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6,7-difluoro-1H-benzo[d]imidazole-5-carboxylate (I-141a)

›Step 1

Methyl 5-amino-4-(cyclopropylamino)-2,3-difluorobenzoate (190 mg, 0.78 mmol) and tert-butyl (R)-(1-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (227 mg, 0.78 mmol) were charged in a vial equipped with a stir bar and acetic acid was added (5 mL). The resulting mixture was stirred at 50° C. for 12 h. The acetic acid was removed under vacuo and the residue was purified by flash chromatography over silica gel (10-100% EtOAc in DCM) to afford methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6,7-difluoro-1H-benzo[d]imidazole-5-carboxylate. ES/MS: 511.9 (M+H)+. 1 H NMR (400 MHz, DMSO-d6) δ 12.41 (brs, 1H), 8.08 (d, J=8.2 Hz, 1H), 7.98-7.95 (m, 1H), 7.38 (d, J=7.9 Hz, 1H), 7.34 (d, J=2.1 Hz, 1H), 7.19 (d, J=8.2 Hz, 1H), 4.85-4.66 (m, 1H), 4.06-4.00 (m, 1H), 3.91 (s, 3H), 1.42 (s, 3H), 1.40 (s, 9H), 1.31-1.25 (m, 2H), 1.04-0.96 (m, 2H).

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-141b)

Prepared following a similar procedure to I-141a using I-140b instead of I-140a. ES/MS: m/z 461.9 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-141c)

Prepared following a similar procedure to I-141a using methyl 3-amino-4-(cyclopropylamino)-5-fluorobenzoate (I-140c) and I-139. ES/MS: m/z 493.94 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-141d)

Prepared following a similar procedure to I-141a using I-140j and I-139. ES/MS: m/z 467.96 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-chloro-1-cyclopropyl-1H-benzo[d]imidazole-5-carboxylate (I-141e)

Prepared following a similar procedure to I-141a using I-140k and I-139. ES/MS: m/z 509.84 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-indol-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-141f)

Prepared following a similar procedure to I-141a using methyl 3-amino-4-(cyclopropylamino)-5-fluorobenzoate (I-140c) and I-148a. ES/MS: m/z 493.03 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 11.98 (s, 1H), 8.07 (d, J=2.8 Hz, 1H), 7.66-7.60 (m, 2H), 7.50-7.35 (m, 3H), 7.07 (d, J=8.6 Hz, 1H), 4.83-4.66 (m, 1H), 3.33 (s, 3H), 3.07-2.95 (m, 1H), 1.43-1.34 (m, 12H), 1.29-0.99 (in, 4H).

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-indol-2-yl)-cyclopropyl-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-141f)

Prepared following a similar procedure to I-141a using I-23i and I-148a. ES/MS: m/z 479.0 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-chloro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-141h)

Prepared following a similar procedure to I-141a using I-140o. ES/MS: m/z 484.3 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole-5-carboxylate (I-141i)

Prepared following a similar procedure to I-141a using I-140r. ES/MS: m/z 506.3 [M+H] + .

methyl 2-(6-((R)-1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-fluoro-1-((1R,2R)-2-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxylate (I-141j)

Prepared following a similar procedure to I-141a using I-140u. ES/MS: m/z 512.77 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 8.16-8.08 (m, 3H), 7.69 (d, J=11.9 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.34 (d, J=2.0 Hz, 1H), 7.20 (d, J=8.2 Hz, 1H), 5.28-4.98 (m, 1H), 4.87 (t, J=7.4 Hz, 1H), 4.63-4.54 (m, 1H), 3.91 (s, 3H), 2.06-1.91 (m, 1H), 1.42 (brs, 3H), 1.39 (s, 9H).

methyl 2-(6-(2-((tert-butoxycarbonyl)amino)propan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-141k)

Prepared following a similar procedure to I-141a using tert-butyl (2-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-yl)carbamate (I-34) and I-140q. ES/MS: m/z 494.3 [M+H] + .

Preparation of (2R,5R,7R,9E)-2-methyl-4-oxo-3,13,19-triazatetracyclo[11.5.2.05,7.016,20]icosa-1(19),9,14,16(20),17-pentaene-14-carbaldehyde (I-142a)

›Step 1

A mixture of tert-butyl N-[(1R)-1-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl]carbamate (3 g, 10.4 mmol), 4-bromobut-1-ene (1.5 mL, 14.5 mmol), and cesium carbonate (10.1 g, 31.1 mmol) in N,N-dimethylformamide (55.0 mL) was heated at 60° C. for 45 minutes. The reaction was cooled to room temperature. The mixture was quenched with saturated ammonium chloride solution and diluted with brine and 5% lithium chloride solution. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over magnesium sulfate. Filtration and evaporation of solvents yielded the crude product, which was purified by silica gel chromatography (0 to 20% EtOAc/hexanes) to afford tert-butyl (R)-(1-(1-(but-3-en-1-yl)-2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate. ES/MS: m/z 343.8 [M+H] + .

›Step 2

A mixture of tert-butyl N-[(1R)-1-(1-but-3-enyl-2-formyl-pyrrolo[2,3-b]pyridin-6-yl)ethyl]carbamate (3.3 g, 9.6 mmol), and trifluoroacetic acid (4.0 mL, 331 mmol) in dichloromethane (50 mL) was stirred at room temperature for 4 h. The solvents were evaporated and the crude intermediate was dissolved in N,N-dimethylformamide (50 mL). N,N-Diisopropylethylamine (8.4 mL, 48.1 mmol) and (1R,2R)-2-allylcyclopropanecarboxylic acid (L48) (1.3 g, 10.6 mmol) pre-mixed with HATU (4.0 g 10.6 mmol) were added. The reaction mixture was stirred at room temperature for 1 h. Saturated ammonium chloride and dichloromethane were added. The aqueous layer was extracted with dichloromethane and the combined organic layers were dried over magnesium sulfate. Filtration and evaporation of solvents yielded the crude product, which was purified by silica gel chromatography (eluent: 0 to 50% EtOAc/hexanes) to afford (1R,2R)-2-allyl-N—((R)-1-(1-(but-3-en-1-yl)-2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)cyclopropane-1-carboxamide. ES/MS: m/z 352.1 [M+H] + .

›Step 3

(1R,2R)-2-allyl-N-[(1R)-1-(1-but-3-enyl-2-formyl-pyrrolo[2,3-b]pyridin-6-yl)ethyl]cyclopropanecarboxamide (2.4 g, 6.8 mmol) was dissolved in 1,2-Dichloroethane (327 mL). To the mixture, added Zhan 1b catalyst (512 mg, 0.7 mmol) and purged vessel with Argon. The resulting mixture was heated at 80° C. for 3 hours. The solvents were evaporated to yield the crude material, which was purified by silica gel chromatography (eluent: 0 to 50% EtOAc/dichloromethane) to afford (2R,5R,7R,9E)-2-methyl-4-oxo-3,13,19-triazatetracyclo[11.5.2.05,7.016,20]icosa-1(19),9,14,16(20),17-pentaene-14-carbaldehyde. ES/MS: 324.2 (M+H)+. 1 H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H), 8.55 (d, J=8.0 Hz, 1H), 8.13 (d, J=8.1 Hz, 1H), 7.49 (s, 1H), 7.21 (d, J=8.2 Hz, 1H), 5.69-5.50 (m, 2H), 4.97 (p, J=7.2 Hz, 1H), 4.71-4.60 (m, 2H), 2.71-2.57 (m, 1H), 2.44 (d, J=18.9 Hz, 2H), 1.47 (m, J=7.9, 4.5 Hz, 1H), 1.40 (d, J=7.1 Hz, 3H), 1.37-1.27 (m, 1H), 0.91-0.76 (m, 2H), 0.58 (m, J=8.2, 5.6, 3.2 Hz, 1H).

(5E,11R)-8,8,11-trimethyl-9-oxo-1,10,19-triazatricyclo[10.5.2.015,18]nonadeca-5,12(19),13,15(18),16-pentaene-17-carbaldehyde (I-142b)

Prepared following a similar procedure to I-142a using 5-bromopent-1-ene and 2,2-dimethyl-4-pentenoic acid. ES/MS: m/z 340.3 [M+H] + .

(2R,5R,7R,9Z)-11,11-difluoro-2-methyl-4-oxo-3,13,19-triazatetracyclo[11.5.2.05,7.016,20]icosa-1(19),9,14,16(20),17-pentaene-14-carbaldehyde (I-142c)

Prepared following a similar procedure to I-142a using 2,2-difluorobut-3-en-1-yl trifluoromethanesulfonate and (1R,2R)-2-allylcyclopropane-1-carboxylic acid. ES/MS: m/z 359.96 [M+H] + .

(2R,5S,7R,8E)-7-fluoro-2-methyl-4-oxo-3,13,19-triazatetracyclo[11.5.2.05,7.016,20]icosa-1(19),8,14,16(20),17-pentaene-14-carbaldehyde (I-142d)

Prepared following a similar procedure to I-142a using 5-bromopent-1-ene and L55a. ES/MS: m/z 342.3 [M+H] + .

Preparation of methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-143a)

›Step 1

Methyl 3-methoxy-4-(methylamino)-5-nitrobenzoate (I-7a, 10 g, 41.6 mmol) and tert-butyl (R)-(1-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-139, 12.2 g, 42.0 mmol) were charged in a flask equipped with a stir bar. The mixture was suspended in EtOH/water (2:1, 300 mL) and sodium dithionite (25.6 g, 125 mmol) was added. The vial was sealed, and the reaction was heated to 80° C. for 3 h. Upon cooling, the precipitate was filtered off, washed with water and dried under vacuum to afford methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 480.2 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-143b)

Prepared following a similar procedure to I-143a using I-7c instead of I-7a. ES/MS: m/z 468.3 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-(2,2-difluoroethyl)-6-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-143c)

Prepared following a similar procedure to I-143a using I-7i instead of I-7a. ES/MS: m/z 517.9 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazole-5-carboxylate (I-143d)

Prepared following a similar procedure to I-143a using I-7j instead of I-7a. ES/MS: m/z 536.3 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-fluoro-1-(2-methoxyethyl)-1H-benzo[d]imidazole-5-carboxylate (I-143e)

Prepared following a similar procedure to I-143a using I-7h instead of I-7a. ES/MS: m/z 512.3 [M+H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-143f)

Prepared following a similar procedure to I-143a using I-7m. ES/MS: m/z 480.0 [M−H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-143g)

Prepared following a similar procedure to I-143a using I-26. ES/MS: m/z 480.0 [M−H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1,6-dimethyl-1H-benzo[d]imidazole-5-carboxylate (I-143h)

Prepared following a similar procedure to I-143a using I-7n. ES/MS: m/z 464.3 [M−H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-6,7-difluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-143i)

Prepared following a similar procedure to I-143a using I-7o. ES/MS: m/z 484.9 [M−H] + .

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-fluoro-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-143j)

Prepared following a similar procedure to I-143a using I-7s. ES/MS: m/z 468.3 [M−H] + .

Preparation of benzyl (3S,4S)-3-[[2-[6-[(1R)-1-aminoethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carbonyl]amino]-4-fluoro-piperidine-1-carboxylate (I-144a)

›Step 1

Isopropyl 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (I-102) (500 mg, 0.99 mmol), 5-bromopent-1-ene (0.24 mL, 1.97 mmol) and cesium carbonate (965 mg, 2.96 mmol) were dissolved in N,N-dimethylformamide (8 mL) and the resulting reaction mixture was stirred at 60° C. for 90 min. The cooled reaction mixture was quenched with saturated ammonium chloride solution, diluted with copious amounts of water, and extracted with dichloromethane three times. The collected organics were dried over magnesium sulfate and concentrated to produce the crude product, which was purified via silica gel column chromatography (0-65% ethyl acetate in hexanes) to yield isopropyl 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate. ES/MS: m/z 576.25 [M+H] + .

›Step 2

2 N lithium hydroxide solution (0.4 mL, 0.80 mmol) was added to a solution of isopropyl 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (110 mg, 0.19 mmol) in methanol (1 mL) and tetrahydrofuran (1 mL). The resulting reaction mixture was heated at 60° C. for 6 h. The reaction mixture was concentrated and re-dissolved in dichloromethane, diluted with water and quenched with 1 N hydrochloride solution (0.8 mL), extracting with dichloromethane (3×). The organics were collected, dried over magnesium sulfate and concentrated to yield 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylic acid, which was carried over to the consequent step without further purification assuming quantitative yield. ES/MS: m/z 534.13 [M+H] + .

›Step 3

N,N-diisopropylethylamine (0.12 mL, 0.71 mmol) was added to a solution of 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylic acid (102 mg, 0.18 mmol) dissolved in dichloromethane (2 mL), followed by addition of [dimethylamino(triazolo[4,5-b]pyridin-3yloxy)methylene]-dimethyl-ammonium (101 mg, 0.27 mmol) and benzyl (3S,4S)-3-amino-4-fluoro-piperidine-1-carboxylate (A1.39) (49 mg, 0.20 mmol). The resulting reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with dichloromethane twice. The collected organics were dried over magnesium sulfate and concentrated to produce the crude product, which was purified via silica gel column chromatography to yield benzyl (3S,4S)-3-[[2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carbonyl]amino]-4-fluoro-piperidine-1-carboxylate. ES/MS: m/z 768.22 [M+H] + .

›Step 4

Trifluoroacetic acid (0.3 mL, 3.92 mmol) was added to a solution of benzyl (3S,4S)-3-[[2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carbonyl]amino]-4-fluoro-piperidine-1-carboxylate (121 mg, 0.16 mmol) dissolved in dichloromethane (2 mL). The resulting reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated to yield benzyl (3S,4S)-3-[[2-[6-[(1R)-1-aminoethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carbonyl]amino]-4-fluoro-piperidine-1-carboxylate, which was carried over to the consequent step without further purification assuming quantitative yield. ES/MS: m/z 668.50 [M+H] + .

benzyl (3S,4S)-3-[[2-[6-[(1R)-1-aminoethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-6-fluoro-1-methyl-benzimidazole-5-carbonyl]amino]-4-fluoro-piperidine-1-carboxylate (I-144b)

Prepared using a similar procedure to I-144a using I-143b as starting material. ES/MS: m/z 656.28 [M+H] + .

Preparation of (11R)-8,8,11-trimethyl-9-oxo-1,10,19-triazatricyclo[10.5.2.015,18]nonadeca-12(19),13,15(18),16-tetraene-17-carbaldehyde (I-145a)

›Step 1

tert-butyl N-[(1R)-1-(2-formyl-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl]carbamate (I-139, 900 mg, 3.11 mmol) and tert-butyl 8-bromo-2,2-dimethyloctanoate (L4a, 1.22g, 4.04 mmol) were dissolved in DMF (50.0 mL). Cesium carbonate (3.07g, 9.42 mmol) was added and the resulting mixture was allowed to stir 1 h at 60° C. The reaction mixture was partitioned between EtOAc and water, and the organic phase was washed with brine, dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (5-20% EtOAc in hexanes) provided tert-butyl 8-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-2-formyl-pyrrolo[2,3-b]pyridin-1-yl]-2,2-dimethyl-octanoate. ES/MS: m/z 516.3 [M+H] + .

›Step 2

The product from above was dissolved in DCM (2 mL) and TFA (0.5 mL) was added. The reaction mixture was stirred 3 h at room temperature and was concentrated in vacuo to afford crude 8-[6-[(1R)-1-aminoethyl]-2-formyl-pyrrolo[2,3-b]pyridin-1-yl]-2,2-dimethyl-octanoic acid which was used below without further purification. The crude product (1.11 mmol) from above was dissolved in DCM (2.5 mL). N,N-diisopropylethylamine (0.97 mL, 5.56 mmol) was added followed by HATU (208 mg, 1.34 mmol). After 1 h, the reaction mixture was partitioned between EtOAc and water, and the organic phase was washed with brine, dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (5-50% EtOAc in hexanes) provided (11R)-8,8,11-trimethyl-9-oxo-1,10,19-triazatricyclo[10.5.2.015,18]nonadeca-12(19),13,15(18),16-tetraene-17-carbaldehyde. ES/MS: m/z 342.1 [M+H] + .

(2R)-2-methyl-4-oxo-3,6,9,16,22-pentazatetracyclo[14.5.2.05,10.019,23]tricosa-1(22),5(10),6,8,17,19(23),20-heptaene-17-carbaldehyde (I-145b)

Prepared using a similar procedure to I-145a using L49. ES/MS: m/z 364.2 [M+H] + .

(2R)-8-chloro-2-methyl-4-oxo-3,9,16,22-tetrazatetracyclo[14.5.2.05,10.019,23]tricosa-1(22),5(10),6,8,17,19(23),20-heptaene-17-carbaldehyde (I-145c)

Prepared using a similar procedure to I-145a using L60a. ES/MS: m/z 397.16 [M+H] + .

Preparation of isopropyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-7-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-146a)

›Step 1

methyl 3-amino-5-methoxy-4-(methylamino)benzoate (1.59 g, 7.56 mmol) and 1-(benzenesulfonyl)-6-bromo-7-fluoro-indole-2-carbaldehyde (2.5 g, 6.54 mmol) were taken up in HOAc (30 mL). The solution was heated to 70° C. and stirred for 18 h. The temperature was then increased to 90° C. and stirred for an additional 2 h. The mixture was concentrated, leading to precipitation of solids. Solids were collected by filtration, and the filtrate was concentrated and purified by silica gel chromatography. The solids were combined with the product purified by chromatography to afford methyl 2-(6-bromo-7-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-benzimidazole-5-carboxylate. ES/MS: m/z 432.0 [M+H] + .

›Step 2

methyl 2-(6-bromo-7-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-benzimidazole-5-carboxylate (2.15 g, 4.97 mmol) was dissolved in DCM (25 mL) and triethylamine (2.1 mL, 15 mmol) was added, followed by DMAP (122 mg, 1 mmol) and di-tert-butyl decarbonate (1.19 g, 5.47 mmol). The reaction mixture was stirred at r.t., and additional portions of triethylamine and di-tert-butyl decarbonate were added to effect full conversion. The mixture was then partitioned between DCM and water, and the organic phase was washed with water, dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel provided methyl 2-(6-bromo-1-(tert-butoxycarbonyl)-7-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 531.9 [M+H] + .

›Step 3

methyl 2-(6-bromo-1-(tert-butoxycarbonyl)-7-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (1.65 g, 3.1 mmol) was taken up in EtOH (40 mL). Potassium isopropenyltrifluoroborate (690 mg, 4.7 mmol) was added, followed by Dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloromethane (177 mg, 0.22 mmol) and triethylamine (2.16 mL, 0.016 mmol). The reaction vessel was flushed with N 2 , and the mixture was heated to 80° C. Once complete, the reaction mixture was partitioned between EtOAc and water. The phases were separated, and the organic phase was dried over Na 2 SO 4 , filtered, and concentrated. The obtained residue was purified by silica gel chromatography to afford methyl 2-(1-tert-butoxycarbonyl-7-fluoro-6-isopropenyl-indol-2-yl)-7-methoxy-1-methyl-benzimidazole-5-carboxylate. ES/MS: m/z 493.82 [M+H] + .

›Step 4

methyl 2-(1-tert-butoxycarbonyl-7-fluoro-6-isopropenyl-indol-2-yl)-7-methoxy-1-methyl-benzimidazole-5-carboxylate (1.0 g, 2.0 mmol) was dissolved in THF (30 mL) and water (15 mL). Potassium osmate(VI) dihydrate (22 mg, 0.07 mmol) was added followed by sodium periodate (1.3 g, 6.1 mmol). The reaction mixture was stirred overnight, and was then partitioned between EtOAc and water. The phases were separated, and the organic phase was washed with brine, dried over Na 2 SO 4 , filtered and concentrated. Purification by silica gel provided methyl 2-(6-acetyl-1-tert-butoxycarbonyl-7-fluoro-indol-2-yl)-7-methoxy-1-methyl-benzimidazole-5-carboxylate. ES/MS: m/z 495.78 [M+H] + .

›Step 5

methyl 2-(6-acetyl-1-tert-butoxycarbonyl-7-fluoro-indol-2-yl)-7-methoxy-1-methyl-benzimidazole-5-carboxylate (740 mg, 1.5 mmol) and (S)-2-methylpropane-2-sulfinamide (740 mg, 6.1 mmol) were dissolved in THF (30 mL) under N 2 . Ti(OiPr) 4 (3.54 mL, 12 mmol) was added, and the mixture was stirred at 60° C. for 22 h. The temperature was then increased to 75° C. and the reaction mixture was stirred an additional 24 h. The mixture was then poured into a vigorously stirred mixture of EtOAc and brine. The organic layer was decanted, and the aqueous mixture was extracted with EtOAc several times. Celite was added to the combined organic phase, which was then filtered and concentrated to provide a crude residue that was purified by silica gel chromatography (10-40% acetone in hexanes) to provide [(E)-1-[1-tert-butoxycarbonyl-7-fluoro-2-(5-isopropoxycarbonyl-7-methoxy-1-methyl-benzimidazol-2-yl)indol-6-yl]ethylideneamino]-tert-butyl-oxido-sulfonium. ES/MS: m/z 627.81 [M+H] + .

›Step 6

[(E)-1-[1-tert-butoxycarbonyl-7-fluoro-2-(5-isopropoxycarbonyl-7-methoxy-1-methyl-benzimidazol-2-yl)indol-6-yl]ethylideneamino]-tert-butyl-oxido-sulfonium (712 mg, 1.1 mmol) was dissolved in THF (15 mL) and the mixture was cooled in a dry ice/acetone bath to −78° C. A solution of L-selectride (1 M, 1.19 mL, 1.19 mmol) was added dropwise, and the mixture was stirred for 2 h. The mixture was removed from the cold bath, allowed to slowly warm to ca. 0° C., and was then placed in an ice water bath. After an additional 30 min, the reaction was quenched by addition of saturated aqueous NH 4 Cl and diluted with EtOAc. The phases were separated, and the organic phase was dried over Na 2 SO 4 , filtered, and concentrated. Purification by silica gel provided [[(1R)-1-[1-tert-butoxycarbonyl-7-fluoro-2-(5-isopropoxycarbonyl-7-methoxy-1-methyl-benzimidazol-2-yl)indol-6-yl]ethyl]amino]-tert-butyl-oxido-sulfonium. ES/MS: m/z 628.80 [M+H] + .

›Step 7

[[(1R)-1-[1-tert-butoxycarbonyl-7-fluoro-2-(5-isopropoxycarbonyl-7-methoxy-1-methyl-benzimidazol-2-yl)indol-6-yl]ethyl]amino]-tert-butyl-oxido-sulfonium (600 mg, 0.95 mmol) was dissolved in 1,4-dioxane (10 mL). A solution of HCl in dioxane (4 M, 2.4 mL, 9.5 mmol) was added. DCM (10 mL) was added, followed by additional HCl in dioxane (4 M, 2.4 mL, 9.5 mmol) and the reaction mixture was heated to 40° C. After stirring 2 days, the mixture was cooled and diluted with Et 2 O. Solids were collected by filtration and were then dissolved in DCM (20 mL). Triethylamine (1.2 mL, 0.89 mmol) was added followed by di-tert-butyl decarbonate (192 mg, 0.88 mmol). The mixture was stirred 30 min and was partitioned between DCM and water. The phases were separated, and the organic phase was concentrated to afford a residue that was purified by silica gel chromatography (20-70% EtOAc in hexanes) to afford isopropyl 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-7-fluoro-1H-indol-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate. ES/MS: m/z 525.08 [M+H] + .

Preparation of tert-butyl (R)-(1-(2-formyl-1-(phenylsulfonyl)-1H-indol-6-yl)ethyl)carbamate (I-147a)

›Step 1

A dry reaction vial equipped with stir bar was charged with tert-butyl (R)-(1-(1-(phenylsulfonyl)-1H-indol-6-yl)ethyl)carbamate (I-25c) (51.0 g, 127.0 mmol, 1.0 eq). The vial was evacuated and backfilled with argon (three times). Anhydrous THF (510 mL) was added and the mixture was cooled to −78° C. A commercial solution of LDA (2 M, 255 mL, 509 mmol, 4.0 eq) was added dropwise to the mixture at −78° C. followed by dropwise addition of dry TMEDA (74.0 g, 636.0 mmol, 5.0 eq). The mixture was allowed to stir at −78° C. for 15 minutes. Anhydrous DMF (55.9 g, 764 mmol, 6.0 eq) was then added dropwise to the mixture. The mixture was stirred for 1 hour at −78° C. The reaction mixture was quenched with sat. NH 4 Cl aq. (500 mL) at −78° C. Then the mixture was allowed to warm to room temperature. The mixture was further diluted with water (1 L) and the aqueous phase was extracted with EtOAc (1 L×2). The combined organic extracts were washed with brine (500 mL), dried over Na 2 SO 4 and concentrated under vacuum. The crude residue was purified by silica gel column chromatography (eluted with petroleum ether/EtOAc=2:1) to afford tert-butyl (R)-(1-(2-formyl-1-(phenylsulfonyl)-1H-indol-6-yl)ethyl)carbamate. ES/MS: m/z 429.1 [M+H] + . 1 H NMR (400 MHz, CDCl3): δ 10.47 (s, 1H), 8.18 (s, 1H), 7.74 (d, J=7.2 Hz, 2H), 7.56-7.49 (m, 2H), 7.42-7.36 (m, 3H), 7.25 (d, J=3.6 Hz, 1H), 4.89-4.92 (m, 2H), 1.48 (d, J=6.4 Hz, 3H), 1.43 (s, 9H).

tert-butyl (R)-(1-(5-fluoro-2-formyl-1-(phenylsulfonyl)-1H-indol-6-yl)ethyl)carbamate (I-147b)

Prepared using a similar procedure to I-147a using I-25b. ES/MS: m/z 364.2 [M+H] + .

Preparation of tert-butyl (R)-(1-(2-formyl-1H-indol-6-yl)ethyl)carbamate (I-148a)

›Step 1

To the stirred solution of tert-butyl (R)-(1-(2-formyl-1-(phenylsulfonyl)-1H-indol-6-yl)ethyl)carbamate (37.5 g, 87.7 mmol, 1.0 eq) in THF (450 mL), was added solution of tetrabutyl ammonium fluoride in THF (1 M, 175 mL, 175.4 mmol, 2.0 eq) and stirred at 40° C. for 1 h. Reaction mixture was cooled to room temperature, added water (500 mL) and extracted with EtOAc (2 L). Organic layer was dried over anhydrous Na 2 SO 4 and evaporated under vacuum. The crude product was triturated with EtOAc/hexanes (2:1, 500 mL) and filtered to afford tert-butyl (R)-(1-(2-formyl-1H-indol-6-yl)ethyl)carbamate. ES/MS: m/z 599.2 [2M+Na] + . 1 H NMR (400 MHz, CDCl3): δ 9.81 (s, 1H), 9.17 (brs, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.37 (s, 1H), 7.23 (s, 1H), 7.13 (d, J=8.4 Hz, 1H), 4.90 (brs, 2H), 1.49 (d, J=6.4 Hz, 3H), 1.42 (s, 9H).

Preparation of methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-149a)

›Step 1

Methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1-(phenylsulfonyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was prepared following a similar procedure to step 1 of I-141a using I-147b and I-23i. ES/MS: m/z 497.02 [M−SO 2 Ph+2H] + .

›Step 1

Methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was prepared following a similar procedure to step 1 of I-148a. ES/MS: m/z 497.02 [M−H] + . 1 H NMR (400 MHz, DMSO-d6) δ 12.09 (d, J=2.2 Hz, 1H), 7.93 (d, J=1.2 Hz, 1H), 7.58 (d, J=7.9 Hz, 1H), 7.48 (d, J=6.5 Hz, 1H), 7.41-7.34 (m, 2H), 7.18-7.12 (m, 1H), 4.98-4.83 (m, 1H), 4.33 (s, 3H), 4.03 (s, 3H), 3.90 (s, 3H), 1.40 (s, 9H), 1.36 (d, J=7.0 Hz, 3H).

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1H-indol-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-149b)

Prepared using a similar procedure to I-149a using I-140c. ES/MS: m/z 511.01 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.05 (s, 1H), 9.83 (s, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.48 (d, J=11.1 Hz, 1H), 7.44 (d, J=6.4 Hz, 1H), 7.35 (s, 1H), 5.02-4.79 (m, 1H), 3.42-3.27 (m, 1H) 3.33 (s, 3H), 1.44-1.29 (m, 2H), 1.38 (s, 9H), 1.34 (d, J=7.0 Hz, 3H), 1.28-1.10 (m, 1H).

Preparation of methyl 2-(1-(8-(tert-butoxy)-7,7-dimethyl-8-oxooctyl)-6-(((tert-butylsulfinyl)amino)(cyclopropyl)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-150a)

›Step 1

To a cooled solution of methyl 2-[1-(8-tert-butoxy-7,7-dimethyl-8-oxo-octyl)-6-[(E)-tert-butylsulfinyliminomethyl]pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (200 mg, 0.288 mmol) in dry THF (4 mL) at 0° C. was added dropwise a solution of 1 M cyclopropylmagnesium bromide in 2-MeTHF (0.72 mL, 0.72 mmol). After 4 hours, an additional of 1 M cyclopropylmagnesium bromide in 2-MeTHF (1.4 mL, 1.4 mmol). After 5 minutes, warmed to rt and stirred for 3 hours. The reaction mixture was diluted with a saturated aqueous solution of ammonium chloride and ethyl acetate. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organics were dried, filtered, and concentrated under reduced pressure to yield methyl 2-(1-(8-(tert-butoxy)-7,7-dimethyl-8-oxooctyl)-6-(((tert-butylsulfinyl)amino)(cyclopropyl)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 736.0 [M+H] + .

methyl 2-(1-(8-(tert-butoxy)-7,7-dimethyl-8-oxooctyl)-6-(1-((tert-butylsulfinyl)amino)propyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-150b)

Prepared following a similar procedure to I-150a using ethylmagnesium bromide instead of cyclopropyl magnesium bromide. ES/MS: m/z 724.2 [M+H] + .

Preparation of methyl 2-(6-(1-aminocylopropyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-151a)

›Step 1

To a solution of 1H-pyrrolo[2,3-b]pyridine-6-carbonitrile (3.40 g, 23.8 mmol) in MeTHF (45 mL) was added 1M NaHMDS in THF (26 mL) at 0 degrees. After stirring for 15 mins, benzenesulfonyl chloride (3.33 mL, 26.1 mmol) was added dropwise maintaining an internal temperature below 5 degrees. After stirring warming slowly to rt overnight, the reaction mixture was quenched with sat. NH 4 Cl (aq). After stirring 15 minutes, the precipitated solid was filtered, washed with water, and dried in vacuo to yield 1-(benzenesulfonyl)pyrrolo[2,3-b]pyridine-6-carbonitrile. ES/MS: m/z 284.0 [M+H] + .

›Step 2

To a solution of 1-(benzenesulfonyl)pyrrolo[2,3-b]pyridine-6-carbonitrile (1.00 g, 3.53 mmol) and Titanium isopropoxide (1.2 mL, 3.88 mmol) in THF (80 mL) at −78 degrees was added dropwise a solution of EtMgBr in THF (3.4 mL, 10.6 mmol). After 10 minutes, the reaction mixture was warmed to rt. BF3-Et2O (0.70 mL, 7.06 mmol) was added. After stirring overnight, the reaction mixture was cooled to −78 degrees and the above process was repeated. After warming to rt, the reaction mixture was stirred for 90 minutes and diluted with ethyl acetate and brine. The resulting solids were filtered, washing with ethyl acetate. The filtrate was separated and the aqueous extracted with ethyl acetate. The combined organics were dried, filtered, and concentrated under reduced pressure. The resulting residue was dissolved in DCM (16 mL) and Di-tert-butyl dicarbonate (0.651 g, 2.98 mmol) and triethylamine (1.32 mL, 9.50 mmol) were added. After 24 hours, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified via silica gel column chromatography (0-70% ethyl acetate in hexanes) to yield tert-butyl (1-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropyl)carbamate. ES/MS: m/z 413.9 [M+H] + .

›Step 3

tert-butyl N-[1-[1-(benzenesulfonyl)-2-formyl-pyrrolo[2,3-b]pyridin-6-yl]cyclopropyl]carbamate was synthesized following the preparation of I-139 using tert-butyl (1-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropyl)carbamate instead of I-25a. ES/MS: m/z 441.8 [M+H] + .

›Step 4

A mixture of tert-butyl N-[1-[1-(benzenesulfonyl)-2-formyl-pyrrolo[2,3-b]pyridin-6-yl]cyclopropyl]carbamate (139 mg, 0.315 mmol) and I-23j in acetic acid (1.7 mL) was heated at 80 degrees for 2 hours. The reaction mixture was concentrated under reduced pressure and dissolved in THF (5 mL). A solution of TBAF in THF (1N, 0.315 mL, 0.315 mmol) was added and the reaction mixture was stirred overnight. An additional quantity of solution of TBAF in THF (1N, 0.315 mL, 0.315 mmol) was added and the reaction mixture was heated at 70 degrees. After 30 minutes, the reaction mixture was diluted with ethyl acetate and water. The layers were separated and the aqueous extracted with ethyl acetate. The combined organics were washed with a saturated solution of NH 4 Cl (aq), dried, filtered, and concentrated under reduced pressure to yield methyl 2-(6-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 492.1 [M+H] + .

›Step 5

methyl 2-(6-(1-aminocyclopropyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was synthesized following the preparation of I-107a using methyl 2-(6-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate instead of I-102. ES/MS: m/z 560.1 [M+H] + .

Preparation of isopropyl 7-methoxy-1-methyl-2-(1-(pent-4-en-1-yl)-6-((1R)-1-((1,1,1-trifluorohex-5-en-2-yl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxylate (I-152)

›Step 1

A solution of isopropyl (R)-2-(6-(1-aminoethyl)-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-107a) (150 mg, 0.49 mmol) and acetic acid (30 mg, 0.49 mmol) in dichloromethane (3 mL) was stirred at room temperature for 5 min, after which a solution of 1,1,1-trifluorohex-5-en-2-one (50 mmol) in dichloromethane (1 mL) was added. After stirring for 5 h under reflux, the solvent was evaporated under reduced pressure. The residue was brought up in methanol (2.5 mL) and to this solution was added sodium cyanoborohydride (32 mg, 0.50 mmol). The reaction was stirred for 30 min and concentrated. Saturated sodium bicarbonate was added and the aqueous layer was washed with dichloromethane 3 times. The combined organic layers were dried over Na 2 SO 4 , filtered and concentrated. The crude residue was purified by flash chromatography eluting with hexanes/EtOAc to give a colorless oil. ES/MS: m/z 612.20 [M+H]+.

Preparation of methyl (R)-7-methoxy-1-methyl-2-(1-(pent-4-en-1-yl)-6-(1-(N-(pent-4-en-1-yl)acetamido)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxylate (I-153a)

›Step 1

The HCl salt of methyl 2-[6-[(1R)-1-aminoethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (180 mg, 0.37 mmol) and cesium carbonate (364 mg, 1.1 mmol) were combined in DMF (6 mL) and stirred at ambient temperature. After 5 minutes, 5-bromopent-1-ene (0.04 mL, 0.37 mmol) was added and the resulting mixture stirred at 60° C. After 4 days, the reaction was allowed to cool and was poured into water. The mixture was extracted 3× with EtOAc, and the combined extracts were washed once with brine, concentrated, and purified by silica chromatography using 1:3 EtOH/EtOAc with 0.25% TEA in heptane to afford methyl 7-methoxy-1-methyl-2-[1-pent-4-enyl-6-[(1R)-1-(pent-4-enylamino)ethyl]pyrrolo[2,3-b]pyridin-2-yl]benzimidazole-5-carboxylate. ES/MS: m/z 516.0 [M+H] + .

›Step 2

To a solution of methyl 7-methoxy-1-methyl-2-[1-pent-4-enyl-6-[(1R)-1-(pent-4-enylamino)ethyl]pyrrolo[2,3-b]pyridin-2-yl]benzimidazole-5-carboxylate (76 mg, 0.15 mmol), DIEA (0.05 mL, 0.30 mmol), and DMAP (2 mg, 0.02 mmol) in DCM (3 mL) was added acetyl chloride (0.014 mL, 0.19 mmol). The reaction was allowed to stir at ambient temperature for 4 days, then was poured into aq. NaHCO 3 . The mixture was extracted 3× into DCM, and the combined extracts were concentrated and purified by silica chromatography using EtOAc in hexane to afford methyl 2-[6-[(1R)-1-[acetyl(pent-4-enyl)amino]ethyl]-1-pent-4-enyl-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate. ES/MS: m/z 558.4 [M+H] + .

Preparation of tert-butyl N-[(1R)-1-[2-[5-[(3S,4R)-3-(benzyloxycarbonylamino)-4-methoxy-piperidine-1-carbonyl]-7-methoxy-1-methyl-benzimidazol-2-yl]-1H-pyrrolo[2,3-b]pyridin-6-yl]ethyl]carbamate (I-153)

›Step 1

2 N lithium hydroxide solution (0.39 mL, 0.79 mmol) was added to a solution of isopropyl 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylate (200 mg, 0.39 mmol) in methanol (1 mL) and tetrahydrofuran (1 mL). The resulting reaction mixture was heated at 60° C. for 90 min. The reaction mixture was concentrated and re-dissolved in dichloromethane, diluted with water and quenched with 4 N hydrochloride solution in dioxane (0.2 mL), extracting with dichloromethane (3×). The resulting mixture was concentrated to yield 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylic acid, which was carried over to the consequent step without further purification assuming quantitative yield. ES/MS: m/z 466.02 [M+H] + .

›Step 2

N,N-diisopropylethylamine (0.27 mL, 1.57 mmol) was added to a solution of 2-[6-[(1R)-1-(tert-butoxycarbonylamino)ethyl]-1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methyl-benzimidazole-5-carboxylic acid (183 mg, 0.39 mmol) dissolved in dichloromethane (2 mL), followed by addition of [dimethylamino(triazolo[4,5-b]pyridin-3yloxy)methylene]-dimethyl-ammonium (224 mg, 0.59 mmol) and benzyl N-[(3S,4R)-4-methoxy-3-piperidyl]carbamate (57.2 mg, 0.22 mmol). The resulting reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with dichloromethane twice. The collected organics were dried over magnesium sulfate, filtrated and concentrated, to produce the crude product, which was purified via silica gel column chromatography (0-15% methanol in dichloromethane) to yield tert-butyl N-[(1R)-1-[2-[5-[(3S,4R)-3-(benzyloxycarbonylamino)-4-methoxy-piperidine-1-carbonyl]-7-methoxy-1-methyl-benzimidazol-2-yl]-1H-pyrrolo[2,3-b]pyridin-6-yl]ethyl]carbamate. ES/MS: m/z 712.25 [M+H] + .

Preparation of isopropyl (R)-2-(6-(1-((2,2-difluoroethyl)amino)ethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-154a)

›Step 1

To a solution of isopropyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (150 mg, 0.293) in DMF (2 mL) were added DIEA (0.102 mL, 0.586 mmol) and 2,2-difluoroethyl trifluoromethanesulfonate (94 mg, 0.586 mmol). After 1 h, the reaction mixture was quenched with water and extracted with EtOAc twice. The collected organics were dried over magnesium sulfate, filtrated and concentrated. The crude produce was used directly is the next step. ES/MS: m/z 576.3 [M+H] + .

Preparation of isopropyl (R)-2-(6-(1-((cyclopropylmethyl)amino)ethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (I-155a)

›Step 1

To a solution of isopropyl (R)-2-(6-(1-aminoethyl)-1-(2,2-difluoropent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (150 mg, 0.293) in DCE (3 mL) were added NaBH(AcO) 3 (87 mg, 0.411 mmol), AcOH (0.017 mL, 0.293 mmol) and cyclopropanecarboxaldehyde (0.023 mL, 0.308 mmol). The reaction mixture was allowed to stir at rt for 2 h and quenched with 1 N NaOH. The mixture was extracted twice with DCM. The collected organics were dried over magnesium sulfate, filtrated and concentrated. The crude produce was used directly is the next step. ES/MS: m/z 566.3 [M+H] + .

Preparation of methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (I-156)

›Step 1

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate was prepared using a similar procedure to that described for I-141a, but starting with I-140c and tert-butyl (R)-(1-(5-fluoro-2-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethyl)carbamate (I-33). ES/MS: m/z 641.87 [M+H] + .

Steps 2 and 3.

methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate (179 mg, 0.28 mmol) was dissolved in MeCN (4 mL). A solution of hydrochloric acid in dioxane (4 M, 2 mL, 8 mmol) was added, and the mixture was heated to 45° C. for 18 h. The mixture was concentrated, and the obtained residue was dissolved in DCM (4 mL). Hunig's base (0.24 mL, 1.4 mmol) was added followed by di-tert-butyl dicarbonate (61 mg, 0.28 mmol). The mixture was stirred until LCMS indicated complete conversion and was then concentrated directly onto silica gel and purified by silica gel chromatography (EA/hexanes gradient) to afford methyl (R)-2-(6-(1-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-cyclopropyl-7-fluoro-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 511.99 [M+H] + .

Preparation of methyl (R,Z)-7-methoxy-1-methyl-2-(1-(pent-3-en-1-yl)-6-(pyrrolidin-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxylate (I-157)

›Step 1

methyl 2-(6-bromo-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was made according to Procedure 8, step 1, using methyl 2-(6-bromo-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate, and 5-bromo-1-pentene. ES/MS: m/z 483.4 [M+H]+.

›Step 2

methyl (R,Z)-2-(6-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1-(pent-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate was made following step 2 of Procedure 12 using methyl 2-(6-bromo-1-(pent-4-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-. ES/MS: m/z 574.3 [M+H]+.

›Step 3

methyl (R,Z)-7-methoxy-1-methyl-2-(1-(pent-3-en-1-yl)-6-(pyrrolidin-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxylate was prepared following a similar procedure to step 2 of I-107a using methyl (R,Z)-2-(6-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1-(pent-3-en-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate. ES/MS: m/z 474.3 [M+H] + .

3. Synthesis of Intermediates L1 to L83

Preparation of tert-butyl 8-bromooctanoate (L1a)

›Step 1

To a solution of 8-bromooctanoic acid (2.0 g, 9.96 mmol) in dichloromethane (25 mL) and tert-butanol (25 mL) were added di-tert-butyl dicarbonate (3.91 g, 17.9 mmol) and DMAP (329 mg, 2.69 mmol). The reaction mixture was stirred at room temperature for 16 h. After concentration in vacuo, ethyl acetate was added and the solution was washed with saturated aqueous NaHCO 3 , followed by saturated aqueous NH 4 Cl and brine. The organic phase was dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-20% EtOAc in hexanes) provided tert-butyl 8-bromooctanoate. 1 H NMR (400 MHz, DMSO-d6) δ 3.40 (td, J=6.8, 1.6 Hz, 2H), 2.20 (td, J=7.4, 1.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.64-1.53 (m, 2H), 1.53-1.25 (m, 8H), 1.44 (s, 9H). Commercially available (cas 77383-17-6).

tert-butyl 7-bromoheptanoate (L1b)

Commercially available (cas 51100-47-1) or prepared following a similar procedure to L1a starting with 7-bromoheptanoic acid.

tert-butyl 9-bromononanoate (L1c)

Commercially available (cas 77383-17-6) or prepared following a similar procedure to L1a starting with 9-bromononanoic.

tert-butyl 6-bromohexanoate (L1d)

Commercially available (cas 65868-63-5) or prepared following a similar procedure to L1a starting with 6-bromohexanoic acid.

tert-butyl 10-bromodecanoate (L1e)

Commercially available (cas 1644575-06-3) or prepared following a similar procedure to L1a starting with 10-bromodecanoic acid.

Preparation of tert-butyl 3-(4-(tosyloxy)butoxy)propanoate (L2a)

›Step 1

To a solution of 4-((tert-butyldiphenylsilyl)oxy)butan-1-ol (1.0 g, 3.04 mmol, Synlett 2014, 25(12), 1764-1768) in tert-butanol (15 mL) were added tert-butyl acrylate (6.7 mL, 45.7 mmol) and Cs 2 CO 3 (992 mg, 3.04 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with ethyl acetate and washed brine. The organic phase was dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-20% EtOAc in hexanes) provided tert-butyl 3-(4-((tert-butyldiphenylsilyl)oxy)butoxy)propanoate. 1 H NMR (400 MHz, Chloroform-d) δ 7.71-7.62 (m, 4H), 7.52-7.30 (m, 6H), 3.72-3.58 (m, 4H), 3.42 (t, J=6.1 Hz, 2H), 2.52-2.36 (m, 2H), 1.69-1.55 (m, 6H), 1.44 (s, 9H), 1.04 (s, 9H).

›Step 2

To a solution of tert-butyl 3-(4-((tert-butyldiphenylsilyl)oxy)butoxy)propanoate (1.1 g, 2.41 mmol) in THF (10 mL) was added 1.0 M TBAF in THF (3.61 mL). The reaction mixture was stirred at room temperature for 1 h. Ethyl acetate was added and the solution was washed with saturated aqueous NaHCO 3 followed by brine. The organic phase was dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-80% EtOAc in hexanes) provided tert-butyl 3-(4-hydroxybutoxy)propanoate. 1 H NMR (400 MHz, Chloroform-d) δ 3.72-3.61 (m, 4H), 3.49 (t, J=5.5 Hz, 2H), 2.49 (td, J=6.4, 0.8 Hz, 2H), 2.12 (t, J=5.6 Hz, 1H), 1.73-1.59 (m, 4H), 1.45 (s, 9H).

›Step 3

To a solution of tert-butyl 3-(4-hydroxybutoxy)propanoate (452 mg, 2.07 mmol) in dichloromethane (10 mL) at 0° C. was added TsCl (671 mg, 3.52 mmol), triethylamine (0.87 mL, 6.21 mmol) and DMAP (25 mg, 0.21 mmol). The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with DCM then washed with water and brine. The organic phase was dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-80% EtOAc in hexanes) provided tert-butyl 3-(4-(tosyloxy)butoxy)propanoate. 1 H NMR (400 MHz, Chloroform-d) δ 7.79 (d, J=8.1 Hz, 2H), 7.34 (d, J=8.0 Hz, 2H), 4.04 (t, J=6.3 Hz, 2H), 3.60 (t, J=6.4 Hz, 2H), 3.38 (t, J=6.1 Hz, 2H), 2.49-2.39 (m, 5H), 1.72 (dq, J=8.2, 6.4 Hz, 2H), 1.62-1.52 (m, 2H), 1.44 (s, 9H).

Preparation of tert-butyl 2-(4-(tosyloxy)butoxy)acetate (L3a)

›Step 1

To a solution of tert-butyl 2-(4-hydroxybutoxy)acetate (329 mg, 1.61 mmol, PCT Int. Appl., 2012143703) in dichloromethane (10 mL) at 0° C. were added TsCl (461 mg, 2.42 mmol), triethylamine (0.67 mL, 4.83 mmol) and DMAP (20 mg, 0.16 mmol). The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with DCM then washed with water and brine. The organic phase was dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-80% EtOAc in hexanes) provided tert-butyl 2-(4-(tosyloxy)butoxy)acetate. 1 H NMR (400 MHz, Chloroform-d) δ 7.82-7.75 (m, 2H), 7.34 (d, J=7.9 Hz, 2H), 4.07 (t, J=6.2, 2H), 3.89 (s, 2H), 3.47 (t, J=6.6, 6.1, 2H), 2.45 (s, 3H), 1.83-1.73 (m, 2H), 1.70-1.59 (m, 2H), 1.47 (s, 9H).

Preparation of tert-butyl 8-bromo-2,2-dimethyloctanoate (L4a)

›Step 1

To a solution of tert-butyl isobutyrate (0.50 g, 3.5 mmol) in anhydrous THF (10 mL) under nitrogen, at −40° C., was added a solution of lithium diisopropylamide (1.0 M solution in THF, 3.5 mL, 3.5 mmol) dropwise over 10 min. After 1 h, 1,6-dibromohexane (1.6 g, 6.5 mmol) was added. The mixture was stirred for 30 min at −40° C. and then allowed to warm to room temperature and stirred overnight. Ice water was added and the THF was removed under reduced pressure. The residue was brought up in ethyl acetate and washed with brine. The organic layer was dried over Na 2 SO 4 and concentrated to afford a crude yellow oil. The residue was purified by silica gel column chromatography (0-30% EtOAc in hexanes) to provide tert-butyl 8-bromo-2,2-dimethyloctanoate. 1 H NMR (400 MHz, Chloroform-d) δ 3.40 (t, J=6.9 Hz, 1H), 1.85 (p, J=6.9 Hz, 2H), 1.50-1.37 (m, 11H), 1.36-1.18 (m, 6H), 1.11 (s, 6H).

tert-butyl 7-bromo-2,2-dimethylheptanoate (L4b)

Prepared following a similar procedure to L4a using 1,5-dibromopentane instead of 1,6-dibromohexane. 1 H NMR (400 MHz, CDCl3): δ 3.38 (m, 2H), 1.85-1.81 (m, 2H), 1.45 (m, 3H), 1.40 (m, 9H), 1.23 (m, 3H), 1.08 (m, 6H).

tert-butyl 1-(6-bromohexyl)cyclobutane-1-carboxylate (L4c)

Prepared following a similar procedure to L4a using tert-butyl cyclobutanecarboxylate instead of tert-butyl isobutyrate. 1 H NMR (400 MHz, Chloroform-d) δ 3.42 (t, J=6.8 Hz, 2H), 2.42-2.32 (m, 2H), 1.92-1.79 (m, 6H), 1.75-1.70 (m, 2H), 1.47 (s, 9H), 1.45 (s, 2H), 1.38-1.27 (m, 2H), 1.27-1.16 (m, 2H).

tert-butyl 1-(6-bromohexyl)cyclopropane-1-carboxylate (L4d)

Prepared following a similar procedure to L4a using tert-butyl cyclopropanecarboxylate instead of tert-butyl isobutyrate. 1 H NMR (400 MHz, Chloroform-d) δ 3.42 (t, J=6.8 Hz, 2H), 1.87 (dt, J=14.7, 6.9 Hz, 2H), 1.56-1.49 (m, 1H), 1.44 (s, 9H), 1.32 (m, J=16.5, 9.3, 4.2, 1.6 Hz, 3H), 1.12 (q, J=3.8 Hz, 2H), 0.95-0.89 (m, 2H), 0.82-0.75 (m, 2H), 0.63-0.59 (m, 2H).

tert-butyl 1-(7-bromoheptyl)cyclobutane-1-carboxylate (L4e)

Prepared following a similar procedure to L4a using 1,7-dibromoheptane instead of 1,6-dibromohexane and tert-butyl cyclobutanecarboxylate instead of tert-butyl isobutyrate. 1 H NMR (400 MHz, Chloroform-d) δ 3.43 (t, J=6.8 Hz, 2H), 2.42-2.31 (m, 2H), 1.93-1.78 (m, 6H), 1.74-1.67 (m, 2H), 1.47 (s, 9H), 1.44 (s, 2H), 1.38-1.26 (m, 4H), 1.25-1.14 (m, 2H).

tert-butyl 1-(7-bromoheptyl)cyclopropane-1-carboxylate (L4f)

Prepared following a similar procedure to L4a using 1,7-dibromoheptane instead of 1,6-dibromohexane and tert-butyl cyclopropanecarboxylate instead of tert-butyl isobutyrate. 1 H NMR (400 MHz, Chloroform-d) δ 3.43 (t, J=6.9 Hz, 2H), 1.92-1.82 (m, 2H), 1.49-1.45 (m, 4H), 1.44 (s, 9H), 1.43 (s, 2H), 1.37-1.27 (m, 4H), 1.12 (q, J=3.8 Hz, 2H), 0.61 (q, J=3.9 Hz, 2H).

Preparation of tert-butyl (R)-8-bromo-2-methyloctanoate (L5a)

›Step 1

To a solution of 8-bromooctanoic acid (630 mg, 2.8 mmol) in dry THF (14 mL) at 0° C. was added with triethylamine (0.98 mL, 7.1 mmol) and pivaloyl chloride (0.37 mL, 3.0 mmol). The suspension was stirred for 20 min. Then, lithium chloride (120 mg, 2.8 mmol) and (R)-4-benzyl-2-oxazolidinone (620 mg, 2.8 mmol) were added. The suspension was warmed to room temperature and stirred for another 30 min. Then, water (5 mL) was added and the solution was concentrated under reduced pressure. The aqueous phase was extracted with EtOAc. The combined organic phases were dried over MgSO 4 , filtered and concentrated. The residue was purified by silica gel column chromatography (0-100% EtOAc in hexanes) to provide (R)-4-benzyl-3-(8-bromooctanoyl)oxazolidin-2-one. 1 H NMR (400 MHz, Chloroform-d) δ 7.34 (t, J=7.1 Hz, 2H), 7.30-7.25 (m, 1H), 7.24-7.17 (m, 2H), 4.67 (ddt, J=10.3, 6.9, 3.3 Hz, 1H), 4.24-4.14 (m, 2H), 3.41 (t, J=6.8 Hz, 2H), 3.30 (dd, J=13.4, 3.4 Hz, 1H), 3.04-2.83 (m, 2H), 2.77 (dd, J=13.3, 9.6 Hz, 1H), 1.87 (p, J=6.9 Hz, 2H), 1.70 (p, J=7.6, 6.8 Hz, 2H), 1.51-1.31 (m, 6H).

›Step 2

To a solution of (R)-4-benzyl-3-(8-bromooctanoyl)oxazolidin-2-one (620 mg, 1.6 mmol) in dry THF (5 mL) at −78° C. was added a solution of sodium bis(trimethylsilyl)amide (1 M in THF, 1.9 mL, 1.9 mmol). The solution was stirred for 20 min and then, methyl iodide (0.60 mL, 9.7 mmol) was added. The solution was allowed to warm to room temperature for 30 min. Then, water (1 mL) was added and the solution was concentrated under reduced pressure. The aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na 2 SO 4 , filtered and concentrated. The residue was purified by silica gel column chromatography (0-100% EtOAc in hexanes) to provide (R)-4-benzyl-3-((R)-8-bromo-2-methyloctanoyl)oxazolidin-2-one. 1 H NMR (400 MHz, Chloroform-d) δ 7.36-7.25 (m, 3H), 7.21 (d, J=7.3 Hz, 2H), 4.68 (ddt, J=10.3, 6.8, 3.2 Hz, 1H), 4.24-4.15 (m, 2H), 3.71 (h, J=6.7 Hz, 1H), 3.40 (t, J=6.8 Hz, 2H), 3.27 (dd, J=13.4, 3.4 Hz, 1H), 2.77 (dd, J=13.3, 9.6 Hz, 1H), 1.85 (p, J=6.9 Hz, 2H), 1.47-1.19 (m, 11H).

›Step 3

To a solution of (R)-4-benzyl-3-((R)-8-bromo-2-methyloctanoyl)oxazolidin-2-one (490 mg, 1.2 mmol) in THF (5 mL) and water (1 mL) at 0° C. was added an solution of 30% hydrogen peroxide in water (0.44 mL, 4.3 mmol) followed lithium hydroxide (100 mg, 2.5 mmol). The solution was allowed to warm to room temperature and stirred for 3 h. Then, a solution of sodium sulfite (880 mg, 6.2 mmol in 5 mL water) and saturated sodium bicarbonate (15 mL) were added. The THF was removed in vacuo and the remaining aqueous solution was washed with dichloromethane three times and these organic layers were discarded. The aqueous layer was acidified to pH 2 with 25% HCl and extracted three times with EtOAc. The EtOAc fractions were combined and concentrated in vacuo to give (R)-8-bromo-2-methyloctanoic acid. 1 H NMR (400 MHz, Chloroform-d) δ 3.40 (t, J=6.8 Hz, 2H), 2.47 (h, J=7.0 Hz, 1H), 1.85 (p, J=6.9 Hz, 2H), 1.50-1.30 (m, 8H), 1.19 (d, J=7.2 Hz, 3H).

›Step 4

A solution of (R)-8-bromo-2-methyloctanoic acid (223 mg, 0.96 mmol), 4-(dimethylamino)pyridine (12 mg, 0.096 mmol), and di-tert-butyl dicarbonate (420 mg, 1.9 mmol) in dichloromethane (1.2 mL) and tert-butanol (1.2 mL) was allowed to stir at room temperature overnight. The reaction was concentrated and brought up in EtOAc and washed with saturated sodium bicarbonate, saturated ammonium chloride, brine, and dried over MgSO 4 , filtered and concentrated. The residue was purified by silica gel column chromatography (0-40% EtOAc in hexanes) to provide tert-butyl (R)-8-bromo-2-methyloctanoate. 1 H NMR (400 MHz, Chloroform-d) δ 3.40 (td, J=6.9, 0.9 Hz, 2H), 2.30 (h, J=6.9 Hz, 1H), 1.85 (p, J=6.9 Hz, 2H), 1.50-1.20 (m, 17H), 1.09 (dd, J=7.0, 1.0 Hz, 3H).

tert-butyl (S)-8-bromo-2-methyloctanoate (L5b)

Prepared following a similar procedure to L5a using (S)-4-benzyl-2-oxazolidinone instead of (R)-4-benzyl-2-oxazolidinone. 1 H NMR (400 MHz, Chloroform-d) δ 3.40 (td, J=6.9, 0.9 Hz, 2H), 2.30 (h, J=6.9 Hz, 1H), 1.85 (p, J=6.9 Hz, 2H), 1.50-1.20 (m, 17H), 1.09 (dd, J=7.0, 1.0 Hz, 3H).

tert-butyl (R)-2-allyl-8-bromooctanoate (L5c)

Prepared using a similar procedure to L5a using (S)-4-benzyl-2-oxazolidinone instead of (R)-4-benzyl-2-oxazolidinone and allyl bromide instead of methyl iodide. 1 H NMR (400 MHz, Chloroform-d) δ 5.76 (ddt, J=16.9, 10.2, 6.9 Hz, 1H), 5.15-5.04 (m, 2H), 3.40 (t, J=6.9 Hz, 2H), 2.55-2.37 (m, 2H), 2.32-2.23 (m, 1H), 1.85 (p, J=6.9 Hz, 2H), 1.73-1.19 (m, 17H).

Preparation of tert-butyl 2-methyl-2-((5-(tosyloxy)pentyl)oxy)propanoate (L6a)

›Step 1

A mixture of tert-butyl 2-hydroxy-2-methyl-propanoate (0.5 g, 3.1 mmol), 3,4-dihydropyran (0.78 g, 9 mmol) in DCM (5 mL) and pyridinium p-toluenesulfonic acid (78 mg, 0.3 mmol) was stirred at rt for 16 h. Water and EtOAc were added. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over sodium sulfate.

Filtration and evaporation of solvents yielded the crude tert-butyl 2-methyl-2-((tetrahydro-2H-pyran-2-yl)oxy)propanoate which was used in the subsequent step with no further purification. ES/MS: m/z 267.0 [M+Na] + .

›Step 2

The crude material from the previous reaction (ca. 2 mmol) was cooled to 0° C. and treated neat with borane-THF (1M, 5 mmol, 4.6 mL). The reaction was allowed to slowly reach rt, and was stirred for 16 h followed by an additional 24 h at 40° C. The reaction was quenched with methanol followed by the addition of water and EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over sodium sulfate and concentrated to a light yellow oil. Purification by silica gel (0-100% EtOAc in hexanes) provided tert-butyl 2-((5-hydroxypentyl)oxy)-2-methylpropanoate. 1 H NMR (400 MHz, Chloroform-d) δ 3.71-3.62 (m, 2H), 3.39 (t, J=6.6 Hz, 2H), 1.66-1.55 (m, 7H), 1.48 (s, 9H), 1.38 (s, 6H). ES/MS: m/z 269.0 [M+Na] + .

›Step 3

tert-Butyl 2-methyl-2-((5-(tosyloxy)pentyl)oxy)propanoate (L6a) was then prepared following a similar procedure to L3a.

tert-butyl 3-((5-hydroxypentyl)oxy)-2,2-dimethylpropanoate (L6b)

Prepared following a similar procedure to L6a using tert-butyl 3-hydroxy-2,2-dimethylpropanoate instead of tert-butyl 2-hydroxy-2-methyl-propanoate. ES/MS: m/z 437.2 [M+Na] + .

Preparation of tert-butyl 1-(5-bromopentyl)-1H-pyrazole-5-carboxylate (L7a) and tert-butyl 1-(5-bromopentyl)-1H-pyrazole-3-carboxylate (L7b)

›Step 1

To a mixture of tert-butyl 1H-pyrazole-3-carboxylate (0.25 g, 1.49 mmol) and cesium carbonate (0.53 g, 1.64 mmol) in MeCN (15 mL) was added 1,5-dibromopentane (0.4 mL, 3.0 mmol). The reaction mixture was stirred overnight at rt. The reaction mixture was filtered through a pad of Celite and the filter pad was rinsed with EtOAc. The filtrate was concentrated onto silica gel and purified via flash chromatography on a silica gel column (0-40% EtOAc in hexanes) to isolate regioisomeric products tert-butyl 1-(5-bromopentyl)-1H-pyrazole-5-carboxylate (L7a) and tert-butyl 1-(5-bromopentyl)-1H-pyrazole-3-carboxylate (L7b). Regiochemistry was determined by HMBC. L7a: 1H NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 6.75 (s, 1H), 4.55 (t, J=7.0 Hz, 2H), 3.39 (t, J=6.2 Hz, 2H), 1.95-1.77 (m, 4H), 1.58 (s, 9H), 1.53-1.37 (m, 2H); ES/MS: m/z 317.1, 319.1 [M+H] + . L7b: 1 H NMR (400 MHz, CDCl3) δ 7.36 (s, 1H), 6.70 (s, 1H), 4.18 (t, J=7.0 Hz, 2H), 3.39 (t, J=6.8 Hz, 2H), 1.99-1.81 (m, 4H), 1.60 (s, 9H), 1.53-1.36 (m, 2H); ES/MS: m/z 339.1, 341.1 [M+Na] + .

tert-butyl 1-(4-bromobutyl)-1H-pyrazole-5-carboxylate (L7c)

Prepared following a similar procedure to L7a using 1,4-dibromobutane instead of 1,5-dibromopentane. ES/MS: m/z 303.1, 305.1 [M+H] + .

tert-butyl 1-(6-bromohexyl)-1H-pyrazole-5-carboxylate (L7d)

Prepared following a similar procedure to L7a using 1,6-dibromohexane instead of 1,5-dibromopentane. ES/MS: m/z 331.1, 333.1 [M+H] + .

tert-butyl 1-(6-bromohexyl)-1H-pyrazole-3-carboxylate (L7e)

Prepared following a similar procedure to L7b using 1,6-dibromohexane instead of 1,5-dibromopentane. ES/MS: m/z 353.1, 355.1 [M+Na] + .

Preparation of tert-butyl 2-fluoro-3-(4-(tosyloxy)butyl)benzoate (L8a)

›Step 1

To a solution of 2-tert-butyl-1,3-diisopropylisourea (0.59 g, 2.94 mmol) in DCM (12 mL) at 0° C. was added 2-fluoro-3-(hydroxymethyl)benzoic acid (0.50 g, 2.94 mmol). The reaction mixture was allowed to warm to rt and was stirred overnight. The reaction mixture was cooled to 0° C. and another portion of 2-tert-butyl-1,3-diisopropylisourea (0.59 g, 2.94 mmol) was added. The mixture was allowed to warm to rt and was stirred overnight. The reaction mixture was cooled to 0° C. and another portion of 2-tert-butyl-1,3-diisopropylisourea (0.59 g, 2.94 mmol) was added. After 1 h, the reaction mixture was filtered. The filtrate was washed successively with 10% citric acid soln, sat bicarb soln and brine. The organic layer was dried (Na 2 SO 4 ), filtered and concentrated. The residue was purified via flash chromatography on a silica gel column (0-100% EtOAc in hexanes) to afford tert-butyl 2-fluoro-3-(hydroxymethyl)benzoate. ES/MS: m/z 249.1 [M+Na] + .

›Step 2

To a solution of oxalyl chloride (0.14 mL, 1.60 mmol) in DCM (10 mL) at −78° C. was added a solution of DMSO (0.24 mL, 3.33 mmol) in DCM (1 mL), dropwise. The reaction mixture was stirred for 10 min before a solution of tert-butyl 2-fluoro-3-(hydroxymethyl)benzoate (0.30 g, 1.33 mmol) in DCM (2 mL) was added, dropwise. The reaction mixture was stirred at −78° C. for 40 min. TEA (0.93 mL, 6.65 mmol) was added. The reaction mixture was stirred for 10 min at −78° C. and was then allowed to warm to rt over 30 min. The reaction mixture was diluted with water and DCM. The aqueous layer was extracted twice with DCM. The combined organic layers were washed sequentially with sat aq. NaHCO 3 and brine, dried (Na 2 SO 4 ), filtered and concentrated to afford tert-butyl 2-fluoro-3-formylbenzoate. ES/MS: m/z 265.1 [M+H 2 O+Na] + .

›Step 3

To a slurry of (3-((tert-butyldimethylsilyl)oxy)propyl)triphenylphosphonium bromide (0.75 g, 1.46 mmol) in THF (22 mL) at −78° C. was added LiHMDS solution (1.7 mL, 1 M in THF, 1.7 mmol), dropwise. The mixture was stirred at −78° C. for 1 h. A solution of tert-butyl 2-fluoro-3-formylbenzoate (0.30 g, 1.33 mmol) in THF (4 mL) was added. The reaction mixture was stirred at −78° C. for 1 h and was then allowed to warm to rt overnight. The reaction mixture was diluted with water and EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with water, dried (Na 2 SO 4 ), filtered and concentrated. The residue was purified via flash chromatography on a silica gel column (0-40% EtOAc in hexanes) to afford tert-butyl 3-(4-((tert-butyldimethylsilyl)oxy)but-1-en-1-yl)-2-fluorobenzoate. ES/MS: m/z 403.2 [M+Na] + .

›Step 4

A mixture of tert-butyl 3-(4-((tert-butyldimethylsilyl)oxy)but-1-en-1-yl)-2-fluorobenzoate (0.35 g, 0.93 mmol) and Pd/C (0.05 g of 10% Pd/C, wet) in EtOAc and MeOH (9 mL and 1 mL, respectively) was shaken on a Parr shaker at 20 psi H 2 for 3 h. The mixture was filtered through Celite and the filter pad was rinsed with EtOAc/MeOH. The filtrate was concentrated to afford tert-butyl 3-(4-((tert-butyldimethylsilyl)oxy)butyl)-2-fluorobenzoate. ES/MS: m/z 405.3 [M+Na] + .

›Step 5

To a solution of tert-butyl 3-(4-((tert-butyldimethylsilyl)oxy)butyl)-2-fluorobenzoate (0.30 g, 0.77 mmol) in THF (7.5 mL) was added TBAF (1.5 mL of a 1 M soln in THF, 1.5 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was diluted with water and EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried (Na 2 SO 4 ), filtered, and concentrated. The residue was purified via flash chromatography on a silica gel column (0-50% EtOAc in hexanes) to afford tert-butyl 2-fluoro-3-(4-hydroxybutyl)benzoate. ES/MS: m/z 291.1 [M+Na] + .

›Step 6

To a solution of tert-butyl 2-fluoro-3-(4-hydroxybutyl)benzoate (0.21 g, 0.77 mmol), TEA (0.32 mL, 2.33 mmol) and DMAP (0.009 g, 0.078 mmol) in DCM (8 mL) at 0° C. was added p-toluenesulfonyl chloride (0.22 g, 1.16 mmol). The reaction mixture was allowed to warm to rt and was stirred overnight. The reaction mixture was diluted with water and DCM. The aqueous layer was extracted twice with DCM. The combined organic layers were washed with brine, dried (Na 2 SO 4 ), filtered, and concentrated. The residue was purified via flash chromatography on a silica gel column (0-50% EtOAc in hexanes) to afford tert-butyl 2-fluoro-3-(4-(tosyloxy)butyl)benzoate. ES/MS: m/z 445.2 [M+Na] + .

Preparation of tert-butyl 6-(4-(tosyloxy)butyl)picolinate (L9a)

›Step 1

To a slurry of (3-((tert-butyldimethylsilyl)oxy)propyl)triphenylphosphonium bromide (1.05 g, 2.03 mmol) in THF (20 mL) at −78° C. was added LiHMDS (2.2 mL of a 1 M soln in THF, 2.2 mmol), dropwise. The mixture was stirred at −78° C. for 1 h. Methyl 6-formylpicolinate (0.34 g, 2.03 mmol) was added. The reaction mixture was stirred at −78° C. for 1 h and was then allowed to warm to rt overnight. The reaction mixture was diluted with water and EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with water, dried (Na 2 SO 4 ), filtered and concentrated. The residue was purified via flash chromatography on a silica gel column (0-50% EtOAc in hexanes) to afford methyl 6-(4-((tert-butyldimethylsilyl)oxy)but-1-en-1-yl)picolinate. ES/MS: m/z 322.3 [M+H] + .

›Step 2

A mixture of methyl 6-(4-((tert-butyldimethylsilyl)oxy)but-1-en-1-yl)picolinate (0.30 g, 0.93 mmol) and Pd/C (0.05 g of 10% Pd/C, wet) in EtOAc and MeOH (18 mL and 3 mL, respectively) was shaken on a Parr shaker at 20 psi H 2 for 3 h. The mixture was filtered through Celite and the filter pad was rinsed with EtOAc/MeOH. The filtrate was concentrated to afford methyl 6-(4-((tert-butyldimethylsilyl)oxy)butyl)picolinate. ES/MS: m/z 324.2 [M+H] + .

›Step 3

To a solution of t-BuOH (0.07 mL, 0.75 mmol) in THF (1 mL) at 0° C. was added n-BuLi (0.30 mL of a 2.5 M soln in hexanes, 0.75 mmol), followed by a solution of methyl 6-(4-((tert-butyldimethylsilyl)oxy)butyl)picolinate (0.24 g, 0.75 mmol) in THF (1.25 mL). The reaction mixture was stirred at 0° C. for 1 h. The reaction was quenched by addition of water, and the mixture was diluted with EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried (Na 2 SO 4 ), filtered, and concentrated. The residue was purified via flash chromatography on a silica gel column (0-50% EtOAc in hexanes) to afford tert-butyl 6-(4-((tert-butyldimethylsilyl)oxy)butyl)picolinate. ES/MS: m/z 366.3 [M+H] + .

›Step 4

To a solution of tert-butyl 6-(4-((tert-butyldimethylsilyl)oxy)butyl)picolinate (0.18 g, 0.50 mmol) in THF (5.0 mL) was added TBAF (1.0 mL of a 1 M soln in THF, 1.0 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was diluted with water and EtOAc. The aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried (Na 2 SO 4 ), filtered, and concentrated. The residue was purified via flash chromatography on a silica gel column (0-100% EtOAc in hexanes) to afford tert-butyl 6-(4-hydroxybutyl)picolinate. ES/MS: m/z 252.2 [M+H] + .

›Step 5

To a solution of tert-butyl 6-(4-hydroxybutyl)picolinate (0.11 g, 0.42 mmol), TEA (0.18 mL, 1.27 mmol) and DMAP (0.005 g, 0.042 mmol) in DCM (4.2 mL) at 0° C. was added p-toluenesulfonyl chloride (0.12 g, 0.63 mmol). The reaction mixture was allowed to warm to rt and was stirred overnight. The reaction mixture was diluted with water and DCM. The aqueous layer was extracted twice with DCM. The combined organic layers were washed with brine, dried (Na 2 SO 4 ), filtered, and concentrated. The residue was purified via flash chromatography on a silica gel column (0-100% EtOAc in hexanes) to afford tert-butyl 6-(4-(tosyloxy)butyl)picolinate. ES/MS: m/z 406.2 [M+H] + .

Preparation of tert-butyl rac-3-(((1S,3R)-3-(hydroxymethyl)-2,2-dimethylcyclopropyl)methoxy)propanoate (L10)

›Step 1

A solution of lithium aluminum hydride (2.0 M in THF, 28.0 mL, 56.0 mmol) was cooled under N 2 atmosphere in an ice water bath. 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (2500 mg, 17.8 mmol) was then added dropwise as a solution in THF (20 mL) over ca. 20 min to maintain internal temperature below 6° C. Additional THF (2×5 mL) was used to wash.

The mixture was allowed to stir for 5 h, during which time the ice bath expired. The reaction mixture was cooled in an ice bath, and water (2.1 mL) was slowly added, maintaining internal temperature below 10° C. Then, 15% aqueous NaOH (2.1 mL) was slowly added, maintaining internal temperature below 10° C. Then, water (6.6. mL) was slowly added. Reaction mixture was removed from cold bath and allowed to stir 10 min. MgSO 4 was added, and the mixture was filtered through Celite and concentrated to afford rac-((1R,3S)-3-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylcyclopropyl)methanol that was used without further purification. 1 H NMR (400 MHz, DMSO-d6) δ 4.28 (t, J=5.2 Hz, 2H), 3.52-3.38 (m, 4H), 1.03 (s, 3H), 1.00 (s, 3H), 0.78 (ddd, J=7.5, 5.2, 2.4 Hz, 2H).

›Step 2

rac-((1R,3S)-3-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethylcyclopropyl)methanol (2.08 g, 16 mmol) was dissolved in THF (100 mL) under N 2 and the resulting solution was cooled in an ice water bath. NaH as a 60% dispersion in mineral oil (0.735 g, 18.4 mmol) was added portionwise. After 2 h, tert-butylchlorodiphenylsilane (4.15 mL, 0.0160 mol) was added. The reaction mixture was stirred for 10 min and allowed to warm to r.t. After 1 h, the reaction was quenched with sat. aq. NH 4 Cl and diluted with Et 2 O. The organic phase was washed with brine, dried over MgSO 4 , filtered, and concentrated. Purification by silica gel (0-40% EtOAc in hexanes) provided rac-((1R,3S)-3-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylcyclopropyl)methanol. 1 H NMR (400 MHz, DMSO-d6) δ 7.68-7.60 (m, 4H), 7.52-7.39 (m, 6H), 4.21 (t, J=5.1 Hz, 1H), 3.79 (dd, J=11.2, 6.2 Hz, 1H), 3.64 (dd, J=11.3, 8.3 Hz, 1H), 3.46-3.35 (m, 2H), 1.05 (s, 3H), 0.99 (s, 9H), 0.99 (s, 3H), 0.91-0.78 (m, 2H).

›Step 3

rac-((1R,3S)-3-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethylcyclopropyl)methanol (2.05 g, 5.56 mmol) was dissolved in tBuOH (25 mL) and tert-butyl prop-2-enoate (16.3 mL, 111 mmol) and cesium carbonate (1.81 g, 5.56 mmol) were added. The resulting mixture was stirred at r.t. for 5 h and at 60° C. for 19 h. Reaction mixture was diluted with Et 2 O and water. Organic phase was washed brine, dried over MgSO 4 , filtered, and concentrated. Purification by silica gel (0-30% EtOAc in hexanes) provided tert-butyl rac-3-(((1R,3S)-3-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylcyclopropyl)methoxy)propanoate.

›Step 4

tert-Butyl rac-3-[[(1S,3R)-3-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,2-dimethylcyclopropyl]methoxy]propanoate (2.78 g, 5.6 mmol) was dissolved in THF (25 mL). TBAF (1.0 M in THF, 8.40 mL, 8.4 mmol) was added and the resulting mixture was stirred 5 h at r.t. Reaction mixture was partitioned between Et 2 O and water. Organic phase was washed brine, dried over MgSO 4 , filtered, and concentrated. Purification by silica gel (20-60% EtOAc in hexanes) provided tert-butyl rac-3-[[(1S,3R)-3-(hydroxymethyl)-2,2-dimethylcyclopropyl]methoxy]propanoate. 1 H NMR (400 MHz, DMSO-d6) δ 3.54 (t, J=6.2 Hz, 2H), 3.50-3.31 (m, 4H), 2.40 (t, J=6.1 Hz, 2H), 1.40 (s, 9H), 1.04 (s, 3H), 1.00 (s, 3H), 0.87-0.73 (m, 2H).

Preparation of tert-butyl rac-3-(((1R,2S)-2-((tosyloxy)methyl)cyclobutyl)methoxy)propanoate (L11)

›Step 1

rac-((1R,2S)-cyclobutane-1,2-diyl)dimethanol was prepared analogously to rac-((1R,3S)-3-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylcyclopropyl)methanol (step 1 of L10), but starting with rac-(1R,5S)-3-oxabicyclo[3.2.0]heptane-2,4-dione. 1 H NMR (400 MHz, DMSO-d6) δ 4.48 (dd, J=5.7, 4.7 Hz, 2H), 3.64-3.51 (m, 2H), 3.46-3.36 (m, 2H), 2.52-2.39 (m, 2H), 1.97-1.81 (m, 2H), 1.63-1.51 (m, 2H).

›Step 2

rac-((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclobutyl)methanol was prepared analogously to rac-((1R,3S)-3-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylcyclopropyl)methanol (step 2 of L10), but starting with rac-((1R,2S)-cyclobutane-1,2-diyl)dimethanol. 1 H NMR (400 MHz, DMSO-d6) δ 7.66-7.57 (m, 4H), 7.51-7.39 (m, 6H), 4.27 (t, J=5.1 Hz, 1H), 3.82 (dd, J=10.4, 7.0 Hz, 1H), 3.69 (dd, J=10.4, 7.0 Hz, 1H), 3.60 (ddd, J=10.6, 6.9, 4.9 Hz, 1H), 3.46 (ddd, J=10.6, 7.6, 5.2 Hz, 1H), 2.63-2.53 (m, 1H), 2.50-2.43 (m, 1H), 1.99-1.85 (m, 2H), 1.73-1.59 (m, 2H), 0.99 (s, 9H).

›Step 3

tert-butyl rac-3-(((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclobutyl)methoxy)propanoate was prepared analogously to tert-butyl rac-3-(((1R,3S)-3-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylcyclopropyl)methoxy)propanoate (step 3 of L10), but starting with rac-((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclobutyl)methanol. 1 H NMR (400 MHz, DMSO-d6) δ 7.64-7.59 (m, 4H), 7.50-7.40 (m, 6H), 3.82-3.73 (m, 1H), 3.72-3.62 (m, 1H), 3.58-3.51 (m, 1H), 3.48 (t, J=6.2 Hz, 2H), 3.46-3.40 (m, 1H), 2.62-2.52 (m, 2H), 2.34 (t, J=6.2 Hz, 2H), 1.97-1.87 (m, 2H), 1.76-1.60 (m, 2H), 1.36 (s, 9H), 1.00 (s, 9H).

›Step 4

tert-butyl rac-3-(((1R,2S)-2-(hydroxymethyl)cyclobutyl)methoxy)propanoate was prepared analogously to tert-butyl rac-3-[[(1S,3R)-3-(hydroxymethyl)-2,2-dimethylcyclopropyl]methoxy]propanoate (step 4 of L10), but starting with tert-butyl rac-3-(((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclobutyl)methoxy)propanoate. 1 H NMR (400 MHz, DMSO-d6) δ 4.18 (dd, J=5.6, 5.0 Hz, 1H), 3.58-3.48 (m, 4H), 3.44-3.35 (m, 2H), 2.58-2.47 (m, 1H), 2.47-2.36 (m, 3H), 1.97-1.83 (m, 2H), 1.71-1.56 (m, 2H), 1.40 (s, 9H).

›Step 5

tert-butyl rac-3-(((1R,2S)-2-(hydroxymethyl)cyclobutyl)methoxy)propanoate (122 mg, 0.499 mmol) was dissolved in DCM (1.5 mL), and trimethylamine (0.21 mL, 1.5 mmol) and 4-dimethylaminopyridine (15 mg, 0.12 mmol) were added. Solution was cooled in an ice water bath and p-toluenesulfonyl chloride (0.14 g, 0.75 mmol) was added. The mixture was stirred 80 min, and then let warm to r.t. Once complete, the mixture was purified directly by silica gel chromatography to afford tert-butyl rac-3-(((1R,2S)-2-((tosyloxy)methyl)cyclobutyl)methoxy)propanoate. ES/MS: 420.93 m/z [M+Na] + .

Preparation of tert-butyl 2-((6-bromohexyl)oxy)benzoate (L12)

›Step 1

PPh 3 (393 mg, 1.5 mmol) was dissolved in THF (3 mL) and the solution was cooled to 0° C. DIAD (303 mg, 1.5 mmol) was added and the resulting solution was warmed to room temperature and stirred for 30 minutes. The yellow suspension was cooled back to 0° C. and a solution tert-butyl 2-hydroxybenzoate (130 mg, 1 mmol) and 6-bromohexan-1-ol (217 mg, 1.2 mmol) in THF (1 mL) was added dropwise. The reaction was warmed to room temperature and stirred overnight. Purification (Hexanes/Diethyl ether 0-10%) afforded tert-butyl 2-((6-bromohexyl)oxy)benzoate. 1 H NMR (400 MHz, Chloroform-d) δ 7.69 (dd, J=7.6, 1.8 Hz, 1H), 7.44-7.37 (m, 1H), 7.01-6.88 (m, 2H), 4.03 (t, J=6.4 Hz, 2H), 3.45 (t, J=6.8 Hz, 2H), 2.05-1.75 (m, 4H), 1.61 (s, 9H), 1.60-1.50 (m, 4H).

Preparation of tert-butyl rac-3-(((1R,2S)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate (L13a)

›Step 1

To a solution of cis-(cyclopropane-1,2-diyl)dimethanol (3.0 g, 29.4 mmol) in THF (50 mL) at 0° C. was added NaH (60%, 1.41 g, 35.2 mmol) and the mixture was stirred for 15 min. TBDPSCl (7.6 mL, 29.4 mmol) was then added and the reaction mixture was warmed to rt and stirred for 2 h. Saturated aqueous NH 4 Cl was added slowly and the mixture was extracted twice with Et 2 O. The combined organic layers were washed with brine, dried with MgSO 4 , filtered and concentrated to provide crude rac-((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methanol which was used below without further purification. ES/MS: m/z 363.0 [M+Na] + .

›Step 2

To a solution of rac-((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methanol (ca. 7.34 mmol) in tert-BuOH (35 mL) was added tert-butyl acrylate (16.1 mL, 110 mmol) and Cs 2 CO 3 (2.39 mg, 7.34 mmol). The reaction mixture was stirred at rt overnight, diluted with EtOAc, washed with brine, dried with MgSO 4 , filtered and concentrated. Purification by silica gel chromatography (0-20% EtOAc in hexanes) provided tert-butyl rac-3-(((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methoxy)propanoate. ES/MS: m/z 491.3 [M+Na] + .

›Step 3

To a solution of tert-butyl rac-3-(((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methoxy)propanoate (1.4 g, 2.99 mmol) in THF (15 mL) was added 1.0M TBAF in THF (4.5 mL, 4.48 mmol). The reaction mixture was stirred at room temperature for 1 h. Ethyl acetate was added and the solution was washed with saturated aqueous NaHCO 3 followed by brine. The organic phase was dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-60% EtOAc in hexanes) provided tert-butyl rac-3-(((1R,2S)-2-(hydroxymethyl)cyclopropyl)methoxy)propanoate. 1 H NMR (400 MHz, Chloroform-d) δ 4.01-3.83 (m, 2H), 3.82-3.61 (m, 2H), 3.28-3.11 (m, 2H), 3.01-2.95 (m, 1H), 2.54-2.48 (m, 2H), 1.46 (s, 9H), 1.41-1.22 (m, 2H), 0.84-0.75 (m, 1H), 0.23-0.17 (m, 1H).

›Step 4

To a solution of tert-butyl rac-3-(((1R,2S)-2-(hydroxymethyl)cyclopropyl)methoxy)propanoate (260 mg, 1.13 mmol) in dichloromethane (5 mL) at 0° C. were added TsCl (323 mg, 1.69 mmol), triethylamine (0.47 mL, 3.39 mmol) and DMAP (14 mg, 0.11 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with DCM then washed with water and brine. The organic phase was dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (0-80% EtOAc in hexanes) provided tert-butyl rac-3-(((1R,2S)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate. ES/MS: m/z 407.2 [M+Na] + . 1H NMR (400 MHz, Chloroform-d) δ 7.86-7.72 (m, 2H), 7.34 (d, J=7.8 Hz, 2H), 4.17-4.03 (m, 2H), 3.66-3.54 (m, 2H), 3.43 (dd, J=10.7, 5.9 Hz, 1H), 3.32 (dd, J=10.6, 6.7 Hz, 1H), 2.50-2.40 (m, 5H), 1.44 (s, 9H), 1.32-1.20 (m, 2H), 0.91-0.81 (m, 1H), 0.32 (q, J=5.7 Hz, 1H).

tert-butyl rac-3-(((1S,2S)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate (L13b)

Prepared following a similar procedure to L13a from rac-((1S,2S)-2-(((tert-butyldimethylsilyl)oxy)methyl)cyclopropyl)methanol (WO 2008115381 A1). 1 H NMR (400 MHz, Chloroform-d) δ 7.78 (d, J=7.9 Hz, 2H), 7.34 (d, J=8.1 Hz, 2H), 3.96 (dd, J=10.6, 7.1 Hz, 1H), 3.92-3.84 (m, 1H), 3.63 (tt, J=6.4, 1.3 Hz, 2H), 3.32 (dd, J=10.4, 6.3 Hz, 1H), 3.26-3.19 (m, 1H), 2.50-2.42 (m, 5H), 1.44 (s, 9H), 1.09-0.92 (m, 2H), 0.60-0.45 (m, 2H).

tert-butyl 3-((1-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate (L13c)

Prepared following a similar procedure to L13a from cyclopropane-1,1-diyldimethanol. ES/MS: m/z 407.2 [M+Na] + .

tert-butyl 3-(((1R,2S)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate (L13d)

Prepared following a similar procedure to L13a from ((1R,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methanol (J. Am. Chem. Soc. 2008, 16424). ES/MS: m/z 407.2 [M+Na] + .

tert-butyl 3-(((1S,2R)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate (L13e)

Prepared following a similar procedure to L13a from ((1S,2R)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methanol (J. Am. Chem. Soc. 2008, 16424). ES/MS: m/z 407.2 [M+Na] + .

tert-butyl 3-(((1R,2S)-2-(hydroxymethyl)cyclopropyl)methoxy)propanoate (L3f)

Prepared following a similar procedure to L13d stopping the sequence after step 3. ES/MS: m/z 253.2 [M+Na] + .

tert-butyl 3-(((1R,2S)-2-(hydroxymethyl)cyclopropyl)methoxy)-2-methylpropanoate (L13g)

Prepared following a similar procedure to L13a using tert-butyl methacrylate instead of tert-butyl acrylate and stopping the sequence after step 3. ES/MS: m/z 267.2 [M+Na] + .

Preparation of tert-butyl rac-3-(((1R,2S)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate (L14a)

›Step 1

To a solution of trans-(cyclopropane-1,2-diyl)dimethanol (3.0 g, 29.4 mmol) in THF (50 mL) at 0° C. was added NaH (60% dispersion, 1.41 g, 35.2 mmol) and the mixture was stirred for 15 min. TBDPSCl (7.6 mL, 29.4 mmol) was then added and the reaction mixture was warmed to rt and stirred for 2 h. Saturated aqueous NH 4 Cl was added slowly and the mixture was extracted twice with Et 2 O. The combined organic layers were washed with brine, dried with MgSO 4 , filtered and concentrated to provide crude rac-((1S,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methanol which was used below without further purification. ES/MS: m/z 363.0 [M+Na] + .

›Step 2

To a solution of rac-((1S,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methanol (375 mg, 1.10 mmol) and Bu 4 NCl (101 mg, 0.33 mmol) in toluene (6 mL) at 0° C. was added 35% aqueous NaOH (6 mL). Tert-butylbromoacetate (0.244 mL, 1.65 mmol) was then added dropwise at 0° C. The reaction mixture was stirred at rt overnight, diluted with EtOAc, washed with water and brine, dried with MgSO 4 , filtered and concentrated. Purification by silica gel chromatography (0-30% EtOAc in hexanes) provided tert-butyl 2-(((1S,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methoxy)acetate. ES/MS: m/z 477.3 [M+Na] + .

›Step 3

tert-butyl 2-(((1S,2S)-2-((tosyloxy)methyl)cyclopropyl)methoxy)acetate was made following steps 3-4 of intermediate L13a using tert-butyl 2-(((1S,2S)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methoxy)acetate. ES/MS: m/z 393.2 [M+Na] + .

tert-butyl 2-(2-(1-(2-(tosyloxy)ethyl)cyclopropyl)ethoxy)acetate (L14b)

Prepared following a similar procedure to L14a from 2,2′-(cyclopropane-1,1-diyl)bis(ethan-1-ol). ES/MS: m/z 421.2 [M+Na] + .

Preparation of tert-butyl 3-((1-(2-(tosyloxy)ethyl)cyclopropyl)methoxy)propanoate (L15a)

›Step 1

To a solution of DMSO (0.57 mL, 8.1 mmol) in DCM (40 mL) at −78° C. was added oxalyl chloride (0.56 mL, 6.6 mmol). The solution was stirred at −78° C. for 30 minutes before the addition of a solution of tert-butyl 3-((1-(hydroxymethyl)cyclopropyl)methoxy)propanoate (intermediate in the synthesis of L13c, 1.16 g, 5.04 mmol) in DCM (10 mL). The mixture was stirred at −78° C. for 30 minutes before the addition of Et 3 N (3.5 mL, 25.2 mmol). The reaction mixture was warmed to room temperature and stirred for 15 minutes. 1N HCl was added slowly and the mixture was extracted twice with DCM. The combined organic layers were washed with brine, dried with MgSO 4 , filtered and concentrated to provide crude tert-butyl 3-((1-formylcyclopropyl)methoxy)propanoate which was used below without further purification. 1 H NMR (400 MHz, Chloroform-d) δ 9.03 (s, 1H), 3.76-3.60 (m, 4H), 2.48 (t, J=6.3 Hz, 2H), 1.45 (s, 9H), 1.25-1.06 (m, 4H).

›Step 2

To a suspension of methyltriphenylphosphonium bromide (1.36 g, 3.8 mmol) in THF (35 mL) at 0° C. was added n-BuLi (1.7 M in hexane, 2.24 mL, 3.8 mmol). The resulting solution was stirred for 10 minutes. A solution of tert-butyl 3-((1-formylcyclopropyl)methoxy)propanoate (580 mg, 2.54 mmol) in THF (15 mL) was added dropwise at 0° C. and the resulting solution was stirred at 0° C. for 1 h. Water was then added and the mixture was extracted with diethyl ether. The combined organic layers were washed with brine, dried over MgSO 4 and concentrated under reduced pressure. Purification by silica gel chromatography (0-30% EtOAc in hexanes) provided tert-butyl 3-((1-vinylcyclopropyl)methoxy)propanoate. 1 H NMR (400 MHz, Chloroform-d) δ 5.63 (dd, J=17.4, 10.7 Hz, 1H), 5.02 (d, J=10.8 Hz, 1H), 4.94 (d, J=10.8 Hz, 1H), 3.68 (t, J=6.5 Hz, 2H), 3.44 (s, 2H), 2.49 (t, J=6.5 Hz, 2H), 1.45 (s, 9H), 0.83-0.52 (m, 4H).

›Step 3

A solution of tert-butyl 3-((1-vinylcyclopropyl)methoxy)propanoate in THF was added to a solution of 1 M borane in THF at 0° C. The solution was stirred at 0° C. for 2 h. The mixture was subsequently treated with water, 15% aqueous NaOH and 30% aqueous H 2 O 2 . The mixture was then stirred 2 h at rt. Water was added slowly and the mixture was extracted twice with EtOAc. The combined organic layers were washed with brine, dried with MgSO 4 , filtered and concentrated to provide crude tert-butyl 3-((1-(2-hydroxyethyl)cyclopropyl)methoxy)propanoate which was used below without further purification. ES/MS: m/z 266.9 [M+Na] + .

›Step 4

tert-butyl 3-((1-(2-(tosyloxy)ethyl)cyclopropyl)methoxy)propanoate was made following step 4 of intermediate L13a using tert-butyl 3-((1-(2-hydroxyethyl)cyclopropyl)methoxy)propanoate. ES/MS: m/z 421.2 [M+Na] + .

tert-butyl 3-(((1R,2R)-2-(2-(tosyloxy)ethyl)cyclopropyl)methoxy)propanoate (L15b)

Prepared using a similar procedure to L15a from tert-butyl 3-(((1R,2S)-2-(hydroxymethyl)cyclopropyl)methoxy)propanoate (intermediate in the synthesis of L13d). ES/MS: m/z 421.2 [M+Na] + .

Preparation of tert-butyl (R)-3-methoxy-8-(tosyloxy)octanoate (L16a)

›Step 1

A solution of (S)-3-acetyl-4-benzyloxazolidin-2-one (2.8 g, 13 mmol) in DCM (35 mL) was cooled to −78° C. before adding TiCl 4 (1.43 mL, 13 mmol). DIEA (2.26 mL, 13 mmol) was then added and the mixture was stirred at −78° C. for 1 h. A solution of 6-((tert-butyldiphenylsilyl)oxy)hexanal (4.6 g, 13 mmol, J. Am. Chem. Soc. 2013, 9358) in DCM (5 mL) was then added. The mixture was stirred at −78° C. for 1 h and quenched with 40 mL of 1N HCl. After stirring for 15 min at rt, saturated aqueous NH 4 Cl was added and the mixture was extracted twice with DCM. The combined organics were washed with water, brine, dried (MgSO 4 ), filtered, and concentrated under reduced pressure. The resulting residue (3:1 mixture of diastereoisomers) was purified via silica gel column chromatography (0-40% ethyl acetate in hexanes) to yield (S)-4-benzyl-3-((R)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoyl)oxazolidin-2-one (major) and (S)-4-benzyl-3-((S)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoyl)oxazolidin-2-one (minor). 1 H NMR of major product (400 MHz, Chloroform-d) δ 7.67 (d, J=7.6 Hz, 4H), 7.48-7.13 (m, 11H), 4.74-4.65 (m, 1H), 4.28-4.00 (m, 4H), 3.66 (t, J=6.4 Hz, 2H), 3.29 (dd, J=13.5, 3.5 Hz, 1H), 3.17-2.98 (m, 2H), 2.93 (d, J=4.3 Hz, 1H), 2.81 (dd, J=13.4, 9.4 Hz, 1H), 1.63-1.32 (m, 6H), 1.05 (s, 9H). 1 H NMR of minor product (400 MHz, Chloroform-d) δ 7.74-7.58 (m, 4H), 7.48-7.13 (m, 11H), 4.69 (ddt, J=10.5, 7.0, 3.3 Hz, 1H), 4.32-4.02 (m, 4H), 3.67 (t, J=6.4 Hz, 2H), 3.31 (dd, J=13.4, 3.4 Hz, 1H), 3.17 (dd, J=17.7, 2.5 Hz, 1H), 2.97 (dd, J=17.5, 9.4 Hz, 1H), 2.87-2.68 (m, 2H), 1.69-1.32 (m, 6H), 1.05 (s, 9H).

›Step 2

30% aqueous H 2 O 2 (3.6 mL, 31.8 mmol) was added to a solution of LiOH·H 2 O (444 mg, 10.6 mmol) in THF (25 mL) and water (10 mL) at 0° C. The mixture was stirred for 15 min at 0° C. followed by the addition of (S)-4-benzyl-3-((R)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoyl)oxazolidin-2-one (2.43 g, 4.23 mmol) in THF (10 mL). The reaction mixture was stirred at rt overnight and quenched with 1N HCl. The reaction mixture was partitioned between DCM and water, and the organic phase was washed with brine, dried with MgSO 4 , filtered, and concentrated to provide crude (R)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoic acid which was used below without further purification. ES/MS: m/z 437.3 [M+Na] + .

›Step 3

A solution of (R)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoic acid (800 mg, 1.93 mmol) and tert-butyl 2,2,2-trichloroethanimidate (1.73 mL, 9.65 mmol) in DCM (20 mL) was stirred at rt for 4 days. Concentration and purification by silica gel chromatography (0-50% EtOAc in hexanes) provided tert-butyl (R)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoate. ES/MS: m/z 493.3 [M+Na] + .

›Step 4

To a stirred solution of tert-butyl (R)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoate (309 mg, 0.66 mmol) in DMF (3 mL) at 0° C. were added Mel (0.2 mL, 3.3 mmol) and NaH (60% oil suspension, 66 mg, 1.6 mmol). The mixture was stirred at rt for 30 min, diluted with water and EtOAc, then extracted with EtOAc. The combined extracts were washed with brine, dried with MgSO 4 , and concentrated. Purification by silica gel chromatography (0-20% EtOAc in hexanes) provided tert-butyl (R)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoate. ES/MS: m/z 507.3 [M+Na] + .

›Step 5

tert-Butyl (R)-3-methoxy-8-(tosyloxy)octanoate (L16a) was made following steps 3-4 of intermediate L13a using tert-butyl (R)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoate. ES/MS: m/z 423.2 [M+Na] + .

tert-Butyl (S)-3-methoxy-8-(tosyloxy)octanoate (L16b)

Prepared following a similar procedure to L16a from (S)-4-benzyl-3-((S)-8-((tert-butyldiphenylsilyl)oxy)-3-hydroxyoctanoyl)oxazolidin-2-one. ES/MS: m/z 423.2 [M+Na] + .

Preparation of tert-butyl 2-methoxy-2-methyl-8-(tosyloxy)octanoate (L17, Approximatively a 2:1 Mixture of Unspecified Enantiomers)

›Step 1

To a solution of ((5-bromopentyl)oxy)(tert-butyl)diphenylsilane (2.0 g, 4.93 mmol) in THF (3.0 mL) at −78° C. was added Li 2 CuCl 4 (19 mg, 0.1 mmol). A solution of chloro(2-methylallyl)magnesium (0.5 M in THF, 19.7 mL, 9.9 mmol) was the added dropwise over 20 min. The reaction mixture was stirred at −78° C. for 1 h followed by 4 h at 0° C. to rt. The reaction mixture was partitioned between EtOAc and brine, and the organic phase was dried with MgSO 4 , filtered, and concentrated. Purification by silica gel chromatography (100% hexanes) provided tert-butyl((7-methyloct-7-en-1-yl)oxy)diphenylsilane. 1 H NMR (400 MHz, Chloroform-d) δ 7.72-7.59 (m, 4H), 7.46-7.31 (m, 6H), 4.67 (d, J=12.1 Hz, 2H), 3.65 (td, J=6.7, 2.2 Hz, 2H), 1.98 (t, J=7.5 Hz, 2H), 1.70 (d, J=2.3 Hz, 3H), 1.61-1.49 (m, 2H), 1.47-1.20 (m, 6H), 1.04 (d, J=2.4 Hz, 9H).

›Step 2

AD-mix-β (1.4 g per mmol of alkene) was dissolved in tBuOH (25 mL) and H 2 O (25 mL) at rt. The clear orange solution was cooled to 0° C. and tert-butyl((7-methyloct-7-en-1-yl)oxy)diphenylsilane (1.88 g, 4.94 mmol) was added dropwise. The mixture was stirred for overnight at 0° C. to rt, quenched with saturated Na 2 SO 3 , stirred for 1 h at rt, diluted with H 2 O and extracted with EtOAc. The organic layers were combined, dried with MgSO 4 and concentrated. Purification by silica gel chromatography (0-100% EtOAc in hexanes) provided 8-((tert-butyldiphenylsilyl)oxy)-2-methyloctane-1,2-diol. ES/MS: m/z 437.2 [M+Na] + .

›Step 3

To a solution of 8-((tert-butyldiphenylsilyl)oxy)-2-methyloctane-1,2-diol (1.45 g, 3.0 mmol), DMSO (0.87 mL, 12.2 mmol), and Et 3 N (1.7 mL, 12.2 mmol) in DCM (17 mL) was added sulfur pyridine trioxide complex (1.39 g, 8.74 mmol) at 0° C. The reaction mixture was stirred at 0° C. to rt for 5 h. The reaction mixture was quenched with saturated aqueous NH 4 Cl. The mixture was extracted twice with DCM. The organic layers were combined, dried with MgSO 4 and concentrated. Purification by silica gel chromatography (0-100% EtOAc in hexanes) provided 8-((tert-butyldiphenylsilyl)oxy)-2-hydroxy-2-methyloctanal. ES/MS: m/z 435.3 [M+Na] + .

›Step 4

To a solution of 8-((tert-butyldiphenylsilyl)oxy)-2-hydroxy-2-methyloctanal (934 mg, 2.26 mmol) in tBuOH (10 mL), THF (5 mL) and water (5 mL) was added KH 2 PO 4 (1.97 g, 11.3 mmol) followed by 2-methyl-2-butene (1.2 mL, 11.3 mmol). Sodium chlorite (512 mg, 5.66 mmol) in water (1 mL) was the added dropwise. The reaction mixture was stirred at rt for 1 h. The reaction mixture was then partitioned between 1 N HCl and EtOAc, and the organic phase was washed with brine, dried with MgSO 4 , filtered, and concentrated to provide crude 8-((tert-butyldiphenylsilyl)oxy)-2-hydroxy-2-methyloctanoic acid which was used below without further purification. ES/MS: m/z 451.3 [M+Na] + .

›Step 5

tert-Butyl 2-methoxy-2-methyl-8-(tosyloxy)octanoate (approximatively a 2:1 mixture of unspecified enantiomers) was made following steps 3-5 of intermediate L16a using 8-((tert-butyldiphenylsilyl)oxy)-2-hydroxy-2-methyloctanoic acid. ES/MS: m/z 437.2 [M+Na] + .

Preparation of tert-butyl rac-2-methoxy-8-(tosyloxy)octanoate (L18)

›Step 1

A solution of 7-((tert-butyldiphenylsilyl)oxy)heptanal (3.64 g, 9.88 mmol), 10-camphorsulfonic acid (344 mg, 1.48 mmol) and methanol (40 mL) in dry DCM (100 mL) was stirred at room temperature for 4h (disappearance of SM by TLC). Saturated NaHCO 3 aq. was added to the reaction mixture and the solution was extracted with DCM. The organic layer was washed with brine, dried with MgSO 4 , filtered, and evaporated under vacuum. Purification by silica gel chromatography (0-15% EtOAc in hexanes) provided tert-butyl((7,7-dimethoxyheptyl)oxy)diphenylsilane. 1 H NMR (400 MHz, Chloroform-d) δ 7.66 (d, J=7.8 Hz, 4H), 7.52-7.31 (m, 6H), 4.37-4.33 (m, 1H), 3.3.67-3.58 (m, 2H), 3.31 (d, J=1.1 Hz, 6H), 1.66-1.49 (m, 4H), 1.45-1.23 (m, 6H), 1.04 (s, 9H).

›Step 2

A solution of tert-butyl((7,7-dimethoxyheptyl)oxy)diphenylsilane (1.5 g, 3.62 mmol) and 2,2′-bipyridyl (1.69 g, 10.9 mmol) in DCM (20 mL) was added TESOTf (1.64 mL, 7.23 mmol) at 0° C. After disappearance of SM by TLC, TMSCN (1.79 g, 18.1 mmol) was added and the solution was warmed to rt and stirred for 4 h. Saturated NaHCO 3 aq. was added to the reaction mixture and the solution was extracted with DCM. The organic layer was washed with brine, dried with MgSO 4 , filtered, and evaporated under vacuum. Purification by silica gel chromatography (0-100% EtOAc in hexanes) provided 8-((tert-butyldiphenylsilyl)oxy)-2-methoxyoctanenitrile. ES/MS: m/z 432.3 [M+Na] + .

›Step 3

A solution of 8-((tert-butyldiphenylsilyl)oxy)-2-methoxyoctanenitrile (1.4 g, 3.42 mmol) and MeONa (25% in MeOH, 2.34 mL, 10.3 mmol) in MeOH (17 mL) was stirred at rt overnight. 10% aqueous citric acid was added and the solution was extracted with EtOAc. The organic layer was washed with brine, dried with MgSO 4 , filtered, and evaporated under vacuum. Purification by silica gel chromatography (0-80% EtOAc in hexanes) provided methyl 8-((tert-butyldiphenylsilyl)oxy)-2-methoxyoctanoate. ES/MS: m/z 465.3 [M+Na] + .

›Step 4

To a solution of methyl 8-((tert-butyldiphenylsilyl)oxy)-2-methoxyoctanoate (331 mg, 0.748 mmol) in THF (4 mL), MeOH (4 mL) and 1 M LiOH (1.5 mL) was stirred at rt for 2 h.

The reaction mixture was then partitioned between 1N HCl and EtOAc, and the organic phase was washed with brine, dried with MgSO 4 , filtered, and concentrated to provide crude 8-((tert-butyldiphenylsilyl)oxy)-2-methoxyoctanoic acid which was used below without further purification. ES/MS: m/z 451.1 [M+Na] + .

›Step 5

tert-butyl rac-2-methoxy-8-(tosyloxy)octanoate was made following step 3 of intermediate L16a and steps 3-4 of L13a using 8-((tert-butyldiphenylsilyl)oxy)-2-methoxyoctanoic acid. ES/MS: m/z 423.2 [M+Na] + .

Preparation of tert-butyl 3-(((1R,2R)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate (L19a)

›Step 1 and 2

See Org. Lett. 2003, 2331 and Org. Biomol. Chem. 2017, 6909.

›Step 3

To a solution of ((1R,2R)-2-((benzyloxy)methyl)cyclopropyl)methanol (60 g, 312 mmol) in THF (420 mL) were added imidazole (21.2 g, 312 mmol) and TBDPSCl (102 g, 374 mmol) at 0° C. The mixture was stirred at rt for overnight. Water was added to the reaction mixture and the solution was extracted with EtOAc. The organic layer was washed with brine, dried with MgSO 4 , filtered, and evaporated under vacuum. Purification by silica gel chromatography (10% EtOAC in petroleum ether) provided (((1R,2R)-2-((benzyloxy)methyl)cyclopropyl)methoxy)(tert-butyl)diphenylsilane.

›Step 4

To a solution of (((1R,2R)-2-((benzyloxy)methyl)cyclopropyl)methoxy)(tert-butyl)diphenylsilane (65 g, 150 mmol) in EtOH (455 mL) was added wet Pd/C (6.5 g, 10%). The flask was degassed twice, purged with H 2 (50 psi) and stirred at 45° C. for overnight. The reaction mixture was filtered and evaporated under vacuum. Purification by silica gel chromatography (10% EtOAC in petroleum ether) provided ((1R,2R)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methanol. 1 H NMR (CDCl 3 400 MHz): δ 7.70-7.67 (m, 4H), 7.44-7.38 (m, 6H), 3.72-3.68 (m, 1H), 3.49-3.44 (m, 3H), 1.35 (s, 1H), 1.06 (s, 9H), 1.00-0.96 (m, 2H), 0.47-0.40 (m, 2H).

›Step 5

tert-butyl 3-(((1R,2R)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate was made following steps 2-4 of L13a using ((1R,2R)-2-(((tert-butyldiphenylsilyl)oxy)methyl)cyclopropyl)methanol. ES/MS: m/z 407.2 [M+Na] + .

tert-Butyl 3-(((1S,2S)-2-((tosyloxy)methyl)cyclopropyl)methoxy)propanoate (L19b)

Prepared following a similar procedure to L19a from (S)-2-((benzyloxy)methyl)oxirane. ES/MS: m/z 407.2 [M+Na] + .

tert-butyl 3-(((1R,2R)-2-(hydroxymethyl)cyclopropyl)methoxy)-2-methylpropanoate (L19c)

Prepared following a similar procedure to L19a using tert-butyl methacrylate instead of tert-butyl acrylate in step 5. ES/MS: m/z 277.2 [M+Na] + .

tert-butyl 3-(((1R,2R)-2-(hydroxymethyl)cyclopropyl)methoxy)butanoate (L19d)

Prepared following a similar procedure to L19a using tert-butyl (E)-but-2-enoate instead of tert-butyl acrylate in step 5. ES/MS: m/z 277.2 [M+Na] + .

tert-butyl 3-(((1S,2S)-2-(hydroxymethyl)cyclopropyl)methoxy)butanoate (L19e)

Prepared following a similar procedure to L19b using tert-butyl (E)-but-2-enoate instead of tert-butyl acrylate. ES/MS: m/z 277.2 [M+Na] + .

Preparation of tert-butyl rac-(1R,2R)-2-(4-(tosyloxy)butyl)cyclopropane-1-carboxylate (L20a)

›Step 1

tert-Butyl 2-(triphenyl-λ5-phosphanylidene)acetate (1.85 g, 4.9 mmol) was added to a solution of 5-[tert-butyl(diphenyl)silyl]oxypentanal (1.67 g, 4.9 mmol) in THF (15 mL). The resulting mixture was stirred overnight. It was evaporated to dryness, redissolved in DCM (8 mL) and purified by column chromatography over silica gel (Hexanes/EtOAc 0-15%) to afford tert-butyl (E)-7-[tert-butyl(diphenyl)silyl]oxyhept-2-enoate. 1 H NMR (400 MHz, Chloroform-d) δ, 7.72-7.65 (m, 4H), 7.48-7.37 (m, 6H), 6.87 (dt, J=15.6, 6.9 Hz, 1H), 5.74 (d, J=15.6 Hz, 1H), 3.68 (t, J=5.8 Hz, 2H), 2.22-2.14 (m, 2H), 1.64-1.55 (m, 2H), 1.51 (s, 9H), 1.39-1.18 (m, 2H), 1.07 (s, 9H).

›Step 2

Trimethylsulfoxonium iodide (610 mg, 2.77 mmol) was suspended in DMSO (10 mL) and NaH (60% in mineral oil, 67 mg, 2.77 mmol) was added. The resulting mixture was stirred for 1 hour before a solution of tert-butyl (E)-7-[tert-butyl(diphenyl)silyl]oxyhept-2-enoate (760 mg, 1.73 mmol) in DMSO (2 mL) was added. The reaction mixture was stirred vigorously for 2 hours and then work up was carried out using water/ethyl acetate. The residue was purified by column chromatography over silica gel (Hexanes/EtOAc 0-10%) to afford tert-butyl rac-(trans)-2-[4-[tert-butyl(diphenyl)silyl]oxybutyl]cyclopropanecarboxylate. 1 H NMR (400 MHz, Chloroform-d) δ 7.68 (dd, J=7.9, 1.7 Hz, 4H), 7.49-7.35 (m, 6H), 3.68 (td, J=6.2, 2.0 Hz, 2H), 2.94-2.75 (m, 2H), 2.50-2.32 (m, 4H), 1.58 (dd, J=8.4, 5.0 Hz, 2H), 1.54-1.36 (m, 2H), 1.46 (s, 9H), 1.07 (s, 9H).

›Step 3

tert-Butyl rac-(1R,2R)-2-(4-(tosyloxy)butyl)cyclopropane-1-carboxylate was made following steps 3-4 of L13a using tert-butyl rac-(trans)-2-[4-[tert-butyl(diphenyl)silyl]oxybutyl]cyclopropanecarboxylate. 1 H NMR (400 MHz, Chloroform-d) δ 7.81 (d, J=8.3 Hz, 2H), 7.37 (d, J=8.3 Hz, 2H), 4.04 (t, J=6.5 Hz, 2H), 2.48 (s, 3H), 1.74-1.63 (m, 1H), 1.63-1.55 (m, 1H), 1.51-1.40 (m, 2H), 1.45 (s, 9H), 1.36-1.15 (m, 4H), 1.08-1.02 (m, 1H), 0.61-0.55 (m, 1H).

tert-butyl rac-(1R,2R)-2-(5-(tosyloxy)pentyl)cyclopropane-1-carboxylate (L20b)

Prepared following a similar procedure to L20a from 6-((tert-butyldiphenylsilyl)oxy)hexanal.

Preparation of tert-butyl rac-3-methoxy-2,2-dimethyl-8-(tosyloxy)octanoate (L21)

›Step 1

Oxalyl chloride (226 mg, 1.78 mmol) and DMF (2 drops) were added to a solution of 6-[tert-butyl(diphenyl)silyl]oxyhexanoic acid (600 mg, 1.62 mmol, Synlett 2006, 2670) in DCM (10 mL) at 0° C. and the solution was stirred for 1 h. The reaction was warmed up to room temperature and evaporated to dryness. The crude acid chloride was dissolved in THF (5 mL). In a separate flask, a solution of tert-butyl 2-methylpropanoate (304 mg, 2.1 mmol) in THF (4 mL) was cooled to −78° C. and a solution of LDA in THF (1 M, 2.1 mL) was added dropwise. The resulting solution was stirred at −78° C. for 1 hour. The solution of acid chloride prepared above was added and the reaction medium was slowly warmed up to 0° C. before it was quenched with aqueous NH 4 Cl(sat.). After work up the residue was purified by flash chromatography over silica gel (Hexanes/EtOAc 0-15%) to afford tert-butyl 8-((tert-butyldiphenylsilyl)oxy)-2,2-dimethyl-3-oxooctanoate.

›Step 2

NaBH 4 (27 mg, 0.72 mmol) was added to a 0° C. solution of tert-butyl 8-((tert-butyldiphenylsilyl)oxy)-2,2-dimethyl-3-oxooctanoate (325 mg, 0.65 mmol) in THF/MeOH (2:1, 2 mL). The resulting solution was stirred until full conversion of the starting material. Work up (NH 4 Cl (aq)/EtOAc) followed by chromatography over silica gel (Hexanes/EtOAc 5-25%) afforded tert-butyl 8-((tert-butyldiphenylsilyl)oxy)-3-hydroxy-2,2-dimethyloctanoate. 1 H NMR (400 MHz, Chloroform-d) δ 7.75-7.67 (m, 4H), 7.48-7.37 (m, 6H), 3.68 (t, J=6.5 Hz, 2H), 3.54 (d, J=9.7 Hz, 1H), 2.49 (brs, 1H), 1.68-1.55 (m, 2H), 1.48 (s, 9H), 1.45-1.23 (m, 6H), 1.17 (s, 3H), 1.14 (s, 3H), 1.07 (s, 9H).

›Step 3

A solution of tert-butyl 8-((tert-butyldiphenylsilyl)oxy)-3-hydroxy-2,2-dimethyloctanoate (240 mg, 0.48 mmol) in THF (1 mL) was cooled to 0° C. LiHMDS (1 M in THF, 0.58 mL) was added dropwise and the resulting solution was stirred for 30 minutes before Mel (150 mg, 0.11 mmol) was added. The reaction mixture was warmed up to room temperature and stirred for an additional hour. Work up (NH 4 Cl (aq)/EtOAc) followed by chromatography over silica gel (Hexanes/EtOAc 0-10%) afforded tert-butyl 8-((tert-butyldiphenylsilyl)oxy)-3-methoxy-2,2-dimethyloctanoate. 1 H NMR (400 MHz, Chloroform-d) δ 7.78-7.65 (m, 4H), 7.47-7.36 (m, 6H), 3.68 (t, J=6.4 Hz, 2H), 3.46 (s, 3H), 3.36-3.33 (m, 1H), 1.59 (q, J=7.6 Hz, 4H), 1.47 (s, 9H), 1.46-1.27 (m, 4H), 1.17 (s, 3H), 1.07 (s, 9H), 1.05 (s, 3H).

›Step 4

tert-butyl rac-3-methoxy-2,2-dimethyl-8-(tosyloxy)octanoate was made following steps 3-4 of L13a using tert-butyl 8-((tert-butyldiphenylsilyl)oxy)-3-methoxy-2,2-dimethyloctanoate. 1 H NMR (400 MHz, Chloroform-d) δ 7.81 (d, J=8.3 Hz, 2H), 7.37 (d, J=8.3 Hz, 2H), 4.05 (td, J=6.4 Hz, 2H), 3.44 (s, 3H), 3.31 (dd, J=9.0, 2.2 Hz, 1H), 2.47 (s, 3H), 1.71-1.52 (m, 3H), 1.46 (s, 9H), 1.45-1.25 (m, 5H), 1.15 (s, 3H), 1.03 (s, 3H).

Preparation of ethyl 2-(45-iodopentyl)oxy)acetate (L22)

L22 was prepared as described in Tetrahedron 2003, 53, 149.

Preparation of ethyl 2-((6-bromohexyl)oxy)acetate (L23)

L23 was prepared as described in U.S. Pat. No. 4,981,873 (example 12a).

Preparation of 3-bromo-2-((7-bromoheptyl)oxy)pyridine (L24a)

›Step 1

3-Bromopyridin-2-ol (200 mg, 1.15 mmol), 7-bromoheptane-1-ol (0.19 mL, 1.38 mmol), and triphenylphosphine (392 mg, 1.49 mmol) were combined in THF (5 mL) under N 2 . Diisopropyl azodicarboxylate (0.29 mL, 1.5 mmol) was added dropwise and the resulting mixture allowed to stir at ambient temperature overnight. The reaction was adsorbed directly to isolute and purified by silica gel chromatography (eluent: EtOAc in hexane) to give 3-bromo-2-((7-bromoheptyl)oxy)pyridine. ES/MS: m/z 351.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.14 (d, J=4.7 Hz, 1H), 8.02 (d, J=7.6 Hz, 1H), 6.93 (dd, J=7.5, 5.2 Hz, 1H), 5.19 (hept, J=6.1 Hz, 2H), 4.31 (t, J=6.6 Hz, 2H), 1.91-1.67 (m, 4H), 1.50-1.22 (m, 6H).

3-bromo-2-((6-bromohexyl)oxy)pyridine (L24b)

Prepared following a similar procedure to L24a from 6-bromohexan-1-ol. ES/MS: m/z 337.8 [M+H] + .

3-bromo-2-((8-bromooctyl)oxy)pyridine (L24c)

Prepared following a similar procedure to L24a from 8-bromooctan-1-ol. ES/MS: m/z 365.9 [M+H] + .

Preparation of 9-((tert-butyldimethylsilyl)oxy)-N-methylnonanamide (L25)

›Step 1

A solution of methyl 9-hydroxynonanoate (300 mg, 1.6 mmol), tert-butyldimethylchlorosilane (480 mg, 3.2 mmol), and imidazole (240 mg, 3.5 mmol) in DCM (5 mL) was allowed to stir overnight. Brine was added and the mixture was washed with DCM three times. The combined organic layers were dried over MgSO 4 , filtered and concentrated. Purification by silica gel column chromatography (0-50% EtOAc in hexanes) provided methyl 9-[tert-butyl(dimethyl)silyl]oxynonanoate. 1 H NMR (400 MHz, Chloroform-d) δ 3.62 (s, 3H), 3.55 (t, J=6.6 Hz, 2H), 2.26 (t, J=7.5 Hz, 2H), 1.61-1.53 (m, 2H), 1.49-1.39 (m, 2H), 1.34-1.18 (m, 8H), 0.85 (s, 9H), −0.00 (s, 6H).

›Step 2

A solution of methyl 9-[tert-butyl(dimethyl)silyl]oxynonanoate (470 mg, 1.6 mmol) and methylamine (33% in ethanol, 5.8 mL) was allowed to stir for 6 h. The reaction was concentrated and purified by silica gel column chromatography (0-100% EtOAc in hexanes) to provide 9-[tert-butyl(dimethyl)silyl]oxy-N-methyl-nonanamide. 1 H NMR (400 MHz, Chloroform-d) δ 5.35 (s, 1H), 3.55 (t, J=6.8 Hz, 2H), 2.76 (d, J=2.9 Hz, 2H), 2.11 (t, J=6.9 Hz, 2H), 1.62-1.55 (m, 2H), 1.51-1.41 (m, 2H), 0.85 (s, 9H), 0.00 (s, 6H).

Preparation of tert-butyl (5-bromopentyl)(methyl)carbamate (L2

›Tables in the description — 6

Abbreviation	Meaning
° C.	Degree Celsius
ATP	Adenosine-5′-triphosphate
AcOH	Acetic acid
Boc	Tert-butyloxycarbonyl
Bn	Benzyl
Bs	Benzenesulfonyl
CDI	1,1′-Carbonyldiimidazole
d	Doublet
Dba	Dibenzylideneacetone
DBU	1,8-Diazabicyclo[5.4.0]undec-7-ene
dd	Doublet of doublets
DCE	1,2-dichloroethane
DCM	Dichloromethane
DEAD	Diethyl azodicarboxylate
Dess-Martin periodinane	1,1,1-Tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one
DIAD	Diisopropyl azodicarboxylate
DIPEA, DIEA	N,N-diisopropylethylamine
DMAP	4-Dimethylaminopyridine
DME	1,2-dimethoxyethane
DMF	Dimethylformamide
DMSO	Dimethylsulfoxide
DMPU	1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone
Dppf	1,1′-Bis(diphenylphosphino)ferrocene
DPPA	Diphenylphosphoryl azide
EDC	1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide
EDTA	Ethylenediaminetetraacetic acid
EGTA	Ethylene glycol tetraacetic acid
EtOAc	Ethyl acetate
equiv/eq	Equivalents
ESI	Electrospray ionization
Ac	Acetate
Et	Ethyl
g	Grams
HATU	2-(7-Aza-1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium
	hexafluorophosphate
HCl	Hydrochloric acid
hERG	human Ether-à-go-go Related Gene
HPLC	High-performance liquid chromatography
h/hr	Hours
Hunig's Base	N,N-diisopropylethylamine
Hz	Hertz
IC 50	The half maximal inhibitory concentration
IPTG	Isopropyl β-d-1-thiogalactopyranoside
Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6	[4,4′-Bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis[3,5-
	difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-
	C]Iridium(III) hexafluorophosphate
J	Coupling constant
Jackiephos	2-{Bis[3,5-bis(trifluoromethyl)phenyl]phosphino}-3,6-
	dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl
Jackiephos Pd G3	[(2-{Bis[3,5-bis(trifluoromethyl)phenyl]phosphine}-3,6-
	dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-
	biphenyl)]palladium(II) methanesulfonate
kg	Kilogram
LC/MS, LCMS	Liquid chromatography mass spectrometry
LDA	Lithium diisopropylamide
LiHMDS	Lithium bis(trimethylsilyl)amide
L-selectride	Lithium tri-sec-butylborohydride solution
M	Molar
m	Multiplet
m/z	mass-to-charge ratio
M+	Mass peak
M + H	Mass peak plus hydrogen
Me	Methyl
MeOH	Methyl alcohol/methanol
Mg	Milligram
MHz	Megahertz
min/m	Minute
ml/mL	Milliliter
mM	Millimolar
mmol	Millimole
MS	Mass spectroscopy
MTBE	Methyl tert-butyl ether
Mw	Microwave
N	Normal
Mol	Mole
NaHMDS	Sodium bis(trimethylsilyl)amide
NCS	N-chlorosuccinimide
NIS	N-iodosuccinimide
NMP	N-methylpyrrolidinone
NMR	Nuclear magnetic resonance
p	Pentuplet
PCR	Polymerase chain reaction
Ph	Phenyl
ppm	Parts per million
PPTS	Pyridinium para-toluenesulfonate
Prep	Preparative
Rf	Retention factor
RP	Reverse phase
RT/rt	Room temperature
s	Second
s	Singlet
SEM	Trimethylsilylethoxymethyl
SPhos	2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl
SUMO	Small ubiquitin-like modifier
t	Triplet
TBAF	Tetrabutylammonium fluoride
TBAI	Tetrabutylammonium iodide
TBS	Tert-butyldimethylsilyl
TBDPS	Tert-butyldiphenylsilyl
TCEP	Tris(2-carboxyethyl)phosphine
TEA	Triethylamine
Tf	Trifluoromethylsulfonyl
TFA	Trifluoroacetic acid
THP	Tetrahydropyranyl
TLC	Thin layer chromatography
Trt/Trityl	Triphenylmethyl
TMS	Trimethylsilyl
Ts	Toluenesulfonyl
WT	Wild type
Xantphos	4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene
XPhos	2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl
XPhos Pd G3	(2-Dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-
	(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate
Zhan 1b	1,3-Bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-
	(i-propoxy)-5-(N,N-
	dimethylaminosulfonyl)phenyl]methyleneruthenium (II)
	dichloride
δ	Chemical shift
μg	Microgram
μL/μl	Microliter
μM	Micromolar
μm	Micrometer
μmol	Micromole

Scheme C-8 describes the preparation of an intramolecular substitution macrocyclization precursor.	Step 1 describes the generalized installation of a fragment -L n -L m -Y, where L m and L n comprise desired combinations of L groups described herein or precursors thereof, and where Y=OH, halogen, or pseudohalide (e.g., triflate, mesylate, etc.). This is accomplished using methods described herein or other methods known to those versed in the art, starting from group X, which may be halogen, acetyl, aminoalkyl fragment, or other functional precursor to any L group described herein.	Step 2 describes the deprotection of a protective group P 1 to reveal a nucleophilic indole or azaindole. Selected examples are described in Step 1 of Scheme C-1. When P 1 =H, this step is omitted. Protecting group P 1 may also be removed before, after, or at any appropriate stage during the sequence used to install L n -L m -Y.	Step 3 describes intramolecular displacement to form a macrocycle, which can be accomplished in cases where Y=halogen or pseudohalide (e.g., tosylate, triflate, mesylate, etc.) by treatment with a suitable base (e.g., —Cs 2 CO 3 , K 2 CO 3 , NaHMDS). When Y=OH, this displacement may be accomplished using a Mitsunobu protocol, for example by treatment with DIAD and PPh 3 . Examples prepared using this sequence are Example 127, Example 291 and Example 25.
Scheme C-9 describes an alternative synthesis of a macrocycle using an intramolecular substitution strategy.	Step 1 describes a general approach to a macrocycle precursor that contains fragments Nu-P 2 where Nu=nucleophilic group (e.g., oxygen, nitrogen, or sulfur) and leaving group Y (e.g., halogen, triflate, mesylate, etc.). In some cases, Y=OH. These fragments may be elaborated in any suitable order using approaches similar to those described herein or by transformations known to those versed in the art.	Step 2 describes the deprotection of Nu-P 2 , which can be accomplished using standard conditions. When P 2 =H, this step is omitted. In the case where Nu-P 2 represents a protected nitrogen nucleophile with suitable nucleophilicity (e.g., NH-nosyl, NHBoc), this deprotection step can be omitted or carried out following the macrocyclization described in Step 3.	Step 3 describes macrocycle synthesis by intramolecular, which can be accomplished in cases where Y=halogen or pseudohalide (e.g., tosylate, triflate, mesylate, etc.) by treatment with a suitable base (e.g., Cs 2 CO 3 , K 2 CO 3 , NaHMDS). When X=OH, this displacement may be accomplished using a Mitsunobu protocol, for example by treatment with DIAD and PPh 3 .

Scheme C-10 describes synthesis of a macrocycle by intramolecular cross-coupling.	Step 1 is as described in Scheme C-1.	Step 2 describes the generalized installation of a fragment -L n -L m -Y, where L m and L n comprise desired combinations of L groups described herein or precursors thereof, and where Y=halogen, boronic acid, ester, other suitable organometallic derivative, or —NH(R 8 ). This is accomplished using protocols similar to those described herein or by transformations known to those versed in the art. In the case where Y=boronic acid, ester, other suitable organometallic derivative, or —NH(R 8 ), the macrocyclization may be accomplished by treatment with a suitable palladium catalyst under appropriate conditions. In the case where Y=halogen, the intermediate may be treated with 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane and a suitable palladium catalyst under appropriate conditions to provide the macrocycle product by intermediacy of a pinacolboronic ester. An example prepared by this strategy is Example 85.
Scheme D-1 describes the installation of —N(R 10 )(R n ) groups via amide bond formation.	Step 1 describes the hydrolysis of an ester motif to afford the corresponding carboxylic acid. This can be accomplished using a variety of conditions well known to those versed in the art, including treatment with hydroxide (e.g., LiOH, NaOH, KOH, etc.) in a suitable solvent mixture and temperature. This can also be accomplished under acidic conditions (e.g., TFA, HCl), especially when R=tert-butyl. Other known R groups that are compatible with the chemistry outlined herein can also be used, and these can be removed using standard conditions known to those versed in the art.	Step 2 shows the preparation of compounds of Formula (I) via amide bond forming chemistry. Suitable coupling conditions, reagents and/or catalysts are well known in the art.

TABLE 2

Example	Intermediate 1	Intermediate 2	A	Procedure
1	I-107a	L27	A1.01	24
2	I-107a	L27	A1.01	24
3	I-107a	L27	A1.01	24
4	I-107a	L27	A1.01	24
5	I-102	L4a	A1.11	8
6	I-107d	L48	A13	25
7	I-102	L39a	A13	27
8	I-100	L11	A2	2
9	I-100	L11	A2	2
10	I-102	L10	A2	29
11	I-102	L10	A2	29
12	I-107a	L27	A2	24
13	I-102	L4a	A3	8
14	I-102	L4a	A5a	8
15	I-102	L4a	A6	8
16	I-102	L4a	A1.01	8
17	I-102	L6b	A1.01	8
18	I-102	L6a	A1.01	8
19	I-102	L6a	A1.15	8
20	I-102	L4a	A2	8
21	I-102	L6a	A2	8
22	I-102	L6b	A2	8
23	I-107f	hex-5-ene-1-sulfonyl	A2	34
		chloride
24	I-107a	2-vinylbenzoic acid	A2	25
25	I-13a	8-bromooct-1-yne	A1.01	35
26	I-136b	L1a	A1.01	31
27	I-136b	L4a	A1.01	31
28	I-102	L28a	A1.01	8
29	I-102	L28b	A1.01	8
30	I-102	L29	A1.01	8
31	I-102	L28a	A1.15	8
32	I-100	L7a	A2	1
33	I-100	L7b	A2	1
34	I-100	L7c	A2	1
35	I-100	L7d	A2	1
36	I-100	L7e	A2	1
37	I-102	L9a	A2	8
38	I-102	L8a	A2	8
39	I-102	L28a	A2	8
40	I-102	L28b	A2	8
41	I-102	L29	A2	8
42	I-102	L28a	A3	8
43	I-102	L28a	A1.03	8
44	I-102	L28a	A8	8
45	I-118	blank	A1.01	16
46	I-108	blank	A1.01	15
47	I-120	blank	A1.01	16
48	I-109	blank	A2	15
49	I-109	blank	A1.01	15
50	I-8a	tert-butyl N-(6-	A1.01	18
		bromohexyl)carbamate
51	I-110a	blank	A1.01	15
52	I-111	blank	A1.01	15
53	I-122	blank	A1.01	16
54	I-123	blank	A1.01	16
55	I-110b	blank	A1.01	15
56	I-113	blank	A1.01	15
57	I-112	blank	A1.01	15
58	I-102	L4b	A1.01	8
59	I-102	L4a	A1.02	8
60	I-102	L4a	A1.03	8
61	I-102	L4b	A1.03	8
62	I-102	L4d	A1.03	8
63	I-102	L4a	A1.04	8
64	I-102	L4a	A1.05	8
65	I-102	L4a	A1.06	8
66	I-102	L4a	A1.06	26
67	I-102	L4a	A1.07	8
68	I-102	L4a	A1.08	8
69	I-102	L4a	A1.09	8
70	I-102	L4a	A1.10	8
71	I-102	L4a	A1.13	8
72	I-102	L4d	A1.14	8
73	I-102	L4a	A1.14	8
74	I-102	L4d	A1.15	8
75	I-102	L4a	A1.15	8
76	I-102	L4b	A1.15	8
77	I-102	L4d	A1.22	8
78	I-102	L4a	A1.22	8
79	I-102	L4a	A1.28	11
80	I-102	L4a	A1.29	8
81	I-102	L4a	A1.28	11
82	I-102	L4a	A10	8
83	I-126	blank	A2	17
84	I-115	blank	A2	16
85	I-125	blank	A2	17
86	I-127	blank	A2	17
87	I-116	blank	A2	16
88	I-114	blank	A2	16
89	I-117	blank	A2	16
90	I-118	blank	A2	16
91	I-108	blank	A2	15
92	I-124	blank	A2	16
93	I-119	blank	A2	16
94	I-120	blank	A2	16
95	I-121	blank	A2	16
96	I-8a	tert-butyl N-(6-	A2	18
		bromohexyl)carbamate
97	I-110a	blank	A2	15
98	I-111	blank	A2	15
99	I-122	blank	A2	16
100	I-123	blank	A2	16
101	I-110b	blank	A2	15
102	I-102	L4b	A2	8
103	I-102	L4a	A5b	8
104	I-102	L4a	A5c	8
105	I-102	L4a	A9	8
106	I-100	L4b	A1.01	1
107	I-8a	L1c	A1.01	12
108	I-8a	L2a	A1.01	12
109	I-8a	L3a	A1.01	12
110	I-102	L5a	A1.01	8
111	I-102	L5b	A1.01	8
112	I-102	L5c	A1.01	14
113	I-104a	L5c	A1.01	14
114	I-102	L47	A1.01	8
115	I-102	L45a	A1.01	28
116	I-102	L45a	A1.01	28
117	I-104c	L4a	A1.01	8
118	I-102	L43	A1.01	27
119	I-102	L44a	A1.01	27
120	I-107g	oct-7-enoic acid	A2	4
121	I-100	L4a	A2	1
122	I-100	L5a	A2	1
123	I-107g	hept-6-enoic acid	A2	4
124	I-100	L5b	A2	1
125	I-8a	L1a	A2	12
126	I-100	L4b	A2	1
127	I-3	L25	A2	5
128	I-8a	L1d	A2	12
129	I-8b	L1a	A2	12
130	I-8a	L1c	A2	12
131	I-8a	L1b	A2	12
132	I-8a	L2a	A2	12
133	I-8a	L3a	A2	12
134	I-8a	L1a	A2	13
135	I-8a	L1a	A2	12
136	I-102	L5a	A2	8
137	I-102	L5b	A2	8
138	I-102	L5c	A2	14
139	I-102	L47	A2	8
140	I-102	L46	A1.01	8
141	I-102	L46	A2	8
142	I-102	L45a	A2	28
143	I-102	L45a	A2	28
144	I-102	L43	A2	27
145	I-102	L44a	A2	27
146	I-100	L26b	A1.01	6
147	I-100	L12	A1.01	1
148	I-104a	L4a	A1.01	8
149	I-102	L19b	A1.01	8
150	I-102	L19a	A1.01	8
151	I-102	L20a	A1.01	8
152	I-102	L20a	A2	8
153	I-102	L21	A1.01	10
154	I-102	L21	A1.01	10
155	I-104a	L4d	A1.01	8
156	I-104a	L6a	A1.01	8
157	I-102	L20b	A1.01	10
158	I-102	L20b	A1.01	10
159	I-104b	L4d	A1.01	8
160	I-104b	L4a	A1.01	8
161	I-102	L42a	A1.01	27
162	I-102	L42b	A1.01	27
163	I-102	L40	A1.01	27
164	I-102	L20b	A1.01	10
165	I-102	L20b	A1.01	10
166	I-102	L41	A1.01	27
167	I-102	L45b	A1.01	28
168	I-102	L45b	A1.01	28
169	I-105b	L4a	A1.01	8
170	I-102	L38a	A1.01	27
171	I-102	L38b	A1.01	27
172	I-102	L38c	A1.01	8
173	I-104a	L4a	A1.03	8
174	I-107d	L48	A1.03	25
175	I-102	L37	A1.03	27
176	I-105b	L4a	A1.10	8
177	I-102	L4a	A1.12	8
178	I-104a	L4a	A1.15	8
179	I-105b	L4a	A1.15	8
180	I-102	L38a	A1.15	27
181	I-102	L38c	A1.15	27
182	I-107e	L48	A1.15	25
183	I-102	L38e	A1.15	27
184	I-107d	L48	A1.15	25
185	I-102	L38d	A1.15	27
186	I-135a	2-vinylbenzoic acid	A1.15	25
187	I-102	L37	A1.15	27
188	I-7f	I-142a	A1.15	33
189	I-135b	L48	A1.15	25
190	I-104a	L4a	A1.17	30
191	I-104a	L4a	A1.20	8
192	I-102	L4a	A1.24	8
193	I-102	L4a	A1.25	8
194	I-105b	L4a	A1.25	8
195	I-102	L4a	A1.26	8
196	I-102	L4a	A1.27	8
197	I-102	L4a	A1.30	8
198	I-102	L4a	A1.31	8
199	I-102	L4a	A1.32	8
200	I-102	L4a	A1.33	8
201	I-102	L4a	A1.34	8
202	I-102	L4a	A1.35	11
203	I-102	L4a	A1.35	11
204	I-102	L4a	A1.36	8
205	I-102	L4a	A1.37	8
206	I-102	L4a	A11a	8
207	I-102	L4d	A12	8
208	I-104a	L4d	A14	8
209	I-100	L26c	A2	6
210	I-100	L26a	A2	6
211	I-100	L26b	A2	6
212	I-100	L26d	A2	6
213	I-100	L12	A2	1
214	I-101b	L13b	A2	1
215	I-104a	L1a	A2	8
216	I-104a	L4a	A2	8
217	I-102	L19b	A2	8
218	I-102	L19a	A2	8
219	I-102	L21	A2	10
220	I-102	L21	A2	10
221	I-104a	L4d	A2	8
222	I-104a	L6a	A2	8
223	I-102	L20b	A2	10
224	I-102	L20b	A2	10
225	I-104b	L4d	A2	8
226	I-102	L40	A2	27
227	I-128	blank	A4	19
228	I-101a	L1a	A1.01	1
229	I-103a	L1a	A1.01	8
230	I-103a	L4a	A1.01	8
231	I-103a	L1b	A1.01	8
232	I-131	blank	A1.01	8
233	I-102	L4d	A1.01	8
234	I-131	blank	A1.01	22
235	I-132	blank	A1.01	21
236	I-132	blank	A1.01	21
237	I-136a	L4a	A1.01	31
238	I-133	blank	A1.01	8
239	I-107b	but-3-enoic acid	A1.03	25
240	I-102	L39a	A1.03	27
241	I-102	L39a	A1.15	27
242	I-105a	L20b	A1.15	10
243	I-105b	L49	A1.15	8
244	I-102	L4a	A1.16	8
245	I-102	L13f	A1.17	30
246	I-102	L13f	A1.17	30
247	I-100	L22	A2	1
248	I-100	L23	A2	1
249	I-101a	L1a	A2	1
250	I-103a	L1a	A2	8
251	I-106	L1a	A2	8
252	I-136a	L1a	A2	31
253	I-103a	L4a	A2	8
254	I-103a	L1b	A2	8
255	I-131	blank	A2	8
256	I-131	blank	A2	22
257	I-132	blank	A2	21
258	I-132	blank	A2	21
259	I-129	L1a	A4	20
260	I-102	L4d	A7	8
261	I-102	L4a	A7	11
262	I-102	L4a	A7	11
263	I-102	L4c	A1.01	8
264	I-102	L30a	A1.01	8
265	I-102	L19c	A1.01	29
266	I-102	L19c	A1.01	29
267	I-102	L19d	A1.01	29
268	I-102	L19d	A1.01	29
269	I-102	L31	A1.01	27
270	I-102	L30b	A1.01	8
271	I-102	L19e	A1.01	27
272	I-102	L32	A1.01	27
273	I-107c	2,2-dimethyl-4-pentenoic	A1.01	25
		acid
274	I-102	L33	A1.01	27
275	I-140a	I-142a	A1.15	32
276	I-102	L4a	A1.18	8
277	I-102	L4a	A1.19	8
278	I-102	L4c	A2	8
279	I-102	L4d	A2	8
280	I-102	L4e	A2	8
281	I-102	L4f	A2	8
282	I-102	L1a	A1.01	8
283	I-102	L1c	A1.01	8
284	I-100	L1e	A1.01	1
285	I-102	L1a	A2	8
286	I-102	L1c	A2	8
287	I-100	L1e	A2	1
288	I-102	L1a	A3	8
289	I-102	L1c	A3	8
290	I-100	L1e	A3	1
291	I-13a	octane-1,8-diol	A1.01	23
292	I-102	L44b	A1.01	27
293	I-138	tert-butyl N-(6-	A1.01	7
		iodohexyl)carbamate
294	I-102	L4a	A1.20	8
295	I-102	L4a	A1.21	8
296	I-102	L4a	A1.23	8
297	I-102	L4a	A13	8
298	I-13a	2,2′-(ethane-1,2-	A1.01	23
		diylbis(oxy))bis(ethan-1-ol)
299	I-102	L4a	A8	8
300	I-100	L1b	A1.01	1
301	I-100	L1a	A1.01	1
302	I-100	L1a	A3	1
303	I-100	L15a	A1.01	1
304	I-102	L13d	A1.01	8
305	I-102	L13e	A1.01	8
306	I-102	L15b	A1.01	8
307	I-104a	L35d	A1.01	27
308	I-102	L35d	A1.01	27
309	I-102	L35c	A1.01	27
310	I-102	L36a	A1.01	27
311	I-102	L36b	A1.01	27
312	I-102	L13g	A1.01	29
313	I-102	L13g	A1.01	29
314	I-102	L13f	A1.03	27
315	I-102	L13f	A1.15	27
316	I-100	L1a	A2	1
317	I-100	L1b	A2	1
318	I-100	L1c	A2	1
319	I-100	L1a	A2	22
320	I-100	L1d	A2	1
321	I-100	L2a	A2	1
322	I-100	L13b	A2	2
323	I-100	L13b	A2	2
324	I-100	L3a	A2	1
325	I-100	L14a	A2	2
326	I-100	L14a	A2	2
327	I-100	L13a	A2	2
328	I-100	L13a	A2	2
329	I-100	L13c	A2	1
330	I-100	L14b	A2	1
331	I-100	L15a	A2	1
332	I-100	L16b	A2	1
333	I-100	L16a	A2	1
334	I-100	L18	A2	3
335	I-100	L18	A2	3
336	I-102	L13d	A2	8
337	I-102	L13e	A2	8
338	I-102	L15b	A2	8
339	I-104a	L17	A2	9
340	I-104a	L17	A2	9
341	I-104a	L34	A2	8
342	I-104a	L35d	A2	27
343	I-102	L4d	A14	8
344	143a	L50a	A1.15	27
345	143a	L50b	A1.15	27
346	I-102	L52a	A1.15	27
347	I-141b	L28a	A1.15	8
348	I-141b	L52a	A1.15	27
349	I-105a	L50c	A1.15	27
350	I-105a	L50a	A1.15	27
351	I-105a	L52b	A1.15	27
352	I-105a	L50d	A1.15	27
353	I-141b	L50a	A1.15	27
354	I-141b	L50f	A1.15	27
355	I-141b	L50e	A1.15	27
356	I-141b	L50v	A1.15	27
357	I-141b	L50w	A1.15	27
358	I-102	L50a	A1.03	27
359	I-102	L50v	A1.03	27
360	I-102	L50b	A1.03	27
361	I-102	L50g	A1.01	27
362	I-102	L50g	A1.03	27
363	I-102	L50g	A1.15	27
364	I-107i	2,2-Dimethyl-4-pentenoic	A1.15	36
		acid
365	I-107i	2,2-Dimethyl-4-pentenoic	A1.15	36
		acid
366	I-107h	2,2-Dimethyl-4-pentenoic	A1.03	25
		acid
367	I-107h	2,2-Dimethyl-4-pentenoic	A1.15	25
		acid
368	I-107a	L53	A1.15	36
369	I-107a	L53	A1.15	36
370	I-107h	L27	A1.03	24
371	I-107h	L27	A1.15	24
372	I-107h	L27	A1.03	24
373	I-107h	L27	A1.15	24
374	I-107a	2,2-Difluoro-4-pentenoic	A1.03	25
		acid
375	I-107a	2,2-Difluoro-4-pentenoic	A.15	25
		acid
376	I-104c	L4a	A1.15	8
377	I-135d	L53	A1.15	36
378	I-135d	L53	A1.15	36
379	I-107j	L62b	A1.15	25
380	I-102	L4a	A1.38	8
381	I-107l	L53	A1.15	37
382	I-107l	L53	A1.15	37
383	I-107l	L53	A1.15	37
384	I-105a	L50h	A1.15	27
385	I-107k	L62a	A1.15	36
386	I-107k	L62a	A1.15	36
387	I-107m	L54a	A1.15	25
388	I-107m	L55a	A1.15	25
389	I-135c	L53	A1.15	37
390	I-135c	L53	A1.15	37
391	I-135c	L53	A1.15	37
392	I-107m	L53	A1.15	37
393	I-107m	L53	A1.15	37
394	I-107m	L53	A1.15	37
395	I-105b	L50j	A1.15	27
396	I-105b	L50i	A1.15	27
397	I-102	L50h	A1.03	27
398	I-102	L56a	A1.15	27
399	I-102	L57a	A1.15	27
400	I-144a	L61a	A15	25
401	I-105a	L59b	A1.15	8
402	I-144b	L61a	A15	25
403	I-21	I-142b	A1.15	33
404	I-7l	I-142a	A1.15	33
405	I-22m	I-142a	blank	38
406	I-22n	I-142a	blank	38
407	I-102	L59n	A1.03	8
408	I-107d	L48	A16	25
409	I-102	L59b	A1.03	8
410	I-23f	I-142a	blank	39
411	I-107d	L48	A17	8
412	I-23f	I-142a	blank	39
413	I-23g	I-142a	blank	39
414	I-102	L59a	A1.03	8
415	I-23i	I-142a	blank	39
416	I-23h	I-142a	blank	39
417	I-7h	I-145a	A1.15	33
418	I-143c	L4a	A1.15	8
419	I-143d	L4a	A1.15	8
420	I-22a	I-145a	blank	38
421	I-22b	I-145a	blank	38
422	I-107n	L48	A1.15	25
423	I-22c	I-145a	blank	38
424	I-22l	I-142b	blank	38
425	I-22d	I-145a	blank	38
426	I-22e	I-142a	blank	38
427	I-22f	I-142a	blank	38
428	I-22g	I-142a	blank	38
429	I-22h	I-142a	blank	38
430	I-23a	I-142a	blank	39
431	I-140p	I-142a	A1.15	32
432	I-140p	I-142a	A1.03	32
433	I-140p	I-142a	A1.01	32
434	I-23c	I-142a	blank	39
435	I-23d	I-145b	blank	39
436	I-23d	I-142a	blank	39
437	I-135f	L48	A18	25
438	I-140c	I-142c	A18	32
439	I-102	L50k	A18	27
440	I-141c	L50e	A18	27
441	I-102	L4a	A18	8
442	I-135g	L48	A18	25
443	I-102	L4b	A18	8
444	I-107d	L48	A18	25
445	I-102	L4d	A18	8
446	I-135a	L63	A18	25
447	I-107a	L54a	A18	25
448	I-135a	L55a	A18	25
449	I-135e	L55a	A18	25
450	I-107o	L55a	A18	25
451	I-107a	L55a	A18	25
452	I-140f	I-145c	A18	32
453	I-140g	I-142c	A18	32
454	I-140g	I-142c	A18	32
455	I-135h	L48	A18	25
456	I-140a	I-145c	A18	32
457	I-141c	L59f	A18	8
458	I-140h	I-142a	A18	32
459	I-135a	L27	A18	24
460	I-135f	L66a	A18	25
461	I-102	L59g	A18	8
462	I-141f	L4a	A18	8
463	I-135j	L48	A18	25
464	I-135i	L48	A18	25
465	I-141g	L4a	A18	8
466	I-135b	L48	A18	25
467	I-140f	I-142c	A18	32
468	I-140i	I-142c	A18	32
469	I-141d	L59n	A18	8
470	I-140l	I-142c	A18	32
471	I-140k	I-142c	A18	32
472	I-141c	L59n	A18	8
473	I-140d	I-145c	A18	32
474	I-141c	L59d	A18	8
475	I-135a	1-allylcyclopropane-1-	A18	25
		carboxylic acid
476	I-141c	L59c	A18	8
477	I-140d	I-142c	A18	32
478	I-141c	L59e	A18	8
479	I-140e	I-142c	A18	32
480	I-141c	L65c	A18	29
481	I-141c	L65c	A18	29
482	I-107p	L62a	A18	25
483	I-135e	L67a	A18	25
484	I-143a	L50l	A18	27
485	I-141c	L50l	A18	27
486	I-107a	L68	A1.15	40
487	I-107a	L68	A1.15	40
488	I-105b	L4a	A2	8
489	I-107d	L48	A5a	25
490	I-107d	L48	A5d	25
491	I-102	L50k	A13	27
492	I-102	L50a	A13	27
493	I-107d	L48	A5f	25
494	I-107d	L48	A5e	25
495	I-107a	2-vinylbenzoic acid	A1.20	25
496	I-107a	2-vinylbenzoic acid	A1.03	25
497	I-107q	hex-5-ene-1-sulfonyl	A1.15	34
		chloride
498	I-105a	L50m	A1.15	27
499	I-107z	L48b	A1.15	25
500	I-104d	L4a	A1.15	8
501	I-7r	I-145a	A1.15	33
502	I-22v	I-145a	A1.15	38
503	I-102	L50m	A1.03	27
504	I-7r	I-145b	A1.03	33
505	I-7r	I-142a	A1.03	33
506	I-7r	I-142a	A1.01	33
507	I-7r	I-142a	A1.15	33
508	I-107d	L48	A1.43	25
509	I-107d	L48	A1.42	25
510	I-22k	I-145b	blank	38
511	I-27a	I-142a	A1.03	33
512	I-7s	I-142a	A1.03	33
513	I-7s	I-145b	A1.03	33
514	I-102	L4a	A19	8
515	I-105b	L4b	A1.15	8
516	I-102	L69a	A1.15	27
517	I-102	L69a	A1.03	27
518	I-102	L69a	A1.15	27
519	I-141b	L69a	A1.15	27
520	I-141b	L69a	A1.15	27
521	I-105a	L69a	A1.15	27
522	I-105a	L69a	A1.15	27
523	I-102	L69b	A1.15	27
524	I-102	L69b	A1.03	27
525	I-102	L69a	A1.03	27
526	I-102	L4a	A1.39	8
527	I-102	L4a	A23	8
528	I-102	L49	A1.41	8
529	I-102	L4a	A1.40	11
530	I-102	L4a	A1.40	11
531	I-107d	L48	A1.28	36
532	I-107d	L48	A1.28	36
533	I-102	L4a	A20	8
534	I-135k	(E)-but-2-enoic acid	A2	25
535	I-102	L4a	A11b	8
536	I-102	L4a	A1.44	8
537	I-143h	L4a	A1.15	8
538	I-143i	L4a	A1.15	8
539	I-105b	L20b	A1.15	10
540	I-107e	L66a	A1.15	25
541	I-141h	L4a	A1.15	8
542	I-102	L4a	A11b	11
543	I-102	L4a	A11b	11
544	I-105b	L37	A1.15	10
545	I-105b	L37	A1.15	10
546	I-105a	L38d	A1.15	27
547	I-135l	L48	A1.15	25
548	I-105a	L37	A1.15	10
549	I-135m	L48d	A1.15	25
550	I-135n	L48b	A1.15	25
551	I-135n	L48	A1.15	25
552	I-135m	L48d	A1.15	25
553	I-135m	L48c	A1.15	25
554	I-135m	L48c	A2	25
555	I-143i	L4a	A2	8
556	I-143h	L4a	A2	8
557	I-107e	L48	A2	25
558	I-7p	I-145a	A1.15	33
559	I-7p	I-142a	A1.15	33
560	I-135l	L48	A1.15	25
561	I-22w	I-142a	blank	38
562	I-22w	I-142a	blank	38
563	I-7f	I-142a	A2	33
564	I-105c	L48	A1.15	25
565	I-105c	2,2-dimethyl-4-pentenoic	A1.15	25
		acid
566	I-135l	L48	A3	25
567	I-135b	L48	A1.15	25
568	I-107e	L48	A1.10	25
569	I-107e	L48	A1.43	25
570	I-102	L38d	A1.03	27
571	I-23k	I-142a	blank	39
572	I-107e	L48	A1.03	25
573	I-140h	I-142a	A1.15	32
574	I-140h	I-142a	A1.03	32
575	I-107e	L48	A1.35	36
576	I-104a	L39	A1.03	27
577	I-104a	L39	A13	27
578	I-141c	L39	A1.03	27
579	I-23m	I-142a	blank	39
580	I-107s	L48	A1.15	25
581	I-107d	L48	A21	25
582	I-107d	L48	A31	25
583	I-107d	L48c	A1.03	25
584	I-107d	L48	A22	36
585	I-135g	L48c	A1.03	25
586	I-107c	L48	A1.03	25
587	I-135g	2,2-dimethyl-4-pentenoic	A1.03	25
		acid
588	I-135g	L66a	A1.03	25
589	I-135g	L66b	A1.03	25
590	I-107b	but-3-enoic acid	A1.15	25
591	I-105a	L4a	A1.15	8
592	I-143f	L4a	A1.15	8
593	I-105a	L50n	A1.15	27
594	I-135a	2,2-dimethyl-4-pentenoic	A1.15	25
		acid
595	I-135d	L62a	A1.15	25
596	I-143g	L4a	A1.15	8
597	I-135d	2-vinylbenzoic acid	A1.15	25
598	I-102	L39a	A2	27
599	I-22t	I-142a	A1.15	38
600	I-22u	I-142a	A1.15	38
601	I-22u	I-142a	A1.15	38 (from
				byproduct
				of step 1
				of example
				600)
602	I-140m	I-145a	A1.15	32
603	I-107m	3-allyloxetane-3-carboxylic	A1.15	25
		acid
604	I-102	L39a	A3	27
606	I-102	L39b	A1.03	27
607	I-140n	I-142a	A1.15	32
608	I-135a	2,2-dimethyl-4-pentenoic	A1.03	25
		acid
609	I-135a	2,2-dimethyl-4-pentenoic	A13	25
		acid
610	I-102	L50o	A1.03	27
611	I-107a	3-allyloxetane-3-carboxylic	A1.03	25
		acid
612	I-103a	L39a	A13	27
613	I-107a	3-allyloxetane-3-carboxylic	A13	25
		acid
614	I-135a	1-	A1.03	25
		allylcyclobutanecarboxylic
		acid
615	I-107a	(2S)-2-hydroxypent-4-enoic	A1.15	41
		acid
616	I-102	L35b	A1.15	27
617	I-102	L72	A1.15	28
618	I-102	L72	A1.15	28
619	I-102	L70	A1.15	27
620	I-102	L70	A1.01	27
621	I-107a	(2R)-2-hydroxypent-4-enoic	A1.15	41
		acid
622	I-105b	L13f	A1.15	27
623	I-135d	(2R)-2-hydroxypent-4-enoic	A1.15	41
		acid
624	I-105a	L73	A1.15	29
625	I-105a	L73	A1.15	29
626	I-142b	methyl 4-amino-2-fluoro-5-	A1.15	42
		nitro-benzoate
627	I-102	L39a	A1.01	27
628	I-107a	(2R)-2-hydroxypent-4-enoic	A1.03	41
		acid
629	I-107a	(2R)-2-hydroxypent-4-enoic	A13	41
		acid
630	I-107a	L71a	A1.03	25
631	I-107d	L48	A1.45	25
632	I-135g	L48	A15b	25
633	I-135g	L48	A15c	25
634	I-107a	L74	A1.03	24
635	I-107a	L74	A1.03	24
636	I-107a	L74	A1.03	24
637	I-135g	L48	A5g	25
638	I-135o	L48	A1.03	25
639	I-135o	L48	A6	25
640	I-135o	L48	A1.46	25
641	I-135o	L48	A5g	25
642	I-135g	L48	A2	25
643	I-146a	L4a	A1.03	8
644	I-102	L4a	A27	11
645	I-146a	L4a	A6	8
646	I-135o	L48	A3	25
647	I-135g	L48	A27	36
648	I-135f	L48	A1.03	25
649	I-143a	L50c	A1.03	27
650	I-143a	L50e	A1.03	27
651	I-143a	L50f	A1.03	27
652	I-104c	L50w	A1.03	27
653	I-143a	L50w	A1.03	27
654	I-143a	L50n	A1.03	27 + 22
655	I-143a	L50s	A1.03	27
656	I-143a	L50t	A1.03	47
657	I-143a	L50r	A6	27
658	I-143a	L50r	A3	27
659	I-143a	L50r	A5g	27
660	I-143a	L50r	A1.26	27
661	I-141c	L50f	A1.03	27
662	I-141c	L50r	A1.03	27
663	I-143a	L60a	A1.03	27
664	I-143a	L60a	A6	27
665	I-143a	L59k	A18	8
666	I-135g	L48	A28	36
667	I-143a	2,2-dimethyl-4-pentenoic	A28	11
		acid
668	I-135g	L48	A29	25
669	I-141c	L59n	A29	27
670	I-141c	L59o	A18	8
671	I-141c	L59m	A18	8
672	I-141c	L59l	A18	8
673	I-141i	L59x	A18	8
674	I-141c	L59p	A18	8
675	I-108	blank	A1.03	15
676	I-135g	L48	A1.47	36
677	I-102	L4a	A32	11
678	I-135g	L48	A33	36
679	I-135a	L63	A6	25
680	I-135g	L48	A1.26	25
681	I-135g	L48	A34b	36
682	I-135e	L79	A18	25
683	I-135e	L79	A18	25 + 22
684	I-141c	L4b	A18	8
685	I-107o	L78	A18	25
686	I-107c	L66c	A1.03	24
687	I-107c	L66c	A1.03	24
688	I-107c	L54b	A1.03	25
689	I-107c	L55a	A1.03	25
690	I-135p	L48	A1.03	25
691	I-107v	L48	A1.03	25
692	I-135g	L48	A1.03	25 + 22
693	I-104c	L59n	A1.03	8
694	I-107d	L51a	A1.03	25
695	I-107d	L54a	A1.03	25
696	I-104c	L50i	A1.03	27
697	I-143a	L50i	A1.03	27
698	I-141c	L50i	A1.03	27
699	I-152	blank	A1.03	24
700	I-135e	L55a	A1.03	25
701	I-135e	L55a	A6	25
702	I-135a	L55a	A1.03	25
703	I-135a	L55a	A6	25
704	I-107o	L55a	A1.03	25
705	I-107o	L55a	A6	25
706	I-107a	L55a	A6	25
707	I-135g	L48	A30	25
708	I-102	L4a	A30	8
709	I-141c	L75a	A18	27
710	I-141c	L75b	A18	27
711	I-107a	L55b	A18	25
712	I-107o	L55b	A18	25
713	I-102	L59n	A18	8
714	I-31	I-145c	A18	33
715	I-31	I-142d	A18	33
716	I-135a	2-vinylbenozic acid	A18	25
717	I-107w	L55a	A18	25
718	I-141c	L76a	A18	27
719	I-107a	L27	A1.03	24
720	I-107a	L27	A1.03	24
721	I-135g	L48	A37	36
722	I-107a	L27	A3	24
723	I-107a	L27	A13	24
724	I-107a	L27	A3	24
725	I-107a	L27	A13	24
726	I-135g	L48	A22	36
727	I-135a	L27	A1.03	24
728	I-135a	L27	A1.46	24
729	I-140aa	I-142a	A1.03	32
730	I-135a	L27	A13	24
731	I-143a	L59g	A1.03	8
732	I-143a	L59g	A13	8
733	I-135a	L27	A1.03	24
734	I-140aa	I-142a	A13	32
735	I-143a	L59g	A1.03	8 + 22
736	I-143a	L59g	A13	8 + 22
737	I-135g	L48	A37	36
738	I-135q	L48	A1.03	25
739	I-135q	L48	A1.03	25
740	I-143j	L59n	A1.03	8
741	I-143j	L59n	A6	8
742	I-135o	L48	A1.03	25
743	I-143j	L59k	A6	8
744	I-143j	L59k	A1.03	8
745	I-140i	I-142c	A1.03	32
746	I-140m	I-142c	A1.03	32
747	I-140m	I-142c	A6	32
748	I-141c	L59f	A6	8
749	I-104a	L4a	A3	8
750	I-105b	L59n	A1.15	8 + 22
751	I-105b	L59n	A1.15	8
752	I-135g	L48	A38	25
753	I-140w	I-142a	A6	25
754	I-141a	L59c	A18	8
755	I-140x	I-142c	A18	32
756	I-140x	I-142c	A18	32
757	I-107a	L53	A18	25
758	I-107aa	L55a	A18	25
759	I-140y	I-142a	A18	32
760	I-140y	I-145c	A18	32
761	I-135g	L66b	A18	25
762	I-140z	I-145c	A18	32
763	I-140z	I-142a	A18	32
764	I-141c	L59n	A35	8
765	I-135g	L48	A35	25
766	I-140r	L48	A18	25
767	I-107x	L48	A18	25
768	I-101b	L59n	A18	1
769	I-135s	L55a	A18	25
770	I-143a	L50k	A35	27
771	I-135r	L66a	A18	25
772	I-107y	L55a	A18	25
773	I-135o	L66b	A18	25
774	I-141c	L59n	A36	8
775	I-107o	L53	A18	25
776	I-141j	L59v	A18	8
777	I-100	L59v	A18	1
778	I-150a	blank	A1.03	21
779	I-150b	blank	A1.03	21
780	I-102	L59i	A1.03	8
781	I-102	L59i	A1.03	8
782	I-8a	blank	A1.03	44
783	I-102	L59h	A1.03	8
784	I-102	L59i	A13	8
785	I-132b	blank	A1.03	21
786	I-143a	L4a	A25a	8
787	I-151a	L62a	A1.03	25
788	I-143a	L59j	A1.03	8
789	I-141c	L59n	A1.03	8
790	I-141c	L59n	A6	8
791	I-141c	L59n	A1.25	8
792	I-135g	L48	A24	25
793	I-143a	L59j	A6	8
794	I-143a	L59j	A1.25	8
795	I-143a	L4a	A24	8
796	I-141c	L59j	A6	8
797	I-141c	L59j	A1.03	8
798	I-141c	L59n	A3	8
799	I-107a	3-allyloxetane-3-carboxylic	A6	25
		acid
800	I-143a	L4a	A25b	8
801	I-135g	L48	A26	25
802	I-140l	I-142c	A6	32
803	I-135g	L48	A14	25
804	I-140l	I-142c	A3	32
805	I-140k	I-142c	A6	32
806	I-140k	I-142c	A1.03	32
807	I-141c	L59n	A1.11	8
808	I-141c	L59n	A2	8
809	I-141i	L59n	A18	8
810	I-141c	L59k	A18	8
811	I-100	L59n	A18	1
812	I-141e	L59n	A18	8
813	I-141c	L59n	A18	45
814	I-135e	I-29	A18	25
815	I-107t	L55a	A18	25
816	I-107u	L55a	A18	25
817	I-140p	I-142a	A18	32
818	I-141i	L59k	A18	8
819	I-141i	L59v	A18	8
820	I-141c	L59n	A18	8 + 46
821	I-135a	L61a	A1.03	25
822	I-135a	L61a	A13	25
823	I-135a	1-	A1.03	25
		allylcyclopropanecarboxylic
		acid
824	I-102	L59a	A13	8
825	I-153	L59q	blank	8
826	I-140s	I-142a	A1.15	32
827	I-140s	I-142a	A1.03	32
828	I-141c	L59a	A1.03	8
829	I-141c	L59c	A1.03	8
830	I-141c	L59c	A6	8
831	I-102	L59r	A1.03	8
832	I-141c	L59c	A6	22 + 8
833	I-141c	L59c	A1.03	22 + 8
834	I-140t	I-142c	A1.03	32
835	I-140t	I-142c	A6	32
836	I-141c	L59s	A1.03	8
837	I-140u	I-142c	A1.03	32
838	I-141c	L59t	A6	8
839	I-141c	L59a	A18	8
840	I-140t	L59n	A18	8
841	I-141c	L59u	A18	8
842	I-102	L59t	A18	8
843	I-141c	L59v	A18	8
844	I-141c	L59w	A18	8
845	I-141c	L59r	A18	8
846	I-140v	I-145c	A18	32
847	I-141i	L59t	A18	8
848	I-135g	L48	A1.03	25
849	I-135g	L48	A1.11	25
850	I-135g	L48	A13	25
851	I-135g	L48	A1.46	25
852	I-135g	L48	A1.41	25
853	I-135g	L48	A3	25
854	I-102	L50aa	A1.03	27
855	I-102	L49	A1.03	22 + 8
856	I-102	L73b	A1.03	29
857	I-102	L73b	A1.03	29
858	I-102	L73a	A1.03	29
859	I-102	L73a	A1.03	29
860	I-102	L64a	A1.03	27
861	I-102	L65a	A1.03	28
862	I-102	L65a	A1.03	28
863	I-107a	L71a	A1.03	25
864	I-107a	L77	A1.03	24
865	I-107a	L77	A1.03	24
866	I-107f	2-(3-bromophenyl)acetic	A1.03	48
		acid
867	I-154a	L62a	A1.03	25
868	I-155a	L62a	A1.03	25
869	I-102	L65b	A1.03	28
870	I-102	L65b	A1.03	28
871	I-141c	L64a	A1.03	27
872	I-141c	L64b	A1.03	29
873	I-141c	L64b	A1.03	29
874	I-107p	L62a	A1.03	25
875	I-141c	L65c	A1.03	29
876	I-141c	L65c	A1.03	29
877	I-141a	L39b	A18	27
878	I-141c	L75c	A18	27
879	I-141c	L75d	A18	27
880	I-141c	L73b	A18	29
881	I-141c	L73b	A18	29
882	I-107o	L62a	A18	25
883	I-102	L65b	A18	28
884	I-102	L65b	A18	28
885	I-141c	L65b	A18	28
886	I-141c	L65b	A18	28
887	I-102	L65c	A18	29
888	I-102	L65c	A18	29
889	I-102	L65d	A18	29
890	I-102	L65d	A18	29
891	I-102	L64a	A18	29
892	I-102	L64a	A18	29
893	I-143a	L80	A18	10
894	I-143a	L80	A18	8
895	I-156	L59n	A18	8
896	I-143a	L59aa	A18	8
897	I-143a	L59bb	A18	8
898	I-143a	L59cc	A18	8
899	I-143a	L59dd	A18	8
900	I-143a	L59ee	A18	8
901	I-143a	L59ff	A18	8
902	I-143a	L59gg	A18	8
903	I-143a	L59y	A18	8
904	I-107x	L66b	A18	25
905	I-107x	L66a	A18	25
906	I-143a	L59z	A18	8
907	I-153a	blank	A18	25 (from
				byproduct
				in step 2)
908	I-153a	blank	A18	25
909	I-107a	L66a	A18	25
910	I-107a	L66b	A18	25
911	I-141c	L82	A18	27
912	I-141c	L7a	A18	8
913	I-107v	L48	A18	25
914	I-135p	L48	A18	25
915	I-107a	L83	A18	24
916	I-107a	L83	A18	24
917	I-107d	L48c	A18	25
918	I-107cc	L55a	A18	25
919	I-140c	I-142d	A18	32
920	I-140ee	I-142d	A18	32
921	I-140ff	I-145c	A18	32
922	I-140ee	I-142c	A18	32
923	I-140gg	I-142d	A18	32
924	I-135r	L48c	A18	25
925	I-140ee	I-145c	A18	32
926	I-140gg	I-145c	A18	32
927	I-143a	L59jj	A18	8
928	I-100	L4a	A18	1
929	I-107t	L53	A18	37
930	I-107u	L53	A18	37
931	I-135r	L66b	A18	25
932	I-141k	L59n	A18	8
933	I-107bb	L55a	A18	25
934	I-141i	L58b	A18	27
935	I-143a	L59ii	A18	8
936	I-100	L28a	A18	1
937	I-8a	blank	A1	49
938	I-140dd	I-142d	A18	32
939	I-140dd	I-145c	A18	32
940	I-135s	1-	A18	25
		allylcyclopropanecarboxylic
		acid
941	I-135s	2,2-dimethylpent-4-enoic	A18	25
		acid
942	I-103a	L59w	A18	8
943	I-135a	2,2-dimethylpent-4-enoic	A18	25
		acid
944	I-141i	L59kk	A18	10
945	I-141i	L59kk	A18	10
946	I-107t	I-145c	A18	33
947	I-107u	I-145c	A18	33
948	I-107a	L81	A18	24
949	I-107a	L81	A18	24
950	I-143a	L59mm	A18	8
951	I-141c	L59hh	A18	8
952	I-140u	I-142d	A18	32
953	I-141i	L59dd	A18	8
954	I-143a	L50s	A18	27
955	I-157	L55a	A18	25

TABLE 3 — ES/MS m/z

Example	[M + H]+	1 H NMR
1	654.3	1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 7.8 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.93 (s, 3H), 7.42 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.04 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.29-5.19 (m, 1H), 4.96-4.81 (m, 1H),
		4.46-4.30 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.27 (s, 3H), 2.08-1.96
		(m, 1H), 1.76 (s, 2H), 1.61 (d, J = 10.4 Hz, 4H), 1.47 (d, J = 7.1 Hz, 3H),
		1.39 (s, 4H), 1.16 (s, 3H), 1.05 (s, 2H).
2	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 7.2 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 7.93 (s, 3H), 7.42 (s, 1H), 7.23 (d, J = 8.2 Hz, 1H), 7.05 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 6.37-6.24 (m, 1H), 5.80 (d, J = 15.7 Hz,
		1H), 5.25-5.13 (m, 1H), 4.79-4.69 (m, 1H), 4.54-4.41 (m, 1H), 4.13 (s,
		3H), 4.00 (s, 3H), 3.47-3.38 (m, 1H), 3.33-3.08 (m, 2H), 2.24 (dd, J =
		14.2, 9.3 Hz, 1H), 2.07-1.99 (m, 1H), 1.99-1.88 (m, 1H), 1.89-1.79
		(m, 2H), 1.80-1.72 (m, 1H), 1.72-1.56 (m, 3H), 1.54 (d, J = 7.2 Hz,
		3H), 1.15 (s, 3H).
3	652.4	1H NMR (400 MHz, DMSO-d6) δ 8.15-8.06 (m, 2H), 7.93 (s, 3H), 7.42
		(s, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.07 (s, 1H), 6.92 (d, J = 1.2 Hz, 1H),
		5.62-5.53 (m, 1H), 5.41-5.20 (m, 2H), 4.96-4.83 (m, 1H), 4.50-4.40
		(m, 1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.25-3.09 (m, 3H), 2.85-2.75 (m,
		1H), 2.30-2.20 (m, 1H), 2.07-1.97 (m, 1H), 1.92-1.69 (m, 2H), 1.70-
		1.32 (m, 10H).
4	654.7	1H NMR (400 MHz, DMSO-d6) δ 8.29 (d, J = 7.4 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 7.94 (s, 3H), 7.42 (s, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.05 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.22-5.11 (m, 1H), 4.84-4.73 (m, 1H),
		4.52-4.40 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.34-3.08 (m, 3H), 2.07-
		1.92 (m, 2H), 1.92-1.82 (m, 1H), 1.81-1.71 (m, 1H), 1.70-1.54 (m,
		4H), 1.50 (d, J = 7.1 Hz, 3H), 1.46 (s, 3H), 1.34 (s, 4H), 1.03 (s, 1H).
5	614.3	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.90 (s, 3H),
		7.84 (d, J = 7.4 Hz, 1H), 7.35 (d, J = 1.1 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H),
		7.03 (s, 1H), 6.87 (d, J = 1.2 Hz, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.87-4.75
		(m, 1H), 4.44-4.33 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.26-3.11 (m,
		1H), 3.04-2.91 (m, 1H), 1.98-1.84 (m, 2H), 1.84-1.53 (m, 5H), 1.45
		(d, J = 7.1 Hz, 3H), 1.42-1.27 (m, 4H), 1.24-1.18 (m, 6H), 1.15-1.01
		(m, 2H), 0.95 (s, 3H).
6	650.4	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.6 Hz, 1H), 8.21 (s, 3H),
		7.99 (d, J = 8.0 Hz, 1H), 7.47 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.02 (s,
		1H), 6.94 (d, J = 1.2 Hz, 1H), 6.86 (t, J = 74.9 Hz, 1H), 5.07-4.95 (m,
		1H), 4.76-4.64 (m, 2H), 4.64-4.54 (m, 1H), 4.12 (s, 3H), 4.00 (s, 3H),
		3.71-3.51 (m, 2H), 3.51-3.36 (m, 1H), 2.06-1.80 (m, 3H), 1.72-1.46
		(m, 4H), 1.43 (d, J = 7.1 Hz, 3H), 1.42-1.32 (m, 1H), 1.31-1.15 (m, 1H),
		0.93-0.79 (m, 1H), 0.77-0.58 (m, 2H), 0.53-0.41 (m, 1H)
7	688.5	1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 7.0 Hz, 1H), 8.61 (d, J =
		2.6 Hz, 1H), 8.50 (d, J = 2.5 Hz, 1H), 8.20 (s, 3H), 8.10 (d, J = 8.0 Hz,
		1H), 7.46 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.95 (d, J = 1.1
		Hz, 1H), 6.86 (t, J = 74.8 Hz, 1H), 5.25 (p, J = 7.0 Hz, 1H), 4.90-4.78
		(m, 1H), 4.72-4.64 (m, 1H), 4.63-4.51 (m, 1H), 4.13 (s, 3H), 4.00 (s,
		3H), 3.70-3.51 (m, 2H), 3.52-3.37 (m, 1H), 2.74-2.63 (m, 1H), 2.49-
		2.32 (m, 2H), 2.06-1.86 (m, 2H), 1.52 (d, J = 7.1 Hz, 3H), 1.49-1.32
		(m, 2H), 1.30-1.15 (m, 1H), 0.72-0.55 (m, 1H).
8	612.3	NA
9	612.3	NA
10	626.4	1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 6.5 Hz, 1H), 8.10 (s, 3H),
		8.06 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 1.2 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H),
		7.10 (s, 1H), 7.04 (s, 1H), 4.98 (p, J = 6.8 Hz, 1H), 4.76-4.66 (m, 2H),
		4.16 (s, 3H), 4.02 (s, 3H), 3.84 (dd, J = 10.7, 7.3 Hz, 1H), 3.79-3.64 (m,
		3H), 3.10 (dd, J = 10.6, 7.3 Hz, 1H), 2.38-2.23 (m, 2H), 1.94-1.76 (m,
		4H), 1.69-1.57 (m, 1H), 1.42 (d, J = 6.9 Hz, 3H), 1.35 (dd, J = 12.9, 4.4
		Hz, 1H), 1.09 (s, 3H), 0.89 (s, 3H), 0.79-0.62 (m, 2H).
11	626.4	1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 7.8 Hz, 1H), 8.20-8.05
		(m, 4H), 7.58 (s, 1H), 7.28 (d, J = 8.2 Hz, 1H), 7.12 (s, 1H), 7.04 (d, J =
		1.2 Hz, 1H), 5.17 (p, J = 7.0 Hz, 1H), 4.60 (dd, J = 14.0, 6.1 Hz, 1H), 4.55-
		4.45 (m, 1H), 4.18 (s, 3H), 4.02 (s, 3H), 3.85-3.64 (m, 4H), 3.46-3.36
		(m, 1H), 2.37-2.24 (m, 2H), 1.93-1.75 (m, 3H), 1.67-1.60 (m, 1H),
		1.57 (d, J = 6.9 Hz, 3H), 1.35 (dd, J = 12.9, 4.4 Hz, 1H), 0.89 (s, 3H), 0.86
		(s, 3H), 0.83-0.77 (m, 1H), 0.67-0.57 (m, 1H).
12	666.4	1H NMR (400 MHz, DMSO-d6) δ 8.34 (d, J = 7.9 Hz, 1H), 8.14-8.00
		(m, 4H), 7.59 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.05 (s, 1H), 7.04 (d, J =
		1.2 Hz, 1H), 5.29-5.18 (m, 1H), 4.95-4.84 (m, 1H), 4.64-4.29 (m,
		2H), 4.12 (s, 3H), 4.01 (s, 3H), 3.80-3.68 (m, 1H), 2.48-2.40 (m, 1H),
		1.93-1.74 (m, 4H), 1.73-1.54 (m, 3H), 1.47 (d, J = 7.1 Hz, 3H), 1.45-
		1.28 (m, 4H), 1.16 (s, 3H), 1.04 (s, 2H).
13	612.4	1H NMR (400 MHz, DMSO-d6) (NOTE: Rotamers observed, in a 0.6:0.4
		ratio. Partial proton counts reported where diagnostic) δ 8.08 (s, 1.2H),
		8.05 (d, J = 8.1 Hz, 1H), 7.93 (d, J = 5.4 Hz, 1.8H), 7.84 (d, J = 7.5 Hz,
		1H), 7.55 (s, 0.4H), 7.41 (s, 0.6H), 7.19 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H),
		7.00 (s, 0.4H), 6.96 (s, 0.6H), 5.12 (p, J = 7.0 Hz, 1H), 4.89-4.76 (m,
		1H), 4.53 (s, 0.4H), 4.47-4.37 (m, 1H), 4.21 (s, 0.6H), 4.12 (s, 3H), 4.00
		(s, 3H), 3.83-3.75 (m, 0.4H), 3.69-3.51 (m, 1.6H), 3.24-3.13 (m, 1H),
		2.05-1.80 (m, 4H), 1.76-1.52 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.44-
		1.27 (m, 4H), 1.21 (s, 3H), 1.15-0.99 (m, 2H), 0.95 (s, 3H).
14	680.6	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 8.02 (s, 3H),
		7.84 (d, J = 7.4 Hz, 1H), 7.45 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04 (s,
		1H), 6.94 (d, J = 1.2 Hz, 1H), 6.19 (tt, J = 55.0, 3.8 Hz, 1H), 5.12 (p, J =
		7.1 Hz, 1H), 4.87-4.76 (m, 1H), 4.40 (dt, J = 13.7, 7.1 Hz, 1H), 4.12 (s,
		3H), 3.99 (s, 3H), 3.98-3.93 (m, 1H), 3.90-3.76 (m, 2H), 3.49-3.39
		(m, 3H), 1.93 (t, J = 12.0 Hz, 2H), 1.86-1.74 (m, 1H), 1.74-1.56 (m,
		2H), 1.45 (d, J = 7.1 Hz, 3H), 1.42-1.26 (m, 4H), 1.21 (s, 3H), 1.08 (s,
		2H), 0.95 (s, 3H).
15	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.91 (s, 3H),
		7.83 (d, J = 7.4 Hz, 1H), 7.36 (d, J = 1.1 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H),
		7.03 (s, 1H), 6.88 (s, 1H), 5.18-5.07 (m, 1H), 4.87-4.76 (m, 1H), 4.48-
		4.35 (m, 1H), 4.12 (t, 3H), 3.99 (s, 3H), 3.42-3.33 (m, 2H), 1.93 (t, J =
		12.3 Hz, 1H), 1.85-1.53 (m, 5H), 1.45 (d, J = 7.1 Hz, 3H), 1.41-1.28
		(m, 4H), 1.26-1.16 (m, 6H), 1.14-1.02 (m, 3H), 0.95 (s, 3H).
16	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.95 (m, 3H),
		7.84 (d, J = 7.5 Hz, 1H), 7.42 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.04 (s,
		1H), 6.92 (m, 1H), 5.12 (m, 1H), 4.82 (m, 1H), 4.40 (m, 1H), 4.12 (s, 3H),
		3.99 (s, 3H), 3.37-3.00 (m, 2H), 2.90 (s, 1H), 2.74 (s, 1H), 1.95-1.85 (m,
		2H), 1.79-1.52 (m, 3H), 1.48-1.25 (m, 7H), 1.21 (s, 3H), 1.15-1.07 (m,
		2H), 0.95 (s, 3H).
17	616.4	1H NMR (400 MHz, Methanol-d4) δ 8.45 (d, J = 8.0 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 7.47 (d, J = 1.2 Hz, 1H), 7.18 (d, J = 8.1 Hz, 1H), 7.07-6.93
		(m, 2H), 5.32-5.10 (m, 1H), 4.82 (m, 1H), 4.40 (m, 1H), 4.15 (s, 3H),
		4.08 (s, 3H), 3.63-3.45 (m, 1H), 3.48-3.35 (m, 6H), 2.25-2.15 (m, 1H),
		2.07-1.60 (m, 6H), 1.60-1.32 (m, 7H), 1.25 (s, 3H), 1.07 (s, 3H).
18	602.4	1H NMR (400 MHz, CD3OD ) d 8.10 (d, J = 8.1 Hz, 1H), 7.47 (s, 1H),
		7.23 (d, J = 8.2 Hz, 1H), 7.09-6.93 (m, 1H), 5.30 (q, J = 6.7 Hz, 1H),
		5.00 (m, 1H), 4.48-4.32 (m, 1H), 4.16 (s, 3H) 4.09 (m, 4H), 3.51-3.38
		(m, 4H), 2.87 (m, 1H), 2.41 (m, 1H), 2.21 (m, 1H), 1.98-1.50 (m, 11H),
		1.43 (s, 3H), 1.33 (m, 5H), 1.12-0.64 (m, 2H).
19	620.3	1H NMR (400 MHz, CD3OD ) d 8.45 (d, J = 9.2 Hz, 1H), 8.09 (d, J = 8.0
		Hz, 1H), 7.92 (s, 1H), 7.44 (s, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.01 (s, 1H),
		5.30 (m, 1 H), 5.08-4.94 (m, 1H), 4.61-4.29 (m, 2H), 4.14 (s, 3H), 4.11
		(s, 3H), 3.68 (d, 1H), 3.62-3.42 (m, 2H), 3.18 (m, 2H)), 2.95-2.77 (m,
		1H), 2.67-2.32 (m, 2H), 2.20-1.88 (m, 1H), 1.78-1.50 (m, 6H), 1.38
		(s, 3H), 1.34 (m, 4H) 0.92-0.57 (m, 1H).
20	612.4	1H NMR (400 MHz, DMSO-d6) δ 8.16-8.00 (m, 4H), 7.84 (d, J = 7.4
		Hz, 1H), 7.59 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04 (d, J = 1.6 Hz, 1H),
		5.12 (m, 1H), 4.88-4.75 (m, 1H), 4.46-4.30 (m, 4H), 4.12 (s, 3H), 4.01
		(s, 3H), 2.33 (m, 2H), 2.04-1.73 (m, 4H), 1.72-1.50 (m, 3H), 1.49-1.25
		(m, 7H), 1.21 (s, 3H), 1.11 (m, 2H), 0.95 (s, 3H).
21	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 3H), 8.05 (d, J = 8.1 Hz, 1H),
		7.84 (d, J = 7.4 Hz, 1H), 7.59 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.04 (s,
		1H), 5.12 (m, 1H), 4.82 (m, 1H), 4.70-4.33 (m, 4H), 4.12 (s, 3H), 4.01 (s,
		3H), 2.90 (s, 1H), 2.74 (s, 1H), 2.02-1.52 (m, 5H), 1.52-1.26 (m, 8H),
		1.21 (s, 3H), 1.09 (m, 2H), 0.95 (s, 3H).
22	628.4	1H NMR (400 MHz, Methanol-d4) δ 8.17-7.97 (m, 1H), 7.62 (d, J = 1.2
		Hz, 1H), 7.27-7.11 (m, 2H), 7.01 (s, 1H), 5.31-5.08 (m, 1H), 4.86-
		4.70 (m, 1H), 4.72-4.31 (m, 1H), 4.16 (s, 3H), 4.09 (s, 3H), 3.95-3.81
		(m, 1H), 3.64-3.54 (m, 1H), 3.46-3.34 (m, 6H), 2.59-2.40 (m, 1H),
		2.19-1.83 (m, 3H), 1.81-1.63 (m, 3H), 1.61-1.33 (m, 7H), 1.25 (s,
		3H), 1.07 (s, 3H).
23	618.3	1H NMR (400 MHz, CD3OD ) d 8.15 (d, J = 8.2 Hz, 1H), 7.62 (d, J = 1.3
		Hz, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.14 (d, J = 1.3 Hz, 1H), 7.08 (s, 1H),
		5.65-5.53 (m, 1H), 5.30-5.00 (m, 2H), 4.86-4.50 (m, 4H), 4.45-4.32 (m,
		1H), 4.20 (s, 3H), 4.09 (s, 3H), 3.92-3.79 (m, 1H), 2.91-2.74 (m, 1H),
		2.58-2.37 (m, 2H), 2.13-1.54 (m, 10 H), 1.56-1.38 (m, 2H), 0.96-0.82
		(m, 2H).
24	630.3	NA
25	582.4	1H NMR (400 MHz, CD3OD ) d 8.00 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H),
		7.10 (d, J = 8.0 Hz, 1H), 6.63, (s, 1H), 6.60 (m, 1H), 6.16 (s, 2H), 5.04 (m,
		1H), 4.63-4.38 (m, 4H), 4.11 (s, 3H), 3.41 (m, 2H), 2.91 (s, 3H), 1.72-
		1.54 (m, 10 H), 1.52-1.37 (m, 4H), 1.0-0.95 (m, 1H), 0.80-0.71 (m, 2H).
26	572.4	1H NMR (400 MHz, DMSO-d6) δ 8.46 (d, J = 1.1 Hz, 1H), 8.29 (d, J =
		8.5 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.91 (s, 3H), 7.12 (d, J = 8.1 Hz,
		1H), 6.76 (s, 1H), 6.61 (d, J = 1.0 Hz, 1H), 5.25-5.11 (m, 1H), 4.94 (dt, J =
		14.3, 7.7 Hz, 1H), 4.49-4.36 (m, 1H), 4.16-4.01 (m, 1H), 3.98 (s,
		3H), 3.36-3.12 (m, 4H), 2.52 (s, 3H), 2.15-1.93 (m, 4H), 1.84-1.33
		(m, 9H), 1.29-0.92 (m, 5H), 0.76-0.58 (m, 1H).
27	600.4	1H NMR (400 MHz, DMSO-d6) δ 8.46 (d, J = 1.0 Hz, 1H), 7.96 (d, J =
		8.0 Hz, 1H), 7.92 (s, 3H), 7.78 (d, J = 7.5 Hz, 1H), 7.12 (d, J = 8.1 Hz,
		1H), 6.75 (s, 1H), 6.61 (d, J = 1.1 Hz, 1H), 5.12 (p, J = 7.0 Hz, 1H), 4.87-
		4.73 (m, 1H), 4.41-4.26 (m, 1H), 4.13-4.01 (m, 1H), 3.98 (s, 3H), 3.39-
		3.09 (m, 4H), 2.52 (s, 3H), 2.08-1.85 (m, 2H), 1.83-1.24 (m, 12H),
		1.20 (s, 3H), 1.17-0.99 (m, 3H), 0.95 (s, 3H).
28	620.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 6.9 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 7.95 (s, 3H), 7.40 (s, 1H), 7.37-7.27 (m, 2H), 7.27-7.15
		(m, 3H), 7.07 (s, 1H), 6.92 (s, 1H), 5.18 (p, J = 7.0 Hz, 1H), 4.93-4.79
		(m, 1H), 4.64-4.50 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.33-3.04 (m,
		5H), 2.43-2.29 (m, 1H), 2.29-2.15 (m, 1H), 2.09-1.95 (m, 1H), 1.82-
		1.05 (m, 11H), 0.61-0.43 (m, 1H).
29	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 7.7 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 7.93 (s, 3H), 7.41 (s, 1H), 7.39-7.27 (m, 3H), 7.27-7.17
		(m, 2H), 7.04 (s, 1H), 6.91 (s, 1H), 5.35 (p, J = 7.0 Hz, 1H), 4.72-4.49
		(m, 2H), 4.11 (s, 3H), 3.99 (s, 3H), 3.37-3.01 (m, 3H), 2.96-2.82 (m,
		1H), 2.48-2.37 (m, 2H), 2.04 (d, J = 25.5 Hz, 1H), 1.75 (s, 1H), 1.67-
		1.15 (m, 12H), 1.10-0.88 (m, 2H).
30	622.3	1H NMR (400 MHz, DMSO-d6) δ 9.73 (d, J = 6.8 Hz, 1H), 8.14 (d, J =
		8.0 Hz, 1H), 8.07 (dd, J = 7.8, 1.9 Hz, 1H), 7.94 (s, 3H), 7.55-7.46 (m,
		1H), 7.45 (s, 1H), 7.33 (d, J = 8.1 Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.13-
		7.03 (m, 2H), 6.93 (s, 1H), 5.34 (p, J = 6.6 Hz, 1H), 4.77-4.63 (m, 1H),
		4.48-4.34 (m, 3H), 4.33-4.23 (m, 2H), 4.13 (s, 3H), 4.00 (s, 3H), 3.35-
		3.02 (m, 3H), 2.74-2.58 (m, 1H), 2.37-2.20 (m, 1H), 2.11-1.49 (m,
		9H).
31	638.3	1H NMR (400 MHz, DMSO-d6) δ 8.85-8.64 (m, 4H), 8.08 (d, J = 8.0
		Hz, 1H), 7.99 (d, J = 1.3 Hz, 1H), 7.40-7.17 (m, 6H), 7.12 (s, 1H), 5.19
		(p, J = 7.0 Hz, 1H), 4.98-4.73 (m, 2H), 4.65-4.54 (m, 1H), 4.52-4.36
		(m, 1H), 4.14 (s, 3H), 4.02 (s, 3H), 3.53-3.32 (m, 2H), 3.15-2.89 (m,
		2H), 2.44-2.29 (m, 2H), 2.29-2.17 (m, 1H), 2.00-1.83 (m, 1H), 1.65-
		1.06 (m, 8H), 0.65-0.47 (m, 1H).
32	622.3	1H NMR (400 MHz, DMSO-d6) δ 8.89 (d, J = 6.7 Hz, 1H), 8.05 (s, 3H),
		7.96 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 1.8 Hz, 1H), 7.42 (s, 1H), 7.15 (d, J =
		8.1 Hz, 1H), 6.68 (d, J = 1.9 Hz, 1H), 6.59 (s, 1H), 6.35 (s, 1H), 5.13-
		5.01 (m, 1H), 4.66-4.30 (m, 5H), 4.15-3.97 (m, 4H), 3.82-3.65 (m,
		1H), 2.81 (s, 3H), 2.35-2.24 (m, 1H), 2.01-1.76 (m, 4H), 1.76-1.59
		(m, 2H), 1.55 (d, J = 7.0 Hz, 3H), 1.52-1.41 (m, 1H), 1.42-1.26 (m,
		2H), 1.13-0.85 (m, 2H).
33	622.3	1H NMR (400 MHz, DMSO-d6) δ 9.07 (d, J = 7.7 Hz, 1H), 8.08 (s, 3H),
		8.00 (d, J = 8.0 Hz, 1H), 7.79 (s, 1H), 7.46 (s, 1H), 7.22 (d, J = 8.0 Hz,
		1H), 6.60 (s, 1H), 6.58 (s, 1H), 6.37 (s, 1H), 5.15 (p, J = 7.0 Hz, 1H), 4.69-
		4.23 (m, 5H), 4.23-4.05 (m, 4H), 3.85-3.69 (m, 1H), 2.81 (s, 3H),
		2.33 (s, 1H), 2.14-1.92 (m, 2H), 1.92-1.68 (m, 5H), 1.70-1.40 (m,
		6H), 1.40-1.29 (m, 1H).
34	608.3	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 6.9 Hz, 1H), 8.07 (s, 3H),
		7.95 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.41 (d, J = 2.5 Hz, 1H), 7.18 (d, J =
		8.0 Hz, 1H), 6.61 (d, J = 2.0 Hz, 1H), 6.39 (s, 1H), 6.36 (s, 1H), 5.21-
		5.05 (m, 1H), 4.72-4.22 (m, 6H), 4.09 (s, 3H), 3.91-3.62 (m, 1H), 2.81
		(s, 3H), 2.38-2.25 (m, 1H), 2.10-1.94 (m, 1H), 1.94-1.71 (m, 4H),
		1.71-1.59 (m, 1H), 1.59-1.29 (m, 6H).
35	636.4	1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 8.2 Hz, 1H), 8.09 (s, 3H),
		7.98 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.42 (s, 1H), 7.20 (d, J = 8.0 Hz,
		1H), 6.80 (s, 1H), 6.61 (s, 1H), 6.37 (s, 1H), 5.39-5.23 (m, 1H), 4.86-
		4.67 (m, 1H), 4.68-4.23 (m, 4H), 4.21-3.99 (m, 4H), 3.88-3.62 (m,
		1H), 2.80 (s, 3H), 2.40-2.19 (m, 1H), 1.95-1.72 (m, 3H), 1.71-1.41
		(m, 6H), 1.42-1.21 (m, 3H), 1.14-0.80 (m, 4H).
36	636.3	1H NMR (400 MHz, DMSO-d6) δ 9.16-9.04 (m, 1H), 8.08 (s, 3H), 8.04
		(d, J = 8.2 Hz, 1H), 7.83 (d, J = 3.0 Hz, 1H), 7.47 (s, 1H), 7.24 (d, J = 8.0
		Hz, 1H), 6.64 (s, 1H), 6.62 (d, J = 2.3 Hz, 1H), 6.37 (s, 1H), 5.31-5.18
		(m, 1H), 4.69-4.24 (m, 6H), 4.10 (s, 3H), 3.89-3.64 (m, 1H), 2.82 (s,
		3H), 2.39-2.24 (m, 1H), 2.01-1.59 (m, 9H), 1.59-1.42 (m, 4H), 1.35
		(d, J = 13.0 Hz, 1H), 1.30-1.16 (m, 1H), 1.07-0.87 (m, 1H).
37	619.3	1H NMR (400 MHz, DMSO-d6) δ 11.05 (d, J = 7.0 Hz, 1H), 8.16 (d, J =
		8.2 Hz, 1H), 8.05 (s, 3H), 7.97-7.81 (m, 2H), 7.63 (s, 1H), 7.46 (d, J =
		7.5 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.12-6.98 (m, 2H), 5.26-5.15 (m,
		1H), 4.72-4.34 (m, 4H), 4.15 (s, 3H), 4.02 (s, 3H), 3.88-3.67 (m, 1H),
		3.17-3.04 (m, 1H), 2.94-2.70 (m, 2H), 2.40-2.25 (m, 1H), 2.15-1.98
		(m, 1H), 1.96-1.54 (m, 9H), 1.40-1.28 (m, 1H).
38	636.3	1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 9.5 Hz, 1H), 8.14 (d, J =
		8.2 Hz, 1H), 8.05 (s, 3H), 7.60 (s, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.32-
		7.15 (m, 3H), 7.04 (s, 1H), 6.97 (s, 1H), 5.41-5.28 (m, 1H), 4.68-4.15
		(m, 4H), 4.08 (s, 3H), 4.01 (s, 3H), 3.74 (s, 1H), 2.82-2.71 (m, 1H), 2.41-
		2.12 (m, 2H), 2.08-1.94 (m, 1H), 1.91-1.71 (m, 4H), 1.70-1.28 (m,
		6H), 0.99-0.85 (m, 1H).
39	632.3	1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 6.9 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 8.04 (s, 3H), 7.58 (s, 1H), 7.38-7.27 (m, 2H), 7.27-7.17
		(m, 3H), 7.08 (s, 1H), 7.03 (s, 1H), 5.25-5.11 (m, 1H), 4.94-4.78 (m,
		1H), 4.66-4.27 (m, 3H), 4.11 (s, 3H), 4.01 (s, 3H), 3.81-3.65 (m, 1H),
		2.44-2.36 (m, 2H), 2.29-2.13 (m, 1H), 1.90-1.72 (m, 4H), 1.70-1.55
		(m, 1H), 1.57-1.05 (m, 8H), 0.60-0.45 (m, 1H).
40	646.3	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 7.7 Hz, 1H), 8.09 (d, J =
		8.1 Hz, 1H), 8.06 (s, 3H), 7.59 (s, 1H), 7.39-7.26 (m, 3H), 7.26-7.16
		(m, 2H), 7.05 (s, 1H), 7.03 (s, 1H), 5.35 (p, J = 7.1 Hz, 1H), 4.74-4.35
		(m, 4H), 4.10 (s, 3H), 4.00 (s, 3H), 3.81-3.67 (m, 1H), 2.95-2.81 (m,
		1H), 2.47-2.23 (m, 2H), 1.91-1.71 (m, 3H), 1.69-1.16 (m, 11H), 1.09-
		0.88 (m, 2H).
41	634.3	1H NMR (400 MHz, DMSO-d6) δ 9.72 (d, J = 6.8 Hz, 1H), 8.22-7.97
		(m, 5H), 7.62 (s, 1H), 7.55-7.44 (m, 1H), 7.33 (d, J = 8.1 Hz, 1H), 7.20
		(d, J = 8.4 Hz, 1H), 7.14-7.00 (m, 3H), 5.34 (p, J = 6.5 Hz, 1H), 4.77-
		4.63 (m, 1H), 4.56-4.34 (m, 4H), 4.32-4.22 (m, 1H), 4.13 (s, 3H), 4.01
		(s, 3H), 3.83-3.68 (m, 1H), 2.75-2.59 (m, 1H), 2.39-2.18 (m, 2H),
		2.00-1.51 (m, 9H), 1.35 (dd, J = 12.9, 4.4 Hz, 1H).
42	632.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 6.9 Hz, 1H), 8.11-7.84
		(m, 4H), 7.57-7.15 (m, 6H), 7.08 (s, 1H), 7.02-6.92 (m, 1H), 5.18 (p, J =
		7.0 Hz, 1H), 4.93-4.79 (m, 1H), 4.68-4.55 (m, 1H), 4.11 (s, 3H), 4.00
		(s, 3H), 3.81-3.50 (m, 3H), 3.18 (t, J = 11.4 Hz, 1H), 2.72-2.53 (m,
		2H), 2.44-2.14 (m, 2H), 2.04-1.76 (m, 3H), 1.67 (d, J = 15.0 Hz, 1H),
		1.56-1.31 (m, 5H), 1.31-1.05 (m, 2H), 0.61-0.41 (m, 1H).
43	650.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 6.9 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 7.96 (s, 3H), 7.43 (s, 1H), 7.38-7.27 (m, 2H), 7.27-7.15
		(m, 3H), 7.07 (s, 1H), 6.93 (s, 1H), 5.18 (p, J = 6.9 Hz, 1H), 4.92-4.77
		(m, 1H), 4.63-4.52 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.75-3.48 (m,
		5H), 3.46-3.31 (m, 4H), 2.46-2.15 (m, 2H), 2.01-1.87 (m, 1H), 1.83-
		1.68 (m, 1H), 1.59-1.33 (m, 5H), 1.33-1.06 (m, 3H), 0.63-0.45 (m,
		1H).
44	635.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 7.0 Hz, 1H), 8.16-7.94
		(m, 4H), 7.48 (s, 1H), 7.38-7.26 (m, 2H), 7.26-7.16 (m, 3H), 7.06 (s,
		1H), 7.00 (s, 1H), 5.18 (p, J = 6.9 Hz, 1H), 4.93-4.79 (m, 1H), 4.66-
		4.53 (m, 1H), 4.53-4.42 (m, 1H), 4.10 (s, 3H), 3.98 (s, 3H), 3.70-3.26
		(m, 2H), 3.16-2.99 (m, 2H), 2.94-2.81 (m, 1H), 2.55 (s, 3H), 2.45-
		2.12 (m, 2H), 2.02-1.86 (m, 1H), 1.73-1.62 (m, 1H), 1.59-1.32 (m,
		5H), 1.32-1.08 (m, 2H), 0.65-0.44 (m, 1H).
45	607.3	1H NMR (400 MHz, DMSO-d6) δ 10.49 (s, 1H), 8.94 (s, 1H), 8.73 (d, J =
		6.8 Hz, 1H), 8.68 (d, J = 6.7 Hz, 1H), 8.41 (d, J = 7.5 Hz, 1H), 8.00 (s,
		3H), 7.67 (d, J = 7.8 Hz, 1H), 7.43 (s, 1H), 7.24 (s, 1H), 6.94 (s, 1H), 4.67
		(t, J = 6.1 Hz, 2H), 4.34-4.16 (m, 2H), 4.14 (s, 3H), 4.00 (s, 3H), 3.36-
		3.02 (m, 3H), 2.48-2.40 (m, 2H), 2.05-2.00 (m, 1H), 1.82-1.64 (m,
		3H), 1.62-1.49 (m, 7H), 1.30-1.25 (m, 2H).
46	607.3	1H NMR (400 MHz, DMSO-d6) δ 8.64-8.58 (m, 1H), 8.50 (t, J = 6.0
		Hz, 1H), 8.23 (d, J = 7.6 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.94 (s, 3H),
		7.64-7.56 (m, 1H), 7.45 (d, J = 7.9 Hz, 1H), 7.41 (s, 1H), 7.14 (s, 1H),
		6.92 (s, 1H), 4.64 (t, J = 7.0 Hz, 2H), 4.16 (s, 3H), 4.12-4.02 (m, 2H),
		4.00 (s, 3H), 3.32-3.08 (m, 5H), 2.04-1.99 (m, 1H), 1.79-1.74 (m,
		1H), 1.61-1.56 (m, 2H), 1.48 (s, 4H), 1.45-1.38 (m, 2H), 1.15-1.10
		(m, 2H).
47	605.3	1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 7.94 (s, 3H), 7.80 (d, J =
		8.2 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.55 (s, 1H), 7.44-7.38 (m, 2H),
		7.35 (td, J = 7.6, 1.8 Hz, 1H), 7.28 (td, J = 7.4, 1.4 Hz, 1H), 7.18 (dd, J =
		8.2, 1.3 Hz, 1H), 7.11 (s, 1H), 6.91 (s, 1H), 4.54-4.48 (m, 2H), 4.10 (s,
		3H), 3.99 (s, 3H), 3.34-3.07 (m, 5H), 2.30-2.22 (m, 2H), 2.10-1.97
		(m, 2H), 1.81-1.37 (m, 8H), 1.18-1.09 (m, 2H).
48	618.3	1H NMR (400 MHz, DMSO-d6) δ 8.28 (t, J = 5.8 Hz, 1H), 8.20 (d, J =
		8.1 Hz, 1H), 8.11 (s, 3H), 7.59 (s, 1H), 7.58-7.43 (m, 4H), 7.41 (d, J =
		8.1 Hz, 1H), 7.13 (s, 1H), 7.04 (d, J = 1.2 Hz, 1H), 4.68 (t, J = 6.4 Hz,
		2H), 4.59-4.22 (m, 2H), 4.16 (s, 3H), 4.02 (s, 3H), 3.81-3.62 (m, 1H),
		3.15 (q, J = 5.5 Hz, 2H), 2.38-2.25 (m, 1H), 1.90-1.72 (m, 4H), 1.67-
		1.59 (m, 1H), 1.53-1.28 (m, 7H), 1.08-0.97 (m, 2H).
49	606.3	1H NMR (400 MHz, DMSO-d6) δ 8.29 (t, J = 5.7 Hz, 1H), 8.20 (d, J =
		8.1 Hz, 1H), 7.95 (s, 3H), 7.58-7.44 (m, 4H), 7.41 (d, J = 8.1 Hz, 1H),
		7.41 (s, 1H), 7.12 (s, 1H), 6.92 (d, J = 1.1 Hz, 1H), 4.68 (t, J = 6.5 Hz,
		2H), 4.58-4.27 (m, 2H), 4.15 (s, 3H), 4.00 (s, 3H), 3.34-3.10 (m, 5H),
		2.05-1.98 (m, 1H), 1.85-1.70 (m, 1H), 1.64-1.55 (m, 2H), 1.49-1.33
		(m, 7H), 1.09-0.97 (m, 2H).
50	579.3	1H NMR (400 MHz, DMSO-d6) δ 10.72 (br. s, 1H), 8.61 (br. d, J = 7.5
		Hz, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.10 (dd, J = 6.0, 1.5 Hz, 1H), 8.02 (s,
		3H), 7.97 (d, J = 8.5 Hz, 1H), 7.44 (s, 1H), 7.21 (s, 1H), 7.00 (t, J = 6.8
		Hz, 1H), 6.95-6.91 (m, 1H), 4.53 (t, J = 7.8 Hz, 2H), 4.18 (s, 3H), 4.00
		(s, 3H), 3.48-3.42 (m, 3H), 3.35-2.92 (m, 4H), 2.09-1.92 (m, 3H),
		1.92-1.68 (m, 6H), 1.65-1.50 (m, 2H), 1.49-1.44 (m, 2H).
51	605.3	1H NMR (400 MHz, DMSO-d6) δ 8.41 (t, J = 5.7 Hz, 1H), 7.97 (br. s,
		3H), 7.76 (d, J = 8.2 Hz, 1H), 7.58 (s, 1H), 7.50 (ddd, J = 7.8, 5.7, 2.9 Hz,
		1H), 7.48-7.35 (m, 4H), 7.23 (dd, J = 8.2, 1.4 Hz, 1H), 7.11 (s, 1H), 6.91
		(d, J = 1.2 Hz, 1H), 4.49 (t, J = 6.4 Hz, 2H), 4.41-4.18 (m, 2H), 4.12 (s,
		3H), 3.99 (s, 3H), 3.34-3.02 (m, 5H), 2.07-1.97 (m, 1H), 1.83-1.68
		(m, 1H), 1.66-1.55 (m, 1H), 1.54-1.39 (m, 5H), 1.38-1.28 (m, 2H),
		1.04-0.91 (m, 2H).
52	606.3	1H NMR (400 MHz, DMSO-d6) δ 8.64 (t, J = 5.6 Hz, 1H), 8.55 (dd, J =
		4.8, 1.6 Hz, 1H), 7.94 (br. s, 3H), 7.91 (dd, J = 7.9, 1.6 Hz, 1H), 7.79 (d,
		J = 8.2 Hz, 1H), 7.64 (s, 1H), 7.56 (dd, J = 7.9, 4.8 Hz, 1H), 7.40 (s, 1H),
		7.24 (dd, J = 8.1, 1.4 Hz, 1H), 7.12 (s, 1H), 6.91 (d, J = 1.2 Hz, 1H), 4.53-
		4.45 (m, 2H), 4.12 (s, 3H), 3.99 (s, 3H), 3.81-3.37 (m, 2H buried under
		water peak), 3.33-3.06 (m, 5H), 2.08-1.96 (m, 1H), 1.83-1.68 (m,
		1H), 1.65-1.37 (m, 8H), 1.12-0.99 (m, 2H).
53	648.3	1H NMR (400 MHz, DMSO-d6) δ 9.33 (s, 1H), 8.49 (dd, J = 4.8, 1.8 Hz,
		1H), 7.96 (s, 3H), 7.82 (dd, J = 7.6, 1.9 Hz, 1H), 7.78 (d, J = 8.2 Hz, 1H),
		7.67 (s, 1H), 7.43 (dd, J = 7.6, 4.8 Hz, 1H), 7.40 (s, 1H), 7.18 (dd, J = 8.2,
		1.3 Hz, 1H), 7.10 (s, 1H), 6.92 (d, J = 1.1 Hz, 1H), 4.49 (t, J = 6.7 Hz,
		2H), 4.43-4.33 (m, 2H), 4.12 (s, 3H), 3.99 (s, 3H), 3.33-3.03 (m, 3H),
		2.08-1.99 (m, 1H), 1.82-1.70 (m, 1H), 1.64-1.54 (m, 2H), 1.49-1.41
		(m, 2H), 1.40-1.31 (m, 2H), 1.10-0.98 (m, 2H), 1.01 (s, 6H), 0.92-
		0.84 (m, 2H), 0.81-0.70 (m, 2H).
54	647.4	1H NMR (400 MHz, DMSO-d6) δ 7.96 (br. s, 3H), 7.94 (s, 1H), 7.82 (d,
		J = 8.1 Hz, 1H), 7.77 (dd, J = 8.0, 1.2 Hz, 1H), 7.64 (s, 1H), 7.44-7.32 (m,
		3H), 7.26 (td, J = 7.5, 1.3 Hz, 1H), 7.14 (dd, J = 8.1, 1.3 Hz, 1H), 7.11 (s,
		1H), 6.92 (d, J = 1.1 Hz, 1H), 4.51 (t, J = 6.4 Hz, 2H), 4.39-4.15 (m,
		1H), 4.11 (s, 3H), 4.00 (s, 3H), 3.36-3.05 (m, 4H), 2.08-1.98 (m, 1H),
		1.84-1.69 (m, 1H), 1.66-1.52 (m, 4H), 0.98 (s, 6H), 1.05-0.90 (m,
		4H), 0.88-0.81 (m, 4H).
55	631.6	1H NMR (400 MHz, DMSO-d6) δ 8.06-7.84 (m, 3H), 7.77-7.63 (m,
		1H), 7.61-7.34 (m, 5H), 7.33-7.14 (m, 2H), 7.12-6.93 (m, 1H), 6.93-
		6.87 (m, 1H), 4.76-4.43 (m, 1H), 4.42-4.17 (m, 2H), 4.15-4.04 (m,
		3H), 4.03-3.88 (m, 3H), 3.82-2.97 (m, 8H), 2.84-2.33 (m, 1H), 2.15-
		1.83 (m, 2H), 1.83-1.20 (m, 5H), 1.18-0.93 (m, 1H), 0.90-0.18 (m,
		2H), 0.09-−0.99 (m, 2H).
56	625.3	1H NMR (400 MHz, DMSO-d6) δ 8.71 (t, J = 5.8 Hz, 1H), 8.37 (d, J =
		5.1 Hz, 1H), 8.29 (d, J = 8.1 Hz, 1H), 7.96 (br. s, 3H), 7.58 (dd, J = 5.1,
		1.2 Hz, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.42 (s, 1H), 7.18 (s, 1H), 6.93 (d,
		J = 1.2 Hz, 1H), 4.71 (t, J = 6.4 Hz, 2H), 4.39-4.01 (m, 2H), 4.15 (s, 3H),
		4.00 (s, 3H), 3.36-3.04 (m, 5H), 2.10-1.98 (m, 1H), 1.80-1.72 (m,
		1H), 1.66-1.51 (m, 2H), 1.48-1.27 (m, 6H), 1.08-0.97 (m, 2H).
57	620.3	1H NMR (400 MHz, DMSO-d6) δ 8.19-7.99 (m, 1H), 8.12 (d, J = 8.0
		Hz, 1H), 7.92 (br. s, 3H), 7.43-7.32 (m, 3H), 7.32-7.26 (m, 1H), 7.22
		(d, J = 8.1 Hz, 1H), 7.13 (s, 1H), 6.92 (d, J = 1.2 Hz, 1H), 5.00-4.46 (m,
		3H), 4.16 (s, 3H), 4.00 (s, 3H), 3.65-2.98 (m, 5H), 2.96-2.61 (m, 1H),
		2.13 (s, 3H), 2.08-1.95 (m, 1H), 1.85-1.68 (m, 1H), 1.66-1.50 (m,
		2H), 1.47-1.16 (m, 4H), 1.15-0.40 (m, 4H).
58	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.96 (br. s,
		3H), 7.64 (d, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.03
		(s, 1H), 6.91 (d, J = 1.1 Hz, 1H), 5.16 (p, J = 7.2 Hz, 1H), 4.68-4.54 (m,
		2H), 4.10 (s, 3H), 3.99 (s, 3H), 3.94-3.45 (m, 3H), 3.33-3.04 (m, 2H),
		2.10-1.97 (m, 1H), 1.89-1.43 (m, 7H), 1.53 (d, J = 7.1 Hz, 3H), 1.40-
		1.28 (m, 1H), 1.17 (s, 3H), 1.17-1.07 (m, 1H), 1.00 (s, 3H), 0.90-0.78
		(m, 2H).
59	616.4	1H NMR (400 MHz, DMSO-d6) δ 9.02-8.93 (m, 1H), 8.92-8.78 (m,
		1H), 8.51 (d, J = 7.7 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 1.3 Hz,
		1H), 7.81 (d, J = 7.4 Hz, 1H), 7.35 (d, J = 1.3 Hz, 1H), 7.19 (d, J = 8.1 Hz,
		1H), 7.07 (s, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.87-4.76 (m, 1H), 4.47-
		4.36 (m, 1H), 4.35-4.22 (m, 1H), 4.14 (s, 3H), 4.02 (s, 3H), 3.96-3.84
		(m, 1H), 3.35 (d, J = 10.8 Hz, 1H), 3.27 (d, J = 11.0 Hz, 1H), 2.82 (q, J =
		9.9 Hz, 1H), 2.70 (q, J = 9.7 Hz, 1H), 2.20-2.12 (m, 1H), 1.92 (t, J =
		12.1 Hz, 1H), 1.73-1.60 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.54-1.26
		(m, 4H), 1.21 (s, 3H), 1.18-0.98 (m, 3H), 0.95 (s, 3H).
60	630.4	1H NMR (400 MHz, DMSO-d6) δ 8.10-7.90 (m, 4H), 7.82 (d, J = 7.4
		Hz, 1H), 7.44 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.03 (s, 1H), 6.94 (s, 1H),
		5.12 (p, J = 7.1 Hz, 1H), 4.87-4.75 (m, 1H), 4.44-4.35 (m, 1H), 4.12 (s,
		3H), 3.99 (s, 3H), 3.95-3.76 (m, 2H), 3.75-3.68 (m, 1H), 3.54 (s, 2H),
		3.45-3.29 (m, 1H), 3.37 (s, 3H), 2.02-1.85 (m, 2H), 1.81-1.53 (m,
		3H), 1.45 (d, J = 7.1 Hz, 3H), 1.42-1.26 (m, 5H), 1.21 (s, 3H), 1.17-
		0.99 (m, 2H), 0.95 (s, 3H).
61	616.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.98 (br. s,
		3H), 7.64 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.03
		(s, 1H), 6.93 (s, 1H), 5.16 (p, J = 7.2 Hz, 1H), 4.68-4.54 (m, 2H), 4.10
		(s, 3H), 3.98 (s, 3H), 3.90-3.31 (m, 6H), 3.36 (s, 3H), 2.03-1.86 (m,
		1H), 1.86-1.45 (m, 5H), 1.53 (d, J = 7.1 Hz, 3H), 1.41-1.27 (m, 1H),
		1.17 (s, 3H), 1.16-1.08 (m, 1H), 1.00 (s, 3H), 0.92-0.76 (m, 2H).
62	628.4	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 8.1 Hz, 1H), 8.08 (d, J =
		7.9 Hz, 1H), 8.02 (br. s, 3H), 7.46 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.06
		(s, 1H), 6.94 (s, 1H), 5.27 (p, J = 7.0 Hz, 1H), 4.88-4.76 (m, 1H), 4.48-
		4.35 (m, 1H), 4.13 (s, 3H), 3.99 (s, 3H), 3.95-3.76 (m, 1H), 3.75-3.67
		(m, 1H), 3.66-3.48 (m, 2H), 3.37 (s, 3H), 3.47-3.31 (m, 1H), 2.32-
		2.21 (m, 1H), 2.12-1.87 (m, 2H), 1.85-1.69 (m, 3H), 1.68-1.53 (m,
		1H), 1.45 (d, J = 6.8 Hz, 3H), 1.50-1.33 (m, 2H), 1.31-0.99 (m, 4H),
		0.99-0.89 (m, 1H), 0.65-0.56 (m, 1H), 0.52-0.42 (m, 1H).
63	636.4	1H NMR (400 MHz, DMSO-d6) δ 9.89-9.18 (m, 2H), 8.70 (d, J = 7.4
		Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.98 (s, 1H), 7.80 (d, J = 7.4 Hz, 1H),
		7.35 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.12 (p, J = 7.1 Hz,
		1H), 4.87-4.77 (m, 1H), 4.50-4.34 (m, 2H), 4.14 (s, 3H), 4.02 (s, 3H),
		3.84-3.71 (m, 3H), 3.71-3.54 (m, 1H), 3.49-3.41 (m, 1H), 3.01 (t, J =
		11.6 Hz, 1H), 2.64-2.53 (m, 1H), 2.41-2.21 (m, 1H), 1.92 (t, J = 12.2
		Hz, 1H), 1.76-1.58 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.51-1.27 (m,
		3H), 1.21 (s, 3H), 1.18-1.00 (m, 2H), 0.95 (s, 3H).
64	618.4	1H NMR (400 MHz, DMSO-d6) δ 9.30-9.02 (m, 2H), 8.60 (d, J = 7.7
		Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.98 (s, 1H), 7.80 (d, J = 7.4 Hz, 1H),
		7.35 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.25 (d, J = 45.2 Hz,
		1H), 5.12 (p, J = 7.1 Hz, 1H), 4.87-4.76 (m, 1H), 4.55-4.34 (m, 2H),
		4.14 (s, 3H), 4.27-3.80 (m, 2H), 4.01 (s, 3H), 3.53 (t, J = 12.7 Hz, 1H),
		3.43-3.16 (m, 2H), 2.90 (q, J = 11.3 Hz, 1H), 2.36-2.23 (m, 1H), 2.11-
		1.86 (m, 2H), 1.76-1.60 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.53-1.25
		(m, 3H), 1.21 (s, 3H), 1.18-0.99 (m, 2H), 0.95 (s, 3H).
65	656.3	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.83 (d, J =
		7.5 Hz, 1H), 7.54 (br. s, 1H), 7.34 (d, J = 1.1 Hz, 1H), 7.18 (d, J = 8.2 Hz,
		1H), 7.04 (s, 1H), 6.87 (d, J = 1.2 Hz, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.86-
		4.76 (m, 1H), 4.48-4.33 (m, 1H), 4.18 (dd, J = 10.4, 4.1 Hz, 1H), 4.11 (s,
		3H), 4.14-3.79 (m, 7H), 3.99 (s, 3H), 3.22-3.12 (m, 1H), 1.92 (t, J =
		12.2 Hz, 1H), 1.89-1.76 (m, 1H), 1.76-1.50 (m, 3H), 1.45 (d, J = 7.1
		Hz, 3H), 1.42-1.23 (m, 5H), 1.20 (s, 3H), 1.17-0.97 (m, 2H), 0.94 (s,
		3H).
66	630.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.92 (br. s,
		3H), 7.82 (d, J = 7.5 Hz, 1H), 7.39 (d, J = 1.1 Hz, 1H), 7.19 (d, J = 8.2 Hz,
		1H), 7.03 (s, 1H), 6.90 (d, J = 1.3 Hz, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.86-
		4.76 (m, 1H), 4.71-4.21 (m, 3H), 4.46-4.35 (m, 1H), 4.11 (s, 3H), 3.99
		(s, 3H), 3.60-3.51 (m, 2H), 3.22-3.08 (m, 1H), 3.07-2.91 (m, 2H),
		1.92 (t, J = 11.9 Hz, 1H), 1.88-1.78 (m, 1H), 1.79-1.51 (m, 2H), 1.45
		(d, J = 7.1 Hz, 3H), 1.51-1.26 (m, 7H), 1.21 (s, 3H), 1.17-0.98 (m, 2H),
		0.94 (s, 3H).
67	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.99 (br. s,
		3H), 7.82 (d, J = 7.5 Hz, 1H), 7.46 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.03
		(s, 1H), 6.94 (d, J = 1.2 Hz, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.86-4.75 (m,
		1H), 4.44-4.35 (m, 1H), 4.12 (s, 3H), 3.98 (s, 3H), 3.95-3.61 (m, 1H),
		3.58-3.41 (m, 3H), 2.93-2.83 (m, 1H), 2.09-1.97 (m, 1H), 1.97-1.82
		(m, 2H), 1.78-1.54 (m, 3H), 1.46-1.43 (m, 3H), 1.53-1.26 (m, 4H),
		1.21 (s, 3H), 1.18-0.98 (m, 3H), 0.95 (s, 3H), 0.86 (s, 3H).
68	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.89 (br. d, J = 11.2 Hz, 1H), 8.72 (br.
		q, J = 11.3 Hz, 1H), 8.52 (d, J = 7.6 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.97
		(d, J = 1.3 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H), 7.35 (d, J = 1.3 Hz, 1H), 7.19
		(d, J = 8.1 Hz, 1H), 7.06 (s, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.87-4.76 (m,
		1H), 4.47-4.36 (m, 1H), 4.29-4.16 (m, 1H), 4.13 (s, 3H), 4.01 (s, 3H),
		3.41 (d, J = 11.6 Hz, 1H), 3.23 (d, J = 11.6 Hz, 1H), 2.69 (q, J = 11.2 Hz,
		1H), 2.56-2.43 (m, 1H), 2.06-1.86 (m, 3H), 1.76-1.56 (m, 3H), 1.45
		(d, J = 7.1 Hz, 3H), 1.54-1.22 (m, 5H), 1.21 (s, 3H), 1.18-1.01 (m, 2H),
		0.97 (d, J = 6.6 Hz, 3H), 0.95 (s, 3H).
69	618.4	1H NMR (400 MHz, DMSO-d6) δ 8.91 (br. d, J = 10.9 Hz, 1H), 8.86-
		8.73 (m, 1H), 8.67 (d, J = 7.8 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 8.03 (s,
		1H), 7.81 (d, J = 7.4 Hz, 1H), 7.38 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.07
		(s, 1H), 5.13 (p, J = 7.1 Hz, 1H), 5.11-4.93 (m, 1H), 4.87-4.76 (m, 1H),
		4.61-4.36 (m, 2H), 4.14 (s, 3H), 4.02 (s, 3H), 3.42-3.15 (m, 3H), 3.03
		(q, J = 12.1, 11.6 Hz, 1H), 2.28-2.18 (m, 1H), 2.17-1.94 (m, 1H), 1.92
		(t, J = 12.5 Hz, 1H), 1.77-1.57 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.54-
		1.30 (m, 4H), 1.21 (s, 3H), 1.26-1.06 (m, 3H), 0.95 (s, 3H).
70	600.4	1H NMR (400 MHz, DMSO-d6) δ 8.74-8.61 (m, 2H), 8.49 (d, J = 7.4
		Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.99 (s, 1H), 7.80 (d, J = 7.4 Hz, 1H),
		7.35 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.06 (s, 1H), 5.12 (p, J = 7.1 Hz,
		1H), 4.87-4.76 (m, 1H), 4.46-4.37 (m, 1H), 4.27-4.17 (m, 1H), 4.14
		(s, 3H), 4.01 (s, 3H), 3.41-3.33 (m, 1H), 3.23 (d, J = 12.5 Hz, 1H), 2.95-
		2.80 (m, 2H), 2.01-1.86 (m, 3H), 1.80-1.59 (m, 4H), 1.45 (d, J = 7.1
		Hz, 3H), 1.54-1.27 (m, 4H), 1.21 (s, 3H), 1.27-1.00 (m, 3H), 0.95 (s,
		3H).
71	658.4	1H NMR (400 MHz, DMSO-d6) δ 9.56 (br. s, 1H), 9.14 (br. s, 1H), 8.40
		(d, J = 7.1 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 8.01 (s, 1H), 7.79 (d, J = 7.4
		Hz, 1H), 7.33 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.12 (p, J =
		7.1 Hz, 1H), 4.88-4.76 (m, 1H), 4.47-4.24 (m, 3H), 4.14 (s, 3H), 4.01
		(s, 3H), 3.83 (s, 3H), 3.46-3.23 (m, 2H), 2.26-1.86 (m, 4H), 1.84-1.57
		(m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.54-1.26 (m, 5H), 1.21 (s, 3H), 1.17-
		1.00 (m, 2H), 0.95 (s, 3H).
72	612.4	1H NMR (400 MHz, DMSO-d6) δ 8.85 (br. d, J = 11.2 Hz, 1H), 8.34 (d,
		J = 6.5 Hz, 1H), 8.28 (d, J = 10.1 Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H), 8.09-
		8.01 (m, 2H), 7.36 (d, J = 1.3 Hz, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.10 (s,
		1H), 5.27 (p, J = 6.9 Hz, 1H), 4.89-4.77 (m, 1H), 4.52-4.39 (m, 1H),
		4.27-4.21 (m, 2H), 4.17 (s, 3H), 4.02 (s, 3H), 3.43-3.16 (m, 2H), 2.32-
		2.21 (m, 1H), 2.12-1.98 (m, 1H), 1.95-1.72 (m, 6H), 1.69-1.61 (m,
		1H), 1.45 (d, J = 6.9 Hz, 3H), 1.49-1.38 (m, 2H), 1.28 (d, J = 6.6 Hz,
		3H), 1.33-1.20 (m, 2H), 1.18-0.99 (m, 2H), 0.99-0.89 (m, 1H), 0.65-
		0.56 (m, 1H), 0.52-0.43 (m, 1H).
73	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.83 (br. d, J = 11.3 Hz, 1H), 8.33 (d,
		J = 6.5 Hz, 1H), 8.27 (br. d, J = 10.2 Hz, 1H), 8.08-8.01 (m, 2H), 7.80 (d,
		J = 7.4 Hz, 1H), 7.35 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.12
		(p, J = 7.1 Hz, 1H), 4.88-4.76 (m, 1H), 4.50-4.38 (m, 1H), 4.28-4.21
		(m, 1H), 4.15 (s, 3H), 4.01 (s, 3H), 3.43-3.27 (m, 2H), 3.27-3.17 (m,
		1H), 1.97-1.73 (m, 4H), 1.72-1.58 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H),
		1.43-1.30 (m, 6H), 1.28 (d, J = 6.6 Hz, 3H), 1.21 (s, 3H), 1.16-1.01 (m,
		2H), 0.95 (s, 3H).
74	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (br. s, 2H), 8.72 (d, J = 8.0 Hz,
		1H), 8.12 (d, J = 8.1 Hz, 1H), 8.08 (d, J = 7.9 Hz, 1H), 8.01 (d, J = 1.3 Hz,
		1H), 7.37 (d, J = 1.3 Hz, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.10 (s, 1H), 5.27
		(p, J = 6.9 Hz, 1H), 4.98-4.75 (m, 2H), 4.52-4.37 (m, 2H), 4.16 (s, 3H),
		4.03 (s, 3H), 3.49-3.35 (m, 2H), 3.14-2.91 (m, 2H), 2.42-2.22 (m,
		2H), 2.10-2.02 (m, 1H), 2.00-1.58 (m, 3H), 1.45 (d, J = 6.9 Hz, 3H),
		1.51-1.36 (m, 2H), 1.33-1.17 (m, 3H), 1.17-0.99 (m, 2H), 0.99-0.89
		(m, 1H), 0.66-0.56 (m, 1H), 0.53-0.43 (m, 1H).
75	618.4	1H NMR (400 MHz, DMSO-d6) δ 8.79 (br. s, 2H), 8.71 (d, J = 7.9 Hz,
		1H), 8.05 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 1.2 Hz, 1H), 7.80 (d, J = 7.4 Hz,
		1H), 7.35 (d, J = 1.2 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.12
		(p, J = 7.1 Hz, 1H), 4.97-4.76 (m, 2H), 4.52-4.33 (m, 2H), 4.14 (s, 3H),
		4.02 (s, 3H), 3.49-3.35 (m, 2H), 3.14-2.93 (m, 2H), 2.42-2.29 (m,
		1H), 1.92 (t, J = 11.8 Hz, 2H), 1.76-1.59 (m, 2H), 1.45 (d, J = 7.1 Hz,
		3H), 1.53-1.32 (m, 4H), 1.21 (s, 3H), 1.17-1.00 (m, 3H), 0.95 (s, 3H).
76	604.3	1H NMR (400 MHz, DMSO-d6) δ 8.86 (br. s, 2H), 8.71 (d, J = 8.0 Hz,
		1H), 8.05 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 1.3 Hz, 1H), 7.64 (d, J = 8.0 Hz,
		1H), 7.35 (d, J = 1.3 Hz, 1H), 7.21 (d, J = 8.2 Hz, 1H), 7.08 (s, 1H), 5.17
		(p, J = 7.2 Hz, 1H), 4.86 (dtd, J = 48.9, 9.4, 4.6 Hz, 1H), 4.70-4.55 (m,
		2H), 4.49-4.37 (m, 1H), 4.14 (s, 3H), 4.02 (s, 3H), 3.49-3.35 (m, 2H),
		3.16-2.91 (m, 2H), 2.42-2.28 (m, 1H), 2.01-1.84 (m, 1H), 1.85-1.63
		(m, 3H), 1.63-1.47 (m, 1H), 1.54 (d, J = 7.1 Hz, 3H), 1.42-1.30 (m,
		1H), 1.18 (s, 3H), 1.18-1.09 (m, 1H), 1.01 (s, 3H), 0.87 (s, 2H).
77	612.4	1H NMR (400 MHz, DMSO-d6) δ 8.85 (br. s, 2H), 8.57 (d, J = 7.4 Hz,
		1H), 8.11 (d, J = 8.1 Hz, 1H), 8.08 (d, J = 7.9 Hz, 1H), 7.99 (d, J = 1.3 Hz,
		1H), 7.36 (d, J = 1.3 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 5.27
		(p, J = 6.9 Hz, 1H), 4.88-4.76 (m, 1H), 4.49-4.38 (m, 1H), 4.37-4.27
		(m, 1H), 4.16 (s, 3H), 4.02 (s, 3H), 3.42-3.32 (m, 1H), 3.27-3.08 (m,
		3H), 2.33-2.22 (m, 1H), 2.13-1.96 (m, 2H), 1.94-1.69 (m, 4H), 1.68-
		1.53 (m, 3H), 1.45 (d, J = 6.9 Hz, 3H), 1.51-1.35 (m, 2H), 1.34-1.00
		(m, 5H), 0.99-0.89 (m, 1H), 0.65-0.56 (m, 1H), 0.52-0.43 (m, 1H).
78	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.81 (br. t, J = 4.9 Hz, 2H), 8.55 (d, J =
		7.4 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.97 (d, J = 1.2 Hz, 1H), 7.80 (d, J =
		7.4 Hz, 1H), 7.35 (d, J = 1.2 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.06 (s,
		1H), 5.12 (p, J = 7.1 Hz, 1H), 4.87-4.76 (m, 1H), 4.48-4.24 (m, 2H),
		4.14 (s, 3H), 4.01 (s, 3H), 3.41-3.31 (m, 1H), 3.25-3.09 (m, 4H), 2.10-
		1.51 (m, 7H), 1.45 (d, J = 7.1 Hz, 3H), 1.51-1.26 (m, 4H), 1.21 (s, 3H),
		1.16-1.01 (m, 3H), 0.95 (s, 3H).
79	626.4	1H NMR (400 MHz, DMSO-d6) δ 9.03 (br. s, 1H), 8.49 (br. s, 1H), 8.04
		(d, J = 8.1 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H), 7.45 (s, 1H), 7.18 (d, J = 8.2
		Hz, 1H), 7.02 (s, 1H), 6.94 (d, J = 1.1 Hz, 1H), 5.12 (p, J = 7.1 Hz, 1H),
		4.86-4.76 (m, 1H), 4.43-4.33 (m, 1H), 4.11 (s, 3H), 3.98 (s, 3H), 3.85-
		3.48 (m, 4H), 3.30-3.15 (m, 2H), 2.98-2.88 (m, 1H), 2.17-2.05 (m,
		1H), 1.92 (t, J = 12.3 Hz, 1H), 1.88-1.55 (m, 4H), 1.45 (d, J = 7.1 Hz,
		3H), 1.54-1.27 (m, 6H), 1.21 (s, 3H), 1.13-0.98 (m, 3H), 0.94 (s, 3H).
80	626.4	1H NMR (400 MHz, DMSO-d6) δ 9.12-8.77 (m, 1H), 8.62-8.41 (m,
		1H), 8.04 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.62-7.51 (m,
		1H), 7.19 (d, J = 8.1 Hz, 1H), 7.05-6.98 (m, 2H), 5.13 (p, J = 7.3 Hz,
		1H), 4.86-4.75 (m, 1H), 4.42-4.26 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H),
		3.90-3.44 (m, 4H), 3.33-3.14 (m, 1H), 3.03-2.84 (m, 1H), 2.75-2.56
		(m, 1H), 1.92 (t, J = 12.6 Hz, 1H), 1.84-1.54 (m, 7H), 1.45 (d, J = 7.1
		Hz, 3H), 1.49-1.30 (m, 4H), 1.21 (s, 3H), 1.27-1.00 (m, 3H), 0.95 (s,
		3H).
81	626.4	1H NMR (400 MHz, DMSO-d6) δ 9.02 (br. s, 1H), 8.47 (br. s, 1H), 8.04
		(d, J = 8.0 Hz, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.45 (s, 1H), 7.18 (d, J = 8.2
		Hz, 1H), 7.03 (s, 1H), 6.94 (d, J = 1.2 Hz, 1H), 5.12 (p, J = 7.2 Hz, 1H),
		4.87-4.76 (m, 1H), 4.48-4.36 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.84-
		3.51 (m, 4H), 3.45-3.03 (m, 3H), 2.17-2.04 (m, 1H), 1.92 (t, J = 11.9
		Hz, 1H), 1.88-1.51 (m, 4H), 1.45 (d, J = 7.1 Hz, 3H), 1.54-1.25 (m,
		6H), 1.21 (s, 3H), 1.17-0.98 (m, 3H), 0.94 (s, 3H).
82	630.4	1H NMR (400 MHz, DMSO-d6) δ 8.68 (br. s, 2H), 8.35 (d, J = 7.9 Hz,
		1H), 8.05 (d, J = 8.1 Hz, 1H), 8.02 (s, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.37
		(s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.12 (p, J = 7.1 Hz, 1H),
		4.88-4.76 (m, 1H), 4.51-4.37 (m, 2H), 4.14 (s, 3H), 4.02 (s, 3H), 3.71-
		3.64 (m, 1H), 3.34 (s, 3H), 3.28-3.07 (m, 3H), 3.07-2.92 (m, 1H), 2.21-
		2.11 (m, 1H), 1.92 (t, J = 12.2 Hz, 1H), 1.87-1.75 (m, 1H), 1.71-1.60
		(m, 2H), 1.45 (d, J = 7.0 Hz, 3H), 1.53-1.27 (m, 5H), 1.21 (s, 3H), 1.16-
		1.03 (m, 2H), 0.95 (s, 3H).
83	592.3	1H NMR (400 MHz, DMSO-d6) δ 8.24-8.16 (m, 2H), 8.11 (br. s, 3H),
		7.95 (d, J = 6.8 Hz, 1H), 7.60 (s, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.15-7.09
		(m, 2H), 7.05 (s, 1H), 4.69 (t, J = 6.0 Hz, 2H), 4.22 (t, J = 5.3 Hz, 2H),
		4.16 (s, 3H), 4.02 (s, 3H), 3.75 (s, 1H), 2.38-2.27 (m, 2H), 1.91-1.76
		(m, 6H), 1.67-1.53 (m, 6H), 1.35 (dd, J = 12.9, 4.4 Hz, 1H), 1.27-1.16
		(m, 2H).
84	619.3	1H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 8.47 (d, J = 4.9 Hz, 1H),
		8.23 (d, J = 8.1 Hz, 1H), 8.07 (br. s, 3H), 7.91 (d, J = 7.6 Hz, 1H), 7.59 (s,
		1H), 7.43-7.34 (m, 2H), 7.13 (s, 1H), 7.04 (s, 1H), 4.73 (t, J = 5.6 Hz,
		2H), 4.46-4.41 (m, 3H), 4.15 (s, 3H), 4.01 (s, 3H), 2.40-2.23 (m, 1H),
		2.19-2.12 (m, 2H), 1.85-1.80 (m, 3H), 1.66-1.59 (m, 1H), 1.41-1.23
		(m, 8H), 0.89-0.84 (m, 2H).
85	606.3	1H NMR (400 MHz, DMSO-d6) δ 8.26-8.18 (m, 2H), 8.08 (br. s, 3H),
		7.84 (d, J = 7.3 Hz, 1H), 7.61 (s, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.15 (s,
		1H), 7.14-7.08 (m, 1H), 7.05 (s, 1H), 4.71 (t, J = 6.7 Hz, 2H), 4.62-
		4.24 (m, 2H), 4.40 (t, J = 5.4 Hz, 2H), 4.16 (s, 3H), 4.02 (s, 3H), 3.82-
		3.69 (m, 1H), 2.39-2.19 (m, 2H), 1.91-1.42 (m, 12H), 1.34 (dd, J =
		13.3, 4.2 Hz, 1H), 1.13-1.02 (m, 2H).
86	620.3	1H NMR (400 MHz, DMSO-d6) δ 8.27-8.17 (m, 2H), 8.08 (br. s, 3H),
		7.76 (d, J = 7.1 Hz, 1H), 7.61 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.14-7.07
		(m, 2H), 7.05 (s, 1H), 4.56 (t, J = 7.4 Hz, 2H), 4.49-4.38 (m, 2H), 4.30
		(t, J = 5.3 Hz, 2H), 4.15 (s, 3H), 4.02 (s, 3H), 3.83-3.68 (m, 1H), 2.39-
		2.23 (m, 2H), 1.91-1.57 (m, 8H), 1.40-1.29 (m, 7H), 1.26-1.13 (m,
		2H).
87	618.3	1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 8.27 (d, J = 8.0 Hz, 1H),
		8.14-8.02 (m, 4H), 7.60 (s, 1H), 7.47 (d, J = 7.7 Hz, 1H), 7.45-7.36 (m,
		2H), 7.24 (t, J = 7.6 Hz, 1H), 7.17 (s, 1H), 7.05 (s, 1H), 4.75-4.65 (m,
		2H), 4.57-4.28 (m, 1H), 4.14 (s, 3H), 4.02 (s, 3H), 3.95-3.52 (m, 2H),
		2.27-2.21 (m, 2H), 1.94-1.73 (m, 4H), 1.67-1.59 (m, 1H), 1.58-1.41
		(m, 5H), 1.39-1.29 (m, 1H), 1.19-1.04 (m, 3H).
88	618.3	1H NMR (400 MHz, DMSO-d6) δ 9.99 (s, 1H), 8.46 (br. d, J = 4.8 Hz,
		1H), 8.10 (br. s, 3H), 7.93 (d, J = 7.7 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H),
		7.65 (s, 1H), 7.57 (s, 1H), 7.48-7.39 (m, 1H), 7.20 (d, J = 8.2 Hz, 1H),
		7.12 (s, 1H), 7.03 (s, 1H), 5.01-4.31 (m, 2H), 4.58-4.50 (m, 2H), 4.11
		(s, 3H), 4.01 (s, 3H), 3.81-3.67 (m, 1H), 2.38-2.18 (m, 3H), 1.90-1.56
		(m, 5H), 1.51-1.27 (m, 7H), 1.07-0.95 (m, 2H).
89	633.3	1H NMR (400 MHz, DMSO-d6) δ 10.44 (s, 1H), 8.52-8.46 (m, 1H), 8.27
		(d, J = 8.1 Hz, 1H), 8.19-8.00 (m, 4H), 7.60 (s, 1H), 7.52 (d, J = 8.2 Hz,
		1H), 7.43 (t, J = 6.5 Hz, 1H), 7.16 (s, 1H), 7.05 (s, 1H), 4.69-4.61 (m,
		2H), 4.56-4.16 (m, 2H), 4.15 (s, 3H), 4.02 (s, 3H), 3.75 (s, 1H), 2.39-
		2.21 (m, 3H), 1.86-1.81 (m, 3H), 1.68-1.54 (m, 3H), 1.44-1.13 (m,
		5H), 1.11-0.83 (m, 5H).
90	619.3	1H NMR (400 MHz, DMSO-d6) δ 10.45 (s, 1H), 8.93 (s, 1H), 8.72 (d, J =
		6.4 Hz, 1H), 8.66 (d, J = 7.0 Hz, 1H), 8.41 (d, J = 8.3 Hz, 1H), 8.15 (s,
		3H), 7.66 (d, J = 8.4 Hz, 1H), 7.60 (s, 1H), 7.24 (s, 1H), 7.06 (s, 1H), 4.67
		(t, J = 6.3 Hz, 2H), 4.60-4.15 (m, 2H), 4.14 (s, 3H), 4.02 (s, 3H), 3.77-
		3.72 (m, 1H), 2.46-2.39 (m, 1H), 2.38-2.27 (m, 1H), 1.91-1.75 (m,
		4H), 1.73-1.47 (m, 8H), 1.35 (d, J = 12.6 Hz, 1H), 1.29-1.24 (m, 2H).
91	619.3	1H NMR (400 MHz, DMSO-d6) δ 8.64-8.58 (m, 1H), 8.49 (t, J = 6.0
		Hz, 1H), 8.23 (d, J = 8.1 Hz, 1H), 8.08 (s, 3H), 8.01 (d, J = 7.9 Hz, 1H),
		7.65-7.56 (m, 2H), 7.46 (d, J = 8.4 Hz, 1H), 7.15 (s, 1H), 7.04 (s, 1H),
		4.69-4.64 (m, 2H), 4.47-4.42 (m, 1H), 4.16 (s, 3H), 4.02 (s, 3H), 3.82-
		3.63 (m, 2H), 3.20 (s, 2H), 2.35-2.30 (m, 1H), 1.85-1.80 (m, 4H), 1.66-
		1.59 (m, 1H), 1.48 (s, 4H), 1.44-1.39 (m, 2H), 1.34 (d, J = 13.2 Hz,
		1H), 1.14-1.08 (m, 2H).
92	605.3	1H NMR (400 MHz, DMSO-d6) δ 10.66 (s, 1H), 8.43 (s, 1H), 8.24 (d, J =
		8.8 Hz, 1H), 8.14-8.04 (m, 4H), 7.60 (s, 1H), 7.53 (d, J = 9.0 Hz, 1H),
		7.40-7.32 (m, 1H), 7.15 (s, 1H), 7.04 (s, 1H), 4.70 (s, 2H), 4.65-4.29
		(m, 2H), 4.15 (s, 3H), 4.01 (s, 3H), 3.88-3.70 (m, 3H), 2.17-2.10 (m,
		2H), 1.91-1.69 (m, 5H), 1.64-1.59 (m, 1H), 1.43 (s, 2H), 1.34 (d, J =
		13.4 Hz, 1H), 0.96-0.91 (m, 2H).
93	632.3	1H NMR (400 MHz, DMSO-d6) δ 10.61 (s, 1H), 8.38-8.31 (m, 1H),
		8.30 (d, J = 8.2 Hz, 1H), 8.09 (s, 3H), 7.67 (d, J = 7.8 Hz, 1H), 7.61 (s,
		1H), 7.62-7.56 (m, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.26-7.21 (m, 1H),
		7.17 (s, 1H), 7.05 (s, 1H), 4.65-4.60 (m, 2H), 4.56-4.33 (m, 2H), 4.16
		(s, 3H), 4.02 (s, 3H), 3.90-3.55 (m, 1H), 2.34-2.28 (m, 3H), 1.89-1.69
		(m, 5H), 1.64-1.59 (m, 3H), 1.39-1.29 (m, 5H), 1.26-1.21 (m, 2H).
94	617.3	1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.13 (s, 3H), 7.80 (d, J =
		8.1 Hz, 1H), 7.63-7.52 (m, 3H), 7.40 (dd, J = 7.5, 1.8 Hz, 1H), 7.35 (td, J =
		7.6, 1.8 Hz, 1H), 7.28 (td, J = 7.4, 1.5 Hz, 1H), 7.18 (dd, J = 8.1, 1.3 Hz,
		1H), 7.12 (s, 1H), 7.03 (s, 1H), 4.54-4.48 (m, 2H), 4.58-4.33 (m, 2H),
		4.10 (s, 3H), 4.03-3.98 (m, 3H), 3.83-3.70 (m, 1H), 2.38-2.22 (m,
		3H), 1.91-1.79 (m, 3H), 1.69-1.39 (m, 8H), 1.35 (dd, J = 12.9, 4.4 Hz,
		1H), 1.20-1.11 (m, 2H).
95	619.3	1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.16 (s, 1H), 8.51 (d, J =
		5.2 Hz, 1H), 8.34 (d, J = 8.1 Hz, 1H), 8.09 (s, 3H), 7.65 (d, J = 5.2 Hz,
		1H), 7.60 (s, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.21 (s, 1H), 7.05 (s, 1H), 4.68
		(t, J = 6.2 Hz, 2H), 4.56-4.32 (m, 2H), 4.14 (s, 3H), 4.02 (s, 3H), 3.82-
		3.57 (m, 1H), 2.33-2.25 (m, 3H), 1.93-1.72 (m, 4H), 1.70-1.38 (m,
		6H), 1.34 (dd, J = 12.9, 4.4 Hz, 1H), 1.20-1.07 (m, 2H).
96	591.3	1H NMR (400 MHz, DMSO-d6) δ 10.84 (br. s, 1H), 8.67 (d, J = 7.6 Hz,
		1H), 8.40 (d, J = 8.4 Hz, 1H), 8.19 (s, 3H), 8.10 (dd, J = 6.1, 1.5 Hz, 1H),
		7.99 (d, J = 8.6 Hz, 1H), 7.63-7.57 (m, 1H), 7.22 (s, 1H), 7.08-7.00 (m,
		2H), 4.54 (t, J = 7.8 Hz, 2H), 4.48-4.25 (m, 2H), 4.18 (s, 3H), 4.02 (s,
		3H), 3.77-3.72 (m, 1H), 3.46 (s, 2H), 2.38-2.23 (m, 1H), 2.03-1.96
		(m, 2H), 1.90-1.72 (m, 7H), 1.69-1.56 (m, 1H), 1.51-1.41 (m, 2H),
		1.36 (dd, J = 12.8, 4.4 Hz, 1H).
97	617.3	1H NMR (400 MHz, DMSO-d6) δ 8.40 (t, J = 5.7 Hz, 1H), 8.12 (br. s,
		3H), 7.76 (d, J = 8.2 Hz, 1H), 7.61-7.55 (m, 2H), 7.53-7.47 (m, 1H),
		7.47-7.35 (m, 3H), 7.23 (dd, J = 8.1, 1.4 Hz, 1H), 7.11 (s, 1H), 7.03 (d, J =
		1.3 Hz, 1H), 4.50 (t, J = 6.4 Hz, 2H), 4.44-4.17 (m, 2H), 4.12 (s, 3H),
		4.01 (s, 3H), 3.82-3.63 (m, 1H), 3.21-3.12 (m, 2H), 2.39-2.25 (m,
		1H), 1.90-1.72 (m, 3H), 1.70-1.57 (m, 1H), 1.55-1.39 (m, 4H), 1.39-
		1.25 (m, 3H), 1.03-0.92 (m, 2H).
98	618.3	1H NMR (400 MHz, DMSO-d6) δ 8.64 (t, J = 5.7 Hz, 1H), 8.55 (dd, J =
		4.8, 1.6 Hz, 1H), 8.08 (br. s, 3H), 7.91 (dd, J = 7.9, 1.6 Hz, 1H), 7.79 (d,
		J = 8.2 Hz, 1H), 7.65 (s, 1H), 7.58 (s, 1H), 7.57-7.52 (m, 1H), 7.24 (dd,
		J = 8.1, 1.4 Hz, 1H), 7.13 (s, 1H), 7.03 (d, J = 1.2 Hz, 1H), 4.50 (t, J = 6.5
		Hz, 2H), 4.60-4.35 (m, 1H), 4.12 (s, 3H), 4.01 (s, 3H), 3.87-3.44 (m,
		2H buried under water peak), 3.23-3.18 (m, 2H), 2.38-2.25 (m, 1H),
		1.92-1.73 (m, 3H), 1.69-1.38 (m, 7H), 1.34 (dd, J = 12.8, 4.4 Hz, 1H),
		1.10-0.98 (m, 2H).
99	660.4	1H NMR (400 MHz, DMSO-d6) δ 9.33 (s, 1H), 8.49 (dd, J = 4.8, 1.8 Hz,
		1H), 8.11 (s, 3H), 7.82 (dd, J = 7.6, 1.9 Hz, 1H), 7.78 (d, J = 8.2 Hz, 1H),
		7.67 (s, 1H), 7.58 (s, 1H), 7.44 (dd, J = 7.6, 4.8 Hz, 1H), 7.18 (dd, J = 8.2,
		1.3 Hz, 1H), 7.10 (s, 1H), 7.04 (s, 1H), 4.49 (t, J = 6.7 Hz, 2H), 4.43-
		4.27 (m, 1H), 4.12 (s, 3H), 4.01 (s, 3H), 3.82-3.66 (m, 2H), 2.39-2.25
		(m, 1H), 1.91-1.74 (m, 3H), 1.69-1.57 (m, 1H), 1.49-1.41 (m, 2H),
		1.39-1.30 (m, 3H), 1.10-0.98 (m, 2H), 1.01 (s, 6H), 0.97-0.84 (m,
		2H), 0.82-0.69 (m, 2H).
100	659.3	1H NMR (400 MHz, DMSO-d6) δ 8.10 (br. s, 3H), 7.94 (s, 1H), 7.83 (d,
		J = 8.2 Hz, 1H), 7.77 (dd, J = 8.1, 1.2 Hz, 1H), 7.64 (s, 1H), 7.59 (s, 1H),
		7.39 (td, J = 7.7, 1.7 Hz, 1H), 7.35 (dd, J = 7.6, 1.7 Hz, 1H), 7.26 (td, J =
		7.5, 1.3 Hz, 1H), 7.15 (dd, J = 8.1, 1.3 Hz, 1H), 7.11 (s, 1H), 7.04 (d, J =
		1.2 Hz, 1H), 4.51 (t, J = 6.3 Hz, 2H), 4.47-4.33 (m, 1H), 4.11 (s, 3H),
		4.01 (s, 3H), 3.84-3.43 (m, 2H), 2.37-2.27 (m, 1H), 1.92-1.75 (m,
		3H), 1.69-1.49 (m, 4H), 1.34 (dd, J = 12.8, 4.4 Hz, 1H), 0.98 (s, 6H),
		1.06-0.90 (m, 3H), 0.87-0.80 (m, 4H).
101	643.5	1H NMR (400 MHz, DMSO-d6) δ 8.18-8.07 (m, 3H), 7.79-7.36 (m,
		6H), 7.34-7.14 (m, 2H), 7.13-6.92 (m, 2H), 4.82-4.47 (m, 2H), 4.46-
		4.27 (m, 2H), 4.24-4.06 (m, 3H), 4.05-3.86 (m, 3H), 3.85-3.41 (m,
		5H), 3.16-2.24 (m, 2H), 1.98-1.73 (m, 4H), 1.74-1.21 (m, 3H), 1.16-
		0.96 (m, 1H), 0.89-0.46 (m, 2H), 0.31-0.13 (m, 1H), 0.09-−1.10 (m,
		2H).
102	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.13 (br. s, 3H), 8.04 (d, J = 8.1 Hz,
		1H), 7.64 (d, J = 8.0 Hz, 1H), 7.58 (s, 1H), 7.21 (d, J = 8.2 Hz, 1H), 7.06-
		7.01 (m, 2H), 5.16 (p, J = 7.2 Hz, 1H), 4.69-4.55 (m, 2H), 4.54-4.29
		(m, 2H), 4.10 (s, 3H), 4.00 (s, 3H), 4.07-3.66 (m, 2H), 2.39-2.26 (m,
		1H), 1.90-1.68 (m, 6H), 1.68-1.58 (m, 2H), 1.53 (d, J = 7.1 Hz, 3H),
		1.57-1.42 (m, 1H), 1.39-1.27 (m, 2H), 1.17 (s, 3H), 1.17-1.08 (m,
		1H), 1.00 (s, 3H), 0.91-0.76 (m, 2H).
103	658.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.97 (br. s,
		3H), 7.82 (d, J = 7.4 Hz, 1H), 7.44 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.03
		(s, 1H), 6.93 (s, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.86-4.75 (m, 1H), 4.44-
		4.33 (m, 1H), 4.28-3.84 (m, 2H), 4.11 (s, 3H), 3.99 (s, 3H), 3.83-3.75
		(m, 1H), 3.60-3.31 (m, 5H), 1.92 (t, J = 11.9 Hz, 2H), 1.82-1.51 (m,
		4H), 1.45 (d, J = 7.1 Hz, 3H), 1.52-1.27 (m, 5H), 1.21 (s, 3H), 1.26-
		1.00 (m, 3H), 0.95 (s, 3H), 0.91 (t, J = 7.4 Hz, 3H).
104	644.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.96 (br. s,
		3H), 7.82 (d, J = 7.4 Hz, 1H), 7.44 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.03
		(s, 1H), 6.93 (s, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.88-4.74 (m, 1H), 4.45-
		4.33 (m, 1H), 4.11 (s, 3H), 4.26-3.86 (m, 1H), 3.99 (s, 3H), 3.84-3.76
		(m, 1H), 3.67-3.32 (m, 6H), 1.92 (t, J = 11.9 Hz, 2H), 1.81-1.50 (m,
		3H), 1.45 (d, J = 7.1 Hz, 3H), 1.42-1.26 (m, 5H), 1.23-1.16 (m, 6H),
		1.15-1.00 (m, 2H), 0.95 (s, 3H).
105	644.4	1H NMR (400 MHz, DMSO-d6) δ 8.60 (br. s, 1H), 8.50 (br. s, 1H), 8.04
		(d, J = 8.1 Hz, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.43 (d, J = 1.1 Hz, 1H), 7.19
		(d, J = 8.1 Hz, 1H), 7.03 (s, 1H), 6.91 (d, J = 1.2 Hz, 1H), 5.12 (p, J = 7.2
		Hz, 1H), 4.86-4.76 (m, 1H), 4.44-4.34 (m, 1H), 4.11 (s, 3H), 3.99 (s,
		3H), 4.23-3.74 (m, 2H), 3.89-3.84 (m, 1H), 3.54-3.44 (m, 2H), 3.38
		(s, 3H), 3.43-3.25 (m, 1H), 2.66-2.54 (m, 3H), 2.08-1.96 (m, 1H),
		1.92 (t, J = 12.3 Hz, 1H), 1.74-1.56 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H),
		1.50-1.25 (m, 4H), 1.21 (s, 3H), 1.17-0.98 (m, 3H), 0.94 (s, 3H).
106	586.4	1H NMR (400 MHz, DMSO-d6) δ 8.01-7.85 (m, 4H), 7.58 (d, J = 8.2
		Hz, 1H), 7.29 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 6.59 (s, 1H), 6.36 (s, 1H),
		5.16 (dd, J = 15.2, 7.7 Hz, 1H), 4.58-4.48 (m, 2H), 4.08 (s, 3H), 3.34-
		3.10 (m, 4H), 2.78 (s, 3H), 2.09-1.96 (m, 1H), 1.90-1.41 (m, 10H),
		1.41-1.27 (m, 1H), 1.19-1.07 (m, 4H), 1.00 (s, 3H), 0.94-0.66 (m,
		2H).
107	612.4	Exists as a 6:4 ratio of rotamers. 1H NMR (400 MHz, DMSO-d6) δ 8.15
		(d, J = 8.2 Hz, 0.4H), 8.00 (d, J = 8.0 Hz, 0.6H), 7.98-7.87 (m, 3H), 7.42
		(s, 1H), 7.19 (d, J = 8.1 Hz, 0.6H), 7.17 (d, J = 8.2 Hz, 0.4H), 7.10 (s,
		0.4H), 6.99 (s, 0.6H), 6.92 (s, 0.4H), 6.91 (s, 0.6H), 5.16-5.08 (m, 1H),
		4.88-4.76 (m, 0.4H), 4.73-4.63 (m, 0.6H), 4.54-4.45 (m, 2H), 4.12 (s,
		1.2H), 4.10 (s, 1.8H), 3.99 (s, 3H), 3.93-3.83 (m, 1H), 3.80-3.62 (m,
		2H), 3.34-3.02 (m, 3H), 2.63-2.53 (m, 2H)2.38-2.23 (m, 2H), 2.12-
		0.71 (m, 17H), 0.63-0.49 (m, 1H).
108	600.3	Exists as a 7:3 mixture of rotamers. 1H NMR (400 MHz, DMSO-d6) 8
		8.14 (d, J = 8.0 Hz, 0.3H), 8.03 (d, J = 8.1 Hz, 0.7H), 7.99-7.86 (m, 3H),
		7.42 (s, 1H), 7.25 (d, J = 8.1 Hz, 0.3H), 7.14 (d, J = 8.1 Hz, 0.7H), 7.11 (s,
		0.3H), 6.99 (s, 0.7H), 6.91 (s, 1H), 5.37 (d, J = 7.7 Hz, 0.3H), 5.28-5.23
		(m, 0.7H), 4.90-4.76 (m, 0.3H), 4.69-4.48 (m, 1.7H), 4.42-4.29 (m,
		1H), 4.12 (s, 3H), 4.02-3.91 (m, 4H), 3.82-3.51 (m, 5H), 3.41-2.90
		(m, 6H), 2.40-1.34 (m, 11H), 1.30-1.09 (m, 1H).
109	586.3	Exists as a 1:1 mixture of rotamers. 1H NMR (400 MHz, DMSO-d6) 8
		8.16 (d, J = 8.2 Hz, 0.5H), 8.05 (d, J = 8.1 Hz, 0.5H), 8.01-7.86 (m, 3H),
		7.42 (s, 1H), 7.29 (d, J = 8.2 Hz, 0.5H), 7.19 (d, J = 8.1 Hz, 0.5H), 7.10 (s,
		0.5H), 7.02 (s, 0.5H), 6.91 (d, J = 2.7 Hz, 1H), 5.28-5.19 (m, 1H), 4.70-
		4.59 (m, 1H), 4.53-4.31 (m, 3H), 4.13 (s, 1.5H), 4.11 (s, 1.5H), 4.07-
		3.96 (m, 4H), 3.93-3.39 (m, 5H), 3.33-3.05 (m, 3H), 2.47-2.30 (m,
		1H), 2.08-1.11 (m, 10H), 1.05-0.90 (m, 1H).
110	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.34 (d, J = 8.8 Hz, 1H), 8.04 (dd, J =
		8.2, 2.5 Hz, 1H), 7.99-7.87 (m, 3H), 7.41 (s, 1H), 7.18 (dd, J = 8.0, 2.3
		Hz, 1H), 7.04 (d, J = 2.6 Hz, 1H), 6.91 (d, J = 2.5 Hz, 1H), 5.26-5.15 (m,
		1H), 5.04-4.92 (m, 1H), 4.59-4.46 (m, 1H), 4.10 (s, 3H), 3.99 (s, 3H),
		3.34-3.03 (m, 4H), 2.70-2.58 (m, 1H), 2.13-1.96 (m, 2H), 1.82-0.74
		(m, 18H), 0.59-0.42 (m, 1H).
111	586.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.99-7.90
		(m, 3H), 7.88 (d, J = 7.2 Hz, 1H), 7.41 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H),
		7.03 (s, 1H), 6.91 (s, 1H), 5.15-5.05 (m, 1H), 4.83-4.70 (m, 1H), 4.47-
		4.35 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.35-3.02 (m, 4H), 2.25-2.14
		(m, 1H), 2.08-1.95 (m, 1H), 1.85-1.70 (m, 3H), 1.70-1.28 (m, 9H),
		1.25-0.94 (m, 6H).
112	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.10 (d, J = 8.2 Hz, 1H), 7.93 (s, 4H),
		7.42 (s, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.05 (s, 1H), 6.91 (d, J = 1.2 Hz,
		1H), 5.44 (q, J = 7.3 Hz, 1H), 4.69-4.48 (m, 2H), 4.10 (s, 3H), 3.99 (s,
		3H), 3.47 (t, J = 7.4 Hz, 2H), 3.34-3.06 (m, 4H), 2.64-2.55 (m, 1H),
		2.25-2.11 (m, 1H), 2.07-1.97 (m, 1H), 1.94-1.82 (m, 1H), 1.81-1.21
		(m, 12H), 1.16-0.89 (m, 4H).
113	597.3	1H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 3H), 7.66 (d, J = 8.2 Hz, 1H),
		7.41 (s, 1H), 7.39 (s, 1H), 7.16 (dd, J = 8.2, 1.3 Hz, 1H), 7.01 (s, 1H), 6.90
		(d, J = 1.1 Hz, 1H), 5.51 (q, J = 7.2 Hz, 1H), 4.54-4.44 (m, 1H), 4.37-
		4.27 (m, 1H), 4.10 (s, 3H), 3.98 (s, 3H), 3.41 (td, J = 9.5, 3.6 Hz, 1H),
		3.35-3.07 (m, 3H), 3.02 (q, J = 8.7 Hz, 1H), 2.58-2.50 (m, 2H), 2.21-
		2.08 (m, 1H), 2.08-1.95 (m, 1H), 1.80-1.02 (m, 17H), 0.92-0.74 (m,
		1H).
114	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.49 (d, J = 9.1 Hz, 1H), 8.04 (d, J =
		8.0 Hz, 1H), 7.99-7.85 (m, 3H), 7.37 (s, 1H), 7.19 (d, J = 8.0 Hz, 1H),
		7.03 (s, 1H), 6.92 (d, J = 1.2 Hz, 1H), 5.50 (d, J = 14.0 Hz, 1H), 5.30-
		5.17 (m, 1H), 4.09 (s, 3H), 4.00 (s, 3H), 3.81 (d, J = 14.1 Hz, 1H), 3.32-
		3.20 (m, 1H), 3.20-3.08 (m, 4H), 2.32-2.16 (m, 1H), 2.13-1.95 (m,
		2H), 1.84-1.50 (m, 4H), 1.39 (d, J = 7.0 Hz, 3H), 1.30 (t, J = 12.7 Hz,
		1H), 0.87 (dt, J = 28.1, 12.9 Hz, 2H), 0.53 (t, J = 12.7 Hz, 2H), 0.20 (dt,
		J = 26.7, 7.8 Hz, 4H).
115	596.3	1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 9.2 Hz, 1H), 8.03 (d, J =
		8.1 Hz, 1H), 7.99-7.83 (m, 3H), 7.43 (s, 1H), 7.17 (d, J = 8.2 Hz, 1H),
		7.06 (s, 1H), 6.91 (d, J = 1.2 Hz, 1H), 5.23-5.10 (m, 1H), 4.86 (dd, J =
		13.9, 5.3 Hz, 1H), 4.76-4.66 (m, 1H), 4.14 (s, 3H), 3.99 (s, 3H), 3.35-
		3.04 (m, 5H), 2.00 (d, J = 14.3 Hz, 3H), 1.80-1.70 (m, 1H), 1.52 (dd, J =
		54.8, 8.5 Hz, 7H), 1.09-0.97 (m, 2H), 0.93-0.72 (m, 2H), 0.70-0.61
		(m, 1H), 0.33 (q, J = 5.3 Hz, 1H), 0.17-0.05 (m, 1H).
116	596.3	1H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J = 8.2 Hz, 1H), 8.00-7.84
		(m, 4H), 7.45 (s, 1H), 7.27 (d, J = 8.2 Hz, 1H), 7.10 (s, 1H), 6.91 (d, J =
		1.3 Hz, 1H), 5.02-4.92 (m, 2H), 4.52-4.40 (m, 1H), 4.28-4.02 (m,
		5H), 3.99 (s, 3H), 3.37-2.99 (m, 3H), 2.01 (s, 1H), 1.92-1.81 (m, 1H),
		1.81-1.69 (m, 1H), 1.66-1.48 (m, 7H), 1.34-1.21 (m, 1H), 1.03-0.71
		(m, 3H), 0.65-0.28 (m, 5H).
117	596.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.98-7.86
		(m, 3H), 7.86-7.81 (m, 2H), 7.76 (d, J = 8.3 Hz, 1H), 7.42 (dd, J = 8.3,
		1.5 Hz, 1H), 7.27 (s, 1H), 7.18 (d, J = 8.1 Hz, 1H), 5.11 (q, J = 7.1 Hz,
		1H), 4.96-4.83 (m, 1H), 4.73-4.62 (m, 1H), 3.89-3.70 (m, 2H), 3.33-
		3.07 (m, 4H), 2.09-1.88 (m, 3H), 1.81-1.22 (m, 13H), 1.21 (s, 3H),
		1.15-0.98 (m, 3H), 0.94 (s, 3H), 0.93-0.85 (m, 1H), 0.60-0.49 (m,
		1H).
118	584.3	1H NMR (400 MHz, DMSO-d6) δ 8.18 (d, J = 8.5 Hz, 1H), 8.06 (d, J =
		8.1 Hz, 1H), 7.98-7.79 (m, 3H), 7.44 (s, 1H), 7.20 (d, J = 8.2 Hz, 1H),
		7.08 (s, 1H), 6.91 (s, 1H), 5.19 (p, J = 7.4 Hz, 1H), 4.83 (dd, J = 14.4, 6.6
		Hz, 1H), 4.79-4.67 (m, 1H), 4.14 (s, 3H), 3.99 (s, 3H), 3.43-3.05 (m,
		5H), 2.32-2.23 (m, 1H), 2.23-2.10 (m, 1H), 2.08-1.95 (m, 1H), 1.87-
		1.70 (m, 2H), 1.70-1.31 (m, 10H), 0.91-0.78 (m, 1H), 0.70-0.55 (m,
		1H), 0.20-0.09 (m, 1H), −0.52-−0.64 (m, 1H).
119	612.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.96-7.84
		(m, 3H), 7.79 (d, J = 7.9 Hz, 1H), 7.43 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H),
		7.07 (s, 1H), 6.91 (s, 1H), 5.08 (p, J = 7.3 Hz, 1H), 4.80-4.70 (m, 1H),
		4.70-4.55 (m, 1H), 4.14 (s, 3H), 3.98 (s, 3H), 3.23 (d, J = 37.0 Hz, 5H),
		2.08-1.94 (m, 2H), 1.82-1.18 (m, 11H), 1.12 (s, 3H), 1.01 (s, 3H), 0.74-
		0.61 (m, 2H), 0.26-0.16 (m, 1H), −0.33-−0.47 (m, 1H).
120	596.3	1H NMR (400 MHz, DMSO-d6) δ 8.18 (d, J = 7.0 Hz, 1H), 8.07 (s, 3H),
		7.90 (d, J = 7.9 Hz, 1H), 7.44 (s, 1H), 7.10 (d, J = 7.9 Hz, 1H), 6.60 (s,
		1H), 6.37 (s, 1H), 5.56-5.45 (m, 1H), 5.19-4.86 (m, 4H), 4.47 (s, 2H),
		4.09 (s, 1H), 3.76 (s, 2H), 2.81 (s, 3H), 2.38-2.13 (m, 2H), 2.09-1.70
		(m, 7H), 1.70-1.57 (m, 1H), 1.51-1.15 (m, 6H), 1.12-0.74 (m, 3H).
121	612.4	1H NMR (400 MHz, DMSO-d6) δ 8.11 (s, 3H), 7.94 (d, J = 8.0 Hz, 1H),
		7.77 (d, J = 7.5 Hz, 1H), 7.45 (s, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.60 (s,
		1H), 6.39 (s, 1H), 5.11 (p, J = 7.2 Hz, 1H), 4.80-4.67 (m, 1H), 4.64-
		4.24 (m, 3H), 4.10 (s, 3H), 3.87-3.63 (m, 1H), 2.80 (s, 3H), 2.40-2.23
		(m, 1H), 1.97-1.75 (m, 4H), 1.74-1.24 (m, 11H), 1.20 (s, 3H), 1.15-
		0.98 (m, 3H), 0.95 (s, 3H).
122	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 8.6 Hz, 1H), 8.10-8.00
		(m, 3H), 7.93 (d, J = 7.9 Hz, 1H), 7.44 (s, 1H), 7.10 (d, J = 8.0 Hz, 1H),
		6.60 (s, 1H), 6.36 (s, 1H), 5.25-5.13 (m, 1H), 4.98-4.86 (m, 1H), 4.56-
		4.41 (m, 2H), 4.09 (s, 3H), 3.83-3.46 (m, 2H), 2.80 (s, 3H), 2.66-2.56
		(m, 1H), 2.39-2.24 (m, 1H), 2.15-1.98 (m, 1H), 1.89-1.74 (m, 3H),
		1.68-1.56 (m, 1H), 1.51-0.74 (m, 15H), 0.60-0.42 (m, 1H).
123	582.4	1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 8.4 Hz, 1H), 8.10-8.03
		(m, 3H), 7.94 (d, J = 7.9 Hz, 1H), 7.45 (s, 1H), 7.12 (d, J = 8.0 Hz, 1H),
		6.63 (s, 1H), 6.36 (s, 1H), 5.80-5.69 (m, 1H), 5.38-5.13 (m, 3H), 5.02-
		4.92 (m, 1H), 4.56-4.42 (m, 3H), 4.10 (s, 3H), 2.83 (d, J = 14.9 Hz, 5H),
		2.40-2.25 (m, 1H), 2.17-2.03 (m, 1H), 1.92-1.17 (m, 12H), 1.12-
		1.00 (m, 1H).
124	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.09-8.01 (m, 3H), 7.94 (d, J = 8.2
		Hz, 1H), 7.83 (d, J = 7.7 Hz, 1H), 7.44 (s, 1H), 7.14-7.08 (m, 1H), 6.58
		(s, 1H), 6.35 (s, 1H), 5.15-5.03 (m, 1H), 4.74-4.63 (m, 1H), 4.60-4.27
		(m, 2H), 4.09 (s, 3H) , 3.80-3.60 (m, 2H), 2.81 (s, 3H), 2.36-2.28 (m, 1H),
		2.24-2.11 (m, 1H), 1.90-0.92 (m, 21H).
125	610.3	Exists as 7:3 mixture of rotamers. 1H NMR (400 MHz, DMSO-d6) δ 8.14
		(d, J = 8.1 Hz, 0.3H), 8.12-8.06 (m, 3H), 8.04 (d, J = 8.1 Hz, 0.7H), 7.59
		(s, 1H), 7.23 (d, J = 8.2 Hz, 0.3H), 7.16 (d, J = 8.1 Hz, 0.7H), 7.13 (s,
		0.3H), 7.05-7.01 (m, 1.7H), 5.28 (dt, J = 8.0, 4.2 Hz, 1H), 4.96-4.84
		(m, 0.3H), 4.81-4.62 (m, 1.7H), 4.59-4.33 (m, 2H), 4.12 (s, 0.9H), 4.11
		(s, 2.1H), 4.00 (s, 3H), 3.96-3.86 (m, 0.7H), 3.81-3.67 (m, 2H), 3.64-
		3.53 (m, 0.3H), 2.73-2.61 (m, 1H), 2.37-2.24 (m, 2H), 2.19-2.07 (m,
		1H), 2.05-1.02 (m, 17H), 0.96-0.71 (m, 1H).
126	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.15-8.03 (m, 3H), 7.93 (d, J = 8.0
		Hz, 1H), 7.58 (d, J = 8.2 Hz, 1H), 7.44 (s, 1H), 7.13 (d, J = 8.1 Hz, 1H),
		6.59 (s, 1H), 6.37 (d, J = 1.3 Hz, 1H), 5.17 (p, J = 7.1 Hz, 1H), 4.63-4.35
		(m, 4H), 4.09 (s, 3H), 3.81-3.64 (m, 1H), 2.79 (s, 3H), 2.39-2.26 (m,
		1H), 1.92-1.39 (m, 11H), 1.39-1.25 (m, 2H), 1.20-1.07 (m, 4H), 1.00
		(s, 3H), 0.92-0.67 (m, 2H).
127	584.3	1H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J = 8.1 Hz, 1H), 8.13-8.04
		(m, 3H), 7.46 (s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 6.75 (s, 1H), 6.37 (d, J =
		1.3 Hz, 1H), 4.71 (t, J = 6.4 Hz, 2H), 4.61-4.37 (m, 2H), 4.10 (s, 3H),
		3.85-3.69 (m, 1H), 3.23 (s, 3H), 2.84 (s, 3H), 2.39-2.25 (m, 1H), 2.04-
		1.94 (m, 2H), 1.92-1.59 (m, 5H), 1.41-1.15 (m, 8H), 0.99-0.87 (m,
		2H), 0.79-0.67 (m, 2H).
128	582.5	1H NMR (400 MHz, DMSO-d6) δ 8.15-8.02 (m, 3H), 8.00 (d, J = 8.0
		Hz, 1H), 7.57 (s, 1H), 7.11 (d, J = 8.1 Hz, 1H), 7.03 (s, 1H), 7.01 (s, 1H),
		5.16 (dd, J = 8.2, 4.3 Hz, 1H), 4.71-4.58 (m, 1H), 4.51-4.37 (m, 3H),
		4.12 (s, 3H), 4.06-3.91 (m, 4H), 3.81-3.62 (m, 1H), 2.81 (d, J = 11.9
		Hz, 1H), 2.47-2.36 (m, 2H), 2.37-2.22 (m, 1H), 2.10-1.70 (m, 8H),
		1.69-1.56 (m, 1H), 1.55-1.40 (m, 2H), 1.34 (dd, J = 12.8, 4.4 Hz, 1H),
		1.29-1.03 (m, 2H).
129	609.4	Exists as a 2:8 mixture of rotamers. 1H NMR (400 MHz, DMSO-d6) 8
		8.15-7.91 (m, 3H), 7.69 (d, J = 8.3 Hz, 0.2H), 7.63 (d, J = 8.2 Hz, 0.8H),
		7.57 (s, 0.8H), 7.49 (s, 0.2H), 7.13-7.00 (m, 2.2H), 6.97 (s, 0.8H), 5.30-
		5.23 (m, 0.8H), 5.20-5.13 (m, 0.2H), 4.75-4.35 (m, 3H), 4.30-4.19
		(m, 1H), 4.11 (s, 0.6H), 4.10 (s, 2.4H), 4.02-3.93 (m, 4H), 3.83-3.56
		(m, 2H), 2.86-2.74 (m, 1H), 2.38-2.26 (m, 2H), 2.17-1.10 (m, 18H),
		0.66-0.49 (m, 1H).
130	624.3	Exists as a 1:1 mixture of rotamers. 1H NMR (400 MHz, DMSO-d6) 8
		8.15 (d, J = 8.2 Hz, 0.5H), 8.13-8.04 (m, 3H), 8.01 (d, J = 8.0 Hz, 0.5H),
		7.59 (s, 1H), 7.19 (d, J = 8.0 Hz, 0.5H), 7.18 (d, J = 8.2 Hz, 0.5H), 7.11 (s,
		0.5H), 7.05-7.01 (m, 1H), 7.00 (s, 0.5H), 5.17-5.08 (m, 1H), 4.88-
		4.76 (m, 0.5H), 4.75-4.63 (m, 0.5H), 4.61-4.35 (m, 3H), 4.12 (s, 1.5H),
		4.10 (s, 1.5H), 4.00 (d, J = 1.8 Hz, 3H), 3.92-3.82 (m, 0.5H), 3.81-3.60
		(m, 2.5H), 2.63-2.52 (m, 2H), 2.39-2.19 (m, 4H), 2.14-0.69 (m, 17H),
		0.63-0.49 (m, 1H).
131	596.3	Exists as a mixture of 1:1 rotamers. 1H NMR (400 MHz, DMSO-d6) 8
		8.14 (d, J = 8.2 Hz, 0.5H), 8.10-8.03 (m, 3H), 8.00 (d, J = 8.0 Hz, 0.5H),
		7.59 (s, 1H), 7.27 (d, J = 8.2 Hz, 0.5H), 7.16 (d, J = 8.1 Hz, 0.5H), 7.09 (s,
		0.5H), 7.03 (s, 1H), 7.02 (s, 0.5H), 5.27 (d, J = 7.5 Hz, 0.5H), 5.13 (dd, J =
		8.0, 4.6 Hz, 0.5H), 4.77-4.61 (m, 1H), 4.60-4.36 (m, 2H), 4.10 (s, 3H),
		4.00 (s, 3H), 4.00-3.40 (m, 3H), 2.41-1.04 (m, 17H), 1.02-0.85 (m,
		1H), 0.85-0.53 (m, 2H).
132	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 8.2 Hz, 0.3H), 8.12-8.06
		(m, 3H), 8.03 (d, J = 8.1 Hz, 0.7H), 7.59 (s, 1H), 7.25 (d, J = 8.1 Hz,
		0.3H), 7.15 (d, J = 8.1 Hz, 0.7H), 7.11 (s, 0.3H), 7.03 (s, 1H), 7.00 (s,
		0.7H), 5.40-5.34 (m, 0.3H), 5.29-5.22 (m, 0.7H), 4.88-4.78 (m,
		0.3H), 4.69-4.27 (m, 3.7H), 4.12 (s, 3H), 4.00 (s, 3H), 3.99-3.91 (m,
		0.7H), 3.83-3.52 (m, 4.3H), 3.39-3.29 (m, 0.3H), 3.26-3.14 (m,
		0.7H), 3.07-2.90 (m, 1H), 2.39-2.04 (m, 4H), 1.98-1.56 (m, 8H), 1.52-
		1.09 (m, 4H).
133	598.3	Exists as a 1:1 mixture of rotamers. 1H NMR (400 MHz, DMSO-d6) 8
		8.16 (d, J = 8.2 Hz, 0.5H), 8.09 (s, 3H), 8.05 (d, J = 8.1 Hz, 0.5H), 7.59 (s,
		1H), 7.29 (d, J = 8.2 Hz, 0.5H), 7.19 (d, J = 8.1 Hz, 0.5H), 7.11 (s, 0.5H),
		7.06-6.99 (m, 1.5H), 5.26-5.19 (m, 1H), 4.65 (t, J = 13.3 Hz, 0.5H),
		4.55-4.31 (m, 4.5H), 4.12 (s, 1.5H), 4.10 (s, 1.5H), 4.00 (s, 3H), 3.91-
		3.69 (m, 3H), 3.65 (d, J = 12.6 Hz, 0.5H), 3.60-3.36 (m, 2.5H), 2.49-
		2.25 (m, 4H), 2.01-1.56 (m, 6H), 1.53-1.10 (m, 3.5H), 1.04-0.89 (m,
		0.5H).
134	636.4	Exists as a 7:3 ratio of rotamers. 1H NMR (400 MHz, DMSO-d6) δ 8.15
		(d, J = 8.2 Hz, 0.3H), 8.11-7.99 (m, 3.7H), 7.59 (s, 1H), 7.31 (d, J = 8.1
		Hz, 0.3H), 7.14 (d, J = 7.6 Hz, 0.7H), 7.13 (s, 0.3H), 7.03 (s, 1.7H), 5.43-
		5.36 (m, 1H), 4.92-4.70 (m, 1H), 4.57-4.38 (m, 2H), 4.14 (s, 0.9H),
		4.12 (s, 2.1H), 4.00 (s, 3H), 3.89-3.62 (m, 3H), 2.43-2.35 (m, 1H), 2.18-
		2.06 (m, 1H), 1.92-0.79 (m, 18H), 0.70-0.50 (m, 3H), 0.34-0.23 (m,
		1H).
135	622.3	1H NMR (400 MHz, DMSO-d6) δ 8.16-7.99 (m, 4H), 7.59 (s, 1H), 7.19
		(d, J = 8.2 Hz, 1H), 7.06-6.99 (m, 2H), 5.31 (d, J = 5.6 Hz, 1H), 4.53 (d,
		J = 97.4 Hz, 4H), 4.19-3.67 (m, 9H), 2.36-2.26 (m, 1H), 2.09-1.96
		(m, 2H), 1.82 (s, 4H), 1.68-0.93 (m, 13H), 0.73-0.65 (m, 1H), 0.53-
		0.43 (m, 1H).
136	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 8.6 Hz, 1H), 8.12-7.99
		(m, 4H), 7.58 (s, 1H), 7.19 (d, J = 7.4 Hz, 1H), 7.05 (s, 1H), 7.03 (s, 1H),
		5.27-5.16 (m, 1H), 5.06-4.92 (m, 1H), 4.58-4.30 (m, 3H), 4.10 (s,
		3H), 4.00 (s, 3H), 3.80-3.67 (m, 1H), 2.70-2.59 (m, 1H), 2.36-2.23
		(m, 1H), 2.16-2.00 (m, 1H), 1.91-1.75 (m, 4H), 1.71-1.58 (m, 1H),
		1.53-0.75 (m, 14H), 0.58-0.42 (m, 1H).
137	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.13-7.99 (m, 4H), 7.88 (d, J = 7.9
		Hz, 1H), 7.59 (s, 1H), 7.20 (dd, J = 8.5, 2.6 Hz, 1H), 7.03 (s, 2H), 5.16-
		5.04 (m, 1H), 4.83-4.70 (m, 1H), 4.61-4.32 (m, 3H), 4.12 (s, 3H), 4.01
		(s, 3H), 3.81-3.66 (m, 1H), 2.39-2.25 (m, 1H), 2.25-2.14 (m, 1H),
		1.92-0.94 (m, 20H).
138	610.4	1H NMR (400 MHz, DMSO-d6) δ 8.10 (d, J = 8.1 Hz, 1H), 8.08-7.98
		(m, 3H), 7.60 (s, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.05 (s, 1H), 7.03 (s, 1H),
		5.44 (q, J = 7.2 Hz, 1H), 4.70-4.33 (m, 4H), 4.10 (s, 3H), 4.00 (s, 3H),
		3.81-3.66 (m, 1H), 3.46 (t, J = 7.4 Hz, 2H), 2.65-2.55 (m, 1H), 2.36-
		2.23 (m, 1H), 2.26-2.11 (m, 1H), 1.94-0.89 (m, 19H).
139	610.3	1H NMR (400 MHz, DMSO-d6) δ 8.48 (d, J = 9.1 Hz, 1H), 8.11-8.00
		(m, 4H), 7.55 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04 (s, 2H), 5.50 (d, J =
		14.1 Hz, 1H), 5.30-5.15 (m, 1H), 4.65-4.24 (m, 2H), 4.09 (s, 3H), 4.01
		(s, 3H), 3.80 (d, J = 14.2 Hz, 1H), 3.77-3.64 (m, 1H), 2.39-2.18 (m,
		3H), 2.13-2.01 (m, 1H), 1.91-1.75 (m, 2H), 1.76-1.58 (m, 2H), 1.45-
		1.20 (m, 5H), 1.01-0.77 (m, 2H), 0.62-0.45 (m, 2H), 0.29-0.11 (m,
		3H), −0.18-−0.29 (m, 1H).
140	600.4	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 9.1 Hz, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 8.00-7.89 (m, 3H), 7.41 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H),
		7.05 (s, 1H), 6.91 (s, 1H), 5.38-5.26 (m, 1H), 5.00 (d, J = 13.9 Hz, 1H),
		4.69 (d, J = 13.9 Hz, 1H), 4.17 (s, 3H), 3.99 (s, 3H), 3.31-3.20 (m, 2H),
		3.20-3.05 (m, 3H), 2.37-2.23 (m, 1H), 2.14-1.94 (m, 2H), 1.81-1.67
		(m, 2H), 1.66-1.51 (m, 2H), 1.36 (d, J = 7.0 Hz, 3H), 1.04-0.89 (m,
		2H), 0.81 (s, 3H), 0.76-0.48 (m, 3H), 0.16 (s, 3H).
141	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 9.0 Hz, 1H), 8.13-8.01
		(m, 4H), 7.59 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.06 (s, 1H), 7.03 (s, 1H),
		5.40-5.24 (m, 1H), 5.00 (d, J = 13.9 Hz, 1H), 4.69 (d, J = 14.0 Hz, 1H),
		4.61-4.27 (m, 2H), 4.17 (s, 3H), 4.00 (s, 3H), 3.79-3.67 (m, 1H), 2.41-
		2.22 (m, 3H), 2.14-2.05 (m, 1H), 1.91-1.56 (m, 5H), 1.43-1.30 (m,
		5H), 1.05-0.89 (m, 2H), 0.81 (s, 3H), 0.76-0.63 (m, 2H), 0.63-0.52
		(m, 1H), 0.15 (s, 3H).
142	608.3	1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 9.1 Hz, 1H), 8.11-8.05
		(m, 3H), 8.04 (d, J = 8.1 Hz, 1H), 7.64-7.60 (m, 1H), 7.17 (d, J = 8.2 Hz,
		1H), 7.06 (s, 1H), 7.03 (d, J = 1.2 Hz, 1H), 5.21-5.11 (m, 1H), 4.88 (dd,
		J = 13.7, 5.4 Hz, 1H), 4.77-4.66 (m, 1H), 4.60-3.63 (m, 9H), 2.39-
		2.25 (m, 1H), 2.08-1.92 (m, 2H), 1.92-1.70 (m, 3H), 1.69-1.29 (m,
		7H), 1.07-0.97 (m, 2H), 0.92-0.71 (m, 2H), 0.70-0.57 (m, 1H), 0.32
		(q, J = 5.4 Hz, 1H), 0.19-0.05 (m, 1H).
143	608.3	1H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J = 8.2 Hz, 1H), 8.12-8.00
		(m, 3H), 7.90 (d, J = 8.2 Hz, 1H), 7.62 (s, 1H), 7.27 (d, J = 8.2 Hz, 1H),
		7.11 (s, 1H), 7.03 (d, J = 1.2 Hz, 1H), 5.05-4.90 (m, 2H), 4.52-4.40 (m,
		1H), 4.14 (s, 3H), 4.00 (s, 3H), 3.97-3.62 (m, 3H), 2.38-2.27 (m, 1H),
		1.92-1.76 (m, 5H), 1.66-1.56 (m, 1H), 1.53 (d, J = 6.9 Hz, 3H), 1.40-
		1.21 (m, 2H), 1.00-0.71 (m, 3H), 0.64-0.31 (m, 6H).
144	596.4	1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J = 8.4 Hz, 1H), 8.09-7.99
		(m, 4H), 7.61 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 7.03 (s, 1H),
		5.17 (p, J = 7.3 Hz, 1H), 4.90-4.79 (m, 1H), 4.79-4.66 (m, 1H), 4.62-
		4.35 (m, 3H), 4.15 (s, 3H), 4.00 (s, 3H), 3.82-3.67 (m, 1H), 2.39-2.24
		(m, 2H), 2.24-2.11 (m, 1H), 1.89-1.73 (m, 4H), 1.66-1.28 (m, 10H),
		0.90-0.78 (m, 1H), 0.69-0.55 (m, 1H), 0.18-0.09 (m, 1H), −0.53-
		−0.65 (m, 1H).
145	624.4	1H NMR (400 MHz, DMSO-d6) δ 8.11-8.02 (m, 4H), 7.79 (d, J = 7.8
		Hz, 1H), 7.61 (s, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.08 (s, 1H), 7.03 (s, 1H),
		5.10 (p, J = 7.2 Hz, 1H), 4.81-4.72 (m, 1H), 4.69-4.58 (m, 1H), 4.57-
		4.34 (m, 2H), 4.15 (s, 3H), 4.00 (s, 3H), 3.85-3.64 (m, 1H), 2.38-2.24
		(m, 1H), 1.92-1.18 (m, 14H), 1.12 (s, 3H), 1.00 (s, 3H), 0.74-0.59 (m,
		2H), 0.25-0.15 (m, 1H), −0.35-−0.48 (m, 1H).
146	601.4	1H NMR (400 MHz, DMSO-d6) δ 8.00 (brs, 3H), 7.95 (d, J = 8.0 Hz,
		1H), 7.32 (s, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.63 (s, 1H), 6.40 (s, 1H), 6.33
		(d, J = 7.5 Hz, 1H), 5.08-4.99 (m, 1H), 4.73-4.63 (m, 1H), 4.48-4.39
		(m, 1H), 4.09 (s, 3H), 3.53-3.42 (m, 1H), 3.36-3.03 (m, 3H), 2.80 (s,
		3H), 2.78 (s, 3H), 2.08-2.98 (m, 1H), 1.89-1.71 (m, 2H), 1.67-1.48
		(m, 5H), 1.49-1.39 (m, 1H), 1.42 (d, J = 6.8 Hz, 3H), 1.32-1.09 (m,
		5H), 1.04-0.90 (m, 1H).
147	650.4	1H NMR (400 MHz, DMSO-d6) δ 8.62 (d, J = 7.4 Hz, 1H), 8.07 (dd, J =
		7.9, 1.9 Hz, 1H), 8.02 (d, J = 7.9 Hz, 1H), 7.93 (brs, 3H), 7.54-7.47 (m,
		1H), 7.30 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.09
		(dd, J = 7.9, 7.9 Hz, 1H), 6.68 (s, 1H), 6.34 (s, 1H), 5.45-5.35 (m, 1H),
		4.95-4.81 (m, 1H), 4.69-4.57 (m, 1H), 4.21-4.14 (m, 1H), 4.09 (s,
		3H), 4.07-3.99 (m, 1H), 2.85 (s, 3H), 2.07-1.85 (m, 2H), 1.83-1.58
		(m, 4H), 1.53 (d, J = 6.5 Hz, 3H), 1.49-1.33 (m, 4H), 1.27-1.10 (m,
		3H), 0.72-0.59 (m, 2H).
148	599.6	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 7.7 Hz, 1H), 7.94 (brs,
		3H), 7.61 (d, J = 8.2 Hz, 1H), 7.40 (s, 1H), 7.34 (s, 1H), 7.08 (dd, J = 8.3,
		1.2 Hz, 1H), 6.99 (s, 1H), 6.91 (d, J = 1.2 Hz, 1H), 5.11-5.00 (m, 1H),
		4.69-4.56 (m, 1H), 4.23-4.13 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.35-
		3.02 (m, 4H), 2.14-1.95 (m, 3H), 1.83-1.52 (m, 5H), 1.51-1.36 (m,
		2H), 1.45 (d, J = 7.1 Hz, 3H), 1.24 (s, 3H), 1.19-1.01 (m, 3H), 0.95 (s,
		3H).
149	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.50 (d, J = 7.3 Hz, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 7.95 (brs, 3H), 7.42 (s, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.01 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.10-5.00 (m, 1H), 4.97 (dd, J = 14.2, 4.1
		Hz, 1H), 4.79 (dd, J = 14.2, 3.5 Hz, 1H), 4.12 (s, 3H), 3.99 (s, 3H),
		3.78-3.70 (m, 1H), 3.50-3.42 (m, 2H), 3.33-3.05 (m, 4H), 2.75 (t, J =
		9.8 Hz, 1H), 2.61-2.56 (m, 1H), 2.14-1.96 (m, 2H), 1.83-1.68 (m,
		1H), 1.67-1.52 (m, 2H), 1.49-1.37 (m, 1H), 1.46 (d, J = 6.8 Hz, 3H),
		0.32-0.10 (m, 2H), 0.09-0.00 (m, 1H).
150	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.54 (d, J = 6.6 Hz, 1H), 8.04 (d, J =
		8.0 Hz, 1H), 7.96 (brs, 3H), 7.43 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.02 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.02-4.94 (m, 1H), 4.68 (dd, J = 14.0, 3.5
		Hz, 1H), 4.15 (s, 3H), 4.04-3.94 (m, 1H), 4.00 (s, 3H), 3.67-3.55 (m,
		2H), 3.41 (dd, J = 11.1, 5.6 Hz, 1H), 3.35-3.09 (m, 3H), 2.83 (dd, J =
		11.1, 8.3 Hz, 1H), 2.70-2.60 (m, 1H), 2.12 (ddd, J = 15.0, 5.0, 2.5 Hz,
		1H), 2.07-1.98 (m, 1H), 1.85-1.70 (m, 2H), 1.67-1.53 (m, 2H), 1.44
		(d, J = 6.9 Hz, 3H), 1.01-0.89 (m, 1H), 0.52-0.44 (m, 1H), 0.37-0.29
		(m, 1H).
151	570.4	1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 9.2 Hz, 1H), 8.03 (d, J =
		8.1 Hz, 1H), 7.94 (brs, 3H), 7.44 (s, 1H), 7.18 (d, J = 8.2 Hz, 1H), 6.97 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.09 (dq, J = 9.2, 7.2 Hz, 1H), 4.76-4.64
		(m, 1H), 4.26-4.17 (m, 1H), 4.14 (s, 3H), 3.99 (s, 3H), 3.35-3.06 (m,
		3H), 2.25-2.10 (m, 1H), 2.08-1.97 (m, 1H), 1.91-1.65 (m, 4H), 1.64-
		1.43 (m, 2H), 1.48 (d, J = 7.2 Hz, 3H), 1.06-0.96 (m, 1H), 0.95-0.82
		(m, 2H), 0.71-0.58 (m, 1H).
152	582.4	1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 9.3 Hz, 1H), 8.07 (brs,
		3H), 8.03 (d, J = 8.1 Hz, 1H), 7.61 (s, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.04
		(d, J = 1.2 Hz, 1H), 6.98 (s, 1H), 5.15-5.03 (m, 1H), 4.77-4.64 (m, 1H),
		4.45 (brs, 2H), 4.29-4.18 (m, 1H), 4.14 (s, 3H), 4.01 (s, 3H), 2.35-2.25
		(m, 1H), 2.23-2.09 (m, 1H), 1.92-1.51 (m, 9H), 1.48 (d, J = 7.2 Hz,
		3H), 1.34 (dd, J = 12.9, 4.4 Hz, 1H), 1.07-0.97 (m, 1H), 0.95-0.82 (m,
		2H), 0.69-0.60 (m, 1H).
153	630.5	1H NMR (400 MHz, DMSO-d6) δ 8.06 (d, J = 8.1 Hz, 1H), 7.95 (brs,
		3H), 7.73 (d, J = 8.5 Hz, 1H), 7.43 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.04
		(s, 1H), 6.92 (d, J = 1.2 Hz, 1H), 5.26-5.11 (m, 1H), 4.83-4.72 (m, 1H),
		4.46-4.33 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.53 (s, 3H), 3.38-3.01
		(m, 5H), 2.07-1.96 (m, 1H), 1.95-1.69 (m, 3H), 1.69-1.53 (m, 3H),
		1.51-1.39 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.39-1.28 (m, 2H), 1.26 (s,
		3H), 1.23-1.12 (m, 1H), 1.00 (s, 3H).
154	630.4	1H NMR (400 MHz, DMSO-d6) δ 8.02 (d, J = 8.1 Hz, 1H), 7.97 (d, J =
		6.3 Hz, 1H), 7.95 (brs, 3H), 7.41 (s, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.03 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.04-4.94 (m, 1H), 4.92-4.80 (m, 1H),
		4.49-4.38 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.73 (d, J = 9.0 Hz, 1H),
		3.31-3.08 (m, 2H), 2.10-1.85 (m, 3H), 1.83-1.68 (m, 2H), 1.67-1.49
		(m, 5H), 1.45 (d, J = 7.1 Hz, 3H), 1.40-1.26 (m, 4H), 1.25 (s, 3H), 1.02-
		0.88 (m, 1H), 0.84-0.69 (m, 1H), 0.80 (s, 3H).
155	597.6	1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 8.6 Hz, 1H), 7.94 (s, 3H),
		7.61 (d, J = 8.2 Hz, 1H), 7.55 (s, 1H), 7.41 (s, 1H), 7.08 (dd, J = 8.3, 1.2
		Hz, 1H), 7.00 (s, 1H), 6.91 (d, J = 1.2 Hz, 1H), 5.25-5.15 (m, 1H), 4.68
		4.56 (m, 1H), 4.29-4.18 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.34-3.00
		(m, 3H), 2.42-2.30 (m, 1H), 2.07-1.85 (m, 1H), 1.85-1.68 (m, 3H),
		1.26-1.52 (m, 2H), 1.51-1.33 (m, 4H), 1.46 (d, J = 7.1 Hz, 3H), 1.25-
		1.07 (m, 3H), 1.06-0.95 (m, 1H), 0.84-0.73 (m, 1H), 0.68-0.57 (m,
		1H), 0.38-0.28 (m, 1H).
156	601.4	1H NMR (400 MHz, DMSO-d6) δ 8.51 (d, J = 9.4 Hz, 1H), 7.94 (brs,
		3H), 7.69 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.40 (s, 1H), 7.07 (dd, J = 8.2,
		1.2 Hz, 1H), 7.01 (s, 1H), 6.91 (d, J = 1.2 Hz, 1H), 5.25-5.06 (m, 1H),
		4.79-4.65 (m, 1H), 4.35-4.24 (m, 1H), 4.09 (s, 3H), 3.99 (s, 3H), 3.38-
		3.02 (m, 4H), 2.61-2.50 (m, 1H), 2.36-2.20 (m, 1H), 2.07-1.97 (m,
		1H), 1.83-1.71 (m, 1H), 1.69-1.52 (m, 4H), 1.54-1.42 (m, 1H), 1.47
		(d, J = 7.1 Hz, 3H), 1.38 (s, 3H), 1.36-1.20 (m, 1H), 1.18 (s, 3H), 0.65-
		0.49 (m, 1H).
157	584.4	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.5 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.95 (brs, 3H), 7.42 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.02 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.06-4.93 (m, 1H), 4.78-4.64 (m, 1H),
		4.65-4.54 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.37-2.97 (m, 4H), 2.09-
		1.97 (m, 1H), 1.92-1.81 (m, 1H), 1.81-1.72 (m, 1H), 1.70-1.48 (m,
		7H), 1.47-1.32 (m, 1H), 1.43 (d, J = 7.1 Hz, 3H), 1.29-1.11 (m, 1H),
		0.91-0.81 (m, 1H), 0.79-0.59 (m, 2H), 0.53-0.44 (m, 1H).
158	584.4	1H NMR (400 MHz, DMSO-d6) δ 8.41 (d, J = 7.2 Hz, 1H), 8.02 (d, J =
		8.1 Hz, 1H), 7.95 (brs, 3H), 7.42 (s, 1H), 7.22 (d, J = 8.3 Hz, 1H), 7.03 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 4.75-4.52 (m, 2H), 4.53-4.43 (m,
		1H), 4.13 (s, 3H), 4.00 (s, 3H), 3.35-3.02 (m, 4H), 2.08-1.97 (m, 1H),
		1.88-1.76 (m, 2H), 1.74 (d, J = 7.1 Hz, 3H), 1.71-1.36 (m, 5H), 1.35-
		1.26 (m, 3H), 0.92-0.83 (m, 2H), 0.82-0.65 (m, 1H), 0.49 (dd, J = 7.8,
		2.9 Hz, 1H).
159	623.8	1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 8.6 Hz, 1H), 7.94 (brs,
		3H), 7.59 (d, J = 8.2 Hz, 1H), 7.55 (s, 1H), 7.37 (s, 1H), 7.12 (s, 1H), 7.06
		(dd, J = 8.2, 1.2 Hz, 1H), 6.91 (d, J = 1.2 Hz, 1H), 5.23-5.13 (m, 1H),
		4.88-4.76 (m, 1H), 4.34-4.21 (m, 1H), 3.99 (s, 3H), 3.92-3.84 (m,
		1H), 3.33-3.07 (m, 1H), 2.41-2.29 (m, 1H), 2.08-1.96 (m, 1H), 1.85-
		1.70 (m, 2H), 1.70-1.52 (m, 3H), 1.46 (d, J = 7.1 Hz, 3H), 1.44-1.32
		(m, 4H), 1.26-0.92 (m, 6H), 0.85-0.71 (m, 2H), 0.67-0.58 (m, 1H),
		0.54-0.44 (m, 1H), 0.37-0.27 (m, 1H).
160	625.5	1H NMR (400 MHz, DMSO-d6) δ 8.06 (d, J = 7.6 Hz, 1H), 7.95 (brs,
		3H), 7.59 (d, J = 8.1 Hz, 1H), 7.36 (s, 1H), 7.35 (s, 1H), 7.12 (s, 1H), 7.06
		(dd, J = 8.1, 1.2 Hz, 1H), 6.91 (d, J = 1.2 Hz, 1H), 5.09-4.99 (m, 1H),
		4.90-4.78 (m, 1H), 4.28-4.15 (m, 1H), 3.99 (s, 3H), 3.91-3.83 (m,
		1H), 3.32-3.01 (m, 4H), 2.13-1.92 (m, 2H), 1.79-1.70 (m, 1H), 1.69-
		1.52 (m, 3H), 1.49-1.28 (m, 4H), 1.46 (d, J = 7.2 Hz, 3H), 1.24 (s, 3H),
		1.16-0.92 (m, 4H), 0.94 (s, 3H), 0.83-0.71 (m, 1H), 0.51-0.40 (m,
		1H).
161	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J = 8.4 Hz, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 7.95 (brs, 3H), 7.42 (s, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.01 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.18-5.10 (m, 1H), 5.07 (dd, J = 14.1, 4.2
		Hz, 1H), 4.92 (dd, J = 14.1, 2.6 Hz, 1H), 4.23-4.13 (m, 2H), 4.12 (s, 3H),
		4.00 (s, 3H), 3.56-3.49 (m, 1H), 3.33-3.12 (m, 2H), 2.70-2.54 (m,
		2H), 2.15-1.97 (m, 2H), 2.15-1.96 (m, 2H), 1.48-1.37 (m, 1H), 1.44
		(d, J = 7.0 Hz, 3H), 0.82 (d, J = 6.2 Hz, 3H), 0.02-−0.04 (m, 1H), −0.04-
		−0.11 (m, 1H), −0.16-−0.25 (m, 1H).
162	600.4	1H NMR (400 MHz, DMSO-d6) δ 8.51 (d, J = 6.6 Hz, 1H), 8.03 (d, J =
		8.1 Hz, 1H), 7.95 (brs, 3H), 7.41 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H), 6.99 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.04-4.93 (m, 1H), 4.80 (dd, J = 14.1, 4.2
		Hz, 1H), 4.60 (dd, J = 14.1, 5.6 Hz, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.68-
		3.61 (m, 1H), 3.41-3.09 (m, 5H), 2.15-1.95 (m, 3H), 1.81-1.69 (m,
		1H), 1.65-1.52 (m, 1H), 1.44 (d, J = 6.9 Hz, 3H), 0.78 (d, J = 6.2 Hz,
		3H), 0.56-0.48 (m, 1H), 0.31-0.24 (m, 1H), 0.01-−0.03 (m, 1H).
163	584.4	1H NMR (400 MHz, DMSO-d6) δ 8.29 (d, J = 8.4 Hz, 1H), 8.01 (d, J =
		8.1 Hz, 1H), 7.96 (brs, 3H), 7.40 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 6.97 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.22-5.00 (m, 1H), 4.91 (dd, J = 14.1, 4.6
		Hz, 1H), 4.57 (dd, J = 14.1, 5.2 Hz, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.65-
		3.37 (m, 3H), 3.34-3.06 (m, 3H), 2.40-2.33 (m, 1H), 2.09-1.97 (m,
		1H), 1.87-1.68 (m, 2H), 1.66-1.41 (m, 3H), 1.46 (d, J = 7.0 Hz, 3H),
		1.18-1.02 (m, 1H), 0.90-0.76 (m, 1H), 0.65-0.52 (m, 1H), 0.10-
		0.01 (m, 1H), 0.00-−0.14 (m, 2H).
164	583.4	1H NMR (400 MHz, DMSO-d6) δ 8.68 (d, J = 8.8 Hz, 1H), 7.96 (brs,
		3H), 7.62 (s, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.39 (s, 1H), 7.02 (dd, J = 8.2,
		1.3 Hz, 1H), 6.99 (s, 1H), 6.91 (s, 1H), 5.02-4.89 (m, 1H), 4.85-4.74
		(m, 1H), 4.23-4.13 (m, 1H), 4.10 (s, 3H), 3.99 (s, 3H), 3.85-3.58 (m,
		3H), 3.29-3.06 (m, 2H), 2.07-1.95 (m, 1H), 1.92-1.65 (m, 3H), 1.65-
		1.51 (m, 3H), 1.43 (d, J = 7.1 Hz, 3H), 1.41-1.22 (m, 2H), 0.97-0.90
		(m, 1H), 0.87-0.65 (m, 2H), 0.58-0.51 (m, 1H).
165	583.5	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 6.9 Hz, 0.6H 1st rotamer),
		7.95 (brs, 3H), 7.66 (d, J = 8.3 Hz, 0.4H 2nd rotamer), 7.62 (s, 0.4H 2nd
		rotamer), 7.60 (s, 0.6H 1st rotamer), 7.58 (d, J = 8.3 Hz, 0.6H 1st
		rotamer), ), 7.54 (d, J = 6.1 Hz, 0.4H 2nd rotamer), 7.40 (s, 1H), 7.15 (d,
		J = 8.6 Hz, 0.4H 2nd rotamer), 7.12 (d, J = 8.6 Hz, 0.6H 1st rotamer), 7.04
		(s, 0.4H 2nd rotamer), 7.01 (s, 0.6H 1st rotamer), 6.95 (s, 1H), 5.06-4.95
		(m, 1H), 4.78-4.63 (m, 1H), 4.58-4.48 (m, 1H), 4.29-4.17 (m, 1H),
		4.11 (s, 1.8H 1st rotamer), 4.10 (s, 1.2H 2nd rotamer), 3.99 (s, 3H), 3.36-
		3.06 (m, 3H), 2.07-1.96 (m, 2H), 1.86-1.70 (m, 1H), 1.75 (d, J = 7.1
		Hz, 3H), 1.70-1.49 (m, 4H), 1.47-1.30 (m, 4H), 1.20-1.02 (m, 1H),
		1.02-0.72 (m, 2H), 0.61-0.27 (m, 1H).
166	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 8.2 Hz, 0.5H), 8.06 (d, J =
		8.1 Hz, 0.5H), 8.00 (d, J = 8.0 Hz, 0.5H), 7.96 (brs, 3H), 7.95 (d, J = 8.0
		Hz, 0.5H), 7.42 (s, 0.5H), 7.39 (s, 0.5H), 7.24 (d, J = 8.2 Hz, 0.5H), 7.18
		(d, J = 8.1 Hz, 0.5H), 7.01 (s, 0.5H), 6.96 (s, 0.5H), 6.93 (d, J = 1.2 Hz,
		0.5H), 6.91 (d, J = 1.2 Hz, 0.5H), 5.22 (dd, J = 14.1, 3.7 Hz, 0.5H), 5.19-
		5.11 (m, 0.5H), 5.09-4.98 (m, 1H), 4.82 (dd, J = 14.1, 4.9 Hz, 0.5H),
		4.40 (dd, J = 14.1, 6.1 Hz, 0.5H), 4.13 (s, 1.5H), 4.09 (s, 1.5H), 4.00 (s,
		1.5H), 3.99 (s, 1.5H), 3.34-3.06 (m, 4H), 2.21-1.98 (m, 2H), 1.83-
		1.49 (m, 2H), 1.48 (d, J = 7.1, 1.5H), 1.48 (d, J = 7.1, 1.5H), 1.43-0.96
		(m, 3H), 0.94-0.77 (m, 3H), 0.71-0.54 (m, 2H), 0.45-0.29 (m, 1H),
		0.18-0.11 (m, 1H), 0.10-−0.02 (m, 1H), −0.13-−0.21 (m, 1H), −0.29-−
		0.36 (m, 1H), −0.46-−0.58 (m, 1H).
167	596.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.97 (brs,
		3H), 7.39 (s, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 7.00
		(s, 1H), 6.91 (d, J = 1.2 Hz, 1H), 5.06-4.99 (m, 1H), 4.96 (d, J = 12.8 Hz,
		1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.97-3.38 (m, 2H), 3.32-3.09 (m, 3H),
		2.13-1.86 (m, 4H), 1.83-1.70 (m, 1H), 1.67-1.52 (m, 3H), 1.48 (d, J =
		7.2 Hz, 3H), 1.27-1.16 (m, 1H), 1.14-1.06 (m, 1H), 0.78-0.68 (m,
		1H), 0.63-0.46 (m, 3H), 0.25-0.16 (m, 1H), 0.04-−0.02 (m, 1H).
168	596.4	1H NMR (400 MHz, DMSO-d6) δ 7.99 (d, J = 8.0 Hz, 1H), 7.95 (brs,
		3H), 7.46 (s, 1H), 7.13 (d, J = 8.1 Hz, 1H), 7.03 (s, 1H), 6.92 (d, J = 1.2
		Hz, 1H), 5.18-5.01 (m, 1H), 4.76-4.09 (m, 1H), 4.15 (s, 3H), 4.01-
		3.92 (m, 2H), 4.00 (s, 3H), 3.36-3.01 (m, 3H), 2.08-1.97 (m, 2H), 1.94-
		1.85 (m, 1H), 1.83-1.68 (m, 1H), 1.66-1.64 (m, 1H), 1.54-1.42 (m,
		1H), 1.40 (d, J = 7.1 Hz, 3H), 1.36-1.28 (m, 1H), 1.16-1.09 (m, 1H),
		0.88-0.79 (m, 1H), 0.73-0.53 (m, 5H), 0.57-0.43 (m, 1H), 0.23-0.14
		(m, 1H).
169	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 8.02 (brs,
		1H), 7.85 (d, J = 7.4 Hz, 1H), 7.81 (brs, 3H), 7.68-7.58 (m, 1H), 7.29 (s,
		1H), 7.19 (d, J = 8.2 Hz, 1H), 5.16-5.06 (m, 1H), 4.95-4.82 (m, 1H),
		4.71-4.59 (m, 1H), 3.81 (s, 2H), 3.38-3.01 (m, 4H), 2.11-1.86 (m,
		2H), 1.87-1.48 (m, 5H), 1.46 (d, J = 7.1 Hz, 3H), 1.42-1.26 (m, 3H),
		1.28-1.22 (m, 1H), 1.21 (s, 3H), 1.17-0.99 (m, 2H), 0.98-0.86 (m,
		1H), 0.95 (s, 3H), 0.63-0.49 (m, 1H).
170	624.4	1H NMR (400 MHz, DMSO-d6) δ 8.10 (d, J = 8.1 Hz, 1H), 8.09 (d, J =
		6.4 Hz, 1H), 7.95 (brs, 3H), 7.69 (s, 1H), 7.42 (s, 1H), 7.26 (d, J = 8.2 Hz,
		1H), 7.07 (s, 1H), 6.92 (d, J = 1.2 Hz, 1H), 5.14-5.05 (m, 1H), 4.62-
		4.50 (m, 2H), 4.13 (s, 3H), 4.00 (s, 4H), 3.77 (s, 3H), 3.35-3.04 (m, 4H),
		2.92-2.80 (m, 1H), 2.76-2.65 (m, 1H), 2.07-1.97 (m, 1H), 1.87-1.69
		(m, 3H), 1.68-1.46 (m, 2H), 1.55 (d, J = 6.8 Hz, 3H), 1.28-1.06 (m,
		1H).
171	620.3	1H NMR (400 MHz, DMSO-d6) δ 9.66 (d, J = 5.6 Hz, 1H), 8.22 (d, J =
		8.1 Hz, 1H), 7.96 (brs, 3H), 7.72 (s, 1H), 7.44 (s, 1H), 7.38 (d, J = 8.2 Hz,
		1H), 7.17 (s, 1H), 6.93 (d, J = 1.1 Hz, 1H), 5.34-5.25 (m, 1H), 5.00
		4.88 (m, 1H), 4.80-4.70 (m, 1H), 4.15 (s, 3H), 4.15 (s, 3H), 4.00 (s, 3H),
		3.37-3.04 (m, 3H), 2.48-2.39 (m, 2H), 2.07-1.89 (m, 3H), 1.80-1.70
		(m, 1H), 1.66-1.50 (m, 1H), 1.59 (d, J = 6.5 Hz, 3H).
172	624.4	1H NMR (400 MHz, DMSO-d6) δ 8.50 (d, J = 7.5 Hz, 1H), 8.15 (d, J =
		8.1 Hz, 1H), 7.98 (brs, 3H), 7.43 (s, 1H), 7.34 (s, 1H), 7.31 (d, J = 8.1 Hz,
		1H), 7.10 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.39-5.29 (m, 1H), 4.77-
		4.67 (m, 2H), 4.61-4.50 (m, 2H), 4.13 (s, 3H), 4.00 (s, 3H), 3.93 (s, 3H),
		3.36-3.04 (m, 3H), 2.60-2.50 (m, 1H), 2.38-2.24 (m, 1H), 2.09-1.92
		(m, 1H), 1.82-1.51 (m, 4H), 1.57 (d, J = 6.8 Hz, 3H), 1.29-1.14 (m,
		1H), 1.14-0.96 (m, 1H).
173	629.5	1H NMR (400 MHz, DMSO-d6) δ 8.06 (d, J = 7.7 Hz, 1H), 8.00 (brs,
		3H), 7.61 (d, J = 8.2 Hz, 1H), 7.43 (s, 1H), 7.35 (s, 1H), 7.08 (dd, J = 8.3,
		1.2 Hz, 1H), 7.00 (s, 1H), 6.92 (d, J = 1.2 Hz, 1H), 5.12-5.01 (m, 1H),
		4.67-4.57 (m, 1H), 4.24-4.13 (m, 2H), 4.11 (s, 3H), 3.99 (s, 3H), 3.74-
		3.68 (m, 1H), 3.60-3.50 (m, 2H), 3.37 (s, 3H), 2.13-1.89 (m, 2H), 1.81-
		1.57 (m, 3H), 1.52-1.32 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.24 (s, 3H),
		1.19-0.99 (m, 3H), 0.95 (s, 3H).
174	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.6 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.99 (brs, 3H), 7.45 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.02 (s,
		1H), 6.93 (d, J = 1.2 Hz, 1H), 5.06-4.96 (m, 1H), 4.75-4.55 (m, 2H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.74-3.68 (m, 1H), 3.62-3.49 (m, 2H), 3.45-
		3.35 (m, 1H), 3.37 (s, 3H), 2.01-1.71 (m, 3H), 1.70-1.48 (m, 4H), 1.43
		(d, J = 7.1 Hz, 3H), 1.42-1.32 (m, 1H), 1.27-1.14 (m, 1H), 0.92-0.81
		(m, 1H), 0.78-0.59 (m, 2H), 0.52-0.43 (m, 1H).
175	628.3	1H NMR (400 MHz, DMSO-d6) δ 8.02 (d, J = 8.1 Hz, 1H), 7.96 (brs, 3H),
		7.45 (s, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.01 (s,
		1H), 6.93 (s, 1H), 4.96-4.85 (m, 1H), 4.63-4.52 (m, 1H), 4.52-4.44
		(m, 1H), 4.13 (s, 3H), 3.99 (s, 3H), 3.76-3.68 (m, 1H), 3.63-3.47 (m,
		2H), 3.37 (s, 3H), 2.02-1.83 (m, 3H), 1.82-1.56 (m, 3H), 1.55-1.43
		(m, 3H), 1.51 (d, J = 7.2 Hz, 3H), 1.41-1.19 (m, 2H), 1.15 (s, 3H), 0.36
		(dd, J = 6.5, 4.4 Hz, 1H).
176	614.7	1H NMR (400 MHz, DMSO-d6) δ 8.65 (brs, 2H), 8.45 (d, J = 7.4 Hz,
		1H), 8.05 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 6.3 Hz, 1H), 7.84 (d, J = 7.3 Hz,
		1H), 7.60 (d, J = 10.5 Hz, 1H), 7.31 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 5.16-
		5.05 (m, 1H), 4.96-4.82 (m, 1H), 4.75-4.59 (m, 1H), 4.22-4.13 (m,
		1H), 3.88-3.76 (m, 1H), 3.44-3.32 (m, 1H), 3.28-3.17 (m, 1H), 2.95-
		2.78 (m, 2H), 2.03-1.86 (m, 3H), 1.80-1.52 (m, 4H), 1.46 (d, J = 7.1
		Hz, 3H), 1.43-1.23 (m, 3H), 1.22 (s, 4H), 1.17-0.99 (m, 3H), 0.95 (s,
		3H), 0.92-0.83 (m, 1H), 0.59-0.48 (m, 1H).
177	572.6	1H NMR (400 MHz, DMSO-d6) δ 9.14 (d, J = 6.6 Hz, 1H), 8.72 (brs,
		2H), 8.06 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 1.2 Hz, 1H), 7.82 (d, J = 7.4 Hz,
		1H), 7.36 (d, J = 1.3 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.18-
		5.08 (m, 1H), 4.91-4.77 (m, 2H), 4.47-4.36 (m, 2H), 4.26-4.14 (m,
		2H), 4.14 (s, 3H), 4.02 (s, 3H), 1.93 (t, J = 12.4 Hz, 1H), 1.76-1.61 (m,
		2H), 1.54-1.28 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.21 (s, 3H), 1.18-
		1.03 (m, 2H), 0.95 (s, 4H).
178	617.9	1H NMR (400 MHz, DMSO-d6) δ 8.78 (brs, 2H), 8.72 (d, J = 7.9 Hz,
		1H), 8.05 (d, J = 7.6 Hz, 1H), 7.62 (d, J = 8.2 Hz, 1H), 7.35 (d, J = 1.3 Hz,
		1H), 7.34 (s, 1H), 7.08 (dd, J = 8.3, 1.2 Hz, 1H), 7.04 (s, 1H), 5.13-5.03
		(m, 1H), 4.96-4.88 (m, 1H), 4.85-4.76 (m, 1H), 4.69-4.59 (m, 1H),
		4.51-4.39 (m, 1H), 4.24-4.15 (m, 1H), 4.14 (s, 3H), 4.02 (s, 3H), 3.51-
		3.31 (m, 2H), 3.15-2.91 (m, 3H), 2.40-2.31 (m, 2H), 2.14-2.02 (m,
		1H), 2.00-1.73 (m, 2H), 1.71-1.55 (m, 1H), 1.54-1.35 (m, 2H), 1.45
		(d, J = 7.1 Hz, 3H), 1.25 (s, 3H), 1.20-1.04 (m, 3H), 0.95 (s, 3H).
179	632.4	1H NMR (400 MHz, DMSO-d6) δ 8.82 (brs, 2H), 8.65 (d, J = 8.1 Hz,
		1H), 8.05 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H), 7.86 (d, J = 7.3 Hz,
		1H), 7.63 (d, J = 10.6 Hz, 1H), 7.31 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 5.16-
		5.06 (m, 1H), 4.96-4.84 (m, 2H), 4.81-4.73 (m, 1H), 4.71-4.60 (m,
		1H), 4.42-4.35 (m, 1H), 3.52-3.28 (m, 2H), 3.13-2.90 (m, 2H), 2.42-
		2.27 (m, 1H), 2.00-1.83 (m, 2H), 1.77-1.49 (m, 2H), 1.46 (d, J = 7.1
		Hz, 3H), 1.44-1.22 (m, 5H), 1.22 (s, 3H), 1.17-0.99 (m, 3H), 0.94 (s,
		3H), 0.93-0.83 (m, 1H), 0.60-0.49 (m, 1H).
180	642.4	1H NMR (400 MHz, DMSO-d6) δ 9.62 (brs, 2H), 8.71 (d, J = 8.0 Hz,
		1H), 8.11 (d, J = 8.1 Hz, 1H), 8.09 (d, J = 6.9 Hz, 1H), 8.00 (d, J = 1.1 Hz,
		1H), 7.70 (s, 1H), 7.37 (d, J = 1.3 Hz, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.11
		(s, 1H), 5.15-5.05 (m, 1H), 4.95-4.86 (m, 1H), 4.85-4.74 (m, 1H),
		4.61-4.51 (m, 2H), 4.50-4.36 (m, 1H), 4.16 (s, 3H), 4.03 (s, 3H), 3.78
		(s, 3H), 3.49-3.36 (m, 2H), 3.14-2.81 (m, 3H), 2.78-2.64 (m, 2H),
		1.98-1.72 (m, 2H), 1.67-1.54 (m, 2H), 1.54 (d, J = 6.9 Hz, 3H), 1.29-
		1.14 (m, 2H).
181	642.2	1H NMR (400 MHz, DMSO-d6) δ 8.78 (brs, 2H), 8.72 (d, J = 7.9 Hz,
		1H), 8.49 (d, J = 7.4 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 1.3 Hz,
		1H), 7.37 (d, J = 1.3 Hz, 1H), 7.34 (s, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.14
		(s, 1H), 5.39-5.29 (m, 1H), 4.97-4.67 (m, 3H), 4.63-4.36 (m, 2H),
		4.16 (s, 3H), 4.03 (s, 3H), 3.94 (s, 3H), 3.50-3.34 (m, 2H), 3.14-2.91
		(m, 2H), 2.64-2.51 (m, 1H), 2.42-2.27 (m, 2H), 2.06-1.86 (m, 2H),
		1.86-1.74 (m, 1H), 1.73-1.62 (m, 1H), 1.57 (d, J = 6.8 Hz, 3H), 1.28-
		1.21 (m, 1H), 1.17-1.03 (m, 1H).
182	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 2H), 8.63 (d, J = 8.0 Hz, 1H),
		8.45 (d, J = 8.5 Hz, 1H), 8.00 (d, J = 6.2 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H),
		7.62 (d, J = 10.6 Hz, 1H), 7.30 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 5.08-
		4.95 (m, 1H), 4.94-4.70 (m, 3H), 4.51-4.35 (m, 1H), 3.96-3.79 (m,
		1H), 3.51-3.30 (m, 2H), 3.13-2.89 (m, 2H), 2.40-2.26 (m, 1H), 2.04-
		1.80 (m, 2H), 1.73-1.31 (m, 5H), 1.44 (d, J = 7.1 Hz, 3H), 1.31-1.08
		(m, 3H), 0.95-0.82 (m, 2H), 0.78-0.54 (m, 3H), 0.52-0.42 (m, 1H).
183	643.3	1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 7.4 Hz, 1H), 8.76 (brs,
		2H), 8.71 (d, J = 7.9 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 1.3 Hz,
		1H), 7.37 (d, J = 1.3 Hz, 1H), 7.33 (d, J = 8.1 Hz, 1H), 7.14 (s, 1H), 5.39-
		5.29 (m, 1H), 4.98-4.76 (m, 1H), 4.73-4.62 (m, 1H), 4.62-4.51 (m,
		1H), 4.51-4.40 (m, 1H), 4.17 (s, 3H), 4.13 (s, 3H), 4.09-3.99 (m, 1H),
		4.03 (s, 3H), 3.51-3.32 (m, 2H), 3.16-2.92 (m, 2H), 2.91-2.53 (m,
		3H), 2.44-2.29 (m, 1H), 2.04-1.63 (m, 3H), 1.59 (d, J = 6.9 Hz, 3H),
		1.37-1.15 (m, 2H).
184	602.6	1H NMR (400 MHz, DMSO-d6) δ 8.76 (brs, 2H), 8.71 (d, J = 7.9 Hz,
		1H), 8.43 (d, J = 8.6 Hz, 1H), 8.01 (d, J = 1.3 Hz, 1H), 7.96 (d, J = 8.1 Hz,
		1H), 7.36 (d, J = 1.3 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.06 (s, 1H), 5.07-
		4.97 (m, 1H), 4.92 (td, J = 9.4, 4.5 Hz, 1H), 4.80 (td, J = 9.4, 4.5 Hz, 1H),
		4.74-4.63 (m, 1H), 4.62-4.52 (m, 1H), 4.52-4.38 (m, 1H), 4.15 (s,
		3H), 4.03 (s, 3H), 3.51-3.34 (m, 2H), 3.14-2.88 (m, 2H), 2.41-2.31
		(m, 1H), 2.02-1.81 (m, 2H), 1.75-1.53 (m, 5H), 1.43 (d, J = 7.1 Hz,
		3H), 1.35-1.11 (m, 1H), 0.92-0.81 (m, 1H), 0.77-0.60 (m, 2H), 0.54-
		0.43 (m, 1H).
185	643.5	1H NMR (400 MHz, DMSO-d6) δ 8.77 (brs, 2H), 8.70 (d, J = 7.9 Hz, 1H),
		8.56 (d, J = 6.9 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 8.00 (s, 1H), 7.36 (s,
		1H), 7.25 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 5.20-5.10 (m, 1H), 4.97-
		4.88 (m, 1H), 4.84-4.74 (m, 1H), 4.59-4.36 (m, 3H), 4.16 (s, 3H), 4.16
		(s, 3H), 4.02 (s, 3H), 3.50-3.28 (m, 1H), 3.16-2.88 (m, 1H), 2.87-
		2.61 (m, 2H), 2.42-2.26 (m, 1H), 2.01-1.79 (m, 2H), 1.75-1.41 (m,
		2H), 1.58 (d, J = 7.0 Hz, 3H), 1.34-1.14 (m, 2H), 1.08-0.92 (m, 1H).
186	674.7	1H NMR (400 MHz, DMSO-d6) δ 8.92 (d, J = 7.1 Hz, 1H), 8.84-8.72
		(m, 1H), 8.75 (brs, 2H), 8.69 (d, J = 8.0 Hz, 1H), 8.16 (d, J = 8.0 Hz, 1H),
		7.98 (s, 1H), 7.42-7.31 (m, 4H), 7.28 (d, J = 7.4 Hz, 1H), 7.26-7.21
		(m, 2H), 5.36-5.10 (m, 3H), 4.97-4.74 (m, 1H), 4.49-4.37 (m, 1H),
		4.14 (s, 3H), 4.03 (s, 3H), 3.51-3.31 (m, 1H), 3.14-2.88 (m, 2H), 2.41-
		2.21 (m, 2H), 1.97-1.83 (m, 1H), 1.73-1.55 (m, 1H), 1.54-1.39 (m,
		1H).1.47 (d, J = 7.1 Hz, 3H), 1.28-1.05 (m, 1H).
187	616.7	1H NMR (400 MHz, DMSO-d6) δ 8.77 (brs, 2H), 8.70 (d, J = 7.9 Hz, 1H),
		8.06-7.99 (m, 2H), 7.36 (s, 1H), 7.22 (d, 7.6 Hz, 1H), 7.17 (d, 8.2 Hz,
		1H), 7.05 (s, 1H), 4.97-4.86 (m, 1H), 4.91-4.76 (m, 1H), 4.64-4.54
		(m, 1H), 4.53-4.37 (m, 2H), 4.16 (s, 3H), 4.03 (s, 3H), 3.50-3.30 (m,
		1H), 3.18-2.87 (m, 2H), 2.40-2.32 (m, 1H), 2.00-1.85 (m, 2H), 1.74-
		1.58 (m, 3H), 1.57-1.44 (m, 2H), 1.51 (d, J = 7.2 Hz, 3H), 1.44-1.22
		(m, 4H), 1.16 (s, 3H), 0.40-0.33 (m, 1H).
188	574.4	1H NMR (400 MHz, DMSO-d6) δ 8.95 (d, J = 1.9 Hz, 1H), 8.88 (d, J =
		8.1 Hz, 1H), 8.86 (brs, 2H), 8.68 (d, J = 1.9 Hz, 1H), 8.46 (d, J = 8.5 Hz,
		1H), 8.04 (d, J = 8.0 Hz, 1H), 7.27 (s, 1H), 7.17 (d, J = 8.1 Hz, 1H), 5.09-
		4.98 (m, 1H), 4.97-4.70 (m, 3H), 4.51-4.43 (m, 1H), 4.06 (s, 3H), 3.47
		(d, J = 12.6 Hz, 1H), 3.40 (d, J = 12.6 Hz, 1H), 3.15-2.96 (m, 2H), 2.44-
		2.30 (m, 1H), 2.03-1.53 (m, 7H), 1.53-1.39 (m, 1H), 1.44 (d, J = 7.1
		Hz, 3H), 1.37-1.19 (m, 1H), 0.90-0.82 (m, 1H), 0.77-0.59 (m, 2H),
		0.52-0.45 (m, 1H).
189	670.5	1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 8.0 Hz, 1H), 8.80 (brs,
		2H), 8.58 (d, J = 8.8 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.82 (dd, J = 5.2,
		1.2 Hz, 1H), 7.40 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.85-5.73 (m, 1H),
		5.26-5.16 (m, 1H), 5.12-5.00 (m, 1H), 4.94-4.69 (m, 1H), 4.46-4.35
		(m, 1H), 4.12-4.01 (m, 1H), 3.43 (dd, J = 37.5, 12.5 Hz, 2H), 3.28-2.86
		(m, 2H), 2.43-2.28 (m, 1H), 2.23-2.02 (m, 2H), 2.01-1.87 (m, 2H),
		1.70-1.50 (m, 2H), 1.44 (d, J = 7.0 Hz, 3H), 1.38-1.18 (m, 2H), 1.15-
		0.99 (m, 2H), 0.90-0.81 (m, 1H), 0.73-0.57 (m, 1H), 0.54-0.44 (m,
		3H).
190	641.7	1H NMR (400 MHz, DMSO-d6) δ 9.38 (brs, 1H), 8.89 (brs, 1H), 8.05 (d,
		J = 7.7 Hz, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.41 (dd, J = 2.2, 1.1 Hz, 1H),
		7.35 (s, 1H), 7.08 (dd, J = 8.3, 1.2 Hz, 1H), 7.00 (s, 1H), 6.92 (s, 1H),
		5.12-4.99 (m, 1H), 4.69-4.54 (m, 2H), 4.25-4.14 (m, 1H), 4.11 (s, 3H),
		4.05-3.94 (m, 2H), 3.99 (s, 3H), 3.78-3.53 (m, 3H), 3.38-2.97 (m,
		2H), 2.14-2.00 (m, 1H), 1.92-1.80 (m, 2H), 1.75-1.62 (m, 2H), 1.49-
		1.30 (m, 4H), 1.45 (d, J = 7.1 Hz, 3H), 1.24 (s, 2H), 1.18-0.99 (s, 5H),
		0.94 (s, 3H).
191	635.5	1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.90 (s, 1H), 8.72 (d, J =
		9.0 Hz, 1H), 8.06-7.99 (m, 2H), 7.62 (d, J = 8.2 Hz, 1H), 7.37 (d, J = 1.2
		Hz, 1H), 7.34 (s, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.04 (s, 1H), 5.12-5.02
		(m, 1H), 5.01-4.85 (m, 1H), 4.71-4.58 (m, 1H), 4.23-4.14 (m, 1H),
		4.14 (s, 3H), 4.02 (s, 3H), 3.60-3.44 (m, 4H), 3.28-3.07 (m, 2H), 2.41-
		2.21 (m, 1H), 2.15-2.01 (m, 1H), 1.86-1.74 (m, 1H), 1.71-1.58 (m,
		1H), 1.54-1.36 (m, 2H), 1.45 (d, J = 7.1 Hz, 4H), 1.25 (s, 3H), 1.19-
		1.04 (m, 2H), 0.95 (s, 3H).
192	668.4	1H NMR (400 MHz, DMSO-d6) δ 8.33 (brs, 3H), 8.05 (d, J = 8.1 Hz,
		1H), 7.84 (d, J = 7.4 Hz, 1H), 7.47 (d, J = 1.1 Hz, 1H), 7.19 (d, J = 8.2 Hz,
		1H), 7.04 (s, 1H), 6.96 (s, 1H), 5.18-5.05 (m, 1H), 4.90-4.74 (m, 1H),
		4.50-4.34 (m, 2H), 4.12 (s, 3H), 4.00 (s, 3H), 3.55 (brs, 1H), 3.29-3.03
		(m, 2H), 2.94-2.80 (m, 1H), 2.14-1.85 (m, 2H), 1.75-1.54 (m, 2H),
		1.52-1.26 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.21 (s, 3H), 1.17-1.00 (m,
		3H), 0.95 (s, 3H).
193	618.4	1H NMR (400 MHz, DMSO-d6) δ 8.06 (brs, 3H), 8.05 (d, J = 8.1 Hz,
		1H), 7.84 (d, J = 7.5 Hz, 1H), 7.39 (d, J = 1.1 Hz, 1H), 7.19 (d, J = 8.1 Hz,
		1H), 7.04 (s, 1H), 6.89 (d, J = 1.2 Hz, 1H), 5.17-5.08 (m, 1H), 4.94 (brs,
		1H), 4.87-4.77 (m, 1H), 4.48-4.35 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H),
		3.88-3.66 (m, 4H), 3.49-3.33 (m, 1H), 3.06-2.84 (m, 1H), 2.42-2.31
		(m, 1H), 2.00-1.84 (m, 1H), 1.85-1.52 (m, 2H), 1.45 (d, J = 7.1 Hz,
		3H), 1.43-1.27 (m, 4H), 1.21 (s, 3H), 1.16-1.00 (m, 1H), 0.95 (s, 3H).
194	632.3	1H NMR (400 MHz, DMSO-d6) δ 8.11 (brs, 3H), 8.04 (d, J = 8.1 Hz,
		1H), 7.90 (brs, 1H), 7.86 (d, J = 7.4 Hz, 1H), 7.76-7.66 (m, 1H), 7.63 (d,
		J = 9.6 Hz, 1H), 7.29 (d, J = 4.9 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 5.16-
		5.06 (m, 1H), 5.03-4.55 (m, 4H), 3.91-3.77 (m, 2H), 3.46-3.29 (m,
		2H), 3.19-2.81 (m, 2H), 2.43-2.27 (m, 1H), 2.02-1.52 (m, 4H), 1.46
		(d, J = 7.1 Hz, 3H), 1.43-1.24 (m, 4H), 1.21 (s, 3H), 1.15-0.99 (m, 2H),
		0.94 (s, 3H), 0.65-0.47 (m, 1H).
195	616.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.0 Hz, 1H), 7.91 (brs,
		3H), 7.83 (d, J = 7.5 Hz, 1H), 7.44 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.03
		(s, 1H), 6.93 (d, J = 1.1 Hz, 1H), 5.72 (brs, 1H), 5.18-5.08 (m, 1H), 4.86-
		4.76 (m, 1H), 4.51-4.32 (m, 2H), 4.12 (s, 3H), 4.09-4.01 (m, 1H),
		3.99 (s, 3H), 3.60-3.28 (m, 4H), 1.93 (t, J = 12.2 Hz, 1H), 1.86-1.53
		(m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.42-1.26 (m, 3H), 1.21 (s, 3H), 1.18-
		1.00 (m, 2H), 0.95 (s, 3H).
196	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.92 (brs,
		3H), 7.84 (d, J = 7.5 Hz, 1H), 7.49 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04
		(s, 1H), 6.94 (d, J = 1.2 Hz, 1H), 5.19-5.05 (m, 1H), 4.88-4.77 (m, 1H),
		4.45-4.33 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.89-3.69 (m, 1H), 3.49-
		3.33 (m, 2H), 3.24-3.08 (m, 1H), 2.16-2.03 (m, 1H), 1.99-1.86 (m,
		1H), 1.74-1.53 (m, 4H), 1.45 (d, J = 7.1 Hz, 3H), 1.44-1.27 (m, 4H),
		1.21 (s, 3H), 1.17-1.03 (m, 2H), 1.01 (d, J = 7.0 Hz, 3H), 0.95 (s, 3H).
197	604.4	1H NMR (400 MHz, DMSO-d6) δ 9.47 (brs, 1H), 9.26 (brs, 1H), 8.69 (d,
		J = 6.3 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.98 (d, J = 1.3 Hz, 1H), 7.82
		(d, J = 7.4 Hz, 1H), 7.35 (d, J = 1.3 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.08
		(s, 1H), 5.49-5.32 (m, 1H), 5.17-5.07 (m, 1H), 4.88-4.61 (m, 2H),
		4.48-4.37 (m, 1H), 4.15 (s, 3H), 4.02 (s, 3H), 3.81-3.55 (m, 3H), 3.54-
		3.41 (m, 1H), 1.92 (t, J = 12.3 Hz, 1H), 1.75-1.61 (m, 1H), 1.53-1.28
		(m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.21 (s, 3H), 1.18-1.02 (m, 2H), 0.95
		(s, 3H).
198	604.4	1H NMR (400 MHz, DMSO-d6) δ 9.42 (brs, 1H), 9.02 (brs, 1H), 8.76 (d,
		J = 7.1 Hz, 1H), 8.09-8.06 (d, J = 8.2 Hz, 1H), 8.04 (s, 1H), 7.82 (d, J =
		7.4 Hz, 1H), 7.39 (d, J = 1.2 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.07 (s,
		1H), 5.43-5.24 (m, 1H), 5.18-5.08 (m, 1H), 4.90-4.68 (m, 2H), 4.49-
		4.37 (m, 2H), 4.15 (s, 3H), 4.03 (s, 3H), 3.83-3.53 (m, 3H), 3.49-3.34
		(m, 1H), 1.93 (t, J = 12.4 Hz, 1H), 1.75-1.60 (m, 2H), 1.54-1.28 (m,
		3H), 1.45 (d, J = 7.1 Hz, 3H), 1.21 (s, 3H), 1.16-1.04 (m, 2H), 0.95 (s,
		3H).
199	604.4	1H NMR (400 MHz, DMSO-d6) δ 9.43 (brs, 1H), 9.03 (brs, 1H), 8.76 (d,
		J = 7.1 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 8.04 (s, 1H), 7.82 (d, J = 7.4 Hz,
		1H), 7.39 (d, J = 1.3 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 5.44-
		5.23 (m, 1H), 5.18-5.08 (m, 1H), 4.89-4.69 (m, 2H), 4.52-4.37 (m,
		1H), 4.15 (s, 3H), 4.03 (s, 3H), 3.72-3.55 (m, 3H), 3.50-3.37 (m, 1H),
		1.93 (t, J = 12.4 Hz, 1H), 1.75-1.59 (m, 2H), 1.53-1.27 (m, 3H), 1.45
		(d, J = 7.1 Hz, 3H), 1.21 (s, 3H), 1.19-1.01 (m, 3H), 0.95 (s, 3H).
200	605.2	1H NMR (400 MHz, DMSO-d6) δ 9.43 (s, 1H), 9.19 (s, 1H), 8.67 (d, J =
		6.4 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.98 (d, J = 1.3 Hz, 1H), 7.80 (d, J =
		7.4 Hz, 1H), 7.35 (d, J = 1.3 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.08 (s,
		1H), 5.48-5.32 (m, 1H), 5.19-5.07 (m, 1H), 4.88-4.76 (m, 1H), 4.75-
		4.63 (m, 1H), 4.49-4.36 (m, 1H), 4.15 (s, 3H), 4.02 (s, 3H), 3.78-3.56
		(m, 3H), 3.55-3.42 (m, 1H), 1.92 (t, J = 12.3 Hz, 1H), 1.75-1.59 (m,
		2H), 1.53-1.27 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.21 (s, 3H), 1.17-
		1.00 (m, 2H), 0.95 (s, 3H).
201	612.7	1H NMR (400 MHz, DMSO-d6) δ 8.71 (d, J = 7.3 Hz, 1H), 8.58 (brs, 1H),
		8.34 (brs, 1H), 8.09-8.04 (m, 2H), 7.81 (d, J = 7.4 Hz, 1H), 7.38 (s, 1H),
		7.20 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 5.18-5.07 (m, 1H), 4.88-4.77 (m,
		1H), 4.50-4.38 (m, 2H), 4.15 (s, 3H), 4.03 (s, 3H), 3.65-3.51 (m, 1H),
		3.15-2.96 (m, 2H), 2.01-1.85 (m, 1H), 1.77-1.61 (m, 3H), 1.49-1.22
		(m, 5H), 1.45 (d, J = 7.1 Hz, 3H), 1.22 (s, 3H), 1.14-1.02 (m, 3H), 0.96
		(s, 3H), 0.96-0.85 (m, 1H), 0.66-0.59 (m, 1H).
202	612.7
203	612.6	1H NMR (400 MHz, DMSO-d6) δ 8.53 (brs, 2H), 8.42 (d, J = 7.9 Hz, 1H),
		8.05 (d, J = 8.1 Hz, 1H), 8.02 (s, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.37 (d,
		J = 1.3 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.18-5.07 (m, 1H),
		4.97-4.74 (m, 2H), 4.50-4.38 (m, 1H), 4.15 (s, 3H), 4.02 (s, 3H), 3.62-
		3.52 (m, 1H), 3.30-3.18 (m, 1H), 3.01-2.99 (m, 1H), 1.98-1.87 (m,
		1H), 1.75-1.61 (m, 3H), 1.53-1.27 (m, 5H), 1.45 (d, J = 7.1 Hz, 3H),
		1.22 (s, 3H), 1.16-1.01 (m, 2H), 0.95 (s, 3H), 0.88-0.76 (m, 2H).
204	636.5	1H NMR (400 MHz, DMSO-d6) δ 8.14 (brs, 3H), 8.05 (d, J = 8.1 Hz,
		1H), 7.84 (d, J = 7.5 Hz, 1H), 7.44 (dd, J = 2.4, 1.2 Hz, 1H), 7.19 (d, J =
		8.2 Hz, 1H), 7.04 (d, J = 1.5 Hz, 1H), 6.93 (s, 1H), 5.18-5.07 (m, 1H),
		4.89-4.75 (m, 1H), 4.36-4.35 (m, 2H), 4.13 (s, 3H), 4.00 (s, 3H), 3.58-
		3.41 (m, 1H), 3.40-3.29 (m, 1H), 2.63-2.50 (m, 1H), 2.31-2.11 (m,
		2H), 1.98-1.87 (m, 2H), 1.78-1.54 (m, 3H), 1.44-1.25 (m, 4H), 1.21
		(s, 3H), 1.17-1.02 (m, 3H), 0.95 (s, 3H).
205	626.5	Major conformer: 1H NMR (400 MHz, DMSO-d6) δ 8.63 (d, J = 12.5 Hz,
		1H), 8.56 (d, J = 4.0 Hz, 1H), 8.39-8.21 (m, 1H), 8.10 (d, J = 1.3 Hz,
		1H), 8.05 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.36 (d, J = 1.3 Hz,
		1H), 7.20 (d, J = 8.2 Hz, 1H), 7.07 (s, 1H), 5.18-5.07 (m, 1H), 4.89-
		4.76 (m, 1H), 4.50-4.39 (m, 1H), 4.15 (s, 3H), 4.02 (s, 3H), 3.83-3.76
		(m, 1H), 3.48-3.34 (m, 2H), 3.03-2.90 (m, 2H), 2.62-2.52 (m, 2H),
		1.97-1.85 (m, 3H), 1.85-1.58 (m, 4H), 1.45 (d, J = 7.1 Hz, 3H), 1.42-
		1.25 (m, 3H), 1.21 (s, 3H), 1.17-1.02 (m, 2H), 0.95 (s, 3H).
206	612.8	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.94 (brs, 3H),
		7.83 (d, J = 7.4 Hz, 1H), 7.39 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.04 (d,
		J = 2.4 Hz, 1H), 6.91 (s, 1H), 5.19-5.07 (m, 1H), 4.87-4.77 (m, 1H), 4.48-
		4.33 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.58-3.45 (m, 2H), 1.98-1.87
		(m, 1H), 1.77-1.50 (m, 1H), 1.45 (d, J = 7.1 Hz, 3H), 1.50-1.26 (m,
		5H), 1.21 (s, 3H), 1.17-0.99 (m, 1H), 0.95 (s, 3H), 0.90-0.79 (m, 1H),
		0.77-0.67 (m, 1H).
207	640.5	1H NMR (400 MHz, DMSO-d6) δ 8.12 (d, J = 8.1 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.90 (brs, 2H), 7.47 (s, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.06 (s,
		1H), 6.97 (d, J = 1.1 Hz, 1H), 5.70 (s, 1H), 5.32-5.21 (m, 1H), 4.89-
		4.77 (m, 1H), 4.76-4.57 (m, 1H), 4.49-4.35 (m, 1H), 4.14 (s, 3H), 4.07
		(s, 1H), 4.01 (s, 3H), 3.56-3.40 (m, 2H), 2.45-2.20 (m, 2H), 2.18-1.91
		(m, 4H), 1.93-1.69 (m, 3H), 1.69-1.53 (m, 1H), 1.46 (d, J = 6.9 Hz,
		3H), 1.46-1.31 (m, 2H), 1.30-1.00 (m, 4H), 0.99-0.89 (m, 1H), 0.65-
		0.55 (m, 1H), 0.53-0.43 (m, 1H).
208	639.5	1H NMR (400 MHz, DMSO-d6) δ 9.37 (brs, 1H), 8.89 (brs, 1H), 8.24 (d,
		J = 8.6 Hz, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.55 (s, 1H), 7.42 (d, J = 1.2 Hz,
		1H), 7.08 (dd, J = 8.2, 1.2 Hz, 1H), 7.00 (s, 1H), 6.91 (d, J = 1.2 Hz, 1H),
		5.25-5.14 (m, 1H), 4.70-4.58 (m, 1H), 4.31-4.19 (m, 1H), 4.12 (s,
		3H), 4.06-3.98 (m, 2H), 4.00 (s, 3H), 3.90-3.47 (m, 6H), 3.36-2.93
		(m, 2H), 2.38-2.28 (m, 1H), 1.94-1.66 (m, 4H), 1.52-1.33 (m, 2H),
		1.46 (d, J = 7.1 Hz, 3H), 1.27-1.07 (m, 3H), 1.07-0.97 (m, 1H), 0.85-
		0.73 (m, 1H), 0.69-0.56 (m, 1H), 0.38-0.30 (m, 1H).
209	571.4	1H NMR (400 MHz, DMSO-d6) δ 8.11 (brs, 3H), 7.91 (d, J = 8.0 Hz,
		1H), 7.44 (s, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.59 (s, 1H), 6.55 (brs, 1H),
		6.38 (s, 1H), 4.98-4.88 (m, 1H), 4.73-4.55 (m, 2H), 4.54-4.40 (m,
		2H), 4.10 (s, 3H), 3.18-3.00 (m, 1H), 2.83 (s, 3H), 2.61 (s, 3H), 1.96-
		1.74 (m, 4H), 1.71-1.53 (m, 2H), 1.48 (d, J = 7.1 Hz, 3H), 1.36 (dd, J =
		12.9, 4.4 Hz, 1H), 1.07-1.87 (m, 1H).
210	585.3	1H NMR (400 MHz, DMSO-d6) δ 8.11 (brs, 3H), 7.90 (d, J = 8.0 Hz,
		1H), 7.45 (s, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.59 (s, 1H), 6.39 (s, 1H), 6.10
		(d, J = 8.4 Hz, 1H), 4.90-4.81 (m, 1H), 4.55-4.35 (m, 4H), 4.10 (s,
		3H), 3.23-3.13 (m, 1H), 2.81 (s, 3H), 2.75 (s, 3H), 1.95-1.78 (m, 4H),
		1.70-1.59 (m, 2H), 1.50 (d, J = 7.1 Hz, 3H), 1.36 (dd, J = 12.8, 4.3 Hz,
		1H), 1.26-1.18 (m, 3H).
211	613.4	1H NMR (400 MHz, DMSO-d6) δ 8.11 (brs, 3H), 7.95 (d, J = 8.0 Hz,
		1H), 7.46 (s, 1H), 7.11 (d, J = 8.0 Hz, 1H), 6.62 (s, 1H), 6.39 (s, 1H), 6.33
		(d, J = 7.4 Hz, 1H), 5.09-4.98 (m, 1H), 4.75-4.65 (m, 1H), 4.52-4.43
		(m, 1H), 4.10 (s, 3H), 3.54-3.44 (m, 1H), 3.14-3.05 (m, 1H), 2.81 (s,
		3H), 2.78 (s, 3H), 1.91-1.76 (m, 5H), 1.70-1.52 (m, 4H), 1.48-1.42
		(m, 1H), 1.42 (d, J = 6.8 Hz, 3H), 1.35 (dd, J = 12.9, 4.3 Hz, 1H)1.30-
		1.08 (m, 5H), 1.01-0.90 (m, 1H).
212	599.3	1H NMR (400 MHz, DMSO-d6) δ 8.13 (brs, 3H), 7.99 (d, J = 8.1 Hz,
		1H), 7.47 (s, 1H), 7.16 (d, J = 8.1 Hz, 1H), 6.71 (d, J = 7.3 Hz, 1H), 6.63
		(s, 1H), 6.40 (s, 1H), 5.09-5.01 (m, 1H), 4.74-4.64 (m, 1H), 4.42-4.31
		(m, 1H), 4.11 (s, 3H), 3.76 (brs, 1H), 3.46-3.35 (m, 1H), 3.22-3.10 (m,
		1H), 2.88 (s, 3H), 2.81 (s, 3H), 1.91-1.74 (m, 4H), 1.71-1.48 (m, 5H),
		1.45 (d, J = 6.9 Hz, 3H), 1.44-1.33 (m, 2H), 1.36 (dd, J = 12.7, 4.3 Hz,
		1H), 1.29-1.16 (m, 2H).
213	662.5	1H NMR (400 MHz, DMSO-d6) δ 8.61 (d, J = 7.3 Hz, 1H), 8.11 (brs,
		3H), 8.07 (dd, J = 7.9, 1.9 Hz, 1H), 8.02 (d, J = 7.9 Hz, 1H), 7.55-7.48
		(m, 1H), 7.47 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H),
		7.09 (dd, J = 7.9, 7.9 Hz, 1H), 6.69 (s, 1H), 6.37 (s, 1H), 5.45-5.35 (m,
		1H), 4.95-4.81 (m, 1H), 4.69-4.40 (m, 3H), 4.21-4.14 (m, 1H), 4.11
		(s, 3H), 4.06-3.98 (m, 1H), 2.85 (s, 3H), 1.91-1.94 (m, 5H), 1.73-
		1.61 (m, 2H), 1.53 (d, J = 6.5 Hz, 3H), 1.49-1.39 (m, 2H), 1.35 (dd, J =
		12.7, 4.4 Hz, 1H), 1.19-1.10 (m, 1H), 0.70-0.55 (m, 2H).
214	624.4	1H NMR (400 MHz, Acetonitrile-d3) δ 8.79 (dd, J = 4.5, 1.4 Hz, 0.5H, 1st
		isomer), 8.50 (dd, J = 8.4, 1.4 Hz, 0.5H 2nd isomer), 8.35 (d, J = 6.8 Hz,
		1H), 8.26 (d, J = 7.1 Hz, 1H), 8.04 (d, J = 6.8 Hz, 1H), 8.02 (d, J = 6.8 Hz,
		1H), 7.85 (s, 1.5H, 1st isomer), 7.79 (s, 1.5H, 2nd isomer), 7.55 (dd, J =
		8.4, 4.4 Hz, 0.5H 1st isomer), 7.21 (s, 0.5H 1st isomer), 7.19 (s, 0.5H, 2nd
		isomer), 6.77 (s, 0.5H, 1st isomer), 6.75 (s, 0.5H, 2nd isomer), 6.74 (s,
		0.5H, 1st isomer), 6.70 (s, 0.5H, 2nd isomer), 5.20-5.09 (m, 1H), 4.91-
		4.50 (m, 2H), 4.80 (dd, J = 14.3, 4.5 Hz, 1H), 4.38-4.06 (m, 2H), 4.23 (s,
		1.5H, 1st isomer), 4.22 (s, 1.5H, 2nd isomer), 4.00-3.50 (m, 4H), 2.87-
		2.50 (m, 2H), 2.50-2.38 (m, 2H), 2.33-2.21 (m, 1H), 1.83-1.71 (m,
		1H), 1.60-1.48 (m, 1H), 1.54 (d, J = 6.6 Hz, 1.5H, 1st isomer), 1.52 (d,
		J = 6.6 Hz, 1.5H, 2nd isomer), 1.01-0.85 (m, 2H), 0.60-0.41 (m, 2H),
		0.40-0.26 (m, 1H), 0.21-0.12 (m, 1H).
215	583.5	1H NMR (400 MHz, DMSO-d6) δ 8.40 (d, J = 8.3 Hz, 1H), 8.09 (brs,
		3H), 7.61 (d, J = 8.2 Hz, 1H), 7.58 (s, 1H), 7.48 (s, 1H), 7.09 (d, J = 8.2
		Hz, 1H), 7.03 (s, 1H), 7.01 (s, 1H), 5.15-5.05 (m, 1H), 4.73-4.62 (m,
		1H), 4.59-4.34 (m, 2H), 4.27-4.16 (m, 1H), 4.11 (s, 3H), 4.01 (s, 3H),
		2.37-2.27 (m, 1H) 2.15-2.06 (m, 1H), 1.91-1.51 (m, 7H), 1.44 (d, J =
		7.0 Hz, 3H), 1.41-1.29 (m, 1H), 1.34 (dd, J = 12.9, 4.3 Hz, 1H), 1.29-
		0.95 (m, 6H).
216	611.6	1H NMR (400 MHz, DMSO-d6) δ 8.08 (brs, 3H), 8.06 (d, J = 8.1 Hz,
		1H), 7.61 (d, J = 8.2 Hz, 1H), 7.57 (s, 1H), 7.34 (s, 1H), 7.09 (dd, J = 8.3,
		1.2 Hz, 1H), 7.02 (d, J = 1.2 Hz, 1H), 7.00 (s, 1H), 5.11-5.00 (m, 1H),
		4.69-4.57 (m, 1H), 4.54-4.36 (m, 2H), 4.23-4.15 (m, 1H), 4.10 (s,
		3H), 4.00 (s, 3H), 3.84-3.69 (m, 1H), 2.34-2.24 (m, 1H), 2.34-2.24
		(m, 1H), 2.13-2.01 (m, 1H), 1.91-1.57 (m, 5H), 1.51-1.37 (m, 1H),
		1.45 (d, J = 7.1 Hz, 3H), 1.34 (dd, J = 12.9, 4.4 Hz, 1H), 1.24 (s, 3H),
		1.17-1.01 (m, 3H), 0.94 (s, 3H).
217	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.49 (d, J = 7.3 Hz, 1H), 8.09 (brs,
		3H), 8.06 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.04
		(d, J = 1.2 Hz, 1H), 7.02 (s, 1H), 5.10-5.00 (m, 1H), 4.98 (dd, J = 14.2,
		4.1 Hz, 1H), 4.81 (dd, J = 14.2, 3.4 Hz, 1H), 4.64-4.34 (m, 2H), 4.12 (s,
		3H), 4.01 (s, 3H), 3.92-3.69 (m, 1H), 3.50-3.41 (m, 2H), 2.75 (t, J =
		9.8 Hz, 1H), 2.63-2.53 (m, 1H), 2.37-2.25 (m, 1H), 2.09 (ddd, J = 14.4,
		5.8, 2.5 Hz, 1H), 1.93-1.76 (m, 3H), 1.69-1.58 (m, 1H), 1.49-1.39 (m,
		1H), 1.46 (d, J = 6.8 Hz, 3H), 1.35 (dd, J = 12.9, 4.4 Hz, 1H), 0.35-0.11
		(m, 2H), 0.07-0.09 (m, 1H).
218	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.54 (d, J = 6.5 Hz, 1H), 8.08 (brs,
		3H), 8.04 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.04
		(d, J = 1.2 Hz, 1H), 7.03 (s, 1H), 5.02-4.94 (m, 1H), 4.69 (dd, J = 14.0,
		3.6 Hz, 1H), 4.47 (br, 1H), 4.14 (s, 3H), 4.05-3.96 (m, 1H), 4.01 (s, 3H),
		3.69-3.54 (m, 2H), 3.44-3.37 (m, 2H), 2.83 (dd, J = 11.1, 8.2 Hz, 1H),
		2.69-2.61 (m, 1H), 2.39-2.24 (m, 1H), 2.17-2.08 (m, 1H), 1.92-1.71
		(m, 4H), 1.68-1.57 (m, 1H), 1.44 (d, J = 6.9 Hz, 3H), 1.34 (dd, J = 12.8,
		4.4 Hz, 1H), 1.01-0.87 (m, 1H), 0.51-0.43 (m, 1H), 0.37-0.30 (m,
		1H).
219	642.5	1H NMR (400 MHz, DMSO-d6) δ 8.09 (brs, 3H), 8.06 (d, J = 8.1 Hz,
		1H), 7.72 (d, J = 8.5 Hz, 1H), 7.60 (s, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.04
		(s, 2H), 5.25-5.11 (m, 1H), 4.83-4.72 (m, 1H), 4.44-4.33 (m, 1H),
		4.11 (s, 3H), 4.01 (s, 3H), 3.84-3.69 (m, 2H), 3.53 (s, 3H), 3.10 (dd, J =
		9.8, 2.6 Hz, 1H), 2.38-2.27 (m, 1H), 1.96-1.72 (m, 4H), 1.69-1.55 (m,
		3H), 1.51-1.39 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.38-1.28 (m, 3H),
		1.26 (s, 3H), 1.23-1.10 (m, 1H), 1.00 (s, 3H).
220	642.4	1H NMR (400 MHz, DMSO-d6) δ 8.08 (brs, 3H), 8.03 (d, J = 8.0 Hz,
		1H), 7.96 (d, J = 6.2 Hz, 1H), 7.59 (s, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.04
		(s, 2H), 5.04-4.94 (m, 1H), 4.91-4.79 (m, 1H), 4.48-4.37 (m, 2H),
		4.11 (s, 3H), 4.01 (s, 3H), 3.73 (d, J = 8.9 Hz, 1H), 3.50 (s, 3H), 2.37-
		2.27 (m, 1H), 2.03-1.73 (m, 5H), 1.68-1.49 (m, 3H), 1.45 (d, J = 7.1
		Hz, 3H), 1.38-1.25 (m, 2H), 1.25 (s, 3H), 1.03-0.89 (m, 2H), 0.80 (s,
		3H), 0.82-0.69 (m, 1H).
221	609.5	1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 8.6 Hz, 1H), 8.10 (brs,
		3H), 7.61 (d, J = 8.2 Hz, 1H), 7.58 (s, 1H), 7.55 (s, 1H), 7.08 (dd, J = 8.3,
		1.2 Hz, 1H), 7.03 (d, J = 1.2 Hz, 1H), 7.01 (s, 1H), 5.25-5.13 (m, 1H),
		4.68-4.56 (m, 1H), 4.46 (brs, 2H), 4.29-4.18 (m, 1H), 4.12 (s, 3H),
		4.01 (s, 3H), 3.79 (brs, 1H), 2.41-2.22 (m, 2H), 1.93-1.54 (m, 6H),
		1.52-1.38 (m, 2H), 1.46 (d, J = 7.1 Hz, 3H), 1.34 (dd, J = 12.9, 4.4 Hz,
		1H), 1.26-1.06 (m, 3H), 1.06-0.99 (m, 1H), 0.84-0.76 (m, 1H), 0.67-
		0.59 (m, 1H), 0.37-0.29 (m, 1H).
222	613.5	1H NMR (400 MHz, DMSO-d6) δ 8.50 (d, J = 9.4 Hz, 1H), 8.09 (brs,
		3H), 7.70 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.57 (s, 1H), 7.07 (dd, J = 8.1,
		1.2 Hz, 1H), 7.02 (d, J = 1.2 Hz, 1H), 7.01 (s, 1H), 5.26-5.06 (m, 1H),
		4.80-4.65 (m, 1H), 4.45 (brs, 2H), 4.35-4.21 (m, 1H), 4.09 (s, 3H),
		4.00 (s, 3H), 3.33-3.21 (m, 1H), 2.38-2.20 (m, 2H), 1.91-1.73 (m,
		3H), 1.69-1.64 (m, 3H), 1.54-1.42 (m, 1H), 1.47 (d, J = 7.1 Hz, 3H),
		1.38 (s, 3H), 1.34 (dd, J = 13.0, 4.6 Hz, 1H), 1.30-1.21 (m, 1H), 1.18 (s,
		3H), 0.64-0.49 (m, 1H).
223	596.5	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.5 Hz, 1H), 8.10 (brs,
		3H), 8.00 (d, J = 8.0 Hz, 1H), 7.59 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.04
		(d, J = 1.3 Hz, 1H), 7.03 (s, 1H), 5.08-4.94 (m, 1H), 4.75-4.66 (m, 1H),
		4.64-4.56 (m, 1H), 4.43 (brs, 2H), 4.12 (s, 3H), 4.01 (s, 3H), 3.76 (brs,
		2H), 2.38-2.27 (m, 1H), 1.92-1.73 (m, 4H), 1.72-1.48 (m, 5H), 1.43
		(d, J = 7.1 Hz, 3H), 1.34 (dd, J = 12.8, 4.3 Hz, 1H), 1.29-1.16 (m, 1H),
		0.91-0.82 (m, 1H), 0.77-0.57 (m, 2H), 0.52-0.44 (m, 1H).
224	596.4	1H NMR (400 MHz, DMSO-d6) δ 8.40 (d, J = 7.1 Hz, 1H), 8.08 (brs,
		3H), 8.02 (d, J = 8.2 Hz, 1H), 7.59 (s, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.04
		(d, J = 1.2 Hz, 1H), 7.03 (s, 1H), 4.71-4.53 (m, 2H), 4.52-4.43 (m,
		1H), 4.30 (brs, 2H), 4.13 (s, 3H), 4.01 (s, 3H), 3.75 (brs, 1H), 2.38-2.26
		(m, 1H), 1.89-1.76 (m, 4H), 1.73 (d, J = 7.0 Hz, 3H), 1.68-1.39 (m,
		5H), 1.36-1.21 (m, 3H), 0.94-0.84 (m, 2H), 0.82-0.65 (m, 1H), 0.49
		(dd, J = 8.3, 3.0 Hz, 1H).
225	635.6	1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 8.6 Hz, 1H), 8.10 (brs,
		3H), 7.59 (d, J = 8.2 Hz, 1H), 7.55 (s, 1H), 7.54 (s, 1H), 7.13 (s, 1H), 7.06
		(dd, J = 8.2, 1.2 Hz, 1H), 7.04 (d, J = 1.2 Hz, 1H), 5.24-5.13 (m, 1H),
		4.88-4.75 (m, 1H), 4.43 (brs, 4H), 4.34-4.21 (m, 1H), 4.01 (s, 3H),
		3.93-3.84 (m, 1H), 3.75 (brs, 1H), 2.41-2.21 (m, 2H), 1.92-1.72 (m,
		3H), 1.70-1.56 (m, 2H), 1.46 (d, J = 7.0 Hz, 3H), 1.44-1.26 (m, 3H),
		1.23-0.94 (m, 5H), 0.88-0.72 (m, 2H), 0.70-0.58 (m, 1H), 0.54-0.43
		(m, 1H), 0.39-0.26 (m, 1H).
226	596.4	1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 8.4 Hz, 1H), 8.08 (brs,
		3H), 8.02 (d, J = 8.0 Hz, 1H), 7.58 (s, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.03
		(d, J = 1.2 Hz, 1H), 6.98 (s, 1H), 5.13-5.02 (m, 1H), 4.93 (dd, J = 14.1,
		4.5 Hz, 1H), 4.57 (dd, J = 14.1, 5.1 Hz, 1H), 4.52-4.39 (m, 2H), 4.10 (s,
		3H), 4.01 (s, 3H), 3.94-3.68 (m, 3H), 2.43-2.26 (m, 1H), 1.90-1.70
		(m, 4H), 1.69-1.56 (m, 1H), 1.58-1.39 (m, 2H), 1.46 (d, J = 7.0 Hz,
		3H), 1.34 (dd, J = 12.9, 4.3 Hz, 1H), 1.17-1.03 (m, 1H), 0.90-0.72 (m,
		1H), 0.65-0.52 (m, 1H), 0.11-0.02 (m, 1H), −0.01-−0.18 (m, 2H).
227	585.4	1H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 8.18 (brs, 3H), 8.02 (d,
		J = 8.1 Hz, 1H), 7.78-7.70 (m, 1H), 7.60 (d, J = 9.8 Hz, 1H), 7.17 (d, J =
		8.1 Hz, 1H), 7.05 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), 4.91-4.81 (m, 1H),
		4.68-4.60 (m, 1H), 4.58-4.34 (m, 1H), 4.12 (s, 3H), 4.07-4.01 (m,
		1H), 4.02 (s, 3H), 3.94-3.83 (m, 1H), 3.24-3.14 (m, 2H), 2.81-2.63
		(m, 1H), 2.49-2.38 (m, 1H), 1.92-1.60 (m, 4H), 1.45-1.22 (m, 3H),
		1.32 (d, J = 7.1 Hz, 3H), 1.21-0.99 (m, 3H), 0.90-0.75 (m, 2H).
228	568.4	1H NMR (400 MHz, DMSO-d6) δ 8.61 (d, J = 7.2 Hz, 1H), 8.27 (d, J =
		8.6 Hz, 1H), 7.95 (s, 3H), 7.93 (d, J = 8.0 Hz, 2H), 7.74 (s, 1H), 7.14-
		7.03 (m, 2H), 6.76 (s, 1H), 5.16 (p, J = 7.2 Hz, 1H), 5.03-4.87 (m, 1H),
		4.68-4.53 (m, 1H), 4.21-3.35 (m, 4H), 3.33-3.17 (m, 3H), 2.46-2.39
		(m, 0H), 2.21-2.09 (m, 1H), 2.09-1.85 (m, 3H), 1.84-1.69 (m, 1H),
		1.71-1.48 (m, 2H), 1.40 (d, J = 7.1 Hz, 3H), 1.35-1.19 (m, 1H), 1.20-
		1.01 (m, 2H), 1.03-0.88 (m, 2H), 0.70-0.49 (m, 1H), 0.49-0.35 (m,
		1H), 0.36-0.19 (m, 1H).
229	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.32 (d, J = 8.5 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.91 (s, 3H), 7.36 (s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.14 (s,
		1H), 6.90 (s, 1H), 5.17 (p, J = 7.2 Hz, 1H), 5.10-4.90 (m, 1H), 4.78-
		4.62 (m, 1H), 4.39 (d, J = 133.1 Hz, 4H), 3.97 (s, 3H), 3.93-3.80 (m,
		1H), 3.30-3.00 (m, 3H), 2.12-1.90 (m, 4H), 1.79-1.60 (m, 1H), 1.62-
		1.52 (m, 1H), 1.51-1.43 (m, 1H), 1.41 (d, J = 7.1 Hz, 3H), 1.34-1.23
		(m, 1H), 1.23-1.06 (m, 2H), 1.03-0.92 (m, 3H), 0.88-0.76 (m, 1H),
		0.72-0.55 (m, 1H), 0.47-0.31 (m, 1H).
230	626.5	1H NMR (400 MHz, DMSO-d6) δ 8.00 (d, J = 8.1 Hz, 1H), 7.91 (s, 3H),
		7.81 (d, J = 7.4 Hz, 1H), 7.36 (s, 1H), 7.15 (d, J = 8.2 Hz, 1H), 7.13 (s,
		1H), 6.90 (s, 1H), 5.09 (p, J = 7.1 Hz, 1H), 4.92-4.77 (m, 1H), 4.67
		4.48 (m, 1H), 3.97 (s, 3H), 3.93-3.83 (m, 1H), 3.76-3.40 (m, 6H), 3.30-
		3.20 (m, 1H), 3.19-2.98 (m, 1H), 2.07-1.95 (m, 1H), 1.90 (t, J = 11.6
		Hz, 1H), 1.82-1.59 (m, 1H), 1.61-1.48 (m, 2H), 1.43 (d, J = 7.1 Hz,
		3H), 1.41-1.24 (m, 3H), 1.19 (s, 3H), 1.14-0.94 (m, 2H), 0.93 (s, 3H),
		0.86-0.73 (m, 1H), 0.51-0.37 (m, 1H).
231	584.3	1H NMR (400 MHz, DMSO-d6) δ 8.30 (d, J = 7.3 Hz, 1H), 8.05 (s, 3H),
		7.97 (d, J = 8.0 Hz, 1H), 7.35 (s, 1H), 6.90 (s, 1H), 5.03-4.89 (m, 1H),
		4.86-4.66 (m, 2H), 3.97 (s, 3H), 3.92-3.80 (m, 1H), 3.11-2.92 (m,
		6H), 2.28-2.10 (m, 2H), 2.06-1.92 (m, 1H), 1.92-1.83 (m, 1H), 1.78-
		1.68 (m, 1H), 1.63-1.47 (m, 3H), 1.46 (d, J = 7.1 Hz, 3H), 1.30-0.93
		(m, 7H), 0.85-0.64 (m, 2H), 0.53-0.35 (m, 1H).
232	558.3	1H NMR (400 MHz, DMSO-d6) δ 8.39 (t, J = 6.2 Hz, 1H), 8.02 (d, J =
		8.1 Hz, 1H), 7.90 (s, 3H), 7.39 (s, 1H), 7.12 (d, J = 8.1 Hz, 1H), 7.01 (s,
		1H), 6.89 (s, 1H), 4.61 (t, J = 7.5 Hz, 2H), 4.55 (d, J = 6.1 Hz, 2H), 4.10
		(s, 3H), 3.97 (s, 3H), 3.31-2.93 (m, 2H), 2.29-2.20 (m, 2H), 2.06-1.94
		(m, 1H), 1.79-1.69 (m, 1H), 1.64-1.42 (m, 8H), 1.42-1.29 (m, 2H),
		1.15-1.03 (m, 3H).
233	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 8.1 Hz, 1H), 8.06 (d, J =
		7.9 Hz, 1H), 7.96 (s, 3H), 7.44-7.36 (m, 2H), 7.30-7.19 (m, 2H), 7.04
		(s, 1H), 6.90 (s, 1H), 5.25 (p, J = 7.0 Hz, 1H), 4.90-4.69 (m, 1H), 4.49-
		4.30 (m, 1H), 4.11 (s, 3H), 3.97 (s, 3H), 3.38-2.98 (m, 3H), 2.34-2.15
		(m, 1H), 2.11-1.91 (m, 2H), 1.83-1.68 (m, 4H), 1.68-1.49 (m, 2H),
		1.43 (d, J = 6.9 Hz, 3H), 1.42-1.30 (m, 1H), 1.28-1.15 (m, 1H), 1.15-
		0.97 (m, 2H), 0.92 (ddd, J = 9.6, 6.4, 3.3 Hz, 1H), 0.58 (ddd, J = 9.3, 6.2,
		3.2 Hz, 1H), 0.45 (ddd, J = 9.2, 6.1, 3.1 Hz, 1H).
234	572.4	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 8.0 Hz, 0.4H, rotamer),
		8.04 (d, J = 8.1 Hz, 0.69H, rotamer), 7.89 (s, 3H), 7.40 (s, 1H), 7.22 (d,
		J = 8.1 Hz, 0.42H, rotamer), 7.11 (d, J = 8.1 Hz, 0.72H, rotamer), 7.06 (s,
		0.36H, rotamer), 7.00 (s, 0.61H, rotamer), 6.94-6.85 (m, 1H), 6.59-
		6.33 (m, 1H), 5.61 (d, J = 16.6 Hz, 1H), 4.78 (s, 1H), 4.69-4.61 (m, 1H),
		4.61-4.51 (m, 1H), 4.48-4.31 (m, 1H), 4.09 (d, J = 1.4 Hz, 3H), 3.97 (s,
		3H), 3.16 (s, 2H, rotamer), 2.97 (s, 1H, rotamer), 2.91-2.81 (m, 1H),
		2.18-2.07 (m, 1H), 2.06-1.94 (m, 1H), 1.82-1.66 (m, 1H), 1.66-1.38
		(m, 7H), 1.32 (s, 2H), 1.30-1.18 (m, 1H), 1.19-1.12 (m, 1H), 1.10-
		0.96 (m, 1H), 0.89-0.68 (m, 1H).
235	626.3	1H NMR (400 MHz, DMSO-d6) δ 9.05 (d, J = 9.8 Hz, 1H), 8.19 (d, J =
		8.1 Hz, 1H), 7.96 (s, 3H), 7.45 (d, J = 8.6 Hz, 2H), 7.16 (s, 1H), 6.93 (d,
		J = 1.2 Hz, 1H), 6.19-6.05 (m, 1H), 5.26-5.09 (m, 1H), 4.70-4.51 (m,
		1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.37-3.03 (m, 3H), 2.87-2.72 (m, 1H),
		2.31-2.10 (m, 2H), 2.10-1.94 (m, 1H), 1.83-1.68 (m, 2H), 1.66-1.52
		(m, 2H), 1.51-1.31 (m, 3H), 1.24 (d, J = 2.6 Hz, 1H), 1.16-0.99 (m,
		2H), 0.95-0.77 (m, 2H), 0.72-0.52 (m, 1H), 0.34-−0.03 (m, 1H).
236	626.3	1H NMR (400 MHz, DMSO-d6) δ 9.05 (d, J = 9.8 Hz, 1H), 8.19 (d, J =
		8.1 Hz, 1H), 7.95 (s, 3H), 7.45 (d, J = 8.6 Hz, 2H), 7.16 (s, 1H), 6.93 (s,
		1H), 6.12 (p, J = 8.9 Hz, 1H), 5.28-5.08 (m, 1H), 4.69-4.58 (m, 1H),
		4.12 (s, 3H), 4.00 (s, 3H), 3.36-3.00 (m, 3H), 2.87-2.72 (m, 1H), 2.32-
		2.11 (m, 2H), 2.12-1.89 (m, 1H), 1.86-1.68 (m, 2H), 1.68-1.50 (m,
		2H), 1.51-1.31 (m, 3H), 1.24 (d, 1H), 1.16-0.98 (m, 2H), 0.98-0.77
		(m, 2H), 0.75-0.46 (m, 1H), 0.31-0.08 (m, 1H).
237	584.3	1H NMR (400 MHz, DMSO-d6) δ 8.85 (d, J = 1.5 Hz, 1H), 7.95 (d, J =
		8.0 Hz, 1H), 7.89 (s, 3H), 7.82 (d, J = 9.2 Hz, 1H), 7.76 (d, J = 7.5 Hz,
		1H), 7.25 (dd, J = 9.2, 1.4 Hz, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.74 (s, 1H),
		5.09 (q, J = 7.2 Hz, 1H), 4.86-4.71 (m, 1H), 4.44-4.22 (m, 1H), 4.16-
		3.86 (m, 1H), 3.41-3.16 (m, 3H), 3.15-3.03 (m, 1H), 2.98-2.71 (m,
		2H), 2.05-1.95 (m, 1H), 1.94-1.79 (m, 1H), 1.82-1.67 (m, 1H), 1.70-
		1.50 (m, 3H), 1.42 (d, J = 7.1 Hz, 3H), 1.39-1.25 (m, 4H), 1.18 (s, 3H),
		1.17-1.11 (m, 4H), 1.11-0.97 (m, 2H), 0.93 (s, 3H).
238	608.3	1H NMR (400 MHz, DMSO-d6) δ 8.69 (d, J = 9.4 Hz, 1H), 8.12 (d, J =
		8.1 Hz, 1H), 7.90 (s, 3H), 7.40 (s, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.09 (s,
		1H), 6.90 (s, 1H), 6.54-6.18 (m, 1H), 5.81-5.52 (m, 1H), 5.17-4.97
		(m, 1H), 4.66-4.38 (m, 1H), 4.20-4.11 (m, 2H), 4.09 (s, 3H), 3.97 (s,
		3H), 3.67-2.95 (m, 6H), 2.23-2.08 (m, 2H), 2.07-1.94 (m, 1H), 1.81-
		1.65 (m, 2H), 1.65-1.48 (m, 2H), 1.51-1.29 (m, 1H), 1.16-0.98 (m,
		1H), 1.01-0.61 (m, 3H), 0.57-0.21 (m, 1H).
239	648.5	1H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J = 8.2 Hz, 1H), 7.93 (s, 3H),
		7.36 (s, 1H), 7.29-7.21 (m, 2H), 7.22-7.13 (m, 1H), 7.08 (t, J = 7.4 Hz,
		1H), 6.96 (t, J = 7.6 Hz, 1H), 6.90 (s, 1H), 6.54-6.26 (m, 1H), 6.26-
		5.52 (m, 3H), 5.04-4.90 (m, 1H), 4.29 (s, 3H), 3.98 (s, 3H), 3.86-3.63
		(m, 4H), 3.54-3.38 (m, 9H), 3.19-2.95 (m, 1H), 2.78-2.62 (m, 1H),
		2.01-1.84 (m, 1H), 1.82-1.64 (m, 1H), 1.44 (d, J = 7.0 Hz, 3H).
240	652.4	1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 7.0 Hz, 1H), 8.61 (d, J =
		2.6 Hz, 1H), 8.50 (d, J = 2.6 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.99 (s,
		3H), 7.44 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.94 (s, 1H), 5.25
		(p, J = 7.0 Hz, 1H), 4.96-4.73 (m, 1H), 4.58 (dt, J = 13.6, 4.6 Hz, 1H),
		4.13 (s, 3H), 4.00 (s, 3H), 3.83 (s, 5H), 3.71 (dt, J = 6.0, 2.7 Hz, 3H), 3.37
		(s, 3H), 2.75-2.63 (m, 1H), 2.47-2.28 (m, 1H), 2.03-1.88 (m, 1H),
		1.84-1.69 (m, 1H), 1.64-1.28 (m, 2H), 1.52 (d, J = 7.1 Hz, 3H), 1.31-
		1.09 (m, 1H), 0.72-0.51 (m, 1H).
241	460.5	1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 7.0 Hz, 1H), 8.78 (s, 3H),
		8.70 (d, J = 7.9 Hz, 1H), 8.61 (d, J = 2.6 Hz, 1H), 8.50 (d, J = 2.6 Hz, 1H),
		8.11 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 1.3 Hz, 1H), 7.36 (d, J = 1.3 Hz, 1H),
		7.28 (d, J = 8.1 Hz, 1H), 7.14 (s, 1H), 5.26 (p, J = 7.1 Hz, 1H), 5.04-4.70
		(m, 2H), 4.67-4.56 (m, 1H), 4.53-4.37 (m, 1H), 4.16 (s, 3H), 4.03 (s,
		3H), 3.53-3.32 (m, 3H), 3.18-2.88 (m, 3H), 2.78-2.64 (m, 1H), 2.48-
		2.29 (m, 2H), 2.03-1.84 (m, 1H), 1.52 (d, J = 7.1 Hz, 3H), 1.70-1.31
		(m, 1H), 1.29-1.06 (m, 1H), 0.85-0.39 (m, 1H).
242	590.4	1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2H), 8.65 (d, J = 8.0 Hz, 1H),
		8.44 (d, J = 8.5 Hz, 1H), 8.01 (dd, J = 8.4, 7.2 Hz, 2H), 7.76 (d, J = 10.8
		Hz, 1H), 7.15 (d, J = 8.2 Hz, 1H), 7.13 (s, 1H), 5.02 (p, J = 7.2 Hz, 1H),
		4.94-4.74 (m, 1H), 4.74-4.67 (m, 2H), 4.40 (dt, J = 13.8, 9.1 Hz, 1H),
		3.98 (s, 3H), 3.53-3.44 (m, 1H), 3.44-3.28 (m, 1H), 3.19-2.89 (m,
		2H), 2.43-2.26 (m, 1H), 2.02-1.82 (m, 1H), 1.71-1.61 (m, 3H), 1.56
		(dt, J = 8.2, 4.7 Hz, 1H), 1.43 (d, J = 7.1 Hz, 3H), 1.36-1.09 (m, 2H),
		0.91-0.83 (m, 1H), 0.79-0.58 (m, 2H), 0.53-0.36 (m, 1H).
243	654.5	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 6.9 Hz, 1H), 8.74 (s, 2H),
		8.66-8.61 (m, 1H), 8.60 (d, J = 2.6 Hz, 1H), 8.50 (d, J = 2.6 Hz, 1H),
		8.10 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H), 7.64 (d, J = 10.6 Hz,
		1H), 7.37 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 5.23 (p, J = 7.1 Hz, 1H), 5.00-
		4.71 (m, 3H), 4.52-4.35 (m, 2H), 4.37-3.90 (m, 1H), 3.85 (tt, J = 7.2,
		3.9 Hz, 1H), 3.55-3.32 (m, 2H), 3.14-2.91 (m, 2H), 2.71-2.62 (m,
		1H), 2.46-2.26 (m, 2H), 1.92 (t, J = 12.0 Hz, 1H), 1.52 (d, J = 7.0 Hz,
		3H), 1.50-1.35 (m, 4H), 1.34-1.07 (m, 2H), 1.01-0.87 (m, 1H), 0.68-
		0.52 (m, 1H), 0.53-0.36 (m, 1H).
244	616.6	1H NMR (400 MHz, DMSO-d6) δ 8.64 (s, 2H), 8.38 (d, J = 7.7 Hz, 1H),
		8.15-7.97 (m, 2H), 7.81 (d, J = 7.4 Hz, 1H), 7.35 (s, 1H), 7.19 (d, J = 8.1
		Hz, 1H), 7.07 (s, 1H), 5.13 (p, J = 7.0 Hz, 1H), 4.91-4.75 (m, 1H), 4.51-
		4.35 (m, 1H), 4.15 (s, 3H), 4.12-4.04 (m, 1H), 4.02 (s, 3H), 3.83-3.71
		(m, 1H), 3.43-3.22 (m, 2H), 3.05-2.92 (m, 1H), 2.93-2.78 (m, 1H),
		2.16-2.03 (m, 1H), 1.98-1.85 (m, 1H), 1.75-1.60 (m, 5H), 1.45 (d, J =
		7.1 Hz, 3H), 1.43-1.27 (m, 2H), 1.22 (s, 3H), 1.17-1.03 (m, 3H), 0.96
		(s, 3H).
245	628.4	1H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 8.91 (s, 1H), 8.38 (d, J =
		7.4 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.45 (d, J = 1.2 Hz, 1H), 7.25-7.16
		(m, 1H), 7.08 (d, J = 2.3 Hz, 1H), 6.93 (s, 1H), 5.07 (p, J = 7.0 Hz, 1H),
		5.02-4.82 (m, 1H), 4.76-4.62 (m, 1H), 4.16 (s, 3H), 4.07-4.01 (m,
		2H), 4.00 (s, 3H), 3.89 (t, J = 9.8 Hz, 1H), 3.83-3.66 (m, 3H), 3.66-
		3.47 (m, 3H), 3.38-3.00 (m, 2H), 2.72-2.56 (m, 1H), 2.32-2.13 (m,
		1H), 1.96-1.70 (m, 2H), 1.49 (d, J = 7.1 Hz, 3H), 1.32-1.18 (m, 2H),
		0.98-0.73 (m, 3H), 0.29-0.09 (m, 2H).
246	628.4	NA
247	586.4	1H NMR (400 MHz, DMSO-d6) δ 8.42 (d, J = 8.3 Hz, 1H), 8.04 (s, 3H),
		7.99 (d, J = 7.9 Hz, 1H), 7.43 (s, 1H), 7.17 (d, J = 7.9 Hz, 1H), 6.87 (s,
		1H), 6.60 (s, 1H), 6.34 (s, 1H), 5.27-5.13 (m, 1H), 4.57-4.48 (m, 2H),
		4.15 (d, J = 15.7 Hz, 1H), 4.08 (s, 3H), 3.65 (d, J = 15.7 Hz, 1H), 3.45 (t,
		J = 7.4 Hz, 2H), 2.80 (s, 3H), 2.05 (s, 2H), 1.94-1.73 (m, 4H), 1.75-1.52
		(m, 1H), 1.45 (d, J = 6.7 Hz, 3H), 1.32 (s, 6H), 1.27-1.17 (m, 2H).
248	600.5	1H NMR (400 MHz, DMSO-d6) δ 8.42 (d, J = 7.1 Hz, 1H), 8.07 (s, 3H),
		8.00 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.18 (d, J = 8.0 Hz, 1H), 6.64 (s,
		1H), 6.36 (s, 1H), 5.09 (p, J = 6.5 Hz, 1H), 4.74-4.59 (m, 1H), 4.58-4.40
		(m, 1H), 4.40-4.11 (m, 6H), 4.08 (s, 3H), 4.05 (d, J = 15.2 Hz, 1H), 3.78
		(d, J = 15.2 Hz, 1H), 3.63-3.50 (m, 1H), 3.51-3.40 (m, 1H), 2.80 (s,
		3H), 1.94-1.71 (m, 4H), 1.71-1.57 (m, 1H), 1.59-1.46 (m, 1H), 1.43 (d,
		J = 6.6 Hz, 3H), 1.33 (dd, J = 12.9, 4.3 Hz, 1H), 1.29-1.15 (m, 2H).
249	580.4	1H NMR (400 MHz, DMSO-d6) δ 8.61-8.56 (m, 1H), 8.27 (d, J = 8.5
		Hz, 1H), 8.09 (s, 3H), 7.93 (d, J = 8.0 Hz, 1H), 7.87 (s, 1H), 7.20 (dd, J =
		7.0, 1.6 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.77 (s, 1H), 5.24-5.08 (m,
		1H), 5.03-4.86 (m, 1H), 4.71-4.58 (m, 1H), 4.10-3.72 (m, 2H), 2.46-
		2.40 (m, 1H), 2.37-2.25 (m, 1H), 2.22-2.11 (m, 1H), 2.11-2.00 (m,
		1H), 2.01-1.87 (m, 1H), 1.92-1.71 (m, 4H), 1.71-1.55 (m, 3H), 1.40
		(d, J = 7.1 Hz, 3H), 1.37-1.27 (m, 2H), 1.29-1.20 (m, 1H), 1.20-1.10
		(m, 1H), 1.11-1.00 (m, 1H), 1.02-0.87 (m, 2H), 0.69-0.46 (m, 1H),
		0.49-0.36 (m, 1H), 0.36-0.22 (m, 1H).
250	610.5	1H NMR (400 MHz, DMSO-d6) δ 8.31 (d, J = 8.5 Hz, 1H), 8.05 (s, 3H),
		8.01 (d, J = 8.1 Hz, 1H), 7.53 (s, 1H), 7.17 (d, J = 8.5 Hz, 1H), 7.15 (s,
		1H), 7.03 (s, 1H), 5.17 (p, J = 7.2 Hz, 1H), 5.07-4.94 (m, 1H), 4.78-
		4.65 (m, 1H), 4.61-4.26 (m, 1H), 3.99 (s, 3H), 3.93-3.84 (m, 1H), 3.81-
		3.65 (m, 2H), 3.61-3.17 (m, 2H), 2.37-2.22 (m, 1H), 2.13-2.02 (m,
		1H), 2.03-1.91 (m, 1H), 1.88-1.73 (m, 3H), 1.72-1.54 (m, 2H), 1.51-
		1.44 (m, 1H), 1.41 (d, J = 7.1 Hz, 3H), 1.32 (dd, J = 12.9, 4.5 Hz, 1H),
		1.24-1.06 (m, 2H), 1.06-0.90 (m, 3H), 0.91-0.80 (m, 1H), 0.73-0.54
		(m, 1H), 0.46-0.31 (m, 1H).
251	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 8.04 (d, J = 8.3 Hz, 2H),
		8.02 (s, 3H), 7.57 (s, 1H), 7.27 (d, J = 8.3 Hz, 1H), 7.01 (s, 2H), 4.69-
		4.54 (m, 2H), 4.10 (s, 3H), 3.99 (s, 3H), 2.25-2.17 (m, 2H), 1.88-1.78
		(m, 3H), 1.65 (s, 6H), 1.63-1.56 (m, 2H), 1.54-1.37 (m, 6H), 1.36-
		1.27 (m, 1H), 1.27-1.18 (m, 2H), 1.13-0.97 (m, 2H).
252	568.5	1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.27 (d, J = 8.5 Hz, 1H),
		8.05 (s, 3H), 7.95 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.36 (dd,
		J = 9.2, 1.5 Hz, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.77 (s, 1H), 5.18 (p, J = 7.5
		Hz, 1H), 5.02-4.78 (m, 1H), 4.58-4.35 (m, 3H), 3.78-3.67 (m, 3H),
		3.59-3.29 (m, 2H), 3.00-2.77 (m, 2H), 2.46-2.40 (m, 2H), 2.13-2.02
		(m, 1H), 2.01-1.90 (m, 1H), 1.83 (s, 3H), 1.73-1.56 (m, 2H), 1.40 (d, J =
		7.1 Hz, 3H), 1.33 (dd, J = 13.0, 4.2 Hz, 1H), 1.12 (t, J = 7.5 Hz, 3H),
		1.04-0.83 (m, 2H), 0.73-0.49 (m, 1H).
253	638.5	1H NMR (400 MHz, DMSO-d6) δ 8.06 (s, 3H), 8.01 (d, J = 8.1 Hz, 1H),
		7.81 (d, J = 7.4 Hz, 1H), 7.52 (s, 1H), 7.15 (d, J = 8.2 Hz, 1H), 7.13 (s,
		1H), 7.03 (s, 1H), 5.09 (p, J = 7.1 Hz, 1H), 4.93-4.79 (m, 1H), 4.67-
		4.54 (m, 1H), 4.54-4.30 (m, 2H), 3.99 (s, 3H), 3.93-3.83 (m, 1H), 3.78-
		3.64 (m, 1H), 3.59-3.33 (m, 2H), 2.37-2.23 (m, 1H), 1.96-1.74 (m,
		4H), 1.71-1.56 (m, 1H), 1.56-1.47 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H),
		1.40-1.23 (m, 4H), 1.19 (s, 3H), 1.16-0.95 (m, 4H), 0.93 (s, 3H), 0.87-
		0.75 (m, 1H), 0.51-0.35 (m, 1H).
254	596.6	1H NMR (400 MHz, DMSO-d6) δ 8.30 (d, J = 7.2 Hz, 1H), 8.18-8.00
		(m, 3H), 7.98 (d, J = 8.1 Hz, 1H), 7.52 (s, 1H), 7.15 (d, J = 7.2 Hz, 1H),
		7.13 (s, 2H), 7.03 (s, 1H), 4.95 (p, J = 7.1 Hz, 1H), 4.83-4.70 (m, 2H),
		4.59-4.27 (m, 1H), 3.99 (s, 3H), 3.96-3.83 (m, 1H), 2.37-2.21 (m,
		4H), 2.21-2.10 (m, 1H), 1.95-1.86 (m, 1H), 1.86-1.72 (m, 3H), 1.67-
		1.48 (m, 1H), 1.46 (d, J = 7.1 Hz, 3H), 1.43-1.34 (m, 1H), 1.32 (dd, J =
		12.9, 4.4 Hz, 1H), 1.19-0.94 (m, 5H), 0.83-0.65 (m, 3H), 0.51-0.37
		(m, 1H).
255	570.4	1H NMR (400 MHz, DMSO-d6) δ 8.39 (t, J = 6.2 Hz, 1H), 8.04 (s, 3H),
		8.02 (d, J = 8.0 Hz, 2H), 7.56 (s, 1H), 7.12 (d, J = 8.1 Hz, 1H), 7.01 (s,
		2H), 4.62 (t, J = 7.5 Hz, 2H), 4.55 (d, J = 6.1 Hz, 2H), 4.09 (s, 3H), 3.99
		(s, 3H), 2.27-2.20 (m, 2H), 1.88-1.68 (m, 4H), 1.67-1.41 (m, 8H),
		1.40-1.27 (m, 3H), 1.14-0.93 (m, 2H).
256	584.4	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 8.0 Hz, .33H, rotamer),
		8.04 (d, J = 8.1 Hz, 0.67H, rotamer), 8.02 (s, 3H), 7.57 (s, 1H), 7.23 (d,
		J = 8.1 Hz, 0.42H, rotamer), 7.11 (d, J = 8.0 Hz, 0.60H, rotamer), 7.07 (s,
		.0.32H, rotamer), 7.01 (d, J = 8.1 Hz, 1H), 7.00 (s, 0.70H, rotamer), 5.61
		(d, J = 16.6 Hz, 1H), 4.79 (s, 1H), 4.71-4.33 (m, 2H), 4.09 (s, 3H), 3.99
		(s, 3H), 3.81-3.65 (m, 1H), 3.17 (s, 2H, rotamer), 2.98 (s, 1H, rotamer),
		2.92-2.78 (m, 1H), 2.20-2.06 (m, 1H), 1.85 (s, 3H), 1.72-1.36 (m,
		7H), 1.37-1.18 (m, 2H), 1.19-1.11 (m, 1H), 1.08-0.93 (m, 1H), 0.94-
		0.59 (m, 1H).
257	638.4	1H NMR (400 MHz, DMSO-d6) δ 9.05 (d, J = 9.8 Hz, 1H), 8.19 (d, J =
		8.1 Hz, 1H), 8.13 (s, 3H), 7.61 (s, 1H), 7.45 (d, J = 8.1 Hz, 1H), 7.27-
		6.96 (m, 1H), 7.16 (s, 1H), 7.05 (d, J = 1.2 Hz, 1H), 6.20-6.00 (m, 1H),
		5.26-5.11 (m, 1H), 4.72-4.60 (m, 1H), 4.58-4.27 (m, 5H), 4.12 (s,
		3H), 4.02 (s, 3H), 3.88-3.50 (m, 1H), 2.88-2.73 (m, 1H), 2.40-2.12
		(m, 1H), 1.95-1.69 (m, 3H), 1.69-1.55 (m, 1H), 1.52-1.30 (m, 4H),
		1.14-0.98 (m, 2H), 0.96-0.77 (m, 0H), 0.72-0.49 (m, 1H), 0.28-0.11
		(m, 1H).
258	638.4	1H NMR (400 MHz, DMSO-d6) δ 9.01 (d, J = 9.8 Hz, 1H), 8.16 (d, J =
		8.1 Hz, 1H), 8.06 (s, 3H), 7.58 (d, J = 1.2 Hz, 1H), 7.42 (d, J = 8.1 Hz,
		1H), 7.13 (s, 1H), 7.20-6.90 (m, 2H), 7.02 (d, J = 1.2 Hz, 1H), 6.17-
		6.00 (m, 1H), 5.27-5.04 (m, 1H), 4.67-4.57 (m, 1H), 4.57-4.21 (m,
		2H), 4.09 (s, 3H), 3.99 (s, 3H), 3.80-3.64 (m, 2H), 2.82-2.69 (m, 1H),
		2.31-2.06 (m, 1H), 1.91-1.54 (m, 5H), 1.50-1.27 (m, 4H), 1.25-0.96
		(m, 3H), 0.96-0.74 (m, 1H), 0.72-0.46 (m, 1H), 0.41-−0.08 (m, 1H).
259	610.4	1H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J = 8.5 Hz, 1H), 8.08 (s, 3H),
		8.03 (d, J = 8.1 Hz, 1H), 7.57 (s, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.03 (d, J =
		8.1 Hz, 2H), 5.08-4.87 (m, 1H), 4.51 (t, J = 8.7 Hz, 1H), 4.09 (s, 3H),
		3.99 (s, 3H), 3.80-3.55 (m, 1H), 2.13-1.92 (m, 2H), 1.89-1.72 (m,
		3H), 1.72-1.55 (m, 1H), 1.53-1.33 (m, 4H), 1.32 (s, 3H), 1.28-1.18
		(m, 2H), 1.20-1.09 (m, 3H), 1.02-0.72 (m, 2H), 0.64-0.53 (m, 1H),
		0.53-0.47 (m, 2H), 0.43-0.31 (m, 1H).
260	638.4	1H NMR (400 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.09 (d, J = 8.1 Hz, 1H),
		8.06 (d, J = 8.1 Hz, 1H), 7.53 (s, 1H), 7.23 (d, J = 8.2 Hz, 1H), 7.10-6.99
		(m, 1H), 6.93 (s, 1H), 5.25 (p, J = 7.0 Hz, 1H), 4.80 (t, J = 12.4 Hz, 1H),
		4.50-4.25 (m, 1H), 4.12 (s, 3H), 3.97 (s, 3H), 3.66-3.33 (m, 2H), 3.29-
		3.18 (m, 2H), 3.13-2.97 (m, 1H), 3.01-2.86 (m, 1H), 2.25 (t, J = 12.6
		Hz, 1H), 2.19-2.08 (m, 1H), 2.09-1.95 (m, 1H), 1.95-1.83 (m, 1H),
		1.82-1.68 (m, 4H), 1.69-1.52 (m, 2H), 1.43 (d, J = 6.9 Hz, 4H), 1.49-
		1.26 (m, 2H), 1.28-1.16 (m, 2H), 1.16-1.02 (m, 1H), 1.05-0.94 (m,
		1H), 0.97-0.87 (m, 1H), 0.65-0.55 (m, 1H), 0.50-0.39 (m, 1H).
261	640.4	1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.15 (s, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.53 (s, 1H), 7.27 (s, 2H), 7.19 (d, J =
		8.1 Hz, 1H), 7.14 (s, 2H), 7.04 (s, 1H), 7.01 (s, 2H), 6.94 (d, J = 1.1 Hz,
		1H), 5.13 (p, J = 7.1 Hz, 1H), 4.90-4.72 (m, 1H), 4.49-4.33 (m, 1H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.55-3.39 (m, 1H), 3.29-3.16 (m, 3H), 3.14-
		2.87 (m, 2H), 2.23-2.08 (m, 1H), 2.01-1.83 (m, 2H), 1.81-1.53 (m,
		5H), 1.45 (d, J = 7.1 Hz, 3H), 1.43-1.27 (m, 2H), 1.21 (s, 3H), 1.18-
		1.00 (m, 1H), 0.95 (s, 3H).
262	640.6	1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.23 (d, J = 11.7 Hz, 1H),
		8.05 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 7.4 Hz, 1H), 7.54 (s, 1H), 7.27 (s,
		2H), 7.19 (d, J = 8.1 Hz, 1H), 7.14 (s, 2H), 7.04 (s, 1H), 7.01 (s, 2H), 6.95
		(s, 1H), 5.12 (p, J = 7.2 Hz, 1H), 4.90-4.75 (m, 1H), 4.55-4.35 (m, 1H),
		4.13 (s, 3H), 3.99 (s, 3H), 3.55-3.35 (m, 1H), 3.35-3.18 (m, 2H), 3.14-
		2.82 (m, 2H), 2.23-2.10 (m, 1H), 2.00-1.84 (m, 2H), 1.81-1.54 (m,
		5H), 1.45 (d, J = 7.1 Hz, 3H), 1.42-1.26 (m, 3H), 1.21 (s, 3H), 1.17-
		0.98 (m, 2H), 0.95 (s, 3H).
263	612.3	1H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.2 Hz, 1H), 7.48 (s,
		1H), 7.19 (d, J = 8.2 Hz, 1H), 6.99 (s, 1H), 6.88 (d, J = 8.1 Hz, 1H), 5.42
		(q, J = 7.2 Hz, 1H), 4.89 (m, J = 14.7, 7.6 Hz, 1H), 4.16 (s, 3H), 4.05 (s,
		3H), 3.18 (s, 14H), 2.64 (q, J = 9.4 Hz, 1H), 2.42 (q, J = 9.2 Hz, 1H), 2.15-
		1.66 (m, 2H), 1.59 (d, J = 7.0 Hz, 3H), 1.48-1.22 (m, 5H), 0.92 (s, 1H).
264	614.2	1H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H),
		7.18 (d, J = 8.1 Hz, 1H), 7.02 (s, 1H), 6.92 (d, J = 1.2 Hz, 1H), 4.96 (t, J =
		7.1 Hz, 1H), 4.53 (d, J = 10.3 Hz, 2H), 4.13 (s, 3H), 4.00 (s, 3H), 3.02 (s,
		3H), 1.91-1.81 (m, 2H), 1.76 (d, J = 2.7 Hz, 1H), 1.68-1.53 (m, 3H),
		1.43 (d, J = 7.0 Hz, 4H), 1.26 (d, J = 18.2 Hz, 4H), 1.06 (t, J = 7.0 Hz,
		3H), 0.38 (d, J = 9.0 Hz, 2H), 0.34-0.26 (m, 2H).
265	600.2	1H NMR (400 MHz, DMSO-d6) δ 8.48 (d, J = 6.7 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.43 (s, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.02 (s, 1H), 6.92 (d,
		J = 1.2 Hz, 1H), 4.95 (p, J = 6.8 Hz, 2H), 4.70 (m, J = 14.1, 3.4 Hz, 2H),
		4.14 (s, 3H), 4.00 (s, 3H), 3.98-3.91 (m, 1H), 3.51 (m, J = 10.8, 5.1 Hz,
		1H), 3.39 (t, J = 10.3 Hz, 1H), 3.22 (m, J = 10.8, 3.7 Hz, 3H), 2.76 (m, J =
		13.4, 7.9, 3.5 Hz, 2H), 2.02 (s, 1H), 1.85 (m, J = 9.3, 4.7 Hz, 1H), 1.76 (m,
		J = 8.9, 4.9 Hz, 1H), 1.59 (d, J = 8.8 Hz, 2H), 1.44 (d, J = 6.9 Hz, 3H),
		0.97-0.82 (m, 4H), 0.44 (m, J = 9.0, 4.7 Hz, 1H), 0.30 (m, J = 8.5, 5.0
		Hz, 1H).
266	600.4	1H NMR (400 MHz, DMSO-d6) δ 8.50 (d, J = 6.9 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.43 (s, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.05 (s, 1H), 6.93 (d,
		J = 1.2 Hz, 1H), 5.06 (p, J = 6.7 Hz, 1H), 4.70 (m, J = 14.2, 3.1 Hz, 1H),
		4.14 (s, 3H), 4.12-4.05 (m, 1H), 4.00 (s, 3H), 3.72 (m, J = 9.8, 8.1 Hz,
		1H), 3.62 (m, J = 11.0, 3.5 Hz, 1H), 3.49 (m, J = 9.7, 3.2 Hz, 1H), 3.24 (d,
		J = 34.6 Hz, 4H), 2.85 (m, J = 11.0, 9.3 Hz, 1H), 2.43-2.31 (m, 1H), 2.02
		(s, 1H), 1.75 (d, J = 6.9 Hz, 1H), 1.66-1.50 (m, 2H), 1.46 (d, J = 6.7 Hz,
		3H), 1.15 (d, J = 7.3 Hz, 3H), 1.01 (d, J = 5.3 Hz, 1H), 0.50 (m, J = 9.3,
		4.9 Hz, 1H), 0.37 (m, J = 9.6, 5.1 Hz, 1H).
267	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 6.1 Hz, 1H), 8.03 (d, J =
		8.0 Hz, 1H), 7.44 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.01 (s, 1H), 6.92 (d,
		J = 1.2 Hz, 1H), 4.95 (p, J = 6.8 Hz, 1H), 4.68 (m, J = 13.9, 3.9 Hz, 1H),
		4.13 (s, 3H), 3.99 (s, 3H), 3.85-3.74 (m, 2H), 3.27 (s, 3H), 3.12 (m, J =
		10.6, 8.4 Hz, 2H), 2.94 (m, J = 10.6, 6.0 Hz, 1H), 2.17 (d, J = 14.5 Hz,
		1H), 2.01 (s, 1H), 1.85 (d, J = 5.5 Hz, 1H), 1.81-1.71 (m, 1H), 1.58 (d, J =
		8.7 Hz, 2H), 1.43 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H), 0.81 (m,
		J = 8.6, 4.3 Hz, 1H), 0.50 (m, J = 8.6, 4.8 Hz, 1H), 0.36 (m, J = 8.5, 5.0
		Hz, 1H).
268	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.53 (d, J = 6.6 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.45 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), 6.93 (d,
		J = 1.2 Hz, 1H), 5.03 (t, J = 6.7 Hz, 1H), 4.80 (m, J = 14.3, 2.6 Hz, 2H),
		4.15 (s, 3H), 4.00 (s, 3H), 3.95-3.82 (m, 3H), 3.60 (m, J = 11.0, 4.4 Hz,
		1H), 3.27 (s, 3H), 2.93 (m, J = 11.0, 9.2 Hz, 1H), 2.60 (m, J = 15.1, 3.0
		Hz, 1H), 2.08-1.95 (m, 2H), 1.75 (m, J = 9.0, 8.5, 4.0 Hz, 2H), 1.59 (d,
		J = 8.8 Hz, 2H), 1.48 (d, J = 6.7 Hz, 3H), 1.09-1.01 (m, 1H), 0.97 (d, J =
		6.1 Hz, 3H), 0.48 (m, J = 9.0, 4.8 Hz, 1H), 0.36 (m, J = 8.7, 5.0 Hz, 1H).
269	584.3	1H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J = 7.0 Hz, 1H), 7.43 (s, 1H),
		7.17 (d, J = 8.0 Hz, 1H), 7.01 (s, 1H), 6.92 (s, 1H), 4.98 (p, J = 7.0 Hz,
		1H), 4.57 (m, J = 14.0, 3.7 Hz, 1H), 4.13 (s, 3H), 4.00 (s, 3H), 3.24 (d, J =
		31.9 Hz, 5H), 2.03 (d, J = 11.6 Hz, 1H), 1.88 (m, J = 13.6, 6.9 Hz, 1H),
		1.81-1.50 (m, 5H), 1.43 (d, J = 7.0 Hz, 3H), 1.35-1.18 (m, 3H), 1.02 (q,
		J = 7.6, 6.6 Hz, 1H), 0.73 (m, J = 16.2, 12.4, 8.2, 4.0 Hz, 2H), 0.31 (m, J =
		8.7, 4.5 Hz, 1H), 0.16 (m, J = 9.3, 4.8 Hz, 1H).
270	614.3	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.41 (s, 1H),
		7.20 (d, J = 8.1 Hz, 1H), 7.05 (s, 1H), 6.92 (d, J = 1.2 Hz, 1H), 5.04 (p, J =
		7.0 Hz, 1H), 4.83 (d, J = 13.9 Hz, 1H), 4.34 (m, J = 13.5, 4.7 Hz, 1H),
		4.13 (s, 3H), 4.00 (s, 3H), 3.28 (d, J = 9.4 Hz, 1H), 3.22-3.13 (m, 3H),
		3.12 (s, 3H), 2.44-2.25 (m, 2H), 2.01 (d, J = 12.0 Hz, 1H), 1.86 (d, J =
		8.4 Hz, 2H), 1.75 (d, J = 7.0 Hz, 1H), 1.61 (d, J = 15.5 Hz, 4H), 1.43 (d, J =
		7.1 Hz, 3H), 0.80 (m, J = 8.8, 5.0 Hz, 1H), 0.44 (d, J = 5.8 Hz, 2H), 0.30
		(d, J = 8.3 Hz, 1H).
271	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.05 (t, J = 8.1 Hz, 1H), 7.42 (s, 1H),
		7.22 (t, J = 8.1 Hz, 1H), 7.01 (d, J = 7.2 Hz, 1H), 6.93 (d, J = 1.3 Hz, 1H),
		5.13-5.04 (m, 1H), 5.03-4.94 (m, 1H), 4.89 (d, J = 14.3 Hz, 1H), 4.12
		(d, J = 5.7 Hz, 3H), 4.00 (d, J = 1.2 Hz, 3H), 3.67-3.50 (m, 2H), 3.34-
		3.07 (m, 3H), 2.87 (t, J = 9.5 Hz, 1H), 2.70-2.62 (m, 1H), 2.09-1.94
		(m, 2H), 1.76 (s, 1H), 1.59 (d, J = 8.2 Hz, 2H), 1.44 (m, J = 9.8, 6.8 Hz,
		3H), 1.22 (m, J = 25.7, 5.7 Hz, 2H), 1.03 (m, J = 6.1, 4.8 Hz, 3H), 0.23-−
		0.15 (m, 4H).
272	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 8.0 Hz, 1H), 7.43 (d, J =
		2.9 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 1.2 Hz, 1H), 6.92 (d, J =
		1.3 Hz, 1H), 4.98 (m, J = 7.5, 3.8 Hz, 1H), 4.71-4.62 (m, 1H), 4.50 (m, J =
		14.0, 4.2 Hz, 1H), 4.13 (d, J = 1.2 Hz, 3H), 4.00 (s, 3H), 3.33-3.09 (m,
		4H), 2.03 (m, J = 11.4, 5.8 Hz, 2H), 1.80-1.67 (m, 2H), 1.66-1.51 (m,
		3H), 1.44 (t, J = 7.3 Hz, 3H), 1.23 (m, J = 40.1, 15.7 Hz, 5H), 0.92 (d, J =
		6.7 Hz, 3H), 0.78 (s, 1H), 0.67-0.52 (m, 1H), 0.37 (m, J = 8.9, 4.5 Hz,
		1H), 0.19 (m, J = 32.7, 13.3, 8.9, 4.6 Hz, 2H).
273	597.8	1H NMR (400 MHz, DMSO-d6) δ 7.85 (d, J = 7.9 Hz, 1H), 7.59 (d, J =
		8.2 Hz, 1H), 7.43-7.37 (m, 2H), 7.08 (m, J = 8.4, 1.3 Hz, 1H), 7.01 (s,
		1H), 6.91 (d, J = 1.2 Hz, 1H), 5.61 (m, J = 13.7, 6.3 Hz, 1H), 5.23 (m, J =
		14.7, 6.7 Hz, 1H), 5.09 (p, J = 7.2 Hz, 1H), 4.65-4.54 (m, 1H), 4.22 (m, J =
		14.2, 7.4 Hz, 1H), 4.10 (s, 3H), 3.99 (s, 3H), 3.20 (m, J = 29.0, 14.5 Hz,
		4H), 2.30 (d, J = 5.9 Hz, 1H), 2.02 (s, 1H), 1.87 (s, 1H), 1.75 (d, J = 6.3
		Hz, 2H), 1.58 (d, J = 8.3 Hz, 3H), 1.48 (d, J = 7.1 Hz, 4H), 1.32 (s, 3H),
		1.07 (s, 3H).
274	612.4	1H NMR (400 MHz, DMSO-d6) δ 7.99 (t, J = 7.7 Hz, 2H), 7.43 (s, 1H),
		7.16 (d, J = 8.0 Hz, 1H), 7.01 (s, 1H), 6.92 (d, J = 1.1 Hz, 1H), 4.96 (p, J =
		7.1 Hz, 1H), 4.68 (d, J = 13.8 Hz, 1H), 4.13 (s, 3H), 4.00 (s, 3H), 3.93 (dd,
		J = 14.0, 8.7 Hz, 3H), 2.21 (t, J = 12.8 Hz, 2H), 2.02 (s, 1H), 1.76 (s, 1H),
		1.59 (d, J = 8.2 Hz, 2H), 1.44 (d, J = 7.0 Hz, 3H), 1.41-1.28 (m, 2H),
		1.23 (s, 3H), 1.19 (d, J = 9.8 Hz, 2H), 0.87 (s, 3H), 0.81-0.71 (m, 3H),
		0.67-0.56 (m, 2H), 0.38 (dt, J = 9.2, 4.5 Hz, 1H), 0.19 (dt, J = 9.4, 4.9
		Hz, 1H).
275	634.5	1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 8.0 Hz, 1H), 8.45 (d, J =
		8.5 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.82 (m, J = 5.2, 1.3 Hz, 1H), 7.29
		(s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 5.06-4.96 (m, 1H), 4.88 (m, J = 9.5, 4.6
		Hz, 1H), 4.77 (q, J = 4.8 Hz, 2H), 4.40 (m, J = 13.7, 9.4 Hz, 1H), 4.03 (m,
		J = 7.2, 3.8 Hz, 2H), 3.47 (d, J = 12.3 Hz, 1H), 3.39 (d, J = 13.1 Hz, 1H),
		3.13-2.89 (m, 2H), 2.41-2.29 (m, 1H), 1.99-1.80 (m, 2H), 1.72-1.53
		(m, 3H), 1.49-1.41 (m, 4H), 1.36 (m, J = 11.9, 7.1 Hz, 1H), 1.30-1.20
		(m, 1H), 1.20-1.06 (m, 2H), 0.96 (d, J = 5.7 Hz, 1H), 0.91-0.82 (m,
		1H), 0.79-0.58 (m, 3H), 0.49 (m, J = 9.1, 5.8, 3.6 Hz, 1H).
276	618.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.84 (d, J =
		7.4 Hz, 1H), 7.45 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.04 (s, 1H), 6.94 (d,
		J = 1.0 Hz, 1H), 5.19 (d, J = 4.1 Hz, 1H), 5.13 (q, J = 7.1 Hz, 1H), 5.08 (d,
		J = 7.2 Hz, 1H), 4.82 (t, J = 11.0 Hz, 1H), 4.41 (d, J = 10.1 Hz, 1H), 4.12
		(s, 3H), 4.00 (s, 3H), 3.41-3.28 (m, 1H), 2.12-2.01 (m, 2H), 1.92 (t, J =
		12.0 Hz, 1H), 1.73-1.55 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.37 (m, J =
		20.8, 7.5 Hz, 4H), 1.21 (s, 3H), 1.08 (s, 2H), 0.95 (s, 3H).
277	614.4	1H NMR (400 MHz, DMSO-d6) δ 7.91 (s, 1H), 7.81 (d, J = 7.4 Hz, 1H),
		7.32 (d, J = 1.3 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 5.12 (p, J =
		7.1 Hz, 1H), 4.84 (t, J = 10.9 Hz, 2H), 4.51-4.38 (m, 2H), 4.15 (s, 3H),
		4.12-4.03 (m, 2H), 4.01 (s, 3H), 3.19 (d, J = 13.3 Hz, 1H), 2.93 (m, J =
		22.7, 11.6 Hz, 2H), 2.40 (d, J = 13.8 Hz, 2H), 2.00 (s, 1H), 1.92 (t, J =
		12.7 Hz, 2H), 1.70 (m, J = 31.8, 16.8 Hz, 3H), 1.55 (m, J = 13.4, 3.9 Hz,
		2H), 1.47 (d, J = 4.4 Hz, 2H), 1.42 (s, 3H), 1.35 (d, J = 12.0 Hz, 1H), 1.20
		(d, J = 13.2 Hz, 3H), 1.10 (d, J = 14.9 Hz, 2H), 0.95 (s, 3H).
278	624.5	1H NMR (400 MHz, Chloroform-d) δ 7.98 (d, J = 8.1 Hz, 1H), 7.66 (s,
		1H), 7.15 (d, J = 8.2 Hz, 1H), 7.03-6.88 (m, 2H), 5.40 (t, J = 7.3 Hz,
		1H), 4.90 (s, 1H), 4.17 (s, 3H), 4.05 (s, 3H), 3.85 (s, 4H), 2.61 (q, J = 9.4,
		6.8 Hz, 1H), 2.39 (m, J = 21.2, 12.0 Hz, 2H), 2.11-1.65 (m, 10H), 1.57
		(d, J = 6.9 Hz, 3H), 1.42 (s, 2H), 1.28 (s, 5H), 0.89 (s, 1H).
279	610.5	1H NMR (400 MHz, Chloroform-d) δ 8.04 (d, J = 8.2 Hz, 1H), 7.71 (s,
		1H), 7.17 (d, J = 8.3 Hz, 2H), 7.01 (d, J = 10.8 Hz, 1H), 5.41 (p, J = 6.9
		Hz, 1H), 4.90 (t, J = 12.1 Hz, 1H), 4.22 (s, 3H), 4.08 (s, 3H), 3.84 (s, 1H),
		2.44-1.63 (m, 10H), 1.56 (d, J = 6.7 Hz, 3H), 1.52-1.08 (m, 9H), 0.63
		(m, J = 35.3, 5.9 Hz, 2H).
280	638.6	1H NMR (400 MHz, Chloroform-d) δ 8.05 (d, J = 8.1 Hz, 1H), 7.69 (s,
		1H), 7.26 (s, 1H), 7.19 (s, 1H), 7.01 (d, J = 9.5 Hz, 1H), 5.62 (d, J = 62.5
		Hz, 4H), 5.28 (q, J = 7.1 Hz, 1H), 4.89 (m, J = 14.8, 7.5 Hz, 1H), 4.30 (s,
		1H), 4.20 (s, 3H), 4.07 (s, 3H), 3.84 (s, 1H), 2.60 (q, J = 9.4 Hz, 1H), 2.34
		(m, J = 17.1, 9.1 Hz, 2H), 2.13-1.63 (m, 10H), 1.59 (t, J = 6.3 Hz, 3H),
		1.36 (d, J = 7.6 Hz, 2H), 1.31-1.09 (m, 5H), 0.99 (s, 3H).
281	624.5	1H NMR (400 MHz, Chloroform-d) δ 8.04 (d, J = 8.1 Hz, 1H), 7.72 (s,
		1H), 7.54 (s, 1H), 7.18 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 4.4 Hz, 1H), 5.29
		(p, J = 6.7 Hz, 1H), 4.86-4.70 (m, 2H), 4.28 (s, 1H), 4.21 (s, 3H), 4.08
		(s, 3H), 3.85 (s, 1H), 2.39 (s, 1H), 2.15-2.03 (m, 2H), 1.98-1.65 (m,
		4H), 1.56 (d, J = 6.6 Hz, 7H), 1.30 (d, J = 47.0 Hz, 8H), 0.66 (d, J = 5.6
		Hz, 1H), 0.56 (d, J = 5.7 Hz, 1H).
282	572.3	1H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J = 8.5 Hz, 1H), 8.04 (d, J =
		8.1 Hz, 1H), 7.94 (bs, 3H), 7.41 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04 (s,
		1H), 6.91 (d, J = 1.2 Hz, 1H), 5.29-5.11 (m, 1H), 5.04-4.86 (m, 1H),
		4.60-4.46 (m, 1H), 4.11 (s, 3H), 3.98 (s, 3H), 3.28-3.06 (m, 2H), 2.15-
		1.94 (m, 4H), 1.81-1.08 (m, 14H), 1.06-0.94 (m, 2H), 0.72-0.52 (m,
		1H).
283	586.4	1H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J = 7.2 Hz, 1H), 8.03 (d, J =
		8.0 Hz, 1H), 7.95 (bs, 3H), 7.42 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.01 (s,
		1H), 6.91 (d, J = 1.2 Hz, 1H), 5.13-4.94 (m, 1H), 4.63-4.44 (m, 2H),
		4.10 (s, 3H), 3.98 (s, 3H), 3.37-3.10 (m, 4H), 2.36-2.20 (m, 1H), 2.09-
		1.86 (m, 3H), 1.82-1.68 (m, 1H), 1.65-1.49 (m, 4H), 1.46 (d, J = 7.0
		Hz, 3H), 1.42-1.31 (m, 3H), 1.26-0.83 (m, 7H).
284	600.5	1H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J = 7.9 Hz, 1H), 8.08-7.86
		(m, 4H), 7.32 (s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 6.64 (s, 1H), 6.44 (s, 1H),
		5.37-5.03 (m, 1H), 4.80-4.60 (m, 1H), 4.52-4.39 (m, 1H), 4.09 (s,
		3H), 3.36-3.16 (m, 3H), 2.79 (s, 3H), 2.41-2.28 (m, 1H), 2.20-2.00
		(m, 2H), 1.81-1.71 (m, 1H), 1.70-1.56 (m, 3H), 1.53-1.29 (m, 8H),
		1.29-0.98 (m, 10H).
285	584.4	1H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J = 8.5 Hz, 1H), 8.13-8.01
		(m, 4H), 7.58 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.11-6.91 (m, 2H), 5.28-
		5.12 (m, 1H), 5.07-4.89 (m, 1H), 4.68-4.30 (m, 2H), 4.11 (s, 3H), 4.00
		(s, 3H), 3.80-3.68 (m, 2H), 2.37-2.24 (m, 1H), 2.13-1.94 (m, 2H),
		1.92-1.73 (m, 3H), 1.71-1.59 (m, 2H), 1.54-1.08 (m, 10H), 1.05-
		0.91 (m, 2H), 0.66-0.51 (m, 1H).
286	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J = 7.1 Hz, 1H), 8.08 (bs, 3H),
		8.03 (d, J = 8.1 Hz, 1H), 7.59 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.06-6.94
		(m, 2H), 5.12-4.92 (m, 1H), 4.68-4.35 (m, 3H), 4.10 (s, 3H), 4.00 (s,
		3H), 2.37-2.23 (m, 2H), 2.06-1.73 (m, 5H), 1.68-1.48 (m, 3H), 1.46
		(d, J = 7.0 Hz, 3H), 1.41-1.29 (m, 4H), 1.25-0.90 (m, 7H).
287	612.5	1H NMR (400 MHz, DMSO-d6) δ 8.28-8.11 (m, 4H), 7.98 (d, J = 8.0
		Hz, 1H), 7.47 (s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 6.64 (s, 1H), 6.44 (s, 1H),
		5.23-5.07 (m, 1H), 4.80-4.63 (m, 1H), 4.57-4.39 (m, 1H), 4.11 (s,
		3H), 2.80 (s, 3H), 2.42-2.27 (m, 2H), 2.15-1.98 (m, 1H), 1.92-1.76
		(m, 4H), 1.72-1.55 (m, 2H), 1.52-1.29 (m, 8H), 1.27-0.97 (m, 10H).
288	584.4	1H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J = 8.7 Hz, 1H), 8.10-8.02
		(m, 1H), 7.95-7.86 (m, 2H), 7.59-7.33 (m, 1H), 7.19 (d, J = 8.1 Hz,
		1H), 7.05 (s, 1H), 7.01-6.92 (m, 1H), 5.26-5.15 (m, 1H), 5.04-4.86
		(m, 1H), 4.63-4.50 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.67-3.49 (m,
		3H), 3.26-3.03 (m, 2H), 2.14-1.82 (m, 5H), 1.72-1.60 (m, 2H), 1.55-
		1.07 (m, 10H), 1.04-0.92 (m, 2H), 0.70-0.53 (m, 1H).
289	598.5	1H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J = 7.1 Hz, 1H), 8.07 (d, J =
		5.6 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.92 (bs, 2H), 7.61-7.34 (m, 1H),
		7.19 (d, J = 8.1 Hz, 1H), 7.01 (s, 1H), 7.00-6.91 (m, 1H), 5.15-4.90 (m,
		1H), 4.72-4.43 (m, 2H), 4.10 (s, 3H), 3.99 (s, 3H), 3.28-3.11 (m, 1H),
		2.72-2.63 (m, 1H), 2.38-2.20 (m, 1H), 2.05-1.84 (m, 5H), 1.72-1.50
		(m, 3H), 1.46 (d, J = 7.0 Hz, 3H), 1.43-1.29 (m, 4H), 1.25-0.84 (m,
		7H).
290	612.5	1H NMR (400 MHz, DMSO-d6) δ 8.23-8.04 (m, 2H), 8.03-7.88 (m,
		3H), 7.52-7.23 (m, 1H), 7.14 (d, J = 8.1 Hz, 1H), 6.61 (s, 1H), 6.48-
		6.25 (m, 1H), 5.24-5.07 (m, 1H), 4.83-4.62 (m, 1H), 4.56-4.20 (m,
		3H), 4.10-4.04 (m, 3H), 3.28-3.17 (m, 1H), 2.80 (s, 3H), 2.16-1.79
		(m, 5H), 1.71-1.54 (m, 2H), 1.52-1.32 (m, 8H), 1.27-0.96 (m, 10H).
291	559.3	1H NMR (400 MHz, Methanol-d4) δ 8.12 (d, J = 8.1 Hz, 1H), 7.47 (d, J =
		1.2 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 7.05 (d, J = 1.2 Hz,
		1H), 4.89-4.76 (m, 2H), 4.67-4.53 (m, 1H), 4.50-4.28 (m, 1H), 4.19 (s,
		3H), 4.09 (s, 3H), 3.98-3.64 (m, 1H), 3.49-3.36 (m, 3H), 3.31-3.23 (m,
		1H), 2.30-2.12 (m, 1H), 1.93-1.64 (m, 5H), 1.63-1.18 (m, 11H), 1.04-
		0.83 (m, 3H).
292	612.3	1H NMR (400 MHz, Methanol-d4) δ 8.10 (d, J = 8.1 Hz, 1H), 7.47 (d, J =
		1.1 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.04 (d, J = 1.3 Hz, 1H), 6.99 (s,
		1H), 5.38-5.24 (m, 2H), 4.88-4.82 (m, 1H), 4.56-4.26 (m, 1H), 4.19
		(s, 3H), 4.09 (s, 3H), 3.97-3.60 (m, 1H), 3.50-3.35 (m, 2H), 2.41-2.28
		(m, 1H), 2.27-2.14 (m, 1H), 1.95-1.67 (m, 4H), 1.57 (d, J = 7.0 Hz,
		3H), 1.47-1.27 (m, 5H), 1.12 (s, 3H), 0.91-0.78 (m, 2H), 0.49-0.31
		(m, 1H), −0.08-−0.16 (m, 1H), −0.27-−0.35 (m, 1H), −0.48-−0.62 (m,
		1H).
293	560.3	1H NMR (400 MHz, Methanol-d4) δ 8.09 (t, J = 6.3 Hz, 1H), 8.00 (d, J =
		8.5 Hz, 1H), 7.46 (s, 1H), 6.82 (s, 2H), 6.79 (d, J = 4.4 Hz, 1H), 4.85-
		4.74 (m, 2H), 4.55-4.38 (m, 2H), 4.25 (s, 3H), 4.18-3.81 (m, 1H), 3.75-
		3.55 (m, 1H), 3.56-3.38 (m, 2H), 3.30-3.20 (m, 2H), 3.05-2.86 (m,
		1H), 2.81 (s, 3H), 2.30-2.12 (m, 1H), 2.06-1.64 (m, 3H), 1.61-1.45 (m,
		2H), 1.45-1.33 (m, 2H), 1.33-1.15 (m, 2H), 0.98-0.82 (m, 2H).
294	636.3	1H NMR (400 MHz, Methanol-d4) δ 8.06 (d, J = 8.1 Hz, 1H), 7.94 (d, J =
		1.3 Hz, 1H), 7.45 (d, J = 1.3 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.00 (s,
		1H), 5.33-5.17 (m, 1H), 5.06-4.94 (m, 2H), 4.37-4.21 (m, 1H), 4.17
		(s, 3H), 4.11 (s, 3H), 3.77-3.54 (m, 2H), 3.38 (d, J = 12.3 Hz, 1H), 3.30-
		3.24 (m, 1H), 2.68-2.54 (m, 1H), 2.50-2.29 (m, 1H), 1.96-1.83 (m,
		1H), 1.83-1.68 (m, 1H), 1.61-1.20 (m, 13H), 1.15-0.99 (m, 4H).
295		1H NMR (400 MHz, Methanol-d4) δ 8.07 (d, J = 8.1 Hz, 1H), 7.92 (d, J =
		1.3 Hz, 1H), 7.46 (d, J = 1.3 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.01 (s,
		1H), 5.26 (q, J = 7.0 Hz, 1H), 5.05-4.94 (m, 1H), 4.50-4.38 (m, 1H),
		4.30-4.20 (m, 2H), 4.17 (s, 3H), 4.11 (s, 3H), 3.48-3.35 (m, 2H), 3.31-
		3.23 (m, 1H), 2.15-2.03 (m, 2H), 1.98-1.85 (m, 1H), 1.84-1.69 (m,
		1H), 1.61-1.18 (m, 13H), 1.15-1.00 (m, 4H).
296	636.4	1H NMR (400 MHz, Methanol-d4) δ 8.07 (d, J = 8.1 Hz, 1H), 7.94 (d, J =
		1.3 Hz, 1H), 7.47 (d, J = 1.4 Hz, 1H), 7.23 (d, J = 8.2 Hz, 1H), 7.03 (s,
		1H), 5.26 (q, J = 7.0 Hz, 1H), 5.07-4.93 (m, 2H), 4.32-4.20 (m, 1H),
		4.17 (s, 3H), 4.12 (s, 3H), 3.73-3.56 (m, 2H), 3.39 (d, J = 12.3 Hz, 1H),
		3.31-3.26 (m, 1H), 2.68-2.54 (m, 1H), 2.51-2.30 (m, 1H), 1.90 (t, J =
		12.1 Hz, 1H), 1.83-1.69 (m, 1H), 1.63-1.19 (m, 13H), 1.15-0.99 (m,
		4H).
297	666.3	1H NMR (400 MHz, Methanol-d4) δ 8.04 (d, J = 8.1 Hz, 1H), 7.47 (d, J =
		1.2 Hz, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.04 (d, J = 1.2 Hz, 1H), 6.99 (s,
		1H), 6.63 (t, J = 73.7 Hz, 1H), 5.23 (q, J = 7.0 Hz, 1H), 5.01-4.89 (m,
		1H), 4.83-4.77 (m, 1H), 4.29-4.16 (m, 2H), 4.14 (s, 3H), 4.06 (s, 3H),
		3.82-3.52 (m, 4H), 2.11-1.95 (m, 2H), 1.95-1.81 (m, 1H), 1.81-1.67
		(m, 1H), 1.58-1.17 (m, 14H), 1.07 (s, 4H) .; 1H NMR (400 MHz,
		Chloroform-d) δ 7.41-7.28 (m, 5H), 5.19-5.09 (m, 2H), 4.88 (d, J = 7.6
		Hz, 1H), 4.03-3.91 (m, 1H), 3.86-3.29 (m, 6H), 1.87-1.65 (m, 2H),
		1.44 (s, 9H).
298	563.3	1H NMR (400 MHz, Methanol-d4) δ 8.56 (d, J = 8.1 Hz, 1H), 7.55 (d, J =
		8.1 Hz, 1H), 7.47 (d, J = 1.2 Hz, 1H), 7.34 (s, 1H), 7.04 (d, J = 1.2 Hz,
		1H), 5.05-4.95 (m, 2H), 4.81-4.67 (m, 1H), 4.63-4.30 (m, 1H), 4.24 (s,
		3H), 4.09 (s, 3H), 4.00-3.87 (m, 2H), 3.81-3.34 (m, 11H), 2.30-2.17
		(m, 1H), 2.00-1.70 (m, 3H), 1.68 (d, J = 6.6 Hz, 3H).
299	615.4	1H NMR (400 MHz, Methanol-d4) δ 8.05 (d, J = 8.1 Hz, 1H), 7.61 (s,
		1H), 7.29-7.12 (m, 2H), 7.01 (s, 1H), 5.29-5.16 (m, 1H), 5.03-4.90
		(m, 1H), 4.74-4.58 (m, 1H), 4.25-4.11 (m, 4H), 4.06 (s, 3H), 3.55-
		3.40 (m, 1H), 3.27-3.12 (m, 2H), 3.07-2.93 (m, 1H), 2.70 (s, 3H), 2.14-
		2.02 (m, 1H), 1.80-1.66 (m, 1H), 1.63-1.20 (m, 15H), 1.06 (s,
		4H).; 1H NMR (400 MHz, Methanol-d4) δ 8.07 (d, J = 8.2 Hz, 1H), 7.98-
		7.90 (m, 2H), 7.61-7.54 (m, 2H), 7.54-7.46 (m, 2H), 7.31 (d, J = 8.1
		Hz, 1H), 6.94 (s, 1H), 6.86 (s, 1H), 5.44 (q, J = 7.0 Hz, 1H), 4.65 (dd, J =
		12.7, 4.7 Hz, 1H), 4.39-4.18 (m, 5H), 3.61-3.43 (m, 1H), 3.26 (q, J =
		11.7 Hz, 2H), 3.08-2.96 (m, 1H), 2.82 (s, 3H), 2.73 (s, 3H), 2.23-2.02
		(m, 1H), 1.93-1.82 (m, 1H), 1.70 (d, J = 7.0 Hz, 3H), 1.13-0.98 (m,
		1H), 0.43-0.25 (m, 2H), 0.25-0.12 (m, 2H).
300	558.3	1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 7.4 Hz, 1H), 8.09-7.82
		(m, 5H), 7.29 (s, 1H), 7.09 (d, J = 8.0 Hz, 1H), 6.61-6.54 (m, 1H), 6.38
		(s, 1H), 4.96 (p, J = 7.2 Hz, 1H), 4.63 (dt, J = 13.5, 6.8 Hz, 1H), 4.46 (s,
		1H), 4.08 (d, J = 1.5 Hz, 3H), 3.26 (s, 2H), 2.78 (s, 3H), 2.20 (t, J = 11.4
		Hz, 2H), 2.08-1.87 (m, 2H), 1.76 (s, 1H), 1.67-1.37 (m, 9H), 1.25-
		1.00 (m, 2H), 0.82 (s, 1H).
301	572.3	1H NMR (400 MHz, DMSO-d6) δ 8.29 (d, J = 8.5 Hz, 1H), 8.16-7.85
		(m, 4H), 7.31 (s, 1H), 7.11 (d, J = 8.0 Hz, 1H), 6.63 (s, 1H), 6.43 (s, 1H),
		5.18 (p, J = 7.2 Hz, 1H), 4.89 (dt, J = 14.2, 7.9 Hz, 1H), 4.44-4.33 (m,
		1H), 4.09 (s, 3H), 3.30-3.10 (m, 4H), 2.79 (s, 3H), 2.13-1.91 (m, 3H),
		1.83-1.52 (m, 3H), 1.46-1.35 (m, 5H), 1.28-0.92 (m, 5H), 0.63 (s,
		1H).
302	584.3	1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 8.6 Hz, 1H), 8.05 (s, 1H),
		7.93 (d, J = 8.1 Hz, 2H), 7.43 (s, 0H), 7.25 (s, 1H), 7.10 (d, J = 8.0 Hz,
		1H), 6.60 (s, 1H), 6.34 (d, J = 5.5 Hz, 1H), 5.18 (q, J = 7.3 Hz, 1H), 4.97-
		4.84 (m, 1H), 4.51 (d, J = 18.8 Hz, 1H), 4.08 (s, 3H), 3.22 (dd, J = 18.1,
		9.8 Hz, 1H), 2.80 (s, 3H), 2.14-1.82 (m, 5H), 1.66 (s, 2H), 1.41 (d, J =
		7.1 Hz, 4H), 1.28-0.92 (m, 4H), 0.62 (s, 1H).
303	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J = 6.5 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.27 (s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 6.60 (s, 1H), 6.36 (s,
		1H), 5.06 (p, J = 6.6 Hz, 1H), 4.69 (t, J = 11.5 Hz, 1H), 4.50 (d, J = 16.9
		Hz, 1H), 4.08 (s, 3H), 3.86 (d, J = 9.9 Hz, 1H), 3.71 (dt, J = 27.2, 8.9 Hz,
		2H), 3.37-3.07 (m, 2H), 2.95 (d, J = 9.9 Hz, 1H), 2.84 (s, 3H), 2.39 (dd,
		J = 15.7, 7.4 Hz, 1H), 2.23 (d, J = 12.3 Hz, 1H), 2.02 (s, 1H), 1.76 (s, 1H),
		1.58 (d, J = 14.2 Hz, 4H), 1.48 (d, J = 6.7 Hz, 3H), 0.41-0.20 (m, 4H).
304	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 7.4 Hz, 1H), 8.06 (d, J =
		8.2 Hz, 1H), 7.93 (s, 3H), 7.43 (s, 1H), 7.20 (d, J = 8.3 Hz, 1H), 7.07 (d,
		J = 1.9 Hz, 1H), 6.91 (s, 1H), 5.06 (t, J = 7.2 Hz, 1H), 4.93-4.81 (m, 1H),
		4.74-4.63 (m, 1H), 4.15 (s, 3H), 3.99 (s, 3H), 3.88 (t, J = 9.9 Hz, 1H),
		3.77 (d, J = 11.5 Hz, 1H), 3.62-3.52 (m, 2H), 3.35-3.05 (m, 4H), 2.63
		(dd, J = 24.9, 11.7 Hz, 2H), 2.23 (dd, J = 14.5, 5.1 Hz, 1H), 2.07-2.00
		(m, 1H), 1.79-1.70 (m, 1H), 1.66-1.55 (m, 3H), 1.49 (d, J = 7.1 Hz, 3H),
		0.91 (d, J = 7.5 Hz, 2H), 0.19 (t, J = 7.4 Hz, 2H).
305	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.61 (d, J = 6.9 Hz, 1H), 8.03 (dd, J =
		8.2, 1.8 Hz, 1H), 7.93 (s, 3H), 7.42 (s, 1H), 7.20-7.15 (m, 1H), 7.08 (s,
		1H), 6.91 (s, 1H), 5.01-4.91 (m, 2H), 4.49 (t, J = 12.3 Hz, 1H), 4.15 (s,
		3H), 3.99 (s, 3H), 3.79-3.68 (m, 3H), 3.34-3.03 (m, 5H), 2.20 (d, J =
		15.1 Hz, 1H), 2.05-1.98 (m, 1H), 1.80-1.70 (m, 1H), 1.63-1.53 (m,
		2H), 1.41 (d, J = 7.0 Hz, 3H), 1.07-0.79 (m, 2H), 0.65-0.56 (m, 1H),
		0.24-0.16 (m, 1H).
306	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.56-8.49 (m, 1H), 8.09-8.02 (m,
		1H), 7.94 (s, 3H), 7.43 (s, 1H), 7.19 (dd, J = 8.6, 2.3 Hz, 1H), 7.03 (t, J =
		1.8 Hz, 1H), 6.93 (s, 1H), 5.01 (t, J = 7.0 Hz, 1H), 4.89 (t, J = 12.3 Hz,
		1H), 4.61-4.49 (m, 1H), 4.13 s, 3H), 4.00 (s, 3H), 3.69-3.49 (m, 3H),
		3.34-3.05 (m, 4H), 2.34-2.24 (m, 1H), 2.02 br (s, 1H), 1.75 br (s, 2H),
		1.59 (br s, 2H), 1.47-1.38 (m, 4H), 1.06 (br s, 1H), 0.63 (br s, 1H), 0.50
		(br s, 1H), −0.26 br s, 1H).
307	585.3	1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J = 7.2 Hz, 1H), 7.93 (s, 3H),
		7.58 (d, J = 8.2 Hz, 1H), 7.48 (s, 1H), 7.38 (s, 1H), 7.05-6.99 (m, 2H),
		6.89 (s, 1H), 4.96 (p, J = 7.0 Hz, 1H), 4.74-4.65 (m, 1H), 4.43-4.33 (m,
		1H), 4.08 (s, 3H), 3.98 (s, 3H), 3.58 (dd, J = 9.5, 3.0 Hz, 1H), 3.32-3.07
		(m, 3H), 2.98 (t, J = 10.1 Hz, 1H), 2.76-2.65 (m, 1H), 2.06-1.96 (m,
		2H), 1.89-1.71 (m, 3H), 1.64-1.45 (m, 3H), 1.42 (d, J = 7.0 Hz, 3H),
		0.90-0.82 (m, 1H), 0.80-0.73 (m, 1H).
308	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.64 (d, J = 6.2 Hz, 1H), 7.99 (d, J =
		8.1 Hz, 1H), 7.94 (br s, 3H), 7.39 (s, 1H), 7.12 (d, J = 8.1 Hz, 1H), 7.04 (s,
		1H), 6.91 (d, J = 1.1 Hz, 1H), 5.16 (t, J = 12.8 Hz, 1H), 4.88 (p, J = 6.9
		Hz, 1H), 4.63-4.53 (m, 1H), 4.11 (s, 3H), 3.98 (s, 3H), 3.48 (dd, J = 9.5,
		2.9 Hz, 1H), 3.30-3.08 (m, 3H), 2.99-2.92 (m, 1H), 2.80 (t, J = 10.1 Hz,
		1H), 2.07-1.88 (m, 2H), 1.80-1.52 (m, 5H), 1.42 (d, J = 7.1 Hz, 3H),
		1.40-1.28 (m, 2H), 0.82-0.75 (m, 1H), 0.69-0.62 (m, 1H).
309	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J = 7.3 Hz, 1H), 8.04 (d, J =
		8.2 Hz, 1H), 7.95 (s, 3H), 7.40 (s, 1H), 7.23 (d, J = 8.3 Hz, 1H), 7.06 (s,
		1H), 6.91 (d, J = 1.1 Hz, 1H), 5.03-4.91 (m, 1H), 4.69-4.56 (m, 2H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.42 (dd, J = 9.6, 4.5 Hz, 1H), 3.33-3.03 (m,
		3H), 3.01-2.91 (m, 2H), 2.74-2.65 (m, 1H), 2.06-1.98 (m, 1H), 1.81-
		1.28 (m, 8H), 0.85-0.73 (m, 2H).
310	614.3	1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 6.1 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.95 (s, 3H), 7.43 (s, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.10 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.05 (p, J = 6.6 Hz, 1H), 4.77-4.64 (m,
		2H), 4.17 (s, 3H), 3.99 (s, 3H), 3.90 (dd, J = 11.2, 3.8 Hz, 1H), 3.69-3.61
		(m, 1H), 3.57 (d, J = 9.9 Hz, 1H), 3.50 (d, J = 9.9 Hz, 1H), 3.34-3.02 (m,
		3H), 2.06-1.98 (m, 1H), 1.81-1.71 (m, 1H), 1.66-1.52 (m, 2H), 1.46 (d,
		J = 6.7 Hz, 3H), 1.30-1.18 (m, 1H), 1.17 (s, 3H), 1.07 (s, 3H), 0.43-0.28
		(m, 2H).
311	612.3	1H NMR (400 MHz, DMSO-d6) δ 9.18 (br s, 1H), 8.15 (d, J = 8.2 Hz,
		1H), 7.95 (s, 3H), 7.44 (br s, 1H), 7.27 (d, J = 8.2 Hz, 1H), 7.14 (s, 1H),
		6.92 (d, J = 1.2 Hz, 1H), 5.05 (p, J = 6.5 Hz, 1H), 4.83-4.63 (m, 2H),
		4.19 (s, 3H), 4.00 (s, 3H), 3.88 (dd, J = 11.0, 4.2 Hz, 1H), 3.81-3.71 (m,
		1H), 3.34-3.05 (m, 4H), 2.06-1.99 (m, 1H), 1.76 (d, J = 5.2 Hz, 1H),
		1.65-1.53 (m, 2H), 1.45 (d, J = 6.6 Hz, 3H), 1.35-1.25 (m, 1H), 1.10-
		1.00 (m, 2H), 0.78-0.65 (m, 2H), 0.45 (d, J = 25.2 Hz, 2H).
312	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.29 (d, J = 7.5 Hz, 1H), 8.05 (d, J =
		8.2 Hz, 1H), 7.93 (s, 3H), 7.42 (s, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.06 (s,
		1H), 6.91 (d, J = 1.2 Hz, 1H), 5.05 (p, J = 7.2 Hz, 1H), 4.93-4.84 (m,
		1H), 4.74-4.66 (m, 1H), 4.14 (s, 3H), 3.99 (s, 3H), 3.84-3.77 (m, 1H),
		3.68 (t, J = 9.7 Hz, 1H), 3.54 (dd, J = 11.9, 5.4 Hz, 1H), 3.31-3.08 (m,
		4H), 2.81-2.70 (m, 1H), 2.06-1.98 (m, 1H), 1.80-1.70 (m, 1H), 1.65-
		1.53 (m, 2H), 1.48 (d, J = 7.1 Hz, 3H), 0.96 (d, J = 7.0 Hz, 3H), 0.92-
		0.84 (m, 2H), 0.19-0.10 (m, 2H).
313	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.62 (d, J = 6.4 Hz, 1H), 8.10 (d, J =
		8.1 Hz, 1H), 7.94 (s, 3H), 7.43 (s, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.10 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 4.98 (p, J = 6.7 Hz, 1H), 4.75 (dd, J = 14.3,
		7.4 Hz, 1H), 4.66 (dd, J = 14.1, 7.0 Hz, 1H), 4.17 (s, 3H), 3.99 (s, 3H),
		3.82 (dd, J = 11.0, 4.7 Hz, 1H), 3.70-3.54 (m, 3H), 3.32-3.07 (m, 4H),
		2.06-1.99 (m, 1H), 1.80-1.70 (m, 1H), 1.66-1.53 (m, 2H), 1.50 (d, J =
		6.8 Hz, 3H), 1.25-1.15 (m, 1H), 1.12 (d, J = 7.4 Hz, 3H), 0.43-0.29 (m,
		2H).
314	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 7.4 Hz, 1H), 8.06 (d, J =
		8.2 Hz, 1H), 7.97 (s, 3H), 7.46 (s, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.07 (s,
		1H), 6.93 (s, 1H), 5.06 (p, J = 7.1 Hz, 1H), 4.93-4.83 (m, 1H), 4.74-
		4.65 (m, 1H), 4.15 (s, 3H), 3.99 (s, 3H), 3.88 (t, J = 9.8 Hz, 1H), 3.81-
		3.48 (m, 6H), 3.36 (s, 3H), 2.69-2.57 (m, 1H), 2.23 (dd, J = 14.2, 5.0 Hz,
		1H), 2.00-1.89 (m, 1H), 1.80-1.70 (m, 1H), 1.49 (d, J = 7.0 Hz, 3H),
		0.96-0.87 (m, 2H), 0.19 (t, J = 7.4 Hz, 2H).
315	604.3	1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2H), 8.70 (d, J = 7.9 Hz, 1H),
		8.35 (d, J = 7.4 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 1.2 Hz, 1H),
		7.35 (d, J = 1.2 Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.12 (s, 1H), 5.07 (p, J =
		7.1 Hz, 1H), 4.96-4.76 (m, 2H), 4.72 (dd, J = 13.9, 6.2 Hz, 1H), 4.50-
		4.37 (m, 1H), 4.18 (s, 3H), 4.02 (s, 3H), 3.94-3.85 (m, 1H), 3.78 (dd, J =
		11.7, 3.5 Hz, 1H), 3.63-3.50 (m, 2H), 3.49-3.32 (dd, J = 25.1, 12.5 Hz,
		2H), 3.13-2.90 (m, 2H), 2.69-2.57 (m, 1H), 2.24 (dd, J = 14.3, 5.1 Hz,
		1H), 1.937-1.84 (m, 1H), 1.49 (d, J = 7.1 Hz, 3H), 1.05-0.88 (, 2H),
		0.26-0.15 (m, 2H).
316	584.4	1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 8.6 Hz, 1H), 8.11 (s, 3H),
		7.94 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.61 (s,
		1H), 6.39 (s, 1H), 5.18 (p, J = 7.4 Hz, 1H), 4.90 (dt, J = 14.4, 7.8 Hz, 1H),
		4.55-4.40 (m, 2H), 4.10 (s, 3H), 3.75 (s, 1H), 2.80 (s, 3H), 2.33 (s, 1H),
		2.14-1.55 (m, 8H), 1.52-1.29 (m, 7H), 1.27-0.90 (m, 5H), 0.63 (s,
		1H)
317	570.3	1H NMR (400 MHz, DMSO-d6) δ 8.23 (d, J = 7.4 Hz, 1H), 8.18-8.03
		(m, 3H), 7.90 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.09 (d, J = 8.0 Hz, 1H),
		6.58 (s, 1H), 6.38 (s, 1H), 4.96 (p, J = 7.1 Hz, 1H), 4.70-4.39 (m, 2H),
		4.10 (s, 3H), 2.79 (s, 3H), 2.20 (t, J = 11.4 Hz, 2H), 1.96-1.77 (m, 4H),
		1.69-1.30 (m, 9H), 1.27-0.97 (m, 2H), 0.82 (s, 1H).
318	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J = 7.2 Hz, 1H), 8.10 (s, 4H),
		7.92 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.58 (s,
		1H), 6.39 (s, 1H), 5.02 (p, J = 7.2 Hz, 1H), 4.46 (dtd, J = 27.3, 13.5, 6.8
		Hz, 2H), 4.10 (s, 3H), 2.79 (s, 3H), 2.29 (dd, J = 23.7, 11.3 Hz, 2H), 2.04-
		1.73 (m, 5H), 1.62 (t, J = 16.1 Hz, 2H), 1.46 (d, J = 7.0 Hz, 3H), 1.39-
		1.27 (m, 3H), 1.27-0.88 (m, 8H).
319	598.4	1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 8.5 Hz, 1H), 7.94 (d, J =
		8.0 Hz, 1H), 7.44 (s, 1H), 7.11 (d, J = 8.0 Hz, 1H), 6.61 (s, 1H), 6.38 (s,
		1H), 5.18 (p, J = 7.1 Hz, 1H), 4.90 (dt, J = 14.4, 7.7 Hz, 1H), 4.45 (d, J =
		15.6 Hz, 2H), 4.10 (s, 3H), 3.71 (s, 1H), 2.80 (s, 3H), 2.64 (q, J = 7.6, 5.5
		Hz, 3H), 2.13-1.80 (m, 5H), 1.75-1.57 (m, 2H), 1.53-1.31 (m, 7H),
		1.28-0.90 (m, 5H), 0.63 (s, 1H).
320	556.3	1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 4H), 7.90 (d, J = 8.3 Hz, 1H),
		7.87 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.05 (d, J = 8.1 Hz, 1H), 6.56 (s,
		1H), 6.36 (d, J = 1.4 Hz, 1H), 4.88 (p, J = 7.2 Hz, 1H), 4.65-4.30 (m,
		4H), 4.09 (s, 3H), 2.80 (s, 3H), 1.88 (d, J = 35.3 Hz, 5H), 1.66 (dt, J =
		23.8, 10.3 Hz, 2H), 1.46 (d, J = 7.2 Hz, 3H), 1.35 (dd, J = 12.9, 4.4 Hz,
		1H), 1.28-1.08 (m, 3H).
321	586.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 6.8 Hz, 1H), 8.20-8.04
		(m, 3H), 7.98 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.15 (d, J = 8.0 Hz, 1H),
		6.61 (s, 1H), 6.40 (s, 1H), 5.08 (p, J = 6.7 Hz, 1H), 4.69-4.33 (m, 4H),
		4.11 (s, 3H), 3.94-3.60 (m, 4H), 3.37 (q, J = 6.6, 6.0 Hz, 1H), 2.81 (s,
		3H), 2.71-2.55 (m, 1H), 2.38-2.21 (m, 2H), 1.87 (d, J = 19.9 Hz, 5H),
		1.75-1.58 (m, 1H), 1.55-1.35 (m, 5H), 1.35 (dd, J = 12.9, 4.3 Hz, 1H).
322	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.50 (d, J = 6.7 Hz, 1H), 8.08 (s, 4H),
		7.96-7.88 (m, 1H), 7.44 (s, 1H), 7.11 (d, J = 8.0 Hz, 1H), 6.58 (d, J = 1.7
		Hz, 1H), 6.37 (s, 1H), 5.01-4.92 (m, 1H), 4.64 (d, J = 13.8 Hz, 1H), 4.48
		(s, 2H), 4.10 (d, J = 1.8 Hz, 3H), 3.97 (dd, J = 14.2, 7.3 Hz, 1H), 3.60 (d,
		J = 6.4 Hz, 2H), 3.43 (dd, J = 11.0, 5.1 Hz, 1H), 2.82 (s, 3H), 2.13 (d, J =
		15.4 Hz, 1H), 1.83 (s, 3H), 1.76-1.58 (m, 2H), 1.43 (d, J = 6.7 Hz, 3H),
		1.40-1.25 (m, 1H), 0.88 (dd, J = 15.1, 7.4 Hz, 3H), 0.43 (d, J = 7.1 Hz,
		1H), 0.30 (d, J = 7.8 Hz, 1H).
323	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.47 (d, J = 7.3 Hz, 1H), 8.09 (s, 4H),
		7.94 (d, J = 7.9 Hz, 1H), 7.45 (s, 1H), 7.13 (d, J = 7.9 Hz, 1H), 6.56 (d, J =
		1.5 Hz, 1H), 6.36 (s, 1H), 5.03 (t, J = 6.9 Hz, 1H), 4.92 (d, J = 12.1 Hz,
		1H), 4.79 (d, J = 14.0 Hz, 1H), 4.49 (s, 1H), 4.10 (s, 3H), 3.73 (s, 1H),
		3.46 (q, J = 12.8, 10.0 Hz, 3H), 2.80 (s, 3H), 2.72 (t, J = 9.9 Hz, 1H), 2.10
		(d, J = 12.4 Hz, 1H), 1.84 (s, 3H), 1.64 (d, J = 9.7 Hz, 1H), 1.44 (d, J = 6.7
		Hz, 3H), 1.40-1.25 (m, 3H), 0.88 (dt, J = 21.9, 7.7 Hz, 3H), 0.23-0.12
		(m, 1H), 0.07 (d, J = 4.5 Hz, 1H).
324	572.3	1H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J = 7.5 Hz, 1H), 8.15-8.02
		(m, 3H), 7.99 (dd, J = 8.2, 2.1 Hz, 1H), 7.43 (s, 1H), 7.21 (dd, J = 7.8, 2.3
		Hz, 1H), 6.62 (d, J = 2.5 Hz, 1H), 6.36 (s, 1H), 5.07 (t, J = 7.4 Hz, 1H),
		4.60-4.25 (m, 4H), 4.16-3.97 (m, 5H), 2.82 (d, J = 2.4 Hz, 3H), 2.33 (s,
		1H), 1.98 (s, 1H), 1.90-1.61 (m, 4H), 1.59-1.52 (m, 3H), 1.52-1.41
		(m, 4H), 1.34 (d, J = 12.9 Hz, 1H).
325	584.3	1H NMR (400 MHz, DMSO-d6) δ 8.64 (d, J = 7.9 Hz, 1H), 8.08 (br s,
		3H), 7.97 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.18 (d, J = 8.1 Hz, 1H), 6.59
		(s, 1H), 6.37 (d, J = 1.3 Hz, 1H), 5.08 (p, J = 6.9 Hz, 1H), 4.85 (dd, J =
		14.2, 3.5 Hz, 1H), 4.48 (s, 3H), 4.21 (dd, J = 14.2, 7.3 Hz, 1H), 4.12 (d,
		J = 14.9 Hz, 1H), 4.09 (br s, 3H), 3.58 (d, J = 14.7 Hz, 1H), 3.40 (dd, J =
		10.9, 3.6 Hz, 1H), 3.31-3.25 (m, 1H), 2.79 (s, 3H), 1.90-1.57 (m, 5H),
		1.52 (d, J = 6.9 Hz, 3H), 1.34 (dd, J = 12.9, 4.4 Hz, 1H), 0.91 (s, 1H), 0.38
		(dt, J = 9.2, 5.0 Hz, 1H), 0.17 (td, J = 8.8, 8.2, 4.2 Hz, 1H).
326	584.3	1H NMR (400 MHz, DMSO-d6) δ 8.73-8.65 (m, 1H), 8.07 (s, 3H), 7.97
		(d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.17 (d, J = 8.1 Hz, 1H), 6.59 (s, 1H),
		6.37 (d, J = 1.3 Hz, 1H), 5.17 (p, J = 7.0 Hz, 1H), 4.85 (d, J = 13.7 Hz,
		1H), 4.49 (s, 3H), 4.22 (d, J = 14.7 Hz, 1H), 4.09 (s, 3H), 3.77-3.65 (m,
		2H), 3.24-3.19 (m, 1H), 3.14 (dd, J = 10.6, 4.1 Hz, 1H), 2.81 (s, 3H),
		1.97 (s, 1H), 1.84 (s, 3H), 1.64 (d, J = 8.7 Hz, 1H), 1.47 (d, J = 6.9 Hz,
		3H), 1.34 (dd, J = 12.8, 4.4 Hz, 1H), 0.73 (s, 1H), 0.64 (dt, J = 9.2, 4.8 Hz,
		1H), 0.49 (dt, J = 9.2, 5.2 Hz, 1H).
327	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.61 (d, J = 6.9 Hz, 1H), 7.91 (d, J =
		8.0 Hz, 1H), 7.33 (s, 1H), 7.08 (d, J = 8.0 Hz, 1H), 6.62 (s, 1H), 6.31 (s,
		1H), 4.94 (t, J = 7.0 Hz, 1H), 4.43 (dd, J = 14.2, 10.4 Hz, 1H), 4.08 (s,
		2H), 3.80-3.65 (m, 3H), 3.48 (s, 1H), 2.84 (s, 3H), 2.29-2.06 (m, 3H),
		1.85-1.48 (m, 2H), 1.40 (d, J = 7.0 Hz, 3H), 0.97 (s, 2H), 0.82 (dt, J =
		14.8, 7.4 Hz, 1H), 0.58 (dt, J = 8.8, 4.5 Hz, 1H), 0.20-0.11 (m, 1H).
328	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J = 7.5 Hz, 1H), 7.95 (d, J =
		8.0 Hz, 1H), 7.46 (s, 1H), 7.12 (d, J = 8.1 Hz, 1H), 6.63 (s, 1H), 6.35 (d,
		J = 1.4 Hz, 1H), 5.06 (p, J = 7.0 Hz, 1H), 4.81 (dd, J = 14.0, 7.5 Hz, 1H),
		4.63 (dd, J = 13.8, 6.1 Hz, 1H), 4.09 (s, 3H), 3.92-3.53 (m, 4H), 2.85 (s,
		3H), 2.38-2.17 (m, 1H), 1.84 (s, 4H), 1.64 (d, J = 9.0 Hz, 1H), 1.48 (d, J =
		7.0 Hz, 3H), 1.43-1.30 (m, 1H), 1.02-0.80 (m, 1H), 0.30-0.12 (m,
		2H).
329	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.40 (d, J = 7.7 Hz, 1H), 8.07 (s, 3H),
		7.91 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.58 (s,
		1H), 6.36 (s, 1H), 5.33 (d, J = 14.1 Hz, 1H), 4.99 (p, J = 7.2 Hz, 1H), 4.47
		(s, 2H), 4.21 (d, J = 14.2 Hz, 1H), 4.10 (s, 3H), 2.81 (s, 3H), 2.26 (d, J =
		9.4 Hz, 1H), 2.02 (d, J = 15.3 Hz, 1H), 1.84 (s, 4H), 1.64 (d, J = 9.6 Hz,
		1H), 1.46 (d, J = 7.1 Hz, 3H), 1.34 (dd, J = 12.9, 4.4 Hz, 1H), 0.28 (dt, J =
		9.6, 4.9 Hz, 1H), 0.22-0.15 (m, 1H), −0.04-−0.12 (m, 1H), −0.44-−0.51
		(m, 1H).
330	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J = 8.2 Hz, 1H), 8.10 (s, 3H),
		8.02 (d, J = 8.0 Hz, 1H), 7.38 (s, 1H), 7.21 (d, J = 8.0 Hz, 1H), 6.63 (s,
		1H), 6.36 (s, 1H), 5.25 (p, J = 7.1 Hz, 1H), 4.80 (t, J = 12.4 Hz, 1H), 4.49
		(s, 3H), 4.17 (d, J = 15.6 Hz, 1H), 4.10 (s, 3H), 3.91 (d, J = 6.9 Hz, 1H),
		3.72 (d, J = 15.6 Hz, 1H), 3.53 (q, J = 7.9 Hz, 1H), 2.84 (s, 3H), 2.33 (s,
		1H), 2.16 (t, J = 12.1 Hz, 1H), 1.84 (s, 3H), 1.64 (d, J = 9.4 Hz, 1H), 1.48
		(d, J = 6.8 Hz, 3H), 1.41-1.23 (m, 2H), 1.19-1.04 (m, 1H), 0.29 (s, 3H),
		0.20 (s, 1H).
331	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J = 6.4 Hz, 1H), 8.09 (s, 3H),
		7.99 (d, J = 8.0 Hz, 1H), 7.40 (s, 1H), 7.16 (d, J = 8.1 Hz, 1H), 6.61 (s,
		1H), 6.38 (s, 1H), 5.07 (p, J = 6.8 Hz, 1H), 4.75-4.65 (m, 1H), 4.10 (s,
		3H), 3.87 (d, J = 9.8 Hz, 1H), 3.71 (dt, J = 27.3, 8.7 Hz, 3H), 2.93 (d, J =
		9.8 Hz, 1H), 2.84 (s, 3H), 2.64-2.53 (m, 1H), 2.43-2.28 (m, 1H), 2.26-
		2.15 (m, 1H), 1.84 (s, 3H), 1.64 (d, J = 9.9 Hz, 1H), 1.48 (d, J = 6.8 Hz,
		4H), 1.35 (dd, J = 13.0, 4.3 Hz, 1H), 0.39-0.18 (m, 4H).
332	614.3	1H NMR (400 MHz, DMSO-d6) δ 8.18 (d, J = 7.1 Hz, 1H), 8.11 (s, 3H),
		7.93 (d, J = 7.9 Hz, 1H), 7.45 (s, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.59 (s,
		1H), 6.37 (s, 1H), 5.03 (q, J = 7.0 Hz, 1H), 4.71 (dt, J = 14.5, 7.6 Hz, 1H),
		4.65-4.35 (m, 2H), 4.10 (s, 3H), 3.70 (d, J = 51.4 Hz, 2H), 3.28 (s, 3H),
		2.85-2.78 (m, 1H), 2.80 (s, 3H), 2.01 (dd, J = 13.0, 8.6 Hz, 1H), 1.79 (d,
		J = 34.7 Hz, 3H), 1.62 (q, J = 13.5, 11.2 Hz, 2H), 1.40 (dd, J = 25.9, 5.8
		Hz, 5H), 1.20 (dd, J = 20.2, 9.5 Hz, 2H), 1.02-0.85 (m, 1H).
333	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.46 (d, J = 8.7 Hz, 1H), 8.19-8.05
		(m, 3H), 7.93 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.10 (d, J = 8.0 Hz, 1H),
		6.61 (s, 1H), 6.38 (s, 1H), 5.16 (p, J = 7.3 Hz, 1H), 4.90 (dd, J = 14.2, 7.5
		Hz, 1H), 4.49 (d, J = 14.2 Hz, 2H), 4.10 (s, 3H), 3.76 (s, 1H), 3.53-3.41
		(m, 1H), 3.19 (s, 3H), 2.81 (s, 3H), 1.90 (d, J = 47.7 Hz, 4H), 1.61 (q, J =
		12.8, 11.7 Hz, 2H), 1.41 (d, J = 7.1 Hz, 3H), 1.39-1.31 (m, 1H), 1.16 (d,
		J = 9.4 Hz, 1H), 1.05 (d, J = 13.0 Hz, 2H), 0.57 (s, 1H).
334	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 3H), 7.97 (d, J = 8.0 Hz, 1H),
		7.89 (d, J = 8.7 Hz, 1H), 7.45 (s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 6.61 (s,
		1H), 6.37 (s, 1H), 5.25 (q, J = 7.5 Hz, 1H), 4.73-4.63 (m, 1H), 4.50-
		4.40 (m, 2H), 4.10 (s, 3H), 3.76 (d, J = 4.8 Hz, 2H), 3.37 (s, 3H), 2.80 (s,
		3H), 1.91-1.58 (m, 8H), 1.56-1.29 (m, 7H), 1.12 (d, J = 27.0 Hz, 3H),
		0.80 (s, 1H).
335	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.4 Hz, 1H), 8.08 (s, 3H),
		7.95 (d, J = 7.9 Hz, 1H), 7.44 (s, 1H), 7.13 (d, J = 8.0 Hz, 1H), 6.61 (s,
		1H), 6.37 (s, 1H), 5.27 (q, J = 7.4 Hz, 1H), 4.86 (dt, J = 14.6, 7.4 Hz, 1H),
		4.48 (d, J = 14.3 Hz, 2H), 4.10 (s, 3H), 3.94 (t, J = 7.7 Hz, 1H), 3.22 (s,
		3H), 2.80 (s, 3H), 1.91 (d, J = 54.7 Hz, 5H), 1.60 (d, J = 23.8 Hz, 3H),
		1.51-1.22 (m, 7H), 1.06 (s, 3H), 0.84 (s, 1H), 0.58 (s, 1H).
336	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.36 (d, J = 7.4 Hz, 1H), 8.06 (d, J =
		7.9 Hz, 4H), 7.61 (s, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.08 (s, 1H), 7.03 (s,
		1H), 5.06 (t, J = 7.2 Hz, 1H), 4.92-4.85 (m, 1H), 4.70 (dm, J = 13.6 Hz,
		1H), 4.60-4.35 (s, 4H), 4.15 (s, 3H), 4.00 (s, 3H), 3.88 (t, J = 9.9 Hz,
		1H), 3.75 (t, J = 13.9 Hz, 2H), 3.58 (d, J = 15.4 Hz, 2H), 2.28-2.20 (m,
		1H), 1.83 (br s, 4H), 1.68-1.57br (m, 1H), 1.49 (d, J = 7.0 Hz, 3H), 1.38-
		1.29 (m, 1H), 0.91 (s, 2H), 0.18 (t, J = 7.4 Hz, 2H).
337	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 6.8 Hz, 1H), 8.15-8.00
		(m, 4H), 7.60 (s, 1H), 7.18 (d, J = 8.7 Hz, 1H), 7.08 (s, 1H), 7.04 (s, 1H),
		5.03-4.91 (m, 2H), 4.60-4.35 (t, J = 12.9 Hz, 2H), 4.15 (d, J = 2.0 Hz,
		3H), 4.01 (d, J = 2.1 Hz, 3H), 3.83-3.65 (m, 4H), 3.12-3.04 (m, J = 9.7
		Hz, 1H), 2.20 (d, J = 15.2 Hz, 1H), 1.83 (br s, 4H), 1.63 (d, J = 10.0 Hz,
		1H), 1.41 (d, J = 7.0 Hz, 3H), 1.34 (d, J = 12.8 Hz, 1H), 1.05-0.79 (m,
		2H), 0.61 (br s, 1H), 0.19 (br s, 1H).
338	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 6.5 Hz, 1H), 8.18-8.01
		(m, 4H), 7.60 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.07-7.00 (m, 2H), 5.01
		(t, J = 7.1 Hz, 1H), 4.95-4.79 (m, 1H), 4.63-4.32 (m, 3H), 4.13 (d, J =
		2.2 Hz, 3H), 4.01 (d, J = 2.2 Hz, 3H), 3.74 (s, 1H), 3.68-3.57 (m, 2H),
		3.53 (d, J = 10.7 Hz, 1H), 3.16 (t, J = 10.3 Hz, 1H), 2.38-2.24 (m, 2H),
		1.93-1.57 (m, 6H), 1.42 (d, J = 7.0 Hz, 3H), 1.38-1.28 (m, 1H), 1.05 (s,
		1H), 0.66-0.42 (m, 2H), −0.21-−0.32 (m, 1H).
339	627.3	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 7.2 Hz, 1H), 8.05 (s, 3H),
		7.62 (d, J = 8.2 Hz, 1H), 7.57 (s, 1H), 7.34 (s, 1H), 7.08 (dd, J = 8.3, 1.3
		Hz, 1H), 7.02 (d, J = 1.2 Hz, 1H), 6.99 (s, 1H), 4.93 (p, J = 7.0 Hz, 1H),
		4.60-4.34 (m, 3H), 4.27-4.16 (m, 1H), 4.10 (s, 3H), 4.00 (s, 3H), 3.74
		(br s, 1H), 3.20 (s, 3H), 2.03-1.92 (m, 1H), 1.90-1.71 (m, 4H), 1.68-
		1.43 (m, 5H), 1.42 (s, 3H), 1.33 (dd, J = 12.7, 4.4 Hz, 1H), 1.26-1.13 (m,
		4H).
340	627.3	1H NMR (400 MHz, DMSO-d6) δ 8.18 (d, J = 7.7 Hz, 1H), 8.05 (s, 4H),
		7.61 (d, J = 8.2 Hz, 1H), 7.57 (s, 1H), 7.38 (s, 1H), 7.09 (d, J = 8.2 Hz,
		1H), 7.02 (s, 1H), 6.99 (s, 1H), 5.08 (p, J = 7.0 Hz, 1H), 4.64-4.31 (m,
		3H), 4.24-4.16 (m, 1H), 4.09 (s, 3H), 4.00 (s, 3H), 3.74 (br s, 1H), 2.06-
		1.96 (m, 1H), 1.89-1.75 (m, 2H), 1.74-1.53 (m, 2H), 1.51 (d, J = 7.1 Hz,
		3H), 1.46-1.29 (m, 3H), 1.22 (s, 3H), 1.15 (d, J = 8.1 Hz, 2H).
341	641.4	1H NMR (400 MHz, DMSO-d6) δ 8.07 (br s, 3H), 7.97 (d, J = 7.3 Hz,
		1H), 7.60 (d, J = 8.2 Hz, 1H), 7.57 (s, 1H), 7.35 (s, 1H), 7.06 (dd, J = 8.3,
		1.3 Hz, 1H), 7.02 (d, J = 1.2 Hz, 1H), 6.99 (s, 1H), 5.08-4.98 (m, 1H),
		4.65-4.37 (m, 3H), 4.23-4.14 (m, 1H), 4.10 (s, 3H), 4.00 (s, 3H), 3.75
		(br s, 1H), 3.53 (d, J = 9.3 Hz, 1H), 3.33 (d, J = 9.6 Hz, 1H), 3.31 (s, 3H),
		2.36-2.25 (m, 1H), 2.06-1.97 (m, 1H), 1.88-1.57 (m, 6H), 1.50-1.30
		(m, 8H), 1.15-1.03 (m, 3H), 0.94 (s, 3H).
342	597.3	1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J = 7.1 Hz, 1H), 8.06 (s, 3H),
		7.60-7.55 (m, 2H), 7.48 (s, 1H), 7.05-6.99 (m, 3H), 4.96 (p, J = 6.9 Hz,
		1H), 4.75-4.66 (m, 1H), 4.55-4.32 (m, 2H), 4.08 (s, 3H), 4.00 (s, 3H),
		3.12 (d, J = 9.3 Hz, 1H), 2.98 (t, J = 10.1 Hz, 1H), 2.76-2.66 (m, 1H),
		2.36-2.25 (m, 1H), 2.04-1.98 (m, 1H), 1.90-1.73 (m, 6H), 1.67-1.46
		(m, 2H), 1.42 (d, J = 7.1 Hz, 3H), 1.33 (dd, J = 12.9, 4.4 Hz, 1H), 0.89-
		0.74 (m, 2H).
343	640.5	1H NMR (400 MHz, DMSO-d6) δ 9.32 (s, 1H), 8.84 (s, 1H), 8.09 (d, J =
		8.1 Hz, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 1.1 Hz, 1H), 7.23 (d, J =
		8.2 Hz, 1H), 7.04 (s, 1H), 6.91 (s, 1H), 5.25 (p, J = 7.0 Hz, 1H), 4.87-
		4.72 (m, 1H), 4.48-4.32 (m, 1H), 4.11 (s, 3H), 4.04-4.01 (m, 2H), 3.98
		(s, 3H), 3.79-3.64 (m, 2H), 3.11-2.94 (m, 2H), 2.25 (t, J = 12.6 Hz,
		1H), 2.12-1.93 (m, 1H), 1.89-1.81 (m, 2H), 1.81-1.67 (m, 3H), 1.43
		(d, J = 6.9 Hz, 3H), 1.41-1.30 (m, 1H), 1.29-1.15 (m, 3H), 1.15-0.98
		(m, 1H), 0.96-0.88 (m, 1H), 0.62-0.53 (m, 1H), 0.50-0.40 (m, 1H).
344	639.3	1H NMR (400 MHz, DMSO-d6) δ 9.20 (d, J = 6.9 Hz, 1H), 8.83 (s, 2H),
		8.72 (d, J = 7.9 Hz, 1H), 8.57 (d, J = 5.1 Hz, 1H), 8.55 (s, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 7.99 (s, 1H), 7.49 (d, J = 5.1 Hz, 1H), 7.36 (s, 1H), 7.26 (d,
		J = 8.1 Hz, 1H), 7.13 (s, 1H), 5.21 (p, J = 7.0 Hz, 1H), 4.99-4.72 (m, 2H),
		4.69-4.56 (m, 1H), 4.50-4.38 (m, 1H), 4.15 (s, 3H), 4.03 (s, 3H), 3.56-
		3.31 (m, 2H), 3.17-2.88 (m, 2H), 2.46-2.26 (m, 4H), 2.03-1.82 (m,
		1H), 1.66-1.06 (m, 7H), 0.66-0.48 (m, 1H).
345	656.3	1H NMR (400 MHz, DMSO-d6) δ 9.17 (d, J = 7.4 Hz, 1H), 8.76 (s, 2H),
		8.70 (d, J = 7.9 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 1.2 Hz, 1H),
		7.35 (d, J = 1.2 Hz, 1H), 7.34-7.28 (m, 1H), 7.25 (d, J = 8.1 Hz, 1H),
		7.13 (s, 1H), 7.11-6.97 (m, 2H), 5.28 (p, J = 7.1 Hz, 1H), 5.01-4.73 (m,
		2H), 4.69-4.55 (m, 1H), 4.54-4.35 (m, 1H), 4.14 (s, 3H), 4.02 (s, 3H),
		3.41-3.27 (m, 1H), 3.15-2.86 (m, 2H), 2.43-2.12 (m, 4H), 2.02-1.82
		(m, 1H), 1.67-1.07 (m, 8H), 0.56-0.33 (m, 1H).
346	650.3	1H NMR (400 MHz, DMSO-d6) δ 8.92-8.76 (m, 3H), 8.72 (d, J = 7.9
		Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.01 (s, 1H), 7.44-7.31 (m, 3H), 7.31-
		7.18 (m, 3H), 7.07 (s, 1H), 5.18 (p, J = 7.0 Hz, 1H), 4.86 (dtd, J = 48.8,
		9.4, 4.5 Hz, 1H), 4.69 (dd, J = 14.0, 2.7 Hz, 1H), 4.54-4.38 (m, 1H), 4.17
		(s, 3H), 4.02 (s, 3H), 3.89-3.78 (m, 2H), 3.51-3.30 (m, 2H), 3.15-2.87
		(m, 2H), 2.73-2.56 (m, 1H), 2.43-2.28 (m, 1H), 2.02-1.84 (m, 1H),
		1.74-1.59 (m, 1H), 1.50 (d, J = 7.1 Hz, 3H), 1.41-1.28 (m, 1H), 1.28-
		1.07 (m, 2H), 0.31 (dt, J = 8.9, 4.6 Hz, 1H), 0.23 (dt, J = 9.3, 4.9 Hz, 1H).
347	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 6.8 Hz, 1H), 8.73 (s, 2H),
		8.62 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 6.3 Hz, 1H),
		7.63 (d, J = 10.5 Hz, 1H), 7.40-7.27 (m, 3H), 7.27-7.15 (m, 3H), 5.16
		(p, J = 7.0 Hz, 1H), 5.02-4.68 (m, 3H), 4.50-4.34 (m, 1H), 3.91-3.81
		(m, 1H), 3.53-3.29 (m, 2H), 3.15-2.84 (m, 2H), 2.44-2.27 (m, 2H),
		2.27-2.11 (m, 1H), 1.97-1.81 (m, 1H), 1.58-1.36 (m, 5H), 1.36-1.03
		(m, 5H), 0.94 (d, J = 5.9 Hz, 1H), 0.58-0.34 (m, 2H).
348	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 6.9 Hz, 1H), 8.72 (s, 2H),
		8.63 (d, J = 8.1 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 6.4 Hz, 1H),
		7.62 (d, J = 10.6 Hz, 1H), 7.41-7.32 (m, 2H), 7.30 (s, 1H), 7.28-7.19
		(m, 3H), 5.18 (p, J = 7.0 Hz, 1H), 4.97-4.69 (m, 2H), 4.50-4.32 (m,
		1H), 3.95-3.80 (m, 2H), 3.52-3.30 (m, 2H), 3.14-2.87 (m, 2H), 2.65-
		2.53 (m, 2H), 2.41-2.26 (m, 1H), 2.04-1.80 (m, 1H), 1.76-1.59 (m,
		1H), 1.51 (d, J = 7.0 Hz, 3H), 1.37-1.11 (m, 4H), 1.11-0.97 (m, 1H),
		0.88-0.70 (m, 2H), 0.40-0.26 (m, 1H), 0.26-0.17 (m, 1H).
349	627.3	1H NMR (400 MHz, DMSO-d6) δ 9.14 (d, J = 6.8 Hz, 1H), 8.73 (s, 2H),
		8.64 (d, J = 8.0 Hz, 1H), 8.57 (s, 1H), 8.52 (d, J = 5.1 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H), 7.76 (d, J = 10.8 Hz, 1H), 7.34 (d,
		J = 5.2 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.20 (s, 1H), 5.20 (p, J = 7.1 Hz,
		1H), 4.96-4.66 (m, 3H), 4.47-4.30 (m, 1H), 3.98 (s, 3H), 3.53-3.30
		(m, 2H), 3.14-2.85 (m, 2H), 2.40-2.24 (m, 4H), 2.01-1.82 (m, 1H),
		1.66-1.37 (m, 5H), 1.37-1.06 (m, 2H), 0.72-0.48 (m, 1H).
350	627.3	1H NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 6.9 Hz, 1H), 8.72 (s, 2H),
		8.64 (d, J = 8.1 Hz, 1H), 8.50 (d, J = 4.9 Hz, 1H), 8.48 (s, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H), 7.77 (d, J = 10.8 Hz, 1H), 7.38 (d,
		J = 5.0 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.20 (s, 1H), 5.20 (p, J = 7.0 Hz,
		1H), 4.96-4.67 (m, 3H), 4.48-4.34 (m, 1H), 3.98 (s, 3H), 3.51-3.31
		(m, 2H), 3.13-2.86 (m, 2H), 2.43-2.25 (m, 4H), 2.00-1.84 (m, 1H),
		1.65-1.36 (m, 5H), 1.36-1.06 (m, 2H), 0.64-0.48 (m, 1H).
351	638.3	1H NMR (400 MHz, DMSO-d6) δ 8.81-8.68 (m, 3H), 8.65 (d, J = 8.2
		Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 6.4 Hz, 1H), 7.76 (d, J =
		10.8 Hz, 1H), 7.34-7.04 (m, 6H), 5.22 (p, J = 7.0 Hz, 1H), 4.96-4.70
		(m, 2H), 4.49-4.31 (m, 1H), 4.24 (dd, J = 14.2, 7.5 Hz, 1H), 3.95 (s, 3H),
		3.43-3.34 (m, 2H), 3.14-2.87 (m, 3H), 2.74 (ddd, J = 14.6, 10.6, 4.1
		Hz, 1H), 2.41-2.25 (m, 2H), 2.01-1.71 (m, 2H), 1.62 (d, J = 7.0 Hz,
		3H), 1.58-1.45 (m, 1H), 1.18-1.01 (m, 0H), 0.88-0.72 (m, 1H), 0.44-
		0.29 (m, 2H).
352	644.3	1H NMR (400 MHz, DMSO-d6) δ 8.98 (d, J = 7.1 Hz, 1H), 8.75 (s, 2H),
		8.65 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 6.4 Hz, 1H),
		7.76 (d, J = 10.8 Hz, 1H), 7.35-7.14 (m, 5H), 5.22 (p, J = 7.1 Hz, 1H),
		4.98-4.66 (m, 3H), 4.48-4.33 (m, 1H), 3.98 (s, 3H), 3.52-3.31 (m,
		2H), 3.12-2.88 (m, 2H), 2.48-2.15 (m, 4H), 2.01-1.79 (m, 1H), 1.67-
		1.36 (m, 5H), 1.36-1.08 (m, 2H), 0.61-0.41 (m, 1H).
353	653.3	1H NMR (400 MHz, DMSO-d6) δ 9.14 (d, J = 6.8 Hz, 1H), 8.72 (s, 2H),
		8.63 (d, J = 8.2 Hz, 1H), 8.48 (d, J = 4.9 Hz, 1H), 8.45 (s, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.99 (d, J = 6.4 Hz, 1H), 7.63 (d, J = 10.5 Hz, 1H), 7.36 (s,
		1H), 7.34 (d, J = 4.9 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.23-5.12 (m,
		1H), 5.01-4.68 (m, 3H), 4.48-4.32 (m, 1H), 3.91-3.80 (m, 1H), 3.12-
		2.88 (m, 2H), 2.41-2.25 (m, 3H), 2.01-1.78 (m, 1H), 1.58-1.37 (m,
		5H), 1.36-1.06 (m, 5H), 1.03-0.86 (m, 1H), 0.60-0.35 (m, 2H).
354	687.3	1H NMR (400 MHz, DMSO-d6) δ 9.41 (d, J = 7.7 Hz, 1H), 8.74 (s, 2H),
		8.63 (d, J = 8.0 Hz, 1H), 8.53 (s, 1H), 8.42 (s, 1H), 8.09 (d, J = 8.0 Hz,
		1H), 7.99 (d, J = 6.3 Hz, 1H), 7.63 (d, J = 10.6 Hz, 1H), 7.37 (s, 1H), 7.27
		(d, J = 8.1 Hz, 1H), 5.41-5.24 (m, 1H), 5.04-4.67 (m, 3H), 4.49-4.32
		(m, 2H), 3.91-3.76 (m, 1H), 3.56-3.29 (m, 2H), 3.13-2.84 (m, 2H),
		2.40-2.23 (m, 2H), 2.14-1.80 (m, 2H), 1.60-1.37 (m, 5H), 1.37-1.05
		(m, 4H), 1.02-0.86 (m, 1H), 0.55-0.28 (m, 2H).
355	671.3	1H NMR (400 MHz, DMSO-d6) δ 9.46 (d, J = 7.1 Hz, 1H), 8.82 (d, J =
		8.1 Hz, 2H), 8.63 (d, J = 8.1 Hz, 1H), 8.49 (s, 1H), 8.33 (s, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.99 (d, J = 6.4 Hz, 1H), 7.63 (d, J = 10.5 Hz, 1H), 7.37 (s,
		1H), 7.26 (d, J = 8.0 Hz, 1H), 5.26 (p, J = 7.0 Hz, 1H), 5.02-4.70 (m,
		3H), 4.47-4.33 (m, 2H), 3.85 (tt, J = 7.2, 3.9 Hz, 1H), 3.53-3.31 (m,
		2H), 3.14-2.87 (m, 2H), 2.43-2.24 (m, 2H), 2.14 (td, J = 12.6, 3.8 Hz,
		1H), 2.00-1.81 (m, 1H), 1.58-1.37 (m, 5H), 1.37-1.06 (m, 4H), 1.02-
		0.88 (m, 1H), 0.51-0.29 (m, 2H).
356	687.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 6.6 Hz, 1H), 8.73 (s, 2H),
		8.66-8.56 (m, 1H), 8.28 (s, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 6.4
		Hz, 1H), 7.63 (d, J = 10.6 Hz, 1H), 7.47 (s, 1H), 7.36 (s, 1H), 7.25 (d, J =
		8.1 Hz, 1H), 5.14 (p, J = 7.0 Hz, 1H), 4.98-4.68 (m, 3H), 4.47-4.32 (m,
		1H), 3.89-3.80 (m, 1H), 3.55-3.29 (m, 2H), 3.15-2.87 (m, 2H), 2.42-
		2.23 (m, 5H), 2.01-1.81 (m, 1H), 1.57-1.36 (m, 5H), 1.36-1.03 (m,
		3H), 1.03-0.86 (m, 1H), 0.56-0.35 (m, 2H).
357	687.3	1H NMR (400 MHz, DMSO-d6) δ 9.20 (d, J = 6.7 Hz, 1H), 8.74 (s, 2H),
		8.65-8.56 (m, 1H), 8.37 (s, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 6.4
		Hz, 1H), 7.63 (d, J = 10.6 Hz, 1H), 7.44 (s, 1H), 7.36 (s, 1H), 7.25 (d, J =
		8.1 Hz, 1H), 5.15 (p, J = 7.0 Hz, 1H), 4.98-4.68 (m, 3H), 4.49-4.32 (m,
		1H), 3.91-3.76 (m, 1H), 3.54-3.29 (m, 2H), 3.17-2.86 (m, 2H), 2.49-
		2.44 (m, 1H), 2.41-2.23 (m, 3H), 2.00-1.79 (m, 1H), 1.61-1.05 (m,
		9H), 1.03-0.87 (m, 1H), 0.61-0.33 (m, 2H).
358	651.3	1H NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 6.9 Hz, 1H), 8.51 (d, J =
		5.0 Hz, 1H), 8.49 (s, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.96 (s, 3H), 7.43 (s,
		1H), 7.40 (d, J = 5.0 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.93
		(d, J = 1.2 Hz, 1H), 5.20 (p, J = 7.0 Hz, 1H), 4.92-4.76 (m, 1H), 4.69-
		4.54 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.92-3.79 (m, 1H), 3.76-3.64
		(m, 1H), 3.61-3.46 (m, 2H), 3.46-3.27 (m, 4H), 2.42-2.29 (m, 3H),
		2.03-1.87 (m, 1H), 1.83-1.68 (m, 1H), 1.62-1.07 (m, 8H), 0.63-0.43
		(m, 1H).
359	685.3	1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 6.7 Hz, 1H), 8.29 (s, 1H),
		8.08 (d, J = 8.0 Hz, 1H), 7.97 (s, 3H), 7.47 (s, 1H), 7.43 (s, 1H), 7.25 (d,
		J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.93 (d, J = 1.1 Hz, 1H), 5.16 (p, J = 6.9 Hz,
		1H), 4.89-4.77 (m, 1H), 4.66-4.53 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H),
		3.92-3.80 (m, 1H), 3.76-3.65 (m, 1H), 3.63-3.46 (m, 2H), 3.46-3.30
		(m, 4H), 2.42-2.26 (m, 3H), 2.02-1.85 (m, 1H), 1.83-1.68 (m, 1H),
		1.57-1.32 (m, 5H), 1.31-1.06 (m, 3H), 0.60-0.42 (m, 1H).
360	668.4	1H NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 7.4 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.96 (s, 3H), 7.43 (s, 1H), 7.32 (td, J = 8.0, 6.0 Hz, 1H), 7.25
		(d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 7.07-6.99 (m, 2H), 6.93 (d, J = 1.2 Hz,
		1H), 5.28 (p, J = 7.1 Hz, 1H), 4.96-4.83 (m, 1H), 4.64-4.53 (m, 1H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.74-3.67 (m, 2H), 3.58-3.48 (m, 3H), 3.45-
		3.31 (m, 4H), 2.30-2.12 (m, 2H), 2.02-1.86 (m, 1H), 1.84-1.68 (m,
		1H), 1.59-1.33 (m, 5H), 1.33-1.10 (m, 3H), 0.52-0.32 (m, 1H).
361	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.92 (d, J = 7.9 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.01-7.85 (m, 3H), 7.40 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H),
		7.17 (t, J = 7.5 Hz, 1H), 7.08 (s, 1H), 7.05 (d, J = 7.5 Hz, 1H), 7.01 (d, J =
		7.6 Hz, 1H), 6.92 (d, J = 1.1 Hz, 1H), 5.37 (p, J = 7.1 Hz, 1H), 4.96-4.84
		(m, 1H), 4.62-4.51 (m, 1H), 4.30-4.04 (m, 4H), 3.99 (s, 3H), 3.33-
		3.01 (m, 4H), 2.66-2.52 (m, 1H), 2.31 (s, 3H), 2.25-2.06 (m, 2H), 2.06-
		1.92 (m, 1H), 1.83-1.71 (m, 1H), 1.67-1.34 (m, 7H), 1.32-1.12 (m,
		2H), 0.52-0.34 (m, 1H).
362	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.92 (d, J = 7.9 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.03-7.88 (m, 3H), 7.43 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H),
		7.17 (t, J = 7.5 Hz, 1H), 7.08 (s, 1H), 7.05 (d, J = 7.5 Hz, 1H), 7.01 (d, J =
		7.6 Hz, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.37 (p, J = 7.1 Hz, 1H), 4.97-4.86
		(m, 1H), 4.62-4.50 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.96-3.78 (m,
		1H), 3.75-3.67 (m, 1H), 3.59-3.47 (m, 3H), 3.49-3.31 (m, 5H), 2.62-
		2.52 (m, 1H), 2.31 (s, 3H), 2.25-2.04 (m, 2H), 2.00-1.89 (m, 1H), 1.83-
		1.68 (m, 1H), 1.65-1.36 (m, 5H), 1.34-0.98 (m, 2H), 0.52-0.33 (m,
		1H).
363	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 7.9 Hz, 1H), 8.80-8.65
		(m, 3H), 8.08 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 1.3 Hz, 1H), 7.35 (d, J = 1.3
		Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.12 (s, 1H),
		7.05 (d, J = 7.5 Hz, 1H), 7.01 (d, J = 7.5 Hz, 1H), 5.37 (p, J = 7.1 Hz, 1H),
		4.97-4.75 (m, 2H), 4.63-4.54 (m, 1H), 4.52-4.36 (m, 1H), 4.14 (s,
		3H), 4.02 (s, 3H), 3.50-3.31 (m, 2H), 3.13-2.89 (m, 2H), 2.60-2.51
		(m, 1H), 2.40-2.27 (m, 4H), 2.27-2.06 (m, 2H), 2.02-1.83 (m, 1H),
		1.71-1.54 (m, 1H), 1.51-1.38 (m, 4H), 1.33-1.08 (m, 2H), 0.57-0.37
		(m, 1H).
364	666.3	1H NMR (400 MHz, DMSO-d6) δ 8.80-8.64 (m, 3H), 8.10 (d, J = 7.0
		Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 1.3 Hz, 1H), 7.36 (d, J = 1.3
		Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.12 (s, 1H), 5.02-4.74 (m, 3H), 4.50-
		4.28 (m, 2H), 4.20 (s, 3H), 4.03 (s, 3H), 3.53-3.30 (m, 2H), 3.16-2.89
		(m, 2H), 2.41-2.14 (m, 4H), 1.92 (d, J = 23.8 Hz, 2H), 1.51-1.37 (m,
		4H), 1.32-1.06 (m, 5H), 0.88 (s, 3H), 0.69-0.51 (m, 1H).
365	666.3	1H NMR (400 MHz, DMSO-d6) δ 8.83-8.65 (m, 3H), 8.08 (d, J = 8.1
		Hz, 1H), 7.97 (d, J = 1.3 Hz, 1H), 7.90 (d, J = 7.9 Hz, 1H), 7.34 (d, J = 1.3
		Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 5.17-5.02 (m, 2H), 5.01-
		4.73 (m, 2H), 4.53-4.35 (m, 1H), 4.14 (s, 3H), 4.02 (s, 3H), 3.53-3.30
		(m, 2H), 3.14-2.84 (m, 2H), 2.43-2.24 (m, 1H), 2.08-1.76 (m, 3H),
		1.74-1.61 (m, 1H), 1.53 (d, J = 7.0 Hz, 3H), 1.42-1.31 (m, 1H), 1.24-
		0.76 (m, 10H).
366	642.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 8.02-7.86
		(m, 3H), 7.79 (d, J = 7.9 Hz, 1H), 7.46 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H),
		7.07 (s, 1H), 6.92 (d, J = 1.2 Hz, 1H), 5.09 (p, J = 7.1 Hz, 1H), 4.80-4.69
		(m, 1H), 4.67-4.54 (m, 1H), 4.14 (s, 3H), 3.98 (s, 3H), 3.92-3.78 (m,
		1H), 3.75-3.68 (m, 1H), 3.64-3.49 (m, 2H), 3.48-3.32 (m, 5H), 2.01-
		1.89 (m, 1H), 1.82-1.62 (m, 2H), 1.57-1.17 (m, 8H), 1.12 (s, 3H), 1.01
		(s, 3H), 0.75-0.57 (m, 2H), 0.26-0.14 (m, 1H), −0.40 (d, J = 5.4 Hz,
		1H).
367	630.4	1H NMR (400 MHz, DMSO-d6) δ 8.83-8.73 (m, 2H), 8.69 (d, J = 7.9
		Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 1.3 Hz, 1H), 7.78 (d, J = 7.9
		Hz, 1H), 7.35 (d, J = 1.2 Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.12 (s, 1H),
		5.10 (p, J = 7.3 Hz, 1H), 4.92 (td, J = 9.3, 4.5 Hz, 1H), 4.85-4.72 (m,
		1H), 4.62 (dd, J = 14.1, 7.8 Hz, 1H), 4.51-4.36 (m, 1H), 4.17 (s, 3H),
		4.02 (s, 3H), 3.53-3.33 (m, 2H), 3.15-2.87 (m, 2H), 2.42-2.25 (m,
		1H), 2.01-1.80 (m, 1H), 1.79-1.61 (m, 1H), 1.60-1.19 (m, 8H), 1.12
		(s, 3H), 1.01 (s, 3H), 0.79-0.56 (m, 2H), 0.27-0.15 (m, 1H), −0.31-−
		0.47 (m, 1H).
368	638.3	1H NMR (400 MHz, DMSO-d6) δ 8.78-8.62 (m, 4H), 8.04-7.94 (m,
		2H), 7.35 (d, J = 1.3 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.06 (s, 1H), 5.02-
		4.72 (m, 2H), 4.60-4.51 (m, 2H), 4.50-4.35 (m, 1H), 4.15 (s, 3H), 4.02
		(s, 3H), 3.50-3.30 (m, 2H), 3.14-2.84 (m, 2H), 2.48-2.29 (m, 2H),
		2.00-1.04 (m, 13H).
369	638.3	1H NMR (400 MHz, DMSO-d6) δ 8.80-8.62 (m, 4H), 8.02 (d, J = 8.0
		Hz, 1H), 7.99 (d, J = 1.3 Hz, 1H), 7.34 (d, J = 1.3 Hz, 1H), 7.13 (d, J = 8.1
		Hz, 1H), 7.08 (s, 1H), 4.91-4.73 (m, 2H), 4.68-4.59 (m, 1H), 4.53-
		4.37 (m, 1H), 4.13 (s, 3H), 4.02 (s, 3H), 3.51-3.31 (m, 2H), 3.15-2.86
		(m, 2H), 2.72-2.58 (m, 1H), 2.42-2.24 (m, 1H), 2.13-1.82 (m, 4H),
		1.56-1.32 (m, 6H), 1.32-1.06 (m, 2H), 1.05-0.92 (m, 1H), 0.65-0.49
		(m, 1H).
370	696.4	1H NMR (400 MHz, DMSO-d6) δ 8.31 (d, J = 7.9 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 8.04-7.90 (m, 3H), 7.47 (s, 1H), 7.25 (d, J = 8.2 Hz, 1H),
		7.09 (s, 1H), 6.93 (s, 1H), 5.10 (p, J = 7.1 Hz, 1H), 4.85-4.76 (m, 1H),
		4.58 (t, J = 11.7 Hz, 2H), 4.15 (s, 3H), 3.99 (s, 3H), 3.94-3.77 (m, 1H),
		3.76-3.67 (m, 1H), 3.63-3.47 (m, 2H), 3.46-3.31 (m, 4H), 2.20-2.06
		(m, 1H), 2.04-1.89 (m, 1H), 1.85-1.69 (m, 2H), 1.64-1.33 (m, 7H),
		1.29 (s, 3H), 0.80-0.53 (m, 2H), 0.38-0.24 (m, 1H), −0.27-−0.42 (m,
		1H).
371	684.3	1H NMR (400 MHz, DMSO-d6) δ 8.81-8.72 (m, 2H), 8.69 (d, J = 7.9
		Hz, 1H), 8.30 (d, J = 7.9 Hz, 1H), 8.09 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 3.0
		Hz, 1H), 7.35 (s, 1H), 7.25 (d, J = 8.2 Hz, 1H), 7.14 (s, 1H), 5.11 (p, J =
		7.3 Hz, 1H), 4.97-4.74 (m, 2H), 4.64-4.52 (m, 1H), 4.51-4.34 (m,
		1H), 4.18 (s, 3H), 4.02 (s, 3H), 3.49-3.31 (m, 2H), 3.17-2.85 (m, 2H),
		2.41-2.29 (m, 1H), 2.19-2.05 (m, 1H), 2.03-1.83 (m, 1H), 1.81-1.70
		(m, 1H), 1.67-1.36 (m, 7H), 1.28 (s, 3H), 0.83-0.67 (m, 1H), 0.67-
		0.57 (m, 1H), 0.39-0.22 (m, 1H), −0.22-−0.37 (m, 1H).
372	696.4	1H NMR (400 MHz, DMSO-d6) δ 8.34 (d, J = 8.2 Hz, 1H), 8.06 (d, J =
		8.1 Hz, 1H), 8.04-7.88 (m, 3H), 7.46 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H),
		7.09 (s, 1H), 6.93 (s, 1H), 5.18 (p, J = 7.2 Hz, 1H), 4.90-4.77 (m, 1H),
		4.65-4.52 (m, 2H), 4.15 (s, 3H), 3.98 (s, 3H), 3.94-3.76 (m, 1H), 3.73-
		3.64 (m, 1H), 3.62-3.48 (m, 2H), 3.46-3.30 (m, 4H), 2.38-2.24 (m,
		1H), 2.03-1.88 (m, 1H), 1.82-1.68 (m, 1H), 1.67-1.31 (m, 7H), 1.30-
		1.07 (m, 4H), 0.80-0.67 (m, 2H), 0.32-0.17 (m, 1H), −0.33-−0.46 (m,
		1H).
373	684.3	1H NMR (400 MHz, DMSO-d6) δ 8.82-8.70 (m, 2H), 8.68 (d, J = 8.0
		Hz, 1H), 8.33 (d, J = 8.1 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 8.02 (s, 1H),
		7.34 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.13 (s, 1H), 5.19 (p, J = 7.2 Hz,
		1H), 4.96-4.73 (m, 2H), 4.65-4.50 (m, 1H), 4.50-4.34 (m, 1H), 4.17
		(s, 3H), 4.02 (s, 3H), 3.51-3.27 (m, 2H), 3.14-2.89 (m, 2H), 2.42-2.22
		(m, 2H), 2.03-1.83 (m, 1H), 1.67-1.08 (m, 11H), 0.84-0.60 (m, 2H),
		0.33-0.21 (m, 1H), −0.29-−0.43 (m, 1H).
374	638.3	1H NMR (400 MHz, DMSO-d6) δ 9.04 (d, J = 7.9 Hz, 1H), 8.09 (d, J =
		8.1 Hz, 1H), 8.04-7.88 (m, 3H), 7.44 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H),
		7.05 (s, 1H), 6.93 (s, 1H), 5.25 (p, J = 7.2 Hz, 1H), 4.81-4.69 (m, 1H),
		4.55-4.44 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.95-3.78 (m, 2H), 3.75-
		3.68 (m, 1H), 3.64-3.46 (m, 2H), 3.46-3.30 (m, 4H), 2.23-2.02 (m,
		2H), 2.02-1.89 (m, 1H), 1.86-1.70 (m, 2H), 1.66-1.08 (m, 9H), 0.98-
		0.81 (m, 1H).
375	626.3	1H NMR (400 MHz, DMSO-d6) δ 9.03 (d, J = 7.9 Hz, 1H), 8.81-8.72
		(m, 2H), 8.70 (d, J = 7.9 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 8.00 (s, 1H),
		7.35 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 5.26 (p, J = 7.2 Hz,
		1H), 4.99-4.69 (m, 2H), 4.60-4.36 (m, 2H), 4.14 (s, 3H), 4.02 (s, 3H),
		3.50-3.32 (m, 2H), 3.16-2.88 (m, 2H), 2.42-2.28 (m, 1H), 2.23-2.03
		(m, 2H), 2.01-1.85 (m, 1H), 1.85-1.69 (m, 1H), 1.69-1.38 (m, 6H),
		1.38-1.12 (m, 3H), 1.02-0.87 (m, 1H).
376	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.79-8.63 (m, 3H), 8.33 (s, 1H), 8.05
		(d, J = 8.1 Hz, 1H), 7.90 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 7.3 Hz, 1H), 7.78
		(d, J = 8.5 Hz, 1H), 7.31 (s, 1H), 7.18 (d, J = 8.1 Hz, 1H), 5.11 (p, J = 7.0
		Hz, 1H), 4.96-4.75 (m, 2H), 4.75-4.58 (m, 1H), 4.53-4.36 (m, 1H),
		3.91-3.82 (m, 1H), 3.50-3.33 (m, 2H), 3.15-3.02 (m, 1H), 3.02-2.85
		(m, 1H), 2.41-2.26 (m, 1H), 2.00-1.84 (m, 2H), 1.80-1.56 (m, 2H),
		1.52-1.00 (m, 15H), 0.95 (s, 3H), 0.92-0.82 (m, 1H), 0.63-0.46 (m,
		1H).
377	662.3	1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 5.4 Hz, 1H), 8.77-8.69
		(m, 2H), 8.67 (d, J = 8.2 Hz, 1H), 8.10 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.4
		Hz, 1H), 7.76 (d, J = 10.7 Hz, 1H), 7.25-7.21 (m, 2H), 5.55-5.40 (m,
		1H), 5.10 (dd, J = 31.2, 14.6 Hz, 1H), 4.94-4.71 (m, 2H), 4.47-4.32 (m,
		1H), 3.93 (s, 3H), 3.52-3.30 (m, 2H), 3.14-2.87 (m, 2H), 2.38-2.30
		(m, 1H), 2.21-1.85 (m, 3H), 1.61-1.22 (m, 9H).
378	662.3	1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 7.8 Hz, 1H), 8.74-8.63
		(m, 3H), 8.08 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 6.4 Hz, 1H), 7.77 (d, J =
		10.8 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.23 (s, 1H), 5.68 (t, J = 13.6 Hz,
		1H), 5.14-4.94 (m, 2H), 4.94-4.70 (m, 1H), 4.40 (s, 1H), 3.94 (s, 3H),
		3.46-3.32 (m, 1H), 3.12-2.87 (m, 2H), 2.39-2.25 (m, 1H), 2.14-1.83
		(m, 4H), 1.82-1.54 (m, 2H), 1.52-1.30 (m, 5H), 1.16-0.98 (m, 1H).
379	602.3	1H NMR (400 MHz, DMSO-d6) δ 8.79-8.69 (m, 2H), 8.65 (d, J = 8.0
		Hz, 1H), 8.17 (d, J = 8.2 Hz, 1H), 8.05 (d, J = 6.4 Hz, 1H), 7.91 (d, J = 8.3
		Hz, 1H), 7.76 (d, J = 10.8 Hz, 1H), 7.28 (d, J = 8.2 Hz, 1H), 7.22 (s, 1H),
		5.09 (dd, J = 14.4, 4.0 Hz, 2H), 4.98 (p, J = 7.1 Hz, 1H), 4.81 (dtd, J =
		49.0, 9.4, 4.6 Hz, 1H), 4.49 (dd, J = 14.4, 11.6 Hz, 1H), 4.44-4.35 (m,
		1H), 3.52-3.32 (m, 2H), 3.12-2.89 (m, 2H), 2.39-2.27 (m, 1H), 1.99-
		1.84 (m, 2H), 1.53 (d, J = 6.9 Hz, 3H), 1.37-1.21 (m, 1H), 1.02-0.75
		(m, 3H), 0.71-0.31 (m, 5H), 0.04-0.01 (m, 1H).
380	668.4	1H NMR (400 MHz, DMSO-d6) δ 8.90-8.66 (m, 3H), 8.05 (d, J = 8.1
		Hz, 1H), 7.91 (d, J = 1.2 Hz, 1H), 7.80 (d, J = 7.4 Hz, 1H), 7.32 (d, J = 1.3
		Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.07 (d, J = 2.5 Hz, 1H), 5.12 (p, J = 7.1
		Hz, 1H), 4.87-4.76 (m, 1H), 4.63-4.51 (m, 1H), 4.49-4.34 (m, 1H),
		4.14 (d, J = 2.2 Hz, 3H), 4.01 (s, 3H), 3.48-3.33 (m, 2H), 3.06-2.79 (m,
		3H), 2.23-2.13 (m, 1H), 1.97-1.86 (m, 1H), 1.85-1.57 (m, 3H), 1.55-
		1.26 (m, 8H), 1.21 (s, 3H), 1.17-0.98 (m, 2H), 0.95 (s, 3H).
381	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.76-8.70 (m, 2H), 8.69 (d, J = 5.4
		Hz, 1H), 8.64 (d, J = 7.4 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.5
		Hz, 1H), 7.75 (d, J = 10.9 Hz, 1H), 7.15 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H),
		4.93-4.71 (m, 4H), 4.48-4.33 (m, 1H), 3.96 (s, 3H), 3.52-3.32 (m,
		2H), 3.13-2.88 (m, 2H), 2.69-2.55 (m, 1H), 2.39-2.27 (m, 1H), 2.10-
		1.85 (m, 3H), 1.54-1.36 (m, 6H), 1.31-1.07 (m, 2H), 1.02-0.90 (m,
		1H), 0.63-0.48 (m, 1H).
382	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 7.2 Hz, 1H), 8.76-8.68
		(m, 2H), 8.64 (d, J = 8.0 Hz, 2H), 8.05 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 6.5
		Hz, 1H), 7.76 (d, J = 10.9 Hz, 1H), 7.26 (d, J = 8.2 Hz, 1H), 7.14 (s, 1H),
		4.93-4.64 (m, 2H), 4.64-4.51 (m, 2H), 4.47-4.33 (m, 1H), 4.01-3.95
		(m, 2H), 3.51-3.31 (m, 2H), 3.10-2.88 (m, 2H), 2.39-2.20 (m, 2H),
		2.06-1.85 (m, 3H), 1.75 (d, J = 7.0 Hz, 3H), 1.70-1.61 (m, 2H), 1.56-
		1.33 (m, 4H), 1.23-1.07 (m, 1H).
383	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.77-8.72 (m, 2H), 8.70 (d, J = 7.6
		Hz, 1H), 8.64 (d, J = 7.9 Hz, 1H), 8.04-7.99 (m, 2H), 7.75 (d, J = 10.8
		Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.13 (s, 1H), 4.97 (p, J = 7.1 Hz, 1H),
		4.92-4.66 (m, 2H), 4.58 (dt, J = 12.9, 5.8 Hz, 1H), 4.47-4.34 (m, 1H),
		3.97 (s, 3H), 3.50-3.42 (m, 1H), 3.42-3.32 (m, 1H), 3.11-2.89 (m,
		2H), 2.40-2.29 (m, 1H), 2.00-1.76 (m, 4H), 1.74-1.61 (m, 2H), 1.61-
		1.48 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.41-1.26 (m, 2H), 1.26-1.05
		(m, 1H).
384	676.3	1H NMR (400 MHz, DMSO-d6) δ 9.19 (d, J = 8.0 Hz, 1H), 8.81-8.70
		(m, 2H), 8.68-8.61 (m, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 6.4 Hz,
		1H), 7.76 (d, J = 10.8 Hz, 1H), 7.52-7.37 (m, 3H), 7.27 (d, J = 8.1 Hz,
		1H), 7.20 (s, 1H), 6.99 (t, J = 55.3 Hz, 1H), 5.40 (p, J = 7.1 Hz, 1H),
		5.00-4.66 (m, 3H), 4.47-4.34 (m, 1H), 3.98 (s, 3H), 3.53-3.33 (m, 1H),
		3.12-2.89 (m, 2H), 2.63-2.51 (m, 1H), 2.42-2.25 (m, 2H), 2.19 (td, J =
		12.5, 4.3 Hz, 1H), 2.01-1.82 (m, 1H), 1.73-1.56 (m, 1H), 1.54-1.39
		(m, 4H), 1.39-1.10 (m, 2H), 0.57-0.39 (m, 1H).
385	638.3	1H NMR (400 MHz, DMSO-d6) δ 8.79-8.70 (m, 2H), 8.63 (d, J = 7.9
		Hz, 1H), 8.38 (d, J = 9.4 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 6.4
		Hz, 1H), 7.78 (d, J = 10.8 Hz, 1H), 7.26 (s, 1H), 7.17 (d, J = 8.1 Hz, 1H),
		5.25-5.05 (m, 2H), 4.94-4.70 (m, 2H), 4.48-4.34 (m, 1H), 4.03 (s,
		3H), 3.53-3.43 (m, 1H), 3.43-3.34 (m, 2H), 3.11-2.88 (m, 2H), 2.39-
		2.24 (m, 1H), 1.98-1.65 (m, 3H), 1.64-1.47 (m, 2H), 1.42 (d, J = 7.1
		Hz, 3H), 1.32-1.10 (m, 2H), 1.07-0.97 (m, 1H), 0.77-0.63 (m, 3H).
386	638.3	1H NMR (400 MHz, DMSO-d6) δ 8.63 (d, J = 8.0 Hz, 1H), 8.49 (d, J =
		7.9 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 8.04 (d, J = 6.4 Hz, 1H), 7.77 (d, J =
		10.8 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.14 (s, 1H), 5.09 (q, J = 7.2 Hz,
		1H), 4.93-4.63 (m, 3H), 4.45-4.30 (m, 1H), 3.99 (s, 3H), 3.51-3.34
		(m, 2H), 3.15-2.77 (m, 2H), 2.36-2.25 (m, 1H), 1.96-1.82 (m, 2H),
		1.60-0.68 (m, 11H), 0.59-0.49 (m, 1H).
387	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.76-8.68 (m, 2H), 8.62 (d, J = 8.0
		Hz, 1H), 8.38 (dd, J = 8.5, 1.8 Hz, 1H), 8.03-7.97 (m, 2H), 7.61 (d, J =
		10.6 Hz, 1H), 7.30 (s, 1H), 7.18 (d, J = 8.1 Hz, 1H), 5.13 (p, J = 7.2 Hz,
		1H), 4.92-4.70 (m, 2H), 4.66-4.53 (m, 1H), 4.48-4.31 (m, 1H), 3.81
		(tt, J = 7.3, 3.9 Hz, 1H), 3.51-3.30 (m, 2H), 3.11-2.88 (m, 2H), 2.40-
		2.27 (m, 1H), 1.98-1.84 (m, 2H), 1.76-1.44 (m, 6H), 1.42-1.13 (m,
		6H), 1.09-0.91 (m, 3H), 0.85-0.76 (m, 1H), 0.71-0.62 (m, 1H).
388	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.82-8.69 (m, 2H), 8.63 (d, J = 8.1
		Hz, 1H), 8.42 (d, J = 9.5 Hz, 1H), 8.03-7.97 (m, 2H), 7.62 (d, J = 10.6
		Hz, 1H), 7.31 (s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 5.19 (dq, J = 9.7, 7.0 Hz,
		1H), 4.93-4.71 (m, 3H), 4.47-4.33 (m, 1H), 3.82 (tt, J = 7.1, 3.8 Hz,
		1H), 3.51-3.33 (m, 2H), 3.11-2.87 (m, 2H), 2.41-2.20 (m, 2H), 2.03
		(ddd, J = 9.4, 7.6, 3.7 Hz, 1H), 1.98-1.83 (m, 1H), 1.83-1.04 (m, 13H),
		0.95 (ddd, J = 11.2, 9.4, 6.1 Hz, 1H), 0.88-0.80 (m, 1H), 0.67-0.57 (m,
		1H).
389	688.3	1H NMR (400 MHz, DMSO-d6) δ 8.80 (d, J = 5.2 Hz, 1H), 8.71 (s, 2H),
		8.66 (d, J = 8.0 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 6.4 Hz, 1H),
		7.63 (d, J = 10.4 Hz, 1H), 7.37 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 5.66-
		5.55 (m, 1H), 5.12 (dd, J = 32.0, 14.7 Hz, 1H), 4.96-4.69 (m, 2H), 4.46-
		4.30 (m, 1H), 3.85-3.79 (m, 1H), 3.51-3.32 (m, 2H), 3.13-2.86 (m,
		2H), 2.71-2.63 (m, 1H), 2.40-2.27 (m, 1H), 2.20-1.80 (m, 4H), 1.63-
		1.19 (m, 8H), 1.05-0.95 (m, 1H), 0.94-0.84 (m, 1H), 0.44-0.32 (m,
		1H).
390	688.3	1H NMR (400 MHz, DMSO-d6) δ 8.98 (d, J = 7.2 Hz, 1H), 8.75-8.68
		(m, 2H), 8.66 (d, J = 8.3 Hz, 1H), 8.11 (d, J = 8.2 Hz, 1H), 7.99 (d, J = 6.2
		Hz, 1H), 7.65 (d, J = 10.4 Hz, 1H), 7.40 (s, 1H), 7.34 (d, J = 8.2 Hz, 1H),
		5.89-5.76 (m, 1H), 5.12 (dd, J = 27.3, 14.5 Hz, 1H), 4.92-4.68 (m, 1H),
		4.57-4.47 (m, 1H), 4.46-4.33 (m, 1H), 3.90-3.81 (m, 1H), 3.51-3.32
		(m, 2H), 3.11-2.86 (m, 2H), 2.40-2.22 (m, 1H), 2.08-1.73 (m, 8H),
		1.66-1.53 (m, 1H), 1.51-1.24 (m, 3H), 1.17-1.00 (m, 2H), 0.96-0.85
		(m, 1H), 0.53-0.43 (m, 1H).
391	688.3	1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 7.7 Hz, 1H), 8.81-8.73
		(m, 2H), 8.66 (d, J = 7.4 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 6.3
		Hz, 1H), 7.64 (d, J = 10.5 Hz, 1H), 7.40 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H),
		5.89 (t, J = 13.8 Hz, 1H), 5.10 (dd, J = 27.3, 14.7 Hz, 1H), 4.99 (p, J = 7.3
		Hz, 1H), 4.82 (dtd, J = 49.0, 9.6, 4.6 Hz, 1H), 4.46-4.34 (m, 1H), 3.89-
		3.80 (m, 1H), 3.53-3.30 (m, 2H), 3.11-2.86 (m, 2H), 2.41-2.28 (m,
		1H), 2.17-1.56 (m, 7H), 1.49-1.26 (m, 5H), 1.16-0.86 (m, 3H), 0.48-
		0.37 (m, 1H).
392	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.76-8.68 (m, 3H), 8.62 (d, J = 8.0
		Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 6.4 Hz, 1H), 7.62 (d, J =
		10.6 Hz, 1H), 7.31 (s, 1H), 7.13 (d, J = 8.1 Hz, 1H), 4.92-4.71 (m, 4H),
		4.46-4.33 (m, 1H), 3.86-3.79 (m, 1H), 3.51-3.32 (m, 2H), 3.11-2.88
		(m, 2H), 2.39-2.27 (m, 1H), 2.14-1.79 (m, 3H), 1.49-0.86 (m, 13H),
		0.48-0.32 (m, 2H).
393	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.79 (d, J = 7.4 Hz, 1H), 8.80-8.69
		(m, 2H), 8.65-8.59 (m, 1H), 8.05 (d, J = 8.2 Hz, 1H), 8.00 (d, J = 6.4 Hz,
		1H), 7.62 (d, J = 10.6 Hz, 1H), 7.31 (d, J = 1.2 Hz, 1H), 7.25 (d, J = 8.2
		Hz, 1H), 4.93-4.71 (m, 2H), 4.70-4.52 (m, 2H), 4.47-4.32 (m, 1H),
		3.82 (tt, J = 7.0, 3.9 Hz, 1H), 3.51-3.32 (m, 2H), 3.10-2.89 (m, 2H),
		2.39-2.23 (m, 1H), 2.09-1.82 (m, 3H), 1.75 (d, J = 7.0 Hz, 3H), 1.70-
		1.09 (m, 10H), 0.90-0.80 (m, 1H), 0.70-0.59 (m, 1H).
394	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.78-8.72 (m, 2H), 8.71 (d, J = 7.6
		Hz, 1H), 8.62 (d, J = 8.4 Hz, 1H), 8.03-7.98 (m, 2H), 7.62 (d, J = 10.6
		Hz, 1H), 7.31 (s, 1H), 7.16 (d, J = 8.1 Hz, 1H), 4.97 (p, J = 7.2 Hz, 1H),
		4.92-4.71 (m, 2H), 4.67-4.57 (m, 1H), 4.47-4.34 (m, 1H), 3.82 (tt, J =
		7.1, 3.9 Hz, 1H), 3.51-3.31 (m, 2H), 3.00 (d, J = 33.8 Hz, 2H), 2.40-
		2.28 (m, 1H), 1.98-1.76 (m, 3H), 1.72-1.48 (m, 4H), 1.46 (d, J = 7.1
		Hz, 3H), 1.41-1.26 (m, 2H), 1.26-1.10 (m, 4H), 0.89-0.80 (m, 1H),
		0.69-0.61 (m, 1H).
395	667.3	1H NMR (400 MHz, DMSO-d6) δ 9.30 (d, J = 7.5 Hz, 1H), 8.83-8.72
		(m, 2H), 8.67-8.59 (m, 1H), 8.45 (s, 1H), 8.41 (s, 1H), 8.10 (d, J = 8.0
		Hz, 1H), 7.99 (d, J = 6.4 Hz, 1H), 7.63 (d, J = 10.6 Hz, 1H), 7.38 (s, 1H),
		7.27 (d, J = 8.1 Hz, 1H), 5.35 (p, J = 7.1 Hz, 1H), 5.01-4.71 (m, 3H),
		4.49-4.35 (m, 1H), 3.90-3.79 (m, 1H), 3.52-3.31 (m, 2H), 3.10-2.88
		(m, 2H), 2.40-2.28 (m, 5H), 2.15-2.02 (m, 1H), 1.97-1.86 (m, 1H),
		1.57-1.37 (m, 4H), 1.36-1.05 (m, 5H), 0.94 (q, J = 5.8, 5.4 Hz, 1H),
		0.51-0.32 (m, 3H).
396	667.3	1H NMR (400 MHz, DMSO-d6) δ 9.28 (d, J = 7.7 Hz, 1H), 8.81-8.72
		(m, 2H), 8.63 (dd, J = 8.2, 1.7 Hz, 1H), 8.50 (d, J = 5.5 Hz, 1H), 8.10 (d,
		J = 8.0 Hz, 1H), 7.99 (d, J = 6.3 Hz, 1H), 7.63 (d, J = 10.6 Hz, 1H), 7.40
		(s, 1H), 7.38 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 5.36 (p, J = 7.1 Hz, 1H),
		5.01-4.68 (m, 3H), 4.50-4.32 (m, 1H), 3.89-3.79 (m, 1H), 3.50-3.33 (m,
		2H), 3.09-2.89 (m, 2H), 2.59 (s, 3H), 2.41-2.28 (m, 3H), 2.25-2.13
		(m, 1H), 2.01-1.84 (m, 1H), 1.56-1.39 (m, 4H), 1.38-1.07 (m, 5H),
		0.94 (d, J = 6.0 Hz, 1H), 0.50-0.37 (m, 2H).
397	700.3	1H NMR (400 MHz, DMSO-d6) δ 9.19 (d, J = 8.0 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 8.04-7.91 (m, 3H), 7.52-7.37 (m, 4H), 7.26 (d, J = 8.1 Hz,
		1H), 7.08 (s, 1H), 6.99 (s, 0H), 6.93 (d, J = 1.1 Hz, 1H), 5.39 (p, J = 7.1
		Hz, 1H), 4.95-4.85 (m, 1H), 4.63-4.53 (m, 1H), 4.12 (s, 3H), 3.99 (s,
		3H), 3.95-3.79 (m, 1H), 3.74-3.67 (m, 1H), 3.63-3.47 (m, 2H), 3.47-
		3.31 (m, 5H), 2.62-2.52 (m, 1H), 2.36-2.25 (m, 1H), 2.24-2.11 (m,
		1H), 2.02-1.88 (m, 1H), 1.83-1.69 (m, 1H), 1.68-1.15 (m, 7H), 0.52-
		0.39 (m, 1H).
398	643.7	1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 6.6 Hz, 1H), 8.69 (d, J =
		8.0 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 1.3 Hz, 1H), 7.36 (d, J =
		1.2 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 5.12 (p, J = 6.9 Hz,
		1H), 4.96-4.88 (m, 1H), 4.79 (m, J = 9.5, 4.9 Hz, 1H), 4.68 (t, J = 10.4
		Hz, 1H), 4.63-4.54 (m, 1H), 4.43 (d, J = 10.9 Hz, 1H), 4.15 (s, 3H), 4.03
		(s, 3H), 3.42 (m, J = 25.1, 12.7 Hz, 2H), 3.07 (d, J = 10.3 Hz, 1H), 2.96 (d,
		J = 9.9 Hz, 1H), 2.35 (s, 3H), 2.12 (m, J = 14.4, 8.1 Hz, 1H), 1.98-1.88
		(m, 1H), 1.74 (d, J = 17.2 Hz, 1H), 1.53 (d, J = 7.1 Hz, 3H), 1.45 (d, J =
		8.3 Hz, 1H), 1.26 (q, J = 7.3, 6.6 Hz, 3H), 1.01 (d, J = 11.6 Hz, 2H).
399	641.4	1H NMR (400 MHz, DMSO-d6) δ 9.45 (d, J = 6.9 Hz, 1H), 8.70 (d, J =
		7.9 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 1.3 Hz, 1H), 7.36 (d, J =
		1.3 Hz, 1H), 7.28 (d, J = 8.2 Hz, 1H), 7.16 (s, 1H), 6.48 (ddd, J = 16.1,
		8.1, 5.4 Hz, 1H), 6.21 (d, J = 16.3 Hz, 1H), 5.25 (p, J = 7.0 Hz, 1H), 4.92
		(dd, J = 14.0, 8.7 Hz, 2H), 4.80 (td, J = 9.3, 4.5 Hz, 0H), 4.70-4.61 (m,
		1H), 4.43 (d, J = 12.3 Hz, 1H), 4.18 (s, 3H), 4.04 (s, 3H), 3.43 (dd, J =
		26.2, 12.5 Hz, 2H), 3.02 (dd, J = 42.4, 10.5 Hz, 2H), 2.44 (s, 3H), 1.94 (d,
		J = 7.7 Hz, 2H), 1.54 (d, J = 7.0 Hz, 5H).
400	666.3	1H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 7.1 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 8.00 (d, J = 1.3 Hz, 1H), 7.36 (d, J = 1.3 Hz, 1H), 7.21 (d, J =
		8.2 Hz, 1H), 7.07 (s, 1H), 5.14 (p, J = 7.1 Hz, 1H), 4.97-4.88 (m, 1H),
		4.85-4.71 (m, 2H), 4.51-4.35 (m, 2H), 4.15 (s, 3H), 4.02 (s, 3H), 3.15-
		2.81 (m, 6H), 2.67-2.56 (m, 1H), 2.22 (m, J = 24.6, 12.8 Hz, 3H), 2.00-
		1.84 (m, 2H), 1.68 (s, 3H), 1.48 (d, J = 7.1 Hz, 3H), 1.35 (d, J = 21.0 Hz,
		3H), 1.29-1.10 (m, 3H).
401	627.2	1H NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 7.1 Hz, 1H), 8.75 (s, 2H),
		8.65 (d, J = 8.1 Hz, 1H), 8.54 (dd, J = 5.0, 1.7 Hz, 1H), 8.11 (d, J = 8.0
		Hz, 1H), 8.01 (d, J = 6.4 Hz, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.77 (d, J =
		10.9 Hz, 1H), 7.37 (dd, J = 7.8, 4.9 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.21
		(s, 1H), 5.23 (p, J = 7.0 Hz, 1H), 4.95-4.84 (m, 1H), 4.73 (t, J = 10.8 Hz,
		1H), 4.40 (d, J = 11.3 Hz, 2H), 3.99 (s, 3H), 3.63 (td, J = 6.6, 3.9 Hz, 1H),
		3.52-3.43 (m, 1H), 3.38 (d, J = 12.5 Hz, 1H), 3.20-3.10 (m, 1H), 3.10-
		2.91 (m, 2H), 1.60 (dd, J = 16.2, 7.8 Hz, 2H), 1.50 (d, J = 7.0 Hz, 3H),
		1.26 (q, J = 7.3, 6.7 Hz, 6H).
402	654.3	1H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 8.1 Hz, 1H), 8.22 (d, J =
		7.1 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 6.4 Hz, 1H), 7.76 (d, J =
		10.9 Hz, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.15 (s, 1H), 5.14 (p, J = 7.1 Hz,
		1H), 4.89 (m, J = 9.6, 4.6 Hz, 1H), 4.78 (m, J = 13.7, 10.3 Hz, 2H), 4.52
		(p, J = 7.0, 6.5 Hz, 1H), 4.41 (m, J = 13.7, 9.2, 4.5 Hz, 1H), 3.97 (s, 3H),
		3.13-3.02 (m, 2H), 3.02-2.91 (m, 1H), 2.85 (m, J = 13.7, 2.9 Hz, 1H),
		2.70-2.55 (m, 1H), 2.28 (m, J = 45.3, 25.4, 12.0, 3.8 Hz, 3H), 2.00-
		1.85 (m, 1H), 1.74-1.58 (m, 3H), 1.48 (d, J = 7.1 Hz, 2H), 1.36 (m, J =
		7.7 Hz, 3H), 1.26 (q, J = 5.2, 4.1 Hz, 2H), 1.22-1.09 (m, 2H), 1.01 (d, J =
		6.6 Hz, 1H).
403	656.5	1H NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 7.8 Hz, 1H), 8.08 (dd, J =
		8.3, 6.7 Hz, 2H), 7.86 (d, J = 7.5 Hz, 1H), 7.40 (d, J = 8.3 Hz, 1H), 7.27-
		7.18 (m, 2H), 5.15 (p, J = 7.1 Hz, 1H), 4.95-4.78 (m, 2H), 4.75-4.65
		(m, 1H), 4.60 (d, J = 10.3 Hz, 1H), 4.33 (s, 2H), 4.08 (s, 3H), 3.48 (s, 1H),
		3.40 (d, J = 13.0 Hz, 1H), 3.06 (d, J = 11.6 Hz, 1H), 2.89 (d, J = 10.8 Hz,
		1H), 2.01-1.81 (m, 3H), 1.64 (dd, J = 40.9, 11.9 Hz, 3H), 1.46 (d, J = 7.1
		Hz, 3H), 1.40 (d, J = 11.1 Hz, 4 H), 1.22 (s, 3H), 0.97 (s, 3H).
404	660.6	1H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 8.0 Hz, 1H), 8.44 (d, J =
		8.6 Hz, 1H), 7.99 (dd, J = 13.2, 7.2 Hz, 2H), 7.89 (d, J = 11.0 Hz, 1H),
		7.15-7.07 (m, 2H), 5.06-4.97 (m, 1H), 4.88 (td, J = 9.4, 4.5 Hz, 0H),
		4.79-4.68 (m, 3H), 4.67-4.57 (m, 1H), 4.40 (dt, J = 13.5, 9.4 Hz, 1H),
		3.12-2.92 (m, 3H), 2.67 (s, 3H), 2.40-2.29 (m, 0H), 2.01-1.63 (m,
		5H), 1.55 (tt, J = 10.6, 4.3 Hz, 2H), 1.49-1.35 (m, 5H), 1.30-1.17 (m,
		2H), 0.87 (p, J = 4.0 Hz, 1H), 0.77-0.37 (m, 7H).
405	648.3	1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 2H), 8.68 (d, J = 8.0 Hz, 1H),
		8.44 (d, J = 8.6 Hz, 1H), 8.03 (d, J = 6.4 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H),
		7.88 (d, J = 10.9 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.05-
		4.93 (m, 3H), 4.88 (ddd, J = 14.1, 9.3, 4.6 Hz, 1H), 4.74 (dt, J = 12.1, 9.1
		Hz, 2H), 4.63-4.55 (m, 1H), 4.48-4.36 (m, 2H), 3.47 (d, J = 12.3 Hz,
		1H), 3.39 (d, J = 12.7 Hz, 1H), 3.00 (dt, J = 32.8, 10.6 Hz, 2H), 2.40-
		2.28 (m, 1H), 1.92 (t, J = 10.9 Hz, 1H), 1.82 (d, J = 9.8 Hz, 1H), 1.75-
		1.47 (m, 3H), 1.43 (d, J = 7.1 Hz, 3H), 1.40-1.29 (m, 1H), 1.20 (dt, J =
		19.6, 6.2 Hz, 1H), 1.01-0.80 (m, 3H), 0.79-0.52 (m, 4H), 0.48 (q, J =
		5.8, 3.9 Hz, 1H).
406	655.7	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.6 Hz, 1H), 8.05 (d, J =
		6.4 Hz, 1H), 8.01-7.95 (m, 2H), 7.16 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H),
		5.08-4.98 (m, 1H), 4.95 (d, J = 15.5 Hz, 1H), 4.88 (td, J = 9.4, 4.5 Hz,
		1H), 4.73 (dd, J = 13.9, 9.6 Hz, 2H), 4.59 (d, J = 15.6 Hz, 2H), 4.54 (d, J =
		4.2 Hz, 1H), 4.42 (dt, J = 12.1, 6.1 Hz, 1H), 3.13-2.91 (m, 3H), 2.41-
		2.28 (m, 2H), 2.00-1.82 (m, 3H), 1.80-1.59 (m, 3H), 1.56 (dt, J = 8.2,
		4.5 Hz, 2H), 1.44 (d, J = 7.1 Hz, 3H), 1.22 (ddd, J = 9.5, 7.2, 4.2 Hz, 1H),
		1.12-0.96 (m, 2H), 0.92-0.79 (m, 2H), 0.77-0.59 (m, 1H), 0.52-0.44
		(m, 1H).
407	685.5	1H NMR (400 MHz, DMSO-d6) δ 9.09 (d, J = 7.2 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 7.97 (s, 3H), 7.82 (d, J = 8.0 Hz, 1H), 7.48-7.38 (m, 2H),
		7.27 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.94 (d, J = 1.1 Hz, 1H), 5.23 (p, J =
		7.0 Hz, 1H), 4.90-4.78 (m, 1H), 4.63-4.53 (m, 1H), 4.12 (s, 3H), 4.00
		(s, 3H), 3.40 (s, 1H), 3.37 (s, 3H), 2.70-2.59 (m, 1H), 2.41-2.28 (m,
		3H), 1.93 (d, J = 8.5 Hz, 2H), 1.76 (s, 2H), 1.50 (d, J = 7.0 Hz, 6H), 1.23
		(d, J = 13.2 Hz, 2H), 0.61 (d, J = 12.3 Hz, 2H).
408	614.3	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.5 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.42 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.01 (s, 1H), 5.06-
		4.97 (m, 1H), 4.69 (d, J = 10.5 Hz, 1H), 4.62 (s, 1H), 4.12 (d, J = 2.5 Hz,
		3H), 3.99 (s, 3H), 3.80 (d, J = 9.4 Hz, 1H), 3.66 (s, 1H), 3.40 (s, 2H), 1.80
		(d, J = 30.2 Hz, 4H), 1.58 (s, 7H), 1.43 (d, J = 7.1 Hz, 3H), 1.26 (q, J =
		7.2, 6.7 Hz, 2H), 0.90-0.82 (m, 1H), 0.69 (d, J = 23.4 Hz, 2H), 0.47 (d, J =
		9.1 Hz, 1H).
409	651.3	1H NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 7.1 Hz, 1H), 8.60 (dd, J =
		5.1, 1.7 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.02-7.96 (m, 3H), 7.51-7.40
		(m, 2H), 7.27 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.94 (d, J = 1.2 Hz, 1H),
		5.23 (t, J = 7.1 Hz, 1H), 4.84 (t, J = 11.5 Hz, 1H), 4.63-4.52 (m, 1H),
		4.12 (s, 3H), 4.00 (s, 3H), 3.37 (s, 3H), 2.73-2.62 (m, 1H), 1.93 (d, J =
		12.7 Hz, 1H), 1.76 (d, J = 2.7 Hz, 1H), 1.51 (d, J = 7.0 Hz, 3H), 1.46 (s,
		2H), 1.28-1.13 (m, 2H), 0.61 (d, J = 13.0 Hz, 1H).
410	666.5	1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2H), 8.68 (d, J = 8.0 Hz, 1H),
		8.45 (d, J = 8.5 Hz, 1H), 8.00 (dd, J = 7.2, 3.5 Hz, 2H), 7.73 (d, J = 10.4
		Hz, 1H), 7.21 (s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 5.06-4.97 (m, 1H), 4.93-
		4.83 (m, 1H), 4.75 (dd, J = 9.4, 4.6 Hz, 1H), 4.39 (d, J = 11.9 Hz, 1H),
		4.19 (s, 1H), 4.04 (q, J = 7.1 Hz, 2H), 3.45 (s, 2H), 3.38 (d, J = 13.1 Hz,
		1H), 3.02 (d, J = 34.3 Hz, 2H), 2.08 (s, 2H), 2.00 (s, 2H), 1.96-1.81 (m,
		1H), 1.73-1.53 (m, 4H), 1.45 (d, J = 7.1 Hz, 3H), 1.24 (s, 1H), 1.18 (t, J =
		7.1 Hz, 2H), 0.87 (h, J = 3.8 Hz, 1H), 0.70 (d, J = 24.7 Hz, 2H), 0.49 (t,
		J = 7.1 Hz, 1H).
411	628.6	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.6 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.02 (s, 1H), 6.92 (d, J = 16.5 Hz,
		1H), 5.01 (p, J = 7.2 Hz, 1H), 4.65 (d, J = 34.5 Hz, 2H), 4.12 (s, 3H), 3.99
		(s, 3H), 3.84 (s, 8H), 3.38 (d, J = 48.2 Hz, 4H), 1.93-1.72 (m, 3H), 1.56
		(d, J = 8.8 Hz, 4H), 1.43 (d, J = 7.1 Hz, 3H), 1.31-1.12 (m, 2H), 0.87 (m,
		J = 8.7, 4.6 Hz, 1H), 0.69 (d, J = 22.3 Hz, 2H), 0.54-0.42 (m, 1H).
412	666.6	1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 2H), 8.66 (d, J = 8.1 Hz, 1H),
		8.45 (d, J = 8.6 Hz, 1H), 7.99 (dd, J = 7.2, 3.0 Hz, 2H), 7.67 (d, J = 10.7
		Hz, 1H), 7.31 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 5.07-4.96 (m, 1H), 4.92-
		4.84 (m, 1H), 4.76 (m, J = 9.3, 4.5 Hz, 2H), 4.40 (s, 1H), 4.22 (s, 1H),
		3.40 (s, 3H), 3.01 (d, J = 36.1 Hz, 3H), 2.09 (d, J = 4.6 Hz, 2H), 1.91 (t, J =
		12.4 Hz, 3H), 1.73 (d, J = 26.8 Hz, 3H), 1.56 (m, J = 8.4, 4.5 Hz, 1H),
		1.44 (d, J = 7.1 Hz, 3H), 1.32 (s, 1H), 1.24 (s, 2H), 0.91-0.83 (m, 1H),
		0.77-0.56 (m, 3H), 0.49 (q, J = 5.4, 4.6 Hz, 1H).
413	630.6	1H NMR (400 MHz, DMSO-d6) δ 8.87 (d, J = 24.9 Hz, 2H), 8.64 (dd, J =
		8.1, 1.5 Hz, 1H), 8.46 (d, J = 8.6 Hz, 1H), 8.01 (dd, J = 8.6, 7.2 Hz, 2H),
		7.52 (d, J = 10.5 Hz, 1H), 7.27 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 5.08-
		4.97 (m, 1H), 4.94-4.70 (m, 3H), 4.41 (m, J = 13.9, 9.4 Hz, 1H), 3.56
		(m, J = 7.1, 3.6 Hz, 1H), 3.43 (m, J = 32.7, 12.5 Hz, 2H), 3.00 (m, J =
		31.6, 10.8 Hz, 2H), 2.35 (m, J = 13.7, 11.4, 6.5 Hz, 1H), 2.00-1.80 (m,
		2H), 1.76-1.63 (m, 1H), 1.56 (m, J = 12.0, 4.9 Hz, 3H), 1.44 (d, J = 7.1
		Hz, 3H), 1.34 (m, J = 11.7, 5.2 Hz, 1H), 1.28-1.15 (m, 2H), 1.11 (d, J =
		5.9 Hz, 3H), 1.08-0.98 (m, 2H), 0.96-0.82 (m, 2H), 0.78-0.60 (m,
		2H), 0.49 (m, J = 9.0, 5.6, 3.6 Hz, 1H).
414	702.3	1H NMR (400 MHz, DMSO-d6) δ 9.49 (d, J = 6.9 Hz, 1H), 8.18-8.09
		(m, 2H), 8.07-8.00 (m, 1H), 7.98 (s, 2H), 7.91-7.84 (m, 2H), 7.44 (s,
		1H), 7.32 (d, J = 8.1 Hz, 1H), 7.11 (s, 1H), 6.94 (d, J = 1.2 Hz, 1H), 5.30
		(p, J = 6.9 Hz, 1H), 4.88 (t, J = 11.0 Hz, 1H), 4.60 (d, J = 13.6 Hz, 1H),
		4.13 (s, 3H), 4.00 (s, 3H), 3.54 (s, 4H), 3.37 (s, 3H), 2.84 (dd, J = 12.6, 8.1
		Hz, 1H), 2.60 (d, J = 8.3 Hz, 2H), 1.95 (s, 1H), 1.76 (s, 1H), 1.56 (d, J =
		7.0 Hz, 3H), 1.54-1.21 (m, 4H), 0.59 (d, J = 12.5 Hz, 1H).
415	666.6	1H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 2H), 8.65 (d, J = 8.0 Hz, 1H),
		8.44 (t, J = 9.3 Hz, 1H), 8.06-7.95 (m, 2H), 7.54 (m, J = 10.6, 5.4 Hz,
		1H), 7.24 (d, J = 4.9 Hz, 1H), 7.14 (m, J = 8.1, 1.1 Hz, 1H), 5.09-4.96
		(m, 1H), 4.90 (d, J = 9.6 Hz, 1H), 4.78 (d, J = 10.4 Hz, 1H), 4.66 (t, J =
		11.3 Hz, 1H), 4.56 (d, J = 13.0 Hz, 1H), 4.41 (s, 1H), 4.15 (m, J = 8.0, 4.0
		Hz, 1H), 3.38 (s, 3H), 3.12-2.90 (m, 3H), 2.34 (m, J = 3.9, 2.1 Hz, 1H),
		2.26-2.14 (m, 1H), 2.03-1.87 (m, 3H), 1.86-1.62 (m, 3H), 1.61-1.46
		(m, 3H), 1.44 (m, J = 7.1, 2.5 Hz, 3H), 1.35-1.14 (m, 2H), 0.98-0.90
		(m, 1H), 0.90-0.82 (m, 1H), 0.69 (s, 2H), 0.49 (p, J = 3.9 Hz, 1H).
416	630.6	1H NMR (400 MHz, DMSO-d6) δ 8.75 (s, 3H), 8.63 (d, J = 8.1 Hz, 1H),
		8.45 (m, J = 8.6, 4.3 Hz, 1H), 8.04-7.96 (m, 2H), 7.52 (m, J = 9.7, 2.7
		Hz, 1H), 7.27 (d, J = 1.4 Hz, 1H), 7.17-7.11 (m, 1H), 5.02 (m, J = 7.3
		Hz, 1H), 4.92-4.82 (m, 2H), 4.81-4.68 (m, 2H), 4.42 (d, J = 12.0 Hz,
		1H), 3.01 (d, J = 35.5 Hz, 3H), 1.99-1.79 (m, 3H), 1.68 (s, 2H), 1.56 (d,
		J = 7.2 Hz, 3H), 1.44 (m, J = 7.1, 1.6 Hz, 3H), 1.30-1.20 (m, 2H), 1.18
		(s, 1H), 1.11 (d, J = 5.9 Hz, 2H), 1.08-0.97 (m, 2H), 0.97-0.92 (m, 1H),
		0.92-0.84 (m, 2H), 0.75-0.60 (m, 3H), 0.53-0.44 (m, 1H).
417	649.8	1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2H), 8.66 (d, J = 8.0 Hz, 1H),
		8.03 (dd, J = 17.4, 7.3 Hz, 2H), 7.81 (dd, J = 11.4, 9.2 Hz, 2H), 7.19 (d, J =
		8.1 Hz, 1H), 7.14 (s, 1H), 5.14 (q, J = 7.3 Hz, 1H), 4.91-4.55 (m, 6H),
		4.43 (d, J = 11.4 Hz, 3H), 3.61 (dt, J = 21.7, 6.0 Hz, 2H), 3.51-3.31 (m,
		3H), 1.92 (t, J = 11.7 Hz, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.38 (d, J = 12.7
		Hz, 2H), 1.33 (s, 2H), 1.21 (s, 3H), 1.10 (d, J = 7.0 Hz, 1H), 0.95 (s, 3H).
418	656.5	1H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 2H), 8.70 (d, J = 8.1 Hz, 1H),
		8.05 (dd, J = 10.3, 7.2 Hz, 2H), 7.83 (dd, J = 9.1, 5.1 Hz, 2H), 7.20 (d, J =
		8.2 Hz, 1H), 7.11 (s, 1H), 6.41 (s, 1H), 5.19-4.71 (m, 6H), 4.40 (d, J =
		10.5 Hz, 2H), 3.01 (d, J = 33.1 Hz, 3H), 2.34 (s, 1H), 1.92 (t, J = 12.1 Hz,
		2H), 1.58 (d, J = 8.2 Hz, 3H), 1.51-1.42 (m, 4H), 1.37 (d, J = 23.5 Hz,
		5H), 1.21 (s, 3H), 1.08 (s, 3H), 0.95 (s, 3H).
419	674.6	1H NMR (400 MHz, DMSO-d6) 8.73 (d, J = 9.1 Hz, 2H), 8.12-8.02 (m,
		2H), 7.97 (d, J = 10.6 Hz, 1H), 7.83 (d, J = 7.4 Hz, 1H), 7.21 (t, J = 4.1
		Hz, 2H), 5.68-5.44 (m, 3H), 5.13 (t, J = 7.2 Hz, 1H), 4.91-4.70 (m,
		3H), 4.42 (d, J = 8.0 Hz, 3H), 3.42 (d, J = 36.1 Hz, 3H), 3.01 (d, J = 40.7
		Hz, 3H), 1.92 (t, J = 11.6 Hz, 2H), 1.76-1.50 (m, 3H), 1.45 (d, J = 7.2
		Hz, 3H), 1.42-1.26 (m, 5H), 1.21 (s, 3H), 1.07 (s, 3H), 0.95 (s, 3H).
420	646.6	1H NMR (400 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.66 (d, J = 8.1 Hz, 1H),
		8.04 (t, J = 7.0 Hz, 2H), 7.85 (dd, J = 18.1, 9.2 Hz, 2H), 7.20 (d, J = 8.1
		Hz, 1H), 6.95 (s, 1H), 5.22 (s, 1H), 5.12 (t, J = 7.3 Hz, 2H), 4.86-4.72
		(m, 3H), 4.47-4.23 (m, 5H), 3.53-3.34 (m, 4H), 3.17-2.90 (m, 4H),
		2.70 (d, J = 18.4 Hz, 2H), 2.39-2.24 (m, 3H), 1.94-1.84 (m, 2H), 1.82-
		1.61 (m, 3H), 1.46 (d, J = 7.0 Hz, 2H), 1.39-1.26 (m, 4H), 1.21 (s, 2H),
		0.94 (s, 2H).
421	634.5	1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 1H), 8.65 (d, J = 8.0 Hz, 1H),
		8.04 (dd, J = 14.0, 7.3 Hz, 2H), 7.95 (d, J = 11.2 Hz, 1H), 7.81 (d, J = 7.3
		Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 6.93 (s, 1H), 5.11 (t, J = 7.2 Hz, 1H),
		4.99-4.89 (m, 2H), 4.80 (s, 1H), 4.41 (s, 1H), 4.24 (s, 1H), 3.47 (d, J =
		11.8 Hz, 2H), 3.39 (d, J = 12.9 Hz, 2H), 2.96 (s, 1H), 1.91 (t, J = 13.0 Hz,
		2H), 1.68 (d, J = 7.0 Hz, 2H), 1.48 (dd, J = 21.1, 7.0 Hz, 4H), 1.37 (d, J =
		12.0 Hz, 2H), 1.30 (s, 1H), 1.20 (d, J = 4.9 Hz, 2H), 1.15 (s, 1H), 0.95 (d,
		J = 10.9 Hz, 2H).
422	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 6.3 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.65 (d, J = 10.9 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.03 (s,
		1H), 5.11 (q, J = 7.0 Hz, 1H), 4.71-4.59 (m, 1H), 4.59-4.51 (m, 2H),
		4.49 (s, 1H), 3.72 (ddt, J = 16.9, 14.3, 7.1 Hz, 3H), 3.55 (d, J = 13.5 Hz,
		1H), 3.25-3.10 (m, 5H), 2.50 (tt, J = 9.7, 4.4 Hz, 1H), 2.08 (s, 1H), 1.93
		(s, 1H), 1.75 (s, 1H), 1.65-1.48 (m, 7H), 1.31 (s, 3H), 1.09 (dt, J = 8.5,
		4.5 Hz, 1H), 0.82 (s, 2H), 0.60 (dd, J = 8.4, 3.5 Hz, 1H).
423	620.6	1H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 6.3 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 7.65 (d, J = 10.8 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.02 (s,
		1H), 5.51 (s, 1H), 5.26 (q, J = 6.9, 6.3 Hz, 1H), 5.04-4.91 (m, 2H), 4.57-
		4.31 (m, 5H), 3.71 (d, J = 13.0 Hz, 1H), 3.55 (d, J = 13.5 Hz, 2H), 3.17
		(dt, J = 23.4, 11.9 Hz, 3H), 2.50 (tt, J = 9.6, 4.5 Hz, 2H), 2.07 (s, 2H), 1.91
		(dd, J = 24.3, 11.5 Hz, 2H), 1.78 (s, 2H), 1.57 (d, J = 7.0 Hz, 3H), 1.49 (d,
		J = 11.9 Hz, 2H), 1.42 (t, J = 7.2 Hz, 5H), 1.31 (s, 3H), 1.09 (s, 3H).
424	678.7	1H NMR (400 MHz, MeOD) δ 8.12 (d, J = 6.3 Hz, 1H), 8.05 (d, J = 8.1
		Hz, 1H), 7.68 (d, J = 11.0 Hz, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.13 (s, 1H),
		5.27 (dd, J = 7.2, 5.1 Hz, 1H), 4.96 (dd, J = 9.8, 4.5 Hz, 2H), 4.57 (s, 1H),
		4.50 (dd, J = 10.0, 4.7 Hz, 1H), 4.35 (ddd, J = 14.2, 9.2, 5.7 Hz, 1H), 3.80
		(h, J = 6.0 Hz, 2H), 3.70 (d, J = 12.9 Hz, 1H), 3.59-3.44 (m, 2H), 3.24-
		3.09 (m, 2H), 2.50 (tt, J = 9.9, 4.2 Hz, 1H), 1.90 (t, J = 11.5 Hz, 1H), 1.77
		(s, 1H), 1.57 (d, J = 7.0 Hz, 3H), 1.54-1.32 (m, 4H), 1.31 (s, 2H), 1.09
		(s, 3H), 1.00 (dd, J = 18.7, 6.1 Hz, 4H).
425	664.6	1H NMR (400 MHz, MeOD) δ 8.12 (d, J = 6.3 Hz, 1H), 8.05 (d, J = 8.1
		Hz, 1H), 7.67 (d, J = 11.0 Hz, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.10 (s, 1H),
		5.30-5.22 (m, 1H), 4.96 (dt, J = 9.4, 4.9 Hz, 2H), 4.67-4.45 (m, 3H),
		4.34 (ddd, J = 14.0, 9.3, 5.7 Hz, 1H), 3.85-3.67 (m, 3H), 3.55 (d, J =
		13.2 Hz, 2H), 3.46-3.34 (m, 2H), 3.24-3.10 (m, 2H), 2.50 (tt, J = 9.6,
		4.4 Hz, 1H), 2.07 (s, 2H), 1.90 (t, J = 11.4 Hz, 1H), 1.78 (s, 2H), 1.57 (d,
		J = 7.1 Hz, 3H), 1.52-1.33 (m, 4H), 1.31 (s, 3H), 1.12-1.01 (m, 5H).
426	629.5	1H NMR (400 MHz, MeOD) δ 8.15 (d, J = 6.3 Hz, 1H), 8.01 (d, J = 8.1
		Hz, 1H), 7.76 (d, J = 10.8 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H),
		5.11 (q, J = 7.0 Hz, 1H), 4.96 (dt, J = 9.5, 4.8 Hz, 1H), 4.77 (t, J = 6.4 Hz,
		1H), 4.49 (dt, J = 16.2, 10.9 Hz, 2H), 3.75-3.67 (m, 1H), 3.55 (d, J =
		13.2 Hz, 1H), 3.25-3.15 (m, 1H), 3.06-2.91 (m, 2H), 2.49 (td, J = 9.7,
		5.0 Hz, 1H), 1.71 (s, 1H), 1.64-1.43 (m, 4H), 1.32 (s, 1H), 1.09 (dt, J =
		8.8, 4.5 Hz, 1H), 0.85-0.76 (m, 1H), 0.60 (q, J = 7.1, 5.6 Hz, 1H).
427	678.6	1H NMR (400 MHz, MeOD) δ 8.12 (d, J = 6.3 Hz, 1H), 7.99 (d, J = 8.0
		Hz, 1H), 7.69 (d, J = 11.0 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H),
		5.11 (q, J = 7.0 Hz, 1H), 4.58 (t, J = 5.0 Hz, 1H), 4.54-4.43 (m, 2H),
		3.84 (t, J = 5.1 Hz, 2H), 3.74-3.66 (m, 1H), 3.59-3.44 (m, 3H), 3.43-
		3.35 (m, 2H), 3.29-3.10 (m, 11H), 2.50 (tt, J = 9.5, 4.2 Hz, 1H), 2.13-
		1.90 (m, 2H), 1.68 (ddd, J = 11.8, 10.0, 6.3 Hz, 8H), 1.56 (dd, J = 7.6, 4.9
		Hz, 5H), 1.44 (h, J = 7.4 Hz, 8H), 1.31 (s, 2H), 1.05 (t, J = 7.4 Hz, 11H),
		0.82 (s, 1H), 0.64-0.55 (m, 1H).
428	647.8	1H NMR (400 MHz, MeOD) δ 8.11 (d, J = 6.3 Hz, 1H), 8.10-7.97 (m,
		1H), 7.70 (d, J = 10.9 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), 5.11
		(q, J = 7.0 Hz, 1H), 4.68 (t, J = 7.0 Hz, 2H), 4.48 (ddt, J = 23.9, 18.7, 9.3
		Hz, 2H), 3.70 (dd, J = 12.5, 4.9 Hz, 1H), 3.55 (d, J = 13.2 Hz, 1H), 3.25-
		3.10 (m, 2H), 2.71 (td, J = 6.9, 2.5 Hz, 2H), 2.50 (tt, J = 9.6, 4.4 Hz, 1H),
		2.07 (s, 1H), 1.96 (q, J = 7.7, 6.4 Hz, 1H), 1.67-1.58 (m, 3H), 1.32 (d, J =
		10.8 Hz, 2H), 1.09 (dt, J = 8.7, 4.4 Hz, 1H), 0.83 (s, 2H), 0.59 (ddd, J =
		7.8, 5.7, 4.0 Hz, 1H).
429	696.6	1H NMR (400 MHz, MeOD) δ 8.13 (d, J = 6.3 Hz, 1H), 7.98 (d, J = 8.0
		Hz, 1H), 7.74 (d, J = 10.9 Hz, 1H), 7.18-7.11 (m, 3H), 7.08 (s, 1H), 6.91-
		6.82 (m, 1H), 6.73-6.63 (m, 2H), 5.10 (q, J = 7.0 Hz, 1H), 4.83 (tt, J =
		9.1, 3.2 Hz, 4H), 4.58-4.40 (m, 2H), 4.32 (dt, J = 10.7, 4.1 Hz, 1H), 4.22
		(ddd, J = 10.9, 6.8, 4.2 Hz, 1H), 3.75-3.64 (m, 1H), 3.59-3.50 (m, 1H),
		3.18 (td, J = 13.3, 12.8, 10.1 Hz, 2H), 2.49 (tt, J = 14.1, 4.0 Hz, 1H), 2.16-
		2.00 (m, 1H), 1.86 (ddd, J = 11.6, 7.3, 3.4 Hz, 1H), 1.66 (s, 1H), 1.59-
		1.42 (m, 6H), 1.42-1.28 (m, 2H), 1.25-1.13 (m, 1H), 1.08 (dt, J = 8.8,
		4.6 Hz, 1H), 0.78 (s, 1H), 0.58 (ddd, J = 7.8, 5.7, 4.0 Hz, 1H).
430	648.5	1H NMR (400 MHz, MeOD) δ 8.11 (dd, J = 6.3, 1.1 Hz, 2H), 7.99 (dd,
		J = 8.1, 1.6 Hz, 1H), 7.65 (dd, J = 11.0, 7.6 Hz, 2H), 7.15 (dd, J = 8.0, 1.3
		Hz, 1H), 7.08 (s, 1H), 5.16-5.06 (m, 2H), 4.82 (dd, J = 9.6, 4.3 Hz, 2H),
		4.57-4.43 (m, 5H), 4.41-4.31 (m, 2H), 3.74 (ddt, J = 30.4, 11.9, 4.0 Hz,
		4H), 3.55 (d, J = 13.5 Hz, 2H), 3.25-3.08 (m, 4H), 3.07 (d, J = 4.5 Hz,
		4H), 2.50 (tt, J = 9.8, 4.4 Hz, 2H), 2.07 (s, 2H), 1.73 (s, 3H), 1.56 (d, J =
		7.0 Hz, 9H), 1.32 (s, 2H), 1.16 (dd, J = 6.2, 3.7 Hz, 4H), 1.09 (dt, J = 8.7,
		4.5 Hz, 2H), 0.82 (s, 4H), 0.59 (s, 2H).
431	646.5	1H NMR (400 MHz, MeOD) δ 7.99 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.15
		(d, J = 8.1 Hz, 1H), 7.04 (ddt, J = 14.4, 3.1, 1.6 Hz, 2H), 5.11 (q, J = 7.0
		Hz, 1H), 4.85-4.68 (m, 3H), 4.39 (d, J = 14.6 Hz, 1H), 4.09 (s, 3H), 3.74
		(q, J = 4.9 Hz, 2H), 3.42 (s, 2H), 3.12 (s, 3H), 2.22 (d, J = 12.6 Hz, 1H),
		2.01-1.82 (m, 2H), 1.73 (q, J = 14.9, 13.5 Hz, 4H), 1.61-1.51 (m, 6H),
		1.32 (s, 1H), 1.09 (dt, J = 8.8, 4.4 Hz, 1H), 0.82 (d, J = 8.3 Hz, 2H), 0.60
		(ddd, J = 7.8, 5.6, 4.0 Hz, 1H).
432	658.9	1H NMR (400 MHz, MeOD) δ 7.99 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 1.3
		Hz, 1H), 7.47 (d, J = 1.3 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 7.02 (s, 1H),
		5.11 (q, J = 7.1 Hz, 1H), 4.78 (tdd, J = 14.7, 9.0, 4.3 Hz, 2H), 4.50 (qd, J =
		9.5, 4.7 Hz, 1H), 4.43-4.34 (m, 1H), 4.11 (s, 2H), 3.80-3.61 (m, 3H),
		3.55 (d, J = 13.4 Hz, 1H), 3.27-3.06 (m, 4H), 2.51 (ddd, J = 14.2, 10.2,
		4.1 Hz, 1H), 1.73 (s, 1H), 1.67-1.41 (m, 6H), 1.36-1.29 (m, 1H), 1.09
		(dt, J = 8.8, 4.4 Hz, 1H), 0.60 (ddd, J = 7.8, 5.7, 4.0 Hz, 1H).
433	628.6	1H NMR (400 MHz, MeOD) δ 7.99 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.15
		(d, J = 8.1 Hz, 1H), 7.04 (ddt, J = 14.4, 3.1, 1.6 Hz, 2H), 5.11 (q, J = 7.0
		Hz, 1H), 4.85-4.68 (m, 3H), 4.39 (d, J = 14.6 Hz, 1H), 4.09 (s, 3H), 3.74
		(q, J = 4.9 Hz, 2H), 3.42 (s, 2H), 3.12 (s, 3H), 2.22 (d, J = 12.6 Hz, 1H),
		2.01-1.82 (m, 2H), 1.73 (q, J = 14.9, 13.5 Hz, 4H), 1.61-1.51 (m, 6H),
		1.32 (s, 1H), 1.09 (dt, J = 8.8, 4.4 Hz, 1H), 0.82 (d, J = 8.3 Hz, 2H), 0.60
		(ddd, J = 7.8, 5.6, 4.0 Hz, 1H).
434	697.6	1H NMR (400 MHz, MeOD) δ 8.11 (d, J = 6.3 Hz, 1H), 7.95-7.86 (m,
		2H), 7.69 (d, J = 10.9 Hz, 1H), 7.46 (ddd, J = 8.3, 7.1, 2.0 Hz, 1H), 7.12
		(d, J = 8.1 Hz, 1H), 6.96 (s, 1H), 6.78 (ddd, J = 7.0, 5.0, 0.9 Hz, 1H), 6.43
		(dt, J = 8.4, 0.9 Hz, 1H), 5.11 (q, J = 7.0 Hz, 1H), 4.96 (dt, J = 9.5, 4.9 Hz,
		1H), 4.81 (dd, J = 13.8, 9.3 Hz, 1H), 4.66-4.39 (m, 4H), 3.70 (dt, J =
		13.0, 4.2 Hz, 1H), 3.55 (d, J = 13.3 Hz, 1H), 3.23-3.09 (m, 2H), 2.50 (tt,
		J = 9.7, 4.3 Hz, 1H), 2.16-2.00 (m, 1H), 1.96-1.87 (m, 1H), 1.56 (t, J =
		8.3 Hz, 8H), 1.33-1.20 (m, 1H), 1.09 (dt, J = 8.7, 4.5 Hz, 1H), 0.79 (t, J =
		8.5 Hz, 2H), 0.63-0.54 (m, 1H).
435	684.7	1H NMR (400 MHz, MeOD) δ 8.60 (d, J = 2.6 Hz, 1H), 8.50 (d, J = 2.6
		Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 1.2 Hz, 1H), 7.35-7.28 (m,
		2H), 7.19 (s, 1H), 5.38 (q, J = 7.0 Hz, 1H), 5.07-4.96 (m, 2H), 4.81 (d,
		J = 4.9 Hz, 1H), 4.73 (ddd, J = 14.8, 6.7, 3.8 Hz, 2H), 4.61-4.53 (m, 1H),
		3.84-3.52 (m, 9H), 3.49 (s, 4H), 3.20 (s, 3H), 2.81-2.69 (m, 2H), 2.60-
		2.45 (m, 2H), 1.83 (d, J = 13.8 Hz, 2H), 1.65 (d, J = 7.1 Hz, 6H), 1.54-
		1.41 (m, 2H), 1.31 (s, 2H), 0.72 (q, J = 12.3 Hz, 2H).
436	646.7	1H NMR (400 MHz, MeOD) δ 8.00 (d, J = 8.1 Hz, 1H), 7.73 (d, J = 1.2
		Hz, 1H), 7.32 (dd, J = 11.6, 1.3 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.07 (s,
		1H), 5.11 (q, J = 7.0 Hz, 1H), 4.75 (tdd, J = 21.3, 13.4, 5.0 Hz, 2H), 4.50
		(dt, J = 14.2, 4.1 Hz, 1H), 3.82 (dt, J = 6.1, 3.1 Hz, 1H), 3.73 (q, J = 5.0
		Hz, 3H), 3.63 (s, 1H), 3.49 (s, 3H), 3.15 (s, 3H), 1.72 (d, J = 10.7 Hz, 2H),
		1.57 (t, J = 5.4 Hz, 6H), 1.47 (s, 1H), 1.31 (s, 1H), 1.09 (dt, J = 8.7, 4.4
		Hz, 1H), 0.88-0.74 (m, 2H), 0.60 (ddd, J = 7.9, 5.7, 4.0 Hz, 1H).
437	663.2	1H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 7.9 Hz, 1H), 7.97 (s, 2H),
		7.73 (s, 1H), 7.43-7.36 (m, 2H), 7.19 (d, J = 1.7 Hz, 1H), 7.10 (t, J = 7.2
		Hz, 1H), 6.91 (s, 1H), 5.60-5.45 (m, 1H), 4.95 (dd, J = 30.0, 15.6 Hz,
		1H), 4.86-4.74 (m, 1H), 4.54 (s, 0H), 4.25 (s, 1H), 4.09 (s, 3H), 3.99 (s,
		3H), 3.44-3.22 (m, 1H), 2.75 (d, J = 13.3 Hz, 0H), 1.98 (s, 1H), 1.92-
		1.73 (m, 3H), 1.65 (s, 5H), 1.59 (d, J = 7.2 Hz, 3H), 1.52-1.43 (m, 1H),
		1.37-1.20 (m, 1H), 0.85-0.75 (m, 1H), 0.75-0.61 (m, 1H), 0.54-0.38
		(m, 2H).
438	660.6	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.98 (s, 2H), 7.73 (s, 1H), 7.69-7.58 (m, 2H), 7.37 (s, 1H),
		7.33-7.28 (m, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.84 (t, J = 13.7 Hz, 1H),
		5.20 (dd, J = 27.9, 14.6 Hz, 1H), 5.12-5.01 (m, 1H), 5.01-4.94 (m,
		0.4H), 4.52 (m, 0.6H), 4.19 (s, 1H), 4.09-4.00 (m, 2H), 3.43-3.21 (m,
		1H), 3.17 (s, 0H), 2.84-2.74 (m, 0.6H), 2.27-2.04 (m, 2H), 2.02-1.90
		(m, 2H), 1.80 (d, J = 29.5 Hz, 1H), 1.65 (d, J = 14.5 Hz, 2H), 1.58-1.51
		(m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.40-1.29 (m, 1H), 1.29-1.19 (m,
		1H), 1.11-0.95 (m, 2H), 0.89-0.80 (m, 1H), 0.72-0.58 (m, 1H), 0.49
		(dtd, J = 16.6, 8.4, 5.5 Hz, 3H).
439	646.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 6.9 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.04-7.63 (m, 3H), 7.43-7.27 (m, 3H), 7.27-7.15 (m,
		3H), 7.07 (s, 1H), 6.89 (s, 1H), 5.18 (p, J = 7.0 Hz, 1H), 5.04-4.92 (m,
		1H), 4.92-4.78 (m, 1H), 4.67-4.47 (m, 2H), 4.30-4.17 (m, 1H), 4.11
		(s, 3H), 3.99 (s, 3H), 3.47-2.95 (m, 2H), 2.85-2.70 (m, 1H), 2.44-2.29
		(m, 1H), 2.22 (td, J = 12.4, 4.4 Hz, 1H), 2.06-1.32 (m, 11H), 1.32-1.05
		(m, 2H), 0.62-0.42 (m, 1H).
440	679.2	1H NMR (400 MHz, DMSO-d6) δ 9.47 (d, J = 7.1 Hz, 1H), 8.49 (s, 1H),
		8.34 (d, J = 1.1 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.96 (s, 2H), 7.85-7.50
		(m, 2H), 7.37-7.15 (m, 3H), 5.26 (p, J = 7.0 Hz, 1H), 5.04-4.78 (m,
		2H), 4.59-4.46 (m, 1H), 4.25-4.14 (m, 1H), 4.08-3.98 (m, 2H), 3.44-
		3.02 (m, 2H), 2.82-2.69 (m, 1H), 2.43-2.29 (m, 1H), 2.23-2.08 (m,
		1H), 2.05-1.37 (m, 11H), 1.37-0.94 (m, 5H), 0.53-0.30 (m, 2H).
441	626.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.95 (s, 2H),
		7.82 (d, J = 7.4 Hz, 1H), 7.73 (s, 1H), 7.37 (s, 1H), 7.18 (d, J = 8.1 Hz,
		1H), 7.02 (s, 1H), 6.89 (s, 1H), 5.12 (p, J = 7.0 Hz, 1H), 4.87-4.74 (m,
		1H), 4.63-4.33 (m, 2H), 4.29-4.18 (m, 1H), 4.11 (s, 3H), 3.98 (s, 3H),
		3.46-2.96 (m, 2H), 2.84-2.69 (m, 1H), 2.03-1.48 (m, 9H), 1.48-1.26
		(m, 8H), 1.21 (s, 3H), 1.16-0.98 (m, 2H), 0.94 (s, 3H).
442	646.3	1H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 8.8 Hz, 1H), 8.05 (d, J =
		8.0 Hz, 1H), 8.02-7.61 (m, 3H), 7.39 (s, 1H), 7.23 (d, J = 8.0 Hz, 1H),
		7.13 (s, 1H), 6.91 (s, 1H), 5.51 (t, J = 13.6 Hz, 1H), 5.24-4.88 (m, 2H),
		4.64-4.45 (m, 1H), 4.32-4.18 (m, 1H), 4.09 (s, 3H), 3.99 (s, 3H), 3.46-
		3.03 (m, 2H), 2.85-2.68 (m, 1H), 2.28-1.48 (m, 10H), 1.44 (d, J = 7.1
		Hz, 3H), 1.38-1.15 (m, 2H), 0.93-0.77 (m, 1H), 0.73-0.55 (m, 1H),
		0.55-0.38 (m, 2H).
443	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 8.02-7.67
		(m, 3H), 7.64 (d, J = 8.0 Hz, 1H), 7.36 (br. s, 1H), 7.21 (d, J = 8.1 Hz,
		1H), 7.02 (s, 1H), 6.89 (s, 1H), 5.16 (p, J = 7.1 Hz, 1H), 5.06-4.17 (m,
		1H), 4.61 (br. t, J = 5.8 Hz, 2H), 4.09 (s, 3H), 3.98 (s, 3H), 3.40-3.01 (m,
		2H), 2.85-2.68 (m, 1H), 2.02-1.89 (m, 1H), 1.89-1.70 (m, 7H), 1.63
		(s, 3H), 1.55-1.51 (m, 3H), 1.40-1.27 (m, 1H), 1.17 (s, 3H), 1.21-1.07
		(m, 1H), 1.00 (s, 3H), 0.89-0.77 (m, 2H).
444 1	610.3	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 8.6 Hz, 1H), 7.98 (d, J =
		8.0 Hz, 1H), 8.09-7.69 (m, 3H), 7.36 (br. s, 1H), 7.13 (d, J = 8.1 Hz,
		1H), 7.01 (s, 1H), 6.89 (s, 1H), 5.07-4.94 (m, 1H), 4.76-4.47 (m, 2H),
		4.11 (s, 3H), 3.99 (s, 3H), 3.92-3.18 (m, 3H), 3.18-2.69 (m, 1H), 2.03-
		1.92 (m, 1H), 1.91-1.72 (m, 3H), 1.72-1.44 (m, 9H), 1.43 (d, J = 7.1
		Hz, 3H), 1.41-1.30 (m, 1H), 1.29-1.14 (m, 1H), 0.90-0.81 (m, 1H),
		0.76-0.57 (m, 2H), 0.52-0.43 (m, 1H).
445	624.3	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 8.1 Hz, 1H), 8.08 (d, J =
		7.9 Hz, 1H), 8.05-7.70 (m, 3H), 7.38 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H),
		7.06 (s, 1H), 6.90 (s, 1H), 5.27 (p, J = 7.0 Hz, 1H), 5.07-4.91 (m, 0.5H),
		4.88-4.76 (m, 1H), 4.49-4.37 (m, 1H), 4.13 (s, 3H), 4.29-3.68 (m,
		1.5H), 3.99 (s, 3H), 3.46-2.68 (m, 2H), 2.32-2.20 (m, 1H), 2.07-1.92
		(m, 2H), 1.90-1.70 (m, 5H), 1.69-1.50 (m, 4H), 1.45 (d, J = 6.9 Hz,
		3H), 1.48-1.37 (m, 2H), 1.30-1.17 (m, 2H), 1.16-0.98 (m, 2H), 0.98-
		0.89 (m, 1H), 0.65-0.56 (m, 1H), 0.52-0.42 (m, 1H).
446	701.4	1H NMR (400 MHz, DMSO-d6) δ 9.54 (d, J = 7.5 Hz, 1H), 8.52 (s, 1H),
		8.39 (d, J = 1.1 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.08-7.65 (m, 3H),
		7.41-7.31 (m, 2H), 7.19 (s, 1H), 6.90 (s, 1H), 5.38 (p, J = 7.1 Hz, 1H),
		5.32-5.23 (m, 1H), 5.17 (dd, J = 31.4, 14.6 Hz, 1H), 5.05-4.43 (m, 1H),
		4.31-4.18 (m, 1H), 4.11 (s, 3H), 4.00 (s, 3H), 3.50-3.05 (m, 1H), 2.85-
		2.52 (m, 1H), 2.45 (dd, J = 13.2, 4.3 Hz, 1H), 2.15 (td, J = 12.6, 3.7 Hz,
		1H), 2.03-1.92 (m, 1H), 1.90-1.49 (m, 9H), 1.46 (d, J = 7.0 Hz, 3H),
		1.27-0.99 (m, 1H).
447	628.3	1H NMR (400 MHz, DMSO-d6) δ 8.36 (d, J = 7.6 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.96 (s, 2H), 7.73 (s, 1H), 7.37 (s, 1H), 7.19 (d, J = 8.1 Hz,
		1H), 7.01 (s, 1H), 6.89 (s, 1H), 5.13 (p, J = 7.3 Hz, 1H),   5.04-4.91
		(m, 0.5H),   4.66-4.48 (m, 3H),   4.21-4.11 (m,
		0.5H),   4.11 (s, 3H), 3.98 (s, 3H),   3.80-3.60 (m,
		0.5H),   3.44-3.21 (m, 0.5H), 3.18-3.02 (m, 0.5H), 2.84-2.69
		(m, 0.5H),   2.05-1.15 (m, 19H), 1.09-0.88 (m, 2H).
448	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 9.6 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 7.96 (br s, 2H), 7.72 (br s, 1H), 7.39 (s, 1H), 7.25 (d, J = 8.0
		Hz, 1H), 7.15 (s, 1H), 6.91 (s, 1H), 5.53 (t, J = 13.5 Hz, 1H), 5.28-5.13
		(m, 2H),   5.04-4.91 (m, 0.5H),   4.58-4.49 (m,
		1H),   4.21-4.11 (m, 0.5H),   4.10 (s, 3H), 3.99 (s,
		3H),   3.80-3.60 (m, 0.5H), 3.44-3.21 (m, 0.5H), 3.18-3.02 (m,
		0.5H), 2.84-2.69 (m, 0.5H), 2.42-1.37 (m, 17H), 1.28-0.90 (m, 2H).
449	678.3	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 9.6 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.98 (s, 2H), 7.79-7.58 (m, 2H), 7.37 (s, 1H), 7.34-7.17
		(m, 2H), 5.82 (t, J = 13.7 Hz, 1H), 5.34-5.17 (m, 2H), 5.02-4.92 (m,
		0.5H), 4.58-4.47 (m, 1H), 4.23-4.14 (m, 0.5H), 4.07-3.98 (m, 1H),
		2.44-1.37 (m, 14H),  3.80-3.60 (m, 0.5H), 3.44-3.21 (m, 0.5H),
		3.18-3.02 (m, 0.5H), 2.84-2.69 (m, 0.5H),   1.30-0.91 (m,
		6H),   0.50-0.36 (m, 1H).
450	642.3	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 9.5 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.98 (s, 2H), 7.81-7.54 (m, 2H), 7.31-7.19 (m, 2H), 7.17
		(d, J = 8.0 Hz, 1H), 5.26-5.13 (m, 1H), 5.03-4.95 (m, 0.5H), 4.89-
		4.78 (m, 2H), 4.59-4.44 (m, 1H), 4.22-4.11 (m, 0.5H), 4.03-3.95 (m,
		1H), 3.80-3.61 (m, 0.5H), 3.43-3.21 (m, 0.5H), 3.19-3.02 (m, 0.5H),
		2.84-2.70 (m, 0.5H), 2.31-2.20 (m, 1H), 2.08-1.01 (m, 20H), 1.00-
		0.80 (m, 2H), 0.67-0.56 (m, 1H).
451	628.3	1H NMR (400 MHz, DMSO-d6) δ 8.41 (d, J = 9.5 Hz, 1H), 8.00 (d, J =
		8.0 Hz, 1H), 7.97 (s, 2H), 7.74 (s, 1H), 7.37 (s, 1H), 7.16 (d, J = 8.1 Hz,
		1H), 7.03 (s, 1H), 6.89 (s, 1H), 5.25-5.14 (m, 1H), 5.07-4.92 (m,
		0.5H), 4.80-4.59 (m, 2H), 4.59-4.47 (m, 1H), 4.30-4.18 (m, 0.5H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.88-3.70 (m, 0.5H), 3.46-3.22 (m,
		0.5H),   3.18-3.02 (m, 0.5H),   2.85-2.69 (m, 0.5H), 2.32-
		2.19 (m, 1H), 2.08-1.08 (m, 19H), 0.94 (td, J = 9.9, 6.0 Hz, 1H).
452	713.2	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 6.2 Hz, 1H), 8.12 (d, J =
		8.1 Hz, 0.3H minor rotamer), 8.09 (d, J = 8.1 Hz, 0.7H major rotamer),
		7.99 (brs, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.80-7.57 (m, 3H), 7.46-7.37
		(m, 2H), 7.33-7.19 (m, 2H), 5.28-5.15 (m, 1H), 5.12-4.78 (m, 4H),
		4.53 (brs, 1H), 4.26-4.12 (m, 1H), 2.88-2.61 (m, 2H), 2.46-2.29 (m,
		3H), 2.08-1.34 (m, 9H), 1.55-1.46 (m, 3H), 1.30-1.05 (m, 2H), 0.63
		(brs, 1H).
453	710.2	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.7 Hz, 1H), 8.17-8.05
		(m, 1H), 7.98 (brs, 2H), 7.85-7.57 (m, 3H), 7.37 (s, 1H), 7.35-7.17 (m,
		2H), 6.22 (td, J = 56.8, 3.7 Hz, 1H), 5.79 (t, J = 13.7 Hz, 0.7H major
		rotamer), 6.63 (t, J = 13.7 Hz, 0.3H minor rotamer), 5.28-5.15 (m, 1H),
		5.14-5.01 (m, 1H), 4.98 (s, 0.3H minor rotamer), 4.53 (brs, 0.7H major
		rotamer), 4.33 (brs, 0.7H major rotamer), 4.18 (s, 0.3H minor rotamer),
		3.73 (brs, 1H), 3.14 (brs, 1H) 2.75 (brs, 1H), 2.46-1.46 (m, 9H), 1.45 (d,
		J = 7.1 Hz, 3H), 1.41-1.18 (m, 2H), 0.95-0.58 (m, 4H), 0.58-0.48 (m,
		2H).
454	710.2	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 9.0 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.99 (brs, 2H), 7.86-7.58 (m, 3H), 7.33 (brs, 1H), 7.30 (s,
		1H), 7.24 (d, J = 8.1 Hz, 1H), 5.91 (t, J = 56 Hz, 1H), 5.63 (t, J = 13.7 Hz,
		1H), 5.22 (dd, J = 27.5, 14.6 Hz, 1H), 5.14-5.06 (m, 1H), 4.98 (brs, 1H),
		4.53 (brs, 1H), 4.40-4.19 (m, 1H), 3.73 (brs, 1H), 3.22-3.04 (m, 1H),
		2.31-2.05 (m, 2H), 2.04-1.89 (m, 2H), 1.89-1.45 (m, 8H), 1.44 (d, J =
		7.1 Hz, 3H), 1.39-1.18 (m, 2H), 0.94-0.84 (m, 1H), 0.76-0.60 (m,
		1H), 0.59-0.47 (m, 2H).
455	660.2	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.99 (d, J = 5.5 Hz, 2H), 7.81 (d, J = 5.9 Hz, 0.4H minor
		rotamer), 7.73 (brs, 1H + 0.6H major rotamer), 7.67 (d, J = 8.2 Hz, 0.4H
		minor isomer) 7.65 (d, J = 9.5 Hz, 0.6H majo rotamer), 7.38 (s, 0.4H
		minor rotamer), 7.37 (s, 0.6H major rotamer), 7.23 (d, J = 8.1 Hz, 1H),
		5.86 (t, J = 13.8 Hz, 1H), 5.18 (dd, J = 27.7, 14.6 Hz, 1H), 5.12-4.99 (m,
		1H), 4.64 (brs, 0.6H major rotamer), 4.11-3.91 (m, 1H), 3.83 (brs, 1H),
		3.40-3.20 (m, 1H), 3.09 (brs, 0.4H minor isomer), 2.84-2.72 (m, 1H),
		2.29-1.92 (m, 5H), 1.86-1.49 (m, 7H), 1.44 (d, J = 7.0 Hz, 3H), 1.41-
		1.18 (m, 2H), 1.15-0.94 (m, 2H), 0.91-0.76 (m, 1H), 0.72-0.55 (m,
		1H), 0.57-0.39 (m, 3H).
456	713.2	1H NMR (400 MHz, DMSO-d6) δ 9.16-9.10 (m, 1H), 8.11 (dd, J = 8.1,
		1.3 Hz, 1H), 8.02 (d, J = 5.5 Hz, 2H), 7.82 (d, J = 8.1 Hz, 1H), 7.78 (d, J =
		5.5 Hz, 1H), 7.63 (d, J = 4.8 Hz, 0.4H minor rotamer), 7.56 (brs, 0.6H
		major rotamer), 7.41 (d, J = 8.0 Hz, 1H), 7.34 (s, 0.4H minor rotamer),
		7.33 (s, 0.6H major rotamer), 7.28 (d, J = 8.1 Hz, 0.4H minor rotamer),
		7.27 (d, J = 8.1 Hz, 0.6H major rotamer), 5.25-5.16 (m, 1H), 5.06 (s,
		0.4H minor rotamer), 4.99-4.85 (m, 1H), 4.84-4.74 (m, 1H), 4.62 (dd, J =
		13.2, 6.1 Hz, 0.6H major rotamer), 4.11-3.94 (m, 2H), 3.39 (brs, 0.6H
		major rotamer), 3.26 (brs, 0.4H minor rotamer), 3.07 (t, J = 12.0 Hz, 0.4H
		minor rotamer), 2.78 (t, J = 12.2 Hz, 0.6H major rotamer), 2.72-2.57 (m,
		1H), 2.47-2.27 (m, 2H), 2.07-1.91 (m, 2H), 1.88-1.36 (m, 8H), 1.50
		(d, J = 7.0 Hz, 3H), 1.33-1.01 (m, 4H), 0.65-0.39 (m, 2H).
457	711.3	1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1.3H major rotamer), 9.34 (s,
		0.7H minor rotamer), 8.19 (d, J = 8.2 Hz, 0.7H minor rotamer), 8.14 (d, J =
		8.0 Hz, 1.3H major rotamer), 7.97 (brs, 1H), 7.94-7.87 (m, 2H), 7.79-
		7.66 (m, 2H), 7.68-7.56 (m, 1H), 7.34 (s, 0.65H major rotamer), 7.32 (s,
		0.35H minor rotamer), 7.32-7.17 (m, 1H), 5.61-5.48 (m, 1H), 5.08-
		4.91 (m, 1H), 4.90-4.70 (m, 1H), 4.53 (brs, 0.65H major rotamer), 4.18
		(brs, 0.65H major rotamer), 4.07-3.98 (m, 1H), 3.74 (brs, 2H), 3.16 (brs,
		0.35H minor rotamer), 2.61 (brs, 0.35H minor rotamer), 2.59-2.53 (m,
		2H), 2.47-2.37 (m, 1H), 2.03-1.48 (m, 9H), 1.54 (d, J = 7.0 Hz, 3H),
		1.39-0.94 (m, 5H), 0.65-0.42 (m, 2H).
458	607.7	1H NMR (400 MHz, DMSO-d6) δ 8.48 (brs, 1H), 8.46 (d, J = 8.7 Hz,
		1H), 8.24 (brs, 0.4H minor rotamer), 8.15 (brs, 0.6H major rotamer), 8.04-
		7.94 (m, 1H), 8.02 (d, J = 8.0 Hz, 2H), 7.97 (s, 1H), 7.73 (bs, 1H), 7.38
		(s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 5.08-4.97 (m, 1H), 4.96-4.91 (m, 2H),
		4.57 (brs, 0.4H minor rotamer), 4.18 (brs, 0.6H major rotamer), 3.89-
		3.77 (m, 1H), 3.46-3.25 (m, 2H), 3.23-3.08 (m, 0.4H minor rotamer),
		2.86-2.75 (m, 0.6H major rotamer), 2.05-1.32 (m, 12H), 1.45 (d, J =
		7.1 Hz, 3H), 1.32-0.99 (m, 4H), 0.91-0.59 (m, 4H), 0.53-0.44 (m,
		1H).
459	716.2	1H NMR (400 MHz, DMSO-d6) δ 8.81 (brs, 0.2H minor rotamer), 8.61
		(d, J = 8.6 Hz, 0.2H mimor rotamer), 8.39 (d, J = 7.4 Hz, 0.8H major
		rotamer), 8.21 (d, J = 7.5 Hz, 0.2H minor rotamer), 8.12 (d, J = 8.0 Hz,
		1H), 7.98 (brs, 1H), 7.75 (brs, 1H), 7.56 (brs, 0.2H minor rotamer), 7.36
		(brs, 0.8H major rotamer), 7.29 (d, J = 8.3 Hz, 0.8H major rotamer), 7.16
		(s, 0.8H major rotamer), 6.90 (s, 0.8H major rotamer), 5.75 (brs, 0.2H
		minor rotamer), 5.44-5.08 (m, 3H), 4.99 (brs, 0.2H minor rotamer), 4.53
		(brs, 0.8H major rotamer), 4.24 (brs, 0.8H major rotamer), 4.10 (s, 3H),
		3.99 (s, 3H), 3.80 (brs, 0.2H minor rotamer), 2.76 (brs, 0.8H major
		rotamer), 2.27-1.37 (m, 16H), 1.45 (d, J = 15.5 Hz, 3H), 1.36-0.92 (m,
		4H).
460	664.2	1H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 8.0 Hz, 1H), 8.09 (d, J =
		9.6 Hz, 1H), 7.99 (brs, 2H), 7.75 (brs, 1H), 7.40 (brs, 1H), 7.30 (d, J = 8.2
		Hz, 1H), 7.18 (s, 1H), 6.91 (brs, 1H), 5.52-5.23 (m, 3H), 4.99 (brs,
		0.35H minor rotamer), 4.53 (s, 0.65H major rotamer), 4.36-4.09 (m, 2H),
		4.09 (s, 3H), 3.99 (s, 3H), 3.47-3.06 (m, 3H), 2.86-2.54 (m, 2H), 2.04-
		1.50 (m, 7H), 1.45 (d, J = 6.8 Hz, 3H), 1.34 (s, 3H), 1.20 (s, 3H), 1.17-
		0.97 (m, 1H).
461	697.2	1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 6.6 Hz, 1H), 8.18 (s, 1H),
		8.15-8.03 (m, 2H), 7.97 (brs, 2H), 7.91 (d, J = 8.3 Hz, 1H), 7.80-7.72
		(m, 1H), 7.72 (brs, 1H), 7.65-7.58 (m, 1H), 7.37 (brs, 1H), 7.30 (d, J =
		8.1 Hz, 1H), 7.10 (s, 1H), 6.90 (brs, 1H), 5.32-5.18 (m, 1H), 4.99 (brs,
		0.35H minor rotamer), 4.88 (t, J = 12.8 Hz, 0.65H major rotamer), 4.72-
		4.56 (m, 0.65H major rotamer), 4.52 (brs, 0.35H minor rotamer), 4.23
		(brs, 1H), 4.13 (s, 3H), 4.00 (s, 3H), 3.47-3.05 (m, 3H), 2.86-2.65 (m,
		2H), 2.09-1.58 (m, 8H), 1.55 (d, J = 7.0 Hz, 3H), 1.53-1.34 (m, 1H),
		1.33-1.13 (m, 2H), 0.60-0.42 (m, 1H).
462	639.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 7.6 Hz, 1H), 7.97 (brs,
		2H), 7.74 (brs, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.58 (brs, 1H), 7.36 (s, 1H),
		7.22 (s, 1H), 7.20 (brs, 1H) 7.07 (d, J = 8.3 Hz, 1H), 5.12-5.00 (m, 1H),
		4.98 (brs, 0.35H minor rotamer), 4.88 (brs, 1H), 4.52 (brs, 0.65H major
		rotamer), 4.32-4.14 (m, 2H), 4.02-3.92 (m, 1H), 3.44-2.98 (m, 3H),
		2.90-2.63 (m, 1H), 2.08 (t, J = 12.7 Hz, 1H), 2.03-1.50 (m, 7H), 1.46
		(d, J = 7.3 Hz, 3H), 1.44-1.30 (m, 3H), 1.24 (s, 3H), 1.20-1.00 (m, 4H),
		0.94 (s, 3H), 0.91 (brs, 1H), 0.56 (s, 1H).
463	663.2	1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 9.0 Hz, 0.2H minor
		rotamer), 8.68 (d, J = 9.0 Hz, 0.8H major rotamer), 7.97 (brs, 2H), 7.82-
		7.62 (m, 2H), 7.44 (d, J = 10.4 Hz, 1H), 7.38 (brs, 1H), 7.10 (s, 1H), 6.90
		(brs, 1H), 5.75-5.64 (m, 1H), 5.26-5.09 (m, 1H), 4.99 (brs, 0.2H minor
		rotamer), 4.73 (dd, J = 28.8, 15.5 Hz, 0.8H major rotamer), 4.53 (brs, 0.2H
		minor rotamer), 4.24 (brs, 0.8H major rotamer), 4.07 (s, 3H), 3.99 (s, 3H),
		3.53-2.99 (m, 3H), 2.92-2.57 (m, 1H), 2.07-1.49 (m, 11H), 1.45 (d, J =
		7.1 Hz, 3H), 1.31-1.21 (m, 1H), 1.02-0.69 (m, 2H), 0.68-0.53 (m,
		2H).
464	677.3	1H NMR (400 MHz, DMSO-d6) δ 8.71 (d, J = 8.9 Hz, 1H), 7.97 (brs,
		2H), 7.75 (d, J = 6.2 Hz, 1H), 7.72 (brs, 1H), 7.69-7.65 (m, 1H), 7.45 (d,
		J = 10.2 Hz, 1H), 7.34 (s, 1H), 7.32-7.15 (m, 1H), 6.01 (t, J = 14.0 Hz,
		1H), 5.25-5.11 (m, 1H), 4.97 (brs, 0.35H minor rotamer), 4.77 (dd, J =
		28.8, 15.5 Hz, 1H), 4.52 (brs, 0.35H minor rotamer), 4.20 (brs, 0.65H
		major rotamer), 4.00 (brs, 1H), 3.74 (brs, 0.65H major rotamer), 3.29-
		2.71 (m, 2H), 2.22-1.48 (m, 11H), 1.45 (d, J = 7.1 Hz, 3H), 1.32-1.18
		(m, 2H), 1.11-0.73 (m, 5H), 0.73-0.55 (m, 2H), 0.52-0.34 (m, 1H).
465	625.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 7.9 Hz, 1H), 7.98 (brs,
		2H), 7.75 (s, 1H), 7.61 (d, J = 8.3 Hz, 1H), 7.37 (brs, 1H), 7.35 (s, 1H),
		7.07 (d, J = 8.3 Hz, 1H), 6.99 (s, 1H), 6.88 (s, 1H), 5.13-5.00 (m, 1H),
		4.99 (brs, 0.35H minor rotamer), 4.71-4.44 (m, 2H), 4.35-4.13 (m, 1H +
		0.65H major rotamer), 4.10 (s, 3H), 3.99 (s, 3H), 3.49-2.63 (m, 2H),
		2.16-1.53 (m, 10H), 1.52-1.31 (m, 3H), 1.45 (d, J = 7.2 Hz, 3H), 1.19
		(s, 3H), 1.08-0.98 (m, 3H), 0.94 (s, 3H).
466	678.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.7 Hz, 1H), 8.08 (d, J =
		7.8 Hz, 0.35H minor rotamer), 8.08 (d, J = 7.8 Hz, 0.65H major rotamer),
		8.00 (d, J = 5.5 Hz, 1H), 7.99 (brs, 1H), 7.74 (brs, 1H), 7.66 (d, J = 4.6 Hz,
		0.35H minor rotamer), 7.58 (brs, 0.65H major rotamer), 7.39 (s, 0.35H
		minor rotamer), 7.38 (s, 0.65H major rotamer), 7.25 (d, J = 8.1 Hz, 0.35H
		minor rotamer), 7.25 (d, J = 8.1 Hz, 0.65H major rotamer), 5.81 (t, J =
		13.9 Hz, 1H), 5.20 (dd, J = 27.7, 14.6 Hz, 1H), 5.12-5.00 (m, 1H), 4.69-
		4.57 (m, 1H), 4.04 (brs, 2H), 3.35-2.99 (m, 2H), 2.82-2.67 (m, 1H),
		2.23-1.50 (m, 10H), 1.44 (d, J = 7.0 Hz, 3H), 1.38-0.98 (m, 4H), 0.93-
		0.80 (m, 1H), 0.74-0.41 (m, 4H).
467	678.3	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.8 Hz, 1H), 8.08 (d, J =
		8.3 Hz, 0.35H minor rotamer), 8.05 (d, J = 8.3 Hz, 0.65H major rotamer),
		8.03-7.92 (m, 2H), 7.88-7.56 (m, 2H), 7.49 (s, 0.65H major rotamer),
		7.43 (s, 0.35H minor rotamer), 7.29 (brs, 1H), 7.24 (d, J = 8.3 Hz, 1H),
		6.10 (brs, 1H), 5.27-4.91 (m, 3H), 4.87 (s, 0.35H minor rotamer), 4.54
		(brs, 0.65H major rotamer), 4.28-4.06 (m, 2H), 3.48-3.06 (m, 3H), 2.86-
		2.66 (m, 1H), 2.42-2.04 (m, 2H), 2.03-1.47 (m, 9H), 1.44 (d, J = 7.1
		Hz, 3H), 1.36-1.20 (m, 1H), 0.84 (brs, 1H), 0.73-0.59 (m, 1H), 0.56-
		0.45 (m, 2H).
468	678.3	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.8 Hz, 1H), 8.08 (d, J =
		7.6 Hz, 1H), 7.98 (brs, 2H), 7.85-7.59 (m, 2H), 7.40-7.18 (m, 3H), 5.81
		(t, J = 13.7 Hz, 1H), 5.33-5.02 (m, 3H + 0.35H minor rotamer), 4.97
		(brs, 0.35H minor rotamer), 4.53 (brs, 0.65H major rotamer), 4.18 (brs,
		0.65H major rotamer), 4.13-4.01 (m, 1H), 3.72 (brs, 2H), 3.34-3.09 (m,
		1H), 2.79 (brs, 1H), 2.31-1.48 (m, 10H), 1.45 (d, J = 7.2 Hz, 3H), 1.39-
		1.20 (m, 1H), 0.91-0.73 (m, 2H), 0.73-0.57 (m, 1H), 0.58-0.47 (m,
		2H).
469	669.5	1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 7.2 Hz, 1H), 8.12 (d, J =
		8.0 Hz, 1H), 8.09 (s, 2H), 7.84 (s, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.72-
		7.55 (m, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.26 (s,
		1H), 7.16 (s, 1H), 5.23 (p, J = 7.0 Hz, 1H), 5.10-4.92 (m, 0H), 4.87 (ddd,
		J = 14.6, 10.8, 4.7 Hz, 1H), 4.71-4.60 (m, 1H), 4.60-4.45 (m, 0H), 4.22-
		4.14 (m, 1H), 4.11 (s, 3H), 3.87-3.65 (m, 0H), 3.47-3.24 (m, 1H),
		3.24-3.03 (m, 0H), 2.88-2.72 (m, 0H), 2.70-2.59 (m, 1H), 2.46-2.29
		(m, 2H), 2.07-1.94 (m, 1H), 1.91-1.73 (m, 1H), 1.71-1.53 (m, 7H),
		1.50 (d, J = 7.1 Hz, 3H), 1.46-1.30 (m, 1H), 1.31-1.13 (m, 1H), 0.73-
		0.51 (m, 1H).
470	690.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.12-8.03
		(m, 1H), 7.97 (s, 2H), 7.71 (s, 2H), 7.62 (s, 1H), 7.42 (s, 1H), 7.36-7.17
		(m, 3H), 5.79 (t, J = 13.8 Hz, 1H), 5.19 (dd, J = 28.0, 14.6 Hz, 1H), 5.11-
		5.03 (m, 1H), 5.01-4.86 (m, 0.4H), 4.63-4.39 (m, 0.6H), 4.29-
		4.13 (m, 1H), 3.74 (s, 3H), 3.58-3.55 (m, 3H), 3.44-3.34 (m, 0.5H),
		2.87-2.70 (m, 0.5H), 2.28-2.03 (m, 1H), 1.96 (d, J = 12.2 Hz, 3H), 1.90-
		1.73 (m, 1H), 1.71-1.60 (m, 2H), 1.55 (q, J = 6.1, 5.5 Hz, 1H), 1.45 (t,
		J = 7.4 Hz, 3H), 1.40-1.14 (m, 3H), 1.01-0.81 (m, 1H), 0.74-0.46 (m,
		5H).
471	676.5	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.7 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.97 (s, 2H), 7.80 (s, 0.4H), 7.73 (s, 1.6H), 7.48 (s, 0.5H),
		7.42 (s, 0.5H), 7.36 (s, 1H), 7.25 (d, J = 8.0 Hz, 1H), 5.87 (t, J = 13.7 Hz,
		1H), 5.20 (dd, J = 28.0, 14.6 Hz, 1H), 5.07 (p, 1H), 5.01-4.90 (m, 0.4H),
		4.61-4.42 (m, 0.5H), 4.26-4.14 (m, 0.6H), 4.10-3.99 (m, 1H), 3.46-
		3.34 (m, 0.3H), 3.34-3.22 (m, 1H), 3.19 (m, 0.3H), 2.86-2.70 (m,
		0.5H), 2.28-2.03 (m, 2H), 2.05-1.92 (m, 3H), 1.91-1.75 (m, 1H), 1.72-
		1.59 (m, 3H), 1.59-1.50 (m, 1H), 1.44 (d, J = 7.0 Hz, 3H), 1.32 (d, J =
		17.5 Hz, 3H), 1.13-0.90 (m, 2H), 0.89-0.79 (m, 1H), 0.75-0.60 (m,
		1H), 0.58-0.45 (m, 3H).
472	695.4	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.0 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.96 (s, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.79-7.52 (m, 1H),
		7.42 (d, J = 8.0 Hz, 1H), 7.32 (s, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.35-7.11
		(m, 1H), 5.21 (p, J = 6.9 Hz, 1H), 5.05-4.70 (m, 2H), 4.64-4.43 (m,
		0.5H, rotamer), 4.26-4.13 (m, 0.5H, rotamer), 4.09-3.93 (m, 1H), 3.64-
		3.16 (m, 4H), 2.71-2.59 (m, 1H), 2.41-2.25 (m, 4H), 2.06-1.90 (m,
		1H), 1.90-1.72 (m, 1H), 1.73-1.57 (m, 4H), 1.60-1.29 (m, 1H), 1.50
		(d, J = 7.0 Hz, 3H), 1.29-1.15 (m, 2H), 1.15-0.89 (m, 2H), 0.68-0.37
		(m, 2H).
473	714.2	1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 7.1 Hz, 1H), 8.12 (dd, J =
		8.1, 3.6 Hz, 1H), 7.97 (s, 1H), 7.87-7.81 (m, 1H), 7.42 (d, J = 8.1 Hz,
		1H), 7.38 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 5.23 (p, J = 7.2 Hz, 1H), 4.98
		(s, 1H), 4.90 (t, J = 10.4 Hz, 1H), 4.79 (s, 1H), 4.66 (s, 1H), 4.63-4.46
		(m, 2H), 4.15 (s, 1H), 3.73 (s, 1H), 3.14 (m, 1H) 2.76 (s, 1H), 2.72-2.61
		(m, 1H), 2.46-2.28 (m, 3H), 2.02-1.89 (m, 2H), 1.84 (d, J = 10.0 Hz,
		2H), 1.76 (s, 1H), 1.67 (s, 2H), 1.50 (dd, J = 7.1, 4.1 Hz, 3H), 1.24 (s, 1H),
		0.85 (s, 1H), 0.66 (s, 1H), 0.53 (m, 1H).
474	729.3	1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 7.0 Hz, 1H), 8.12 (d, J =
		8.0 Hz, 1H), 8.04 (d, J = 7.8 Hz, 1H), 7.96 (s, 2H), 7.81 (d, J = 7.9 Hz,
		1H), 7.73 (s, 1H), 7.59 (s, 1H), 7.36-7.26 (m, 2H), 5.23 (p, J = 6.9 Hz,
		1H), 5.01-4.88 (m, 2H), 4.85 (s, 1H), 4.52 (s, 1H), 4.18 (s, 1H), 4.02 (p,
		J = 6.0, 5.5 Hz, 1H), 3.76 (m, 1H) 3.15 (d, J = 15.9 Hz, 2H), 2.76 (s, 1H),
		2.68 (m, J = 5.2, 2.6 Hz, 1H), 1.95 (d, J = 10.5 Hz, 2H), 1.76 (s, 2H), 1.65
		(s, 2H), 1.51 (d, J = 7.0 Hz, 4H), 1.31-1.15 (m, 2H), 1.08 (s, 3H), 0.59-
		0.38 (m, 2H).
475	660.2	1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 8.1 Hz, 1H), 7.97 (d, J =
		8.5 Hz, 1H), 7.74 (s, 1H), 7.38 (s, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.16 (s,
		1H), 6.90 (s, 1H), 5.52 (q, J = 16.1 Hz, 1H), 5.31 (p, J = 7.1 Hz, 1H), 5.20
		(q, J = 12.9, 12.1 Hz, 1H), 4.99 (s, 1H), 4.53 (s, 1H), 4.26 (d, J = 14.7 Hz,
		1H), 4.10 (s, 3H), 4.00 (s, 3H), 3.92 (s, 1H), 3.20-3.05 (m, 1H), 2.77 (s,
		1H), 2.12-1.89 (m, 3H), 1.79 (d, J = 19.8 Hz, 3H), 1.58 (s, 3H), 1.44 (d,
		J = 7.0 Hz, 3H), 1.35-1.18 (m, 3H), 1.03 (m, J = 9.6, 6.2, 3.5 Hz, 1H),
		0.96 (m, J = 9.4, 4.5 Hz, 1H), 0.59 (m, J = 6.1, 3.7 Hz, 1H), 0.42 (m, J =
		9.4, 6.1, 3.3 Hz, 1H).
476	711.3	1H NMR (400 MHz, DMSO-d6) δ 9.29 (d, J = 6.6 Hz, 1H), 8.43 (s, 1H),
		8.10 (dd, J = 20.3, 8.1 Hz, 2H), 7.95 (d, J = 8.5 Hz, 2H), 7.80 (t, J = 7.7
		Hz, 1H), 7.74 (s, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.59 (s, 1H), 7.37-7.26
		(m, 2H), 7.24 (s, 1H), 5.22 (p, J = 6.9 Hz, 1H), 5.02-4.79 (m, 2H), 4.52
		(s, 1H), 4.18 (s, 1H), 4.04 (m, J = 10.6, 5.6, 4.8 Hz, 2H), 2.92 (dd, J =
		12.8, 8.0 Hz, 2H), 2.59-2.52 (m, 2H), 1.95 (d, J = 11.3 Hz, 2H), 1.79 (d,
		J = 20.7 Hz, 2H), 1.65 (s, 2H), 1.55 (d, J = 7.1 Hz, 3H), 1.47 (d, J = 7.3
		Hz, 2H), 1.37 (d, J = 10.3 Hz, 2H), 1.23 (d, J = 8.5 Hz, 2H), 1.09 (s, 2H),
		0.50 (d, J = 34.9 Hz, 2H).
477	678.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 7.96 (s, 2H), 7.67 (d, J = 31.6 Hz, 2H), 7.43 (s, 1H), 7.26 (d,
		J = 8.1 Hz, 1H), 5.77 (t, J = 13.9 Hz, 1H), 5.23 (dd, J = 27.4, 14.6 Hz,
		1H), 5.14-5.03 (m, 1H), 4.97 (s, 1H), 4.60 (t, J = 14.7 Hz, 2H), 4.46 (s,
		1H), 4.30 (d, J = 6.2 Hz, 1H), 4.16 (s, 1H), 2.77 (s, 1H), 2.15 (m, J = 30.7,
		27.6, 15.2 Hz, 3H), 1.95 (q, J = 12.7, 9.6 Hz, 3H), 1.76 (s, 2H), 1.62 (d,
		J = 13.4 Hz, 3H), 1.55 (m, J = 8.2, 4.5 Hz, 2H), 1.45 (d, J = 7.1 Hz, 3H),
		1.38 (d, J = 12.7 Hz, 2H), 0.87 (p, J = 4.0 Hz, 1H), 0.66 (d, J = 10.9 Hz,
		1H), 0.60 (d, J = 9.0 Hz, 1H), 0.51 (m, J = 6.9, 5.8, 3.6 Hz, 1H).
478	729.2	1H NMR (400 MHz, DMSO-d6) δ 9.39 (d, J = 8.0 Hz, 1H), 8.64 (d, J =
		5.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.98 (s, 1H), 7.74 (s, 1H), 7.63 (d,
		J = 5.0 Hz, 1H), 7.37-7.17 (m, 3H), 5.41 (t, J = 7.4 Hz, 1H), 4.96 (t, J =
		11.4 Hz, 1H), 4.85 (d, J = 13.0 Hz, 1H), 4.52 (s, 1H), 4.18 (s, 1H), 4.02 (t,
		J = 6.5 Hz, 1H), 2.61 (d, J = 10.7 Hz, 1H), 2.45-2.35 (m, 2H), 2.15 (t, J =
		12.1 Hz, 2H), 1.94 (d, J = 22.3 Hz, 2H), 1.79 (d, J = 21.7 Hz, 2H), 1.58 (d,
		J = 59.5 Hz, 3H), 1.47 (d, J = 7.1 Hz, 3H), 1.39-1.13 (m, 4H), 1.08 (s,
		3H), 0.45 (s, 2H).
479	678.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.7 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.98 (s, 1H), 7.69 (d, J = 44.5 Hz, 2H), 7.43 (s, 1H), 7.25 (d,
		J = 8.1 Hz, 1H), 5.78 (t, J = 14.1 Hz, 1H), 5.41 (s, 1H), 5.19 (dd, J = 27.7,
		14.6 Hz, 1H), 5.12-5.01 (m, 1H), 4.98 (s, 1H), 4.62-4.45 (m, 2H), 4.19
		(s, 1H), 2.77 (s, 1H), 2.19-2.03 (m, 2H), 2.03-1.91 (m, 2H), 1.77 (d, J =
		19.9 Hz, 3H), 1.64 (d, J = 14.7 Hz, 3H), 1.54 (q, J = 5.3 Hz, 2H), 1.44 (d,
		J = 7.0 Hz, 3H), 1.40-1.26 (m, 2H), 0.85 (q, J = 7.1, 6.1 Hz, 1H), 0.77
		(m, J = 13.7, 6.5 Hz, 1H), 0.65 (d, J = 11.4 Hz, 1H), 0.56-0.44 (m, 2H).
480	741.3	1H NMR (400 MHz, DMSO-d6) δ 8.38 (d, J = 7.2 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 7.99 (t, J = 7.7 Hz, 1H), 7.98 (br s, 2H), 7.75 (br s, 1H),
		7.61-7.57 (m, 2H), 7.27 (s, 1H), 7.22 (d, J = 8.1 Hz, 1H), 5.10 (p, J = 7.0
		Hz, 1H), 5.03-4.85 (m, 1.5H), 4.63 (br s, 1H), 4.53 (s, 0.5H), 4.18 (br s,
		0.5H), 4.04-3.96 (m, 1H), 3.38 (br s, 1H), 2.87-2.64 (m, 2H), 2.24-
		1.35 (m, 6H), 1.47 (d, J = 7.1 Hz, 3H), 1.35-1.01 (m, 3H), 0.92 (brs,
		1H), 0.64 (br s, 1H).
481	741.2	1H NMR (400 MHz, DMSO-d6) δ 8.84-8.78 (m, 1H), 8.09 (d, J = 8.1
		Hz, 1H), 7.98 (t, J = 7.8 Hz, 1H), 8.03-7.51 (m, 3H), 7.64 (d, J = 7.7 Hz,
		1H), 7.57 (d, J = 7.9 Hz, 1H), 7.29 (s, 1H), 7.31-7.18 (m, 1H), 7.24 (d,
		J = 8.1 Hz, 1H), 5.27 (p, J = 7.3 Hz, 1H), 4.95 (dt, J = 14.4, 7.6 Hz, 1H),
		4.83-4.73 (m, 1H), 4.52 (br s, 0.5H), 4.18 (br s, 0.5H), 4.05-3.96 (m,
		1H), 3.16 (br s, 0.5H), 2.76 (br s, 0.5H), 2.12-1.44 (m, 4H), 1.55 (d, J =
		7.1 Hz, 3H), 1.43-1.02 (m, 3H), 0.95 (br s, 1H), 0.81 (br s, 1H), 0.56 (br
		s, 1H).
482	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.5 Hz, 1H), 8.00 (d, J =
		8.0 Hz, 1H), 8.03-7.55 (m, 3H), 7.25 (s, 1H), 7.30-7.19 (m, 1H), 7.14
		(d, J = 8.1 Hz, 1H), 5.00 (p, J = 7.1 Hz, 1H), 4.52 (br s, 0.5H), 4.17 (brs,
		0.5H), 4.02-3.96 (m, 1H), 3.74 (br s, 0.3H), 3.36 (br s, 0.7H), 3.12 (br s,
		0.3H), 2.76 (br s, 0.7H), 2.02-1.46 (m, 7H), 1.44 (d, J = 7.1 Hz, 3H),
		1.40-0.82 (m, 4H), 0.78-0.53 (m, 3H), 0.53-0.44 (m, 1H).
483	698.3	1H NMR (400 MHz, DMSO-d6) δ 9.33 (d, J = 7.2 Hz, 1H), 8.63 (d, J =
		2.6 Hz, 1H), 8.54 (d, J = 2.5 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.96 (s,
		2H), 7.81-7.56 (m, 2H), 7.41-7.36 (m, 2H), 7.35-7.18 (m, 1H), 5.57-
		5.45 (m, 1H), 5.37-5.15 (m, 2H), 4.96 (br s, 0.3H), 4.51 (br s, 0.7H),
		4.18 (br s, 0.7H), 4.07-3.99 (m, 1H), 3.75 (br s, 0.3H), 3.44-3.07 (m,
		2H), 2.83-2.61 (m, 2H), 2.02-1.51 (m, 8H), 1.49 (d, J = 7.0 Hz, 3H),
		1.34-1.16 (m, 2H), 1.11-0.89 (m, 1H), 0.50 (br s, 1H).
484	648.4	1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 7.0 Hz, 1H), 8.60 (d, J =
		2.6 Hz, 1H), 8.49 (d, J = 2.6 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.99 br (s,
		2H), 7.76 (br s, 1H), 7.36 (br s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H),
		6.90 (s, 1H), 5.24 (p, J = 7.0 Hz, 1H), 4.90-4.79 (m, 1H), 4.63-4.48 (m,
		2H), 4.12 (s, 3H), 3.99 (s, 3H), 3.44-3.07 (m, 1H), 2.76 (br s, 1H), 2.46-
		2.30 (m, 1H), 2.01-1.92 (m, 1H), 1.88-1.32 (m, 8H), 1.51 (d, J = 7.0 Hz,
		3H), 1.21 (br s, 1H), 0.61 (br s, 1H).
485	662.4	1H NMR (400 MHz, DMSO-d6) δ 9.26 (d, J = 6.9 Hz, 1H), 8.60 (d, J =
		2.6 Hz, 1H), 8.50 (d, J = 2.6 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.96 (br s,
		2H), 7.80-7.54 (m, 1H), 7.32 (s, 2H), 7.28 (d, J = 8.1 Hz, 1H), 7.23 (br s,
		1H), 5.23 (p, J = 7.0 Hz, 1H), 5.02-4.76 (m, 2H), 4.52 (br s, 0.5H), 4.17
		(br s, 0.5H), 4.05-3.98 (m, 1H), 2.02-1.33 (m, 6H),  1.52 (d, J =
		7.0 Hz, 3H),  1.28-1.14 (m, 2H), 1.14-0.95 (m, 3H), 0.66-0.42
		(m, 2H).
486	616.6	1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2H), 8.70 (d, J = 7.9 Hz, 1H),
		8.09 (d, J = 7.7 Hz, 1H), 8.07 (d, J = 8.2 Hz, 1H), 7.99 (d, J = 1.3 Hz, 1H),
		7.35 (d, J = 1.2 Hz, 1H), 7.23 (d, J = 8.2 Hz, 1H), 7.11 (s, 1H), 4.96-4.87
		(m, 1H), 4.87-4.70 (m, 3H), 4.50-4.38 (m, 1H), 4.15 (s, 3H), 4.03 (s,
		3H), 3.51-3.33 (m, 2H), 3.14-3.02 (m, 2H), 3.02-2.92 (m, 1H), 2.41-
		2.30 (m, 1H), 2.30-2.18 (m, 1H), 2.04-1.86 (m, 4H), 1.67-1.51 (m,
		4H), 1.49-1.33 (m, 3H), 1.32-1.15 (m, 3H), 0.84-0.71 (m, 1H), 0.68-
		0.53 (m, 1H).
487	616.6	1H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 2H), 8.70 (d, J = 8.0 Hz, 1H),
		8.32 (d, J = 7.5 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 1.3 Hz, 1H),
		7.35 (d, J = 1.3 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.11 (s, 1H), 5.10 (p, J =
		7.1 Hz, 1H), 5.03-4.88 (m, 2H), 4.83-4.76 (m, 1H), 4.68-4.60 (m,
		1H), 4.49-4.38 (m, 1H), 4.14 (s, 3H), 4.02 (s, 3H), 3.50-3.34 (m, 2H),
		3.22-3.14 (m, 1H), 3.13-3.02 (m, 1H), 3.02-2.90 (m, 1H), 2.49-2.43
		(m, 1H), 2.41-2.30 (m, 1H), 2.28-2.12 (m, 1H), 1.98-1.85 (m, 3H),
		1.86-1.70 (m, 2H), 1.50-1.29 (m, 1H), 1.38 (d, J = 7.0 Hz, 3H), 1.11-
		0.68 (m, 4H), 0.15 (d, J = 13.2 Hz, 1H).
488	626.4	1H NMR (400 MHz, DMSO-d6) δ 8.21-8.07 (m, 2H), 8.09-7.98 (m,
		2H), 7.89-7.79 (m, 2H), 7.63 (d, J = 9.9 Hz, 1H), 7.29 (s, 1H), 7.19 (d,
		J = 8.1 Hz, 1H), 5.11 (p, J = 7.1 Hz, 1H), 4.95-4.83 (m, 1H), 4.76-4.58
		(m, 2H), 4.02-3.90 (m, 1H), 3.86-3.77 (m, 1H), 3.66 (s, 1H), 2.26 (s,
		1H), 1.99-1.52 (m, 7H), 1.46 (d, J = 7.1 Hz, 3H), 1.42-1.28 (m, 4H),
		1.29-1.22 (m, 1H), 1.22 (s, 3H), 1.18-0.99 (m, 3H), 0.95 (s, 3H), 0.93-
		0.84 (m, 1H), 0.62-0.49 (m, 1H).
489	664.6	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 8.6 Hz, 1H), 8.12-7.94
		(m, 4H), 7.45 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.02 (s, 1H), 6.94 (d, J =
		1.2 Hz, 1H), 6.19 (tt, J = 55.0, 3.7 Hz, 1H), 5.01 (p, J = 7.3 Hz, 1H),
		4.75-4.65 (m, 1H), 4.59 (d, J = 13.9 Hz, 1H), 4.12 (s, 3H), 3.99 (s, 3H),
		3.95 (s, 1H), 3.90-3.78 (m, 2H), 3.60 (s, 1H), 3.44 (s, 1H), 2.02-1.91 (m,
		1H), 1.90-1.75 (m, 2H), 1.72-1.49 (m, 5H), 1.43 (d, J = 7.1 Hz, 3H),
		1.41-1.34 (m, 1H), 1.30-1.17 (m, 1H), 0.91-0.82 (m, 1H), 0.78-0.58
		(m, 2H), 0.53-0.43 (m, 1H).
490	654.7	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.5 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.95 (s, 3H), 7.45 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.02 (s,
		1H), 6.94 (d, J = 1.2 Hz, 1H), 5.06-4.96 (m, 1H), 4.75-4.65 (m, 1H),
		4.64-4.54 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.85 (dd, J = 6.5, 3.3 Hz,
		2H), 3.67-3.48 (m, 2H), 3.45-3.37 (m, 2H), 3.32 (dd, J = 10.5, 7.1 Hz,
		1H), 1.99-1.81 (m, 2H), 1.81-1.69 (m, 1H), 1.69-1.48 (m, 4H), 1.43
		(d, J = 7.1 Hz, 3H), 1.40-1.35 (m, 1H), 1.31-1.17 (m, 1H), 1.14-1.01
		(m, 1H), 0.91-0.83 (m, 1H), 0.76-0.59 (m, 2H), 0.56-0.43 (m, 3H),
		0.31-0.20 (m, 2H).
491	686.4	1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 6.9 Hz, 1H), 8.19 (s, 3H),
		8.08 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.35 (dd, J = 7.4, 1.6 Hz, 1H), 7.31
		(dd, J = 7.5, 1.6 Hz, 1H), 7.25 (d, J = 8.1 Hz, 2H), 7.22-7.18 (m, 1H),
		7.08 (s, 1H), 6.95 (d, J = 1.2 Hz, 1H), 6.86 (t, J = 74.9 Hz, 1H), 5.19 (p, J =
		7.0 Hz, 1H), 4.87 (t, J = 12.5 Hz, 1H), 4.67 (s, 1H), 4.59 (d, J = 13.6 Hz,
		1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.62 (s, 2H), 3.45 (s, 1H), 2.45-2.35 (m,
		1H), 2.28-2.15 (m, 1H), 2.04-1.86 (m, 2H), 1.49 (d, J = 7.1 Hz, 3H),
		1.45-1.36 (m, 1H), 1.33-1.10 (m, 2H), 0.61-0.47 (m, 1H).
492	687.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 6.9 Hz, 1H), 8.63-8.55
		(m, 2H), 8.20 (s, 3H), 8.10 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 5.2 Hz, 1H),
		7.45 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.95 (d, J = 1.2 Hz,
		1H), 6.86 (t, J = 74.9 Hz, 1H), 5.22 (p, J = 7.0 Hz, 1H), 4.91-4.79 (m,
		1H), 4.72-4.56 (m, 2H), 4.13 (s, 3H), 4.00 (s, 3H), 3.69-3.50 (m, 3H),
		3.51-3.39 (m, 1H), 2.43-2.34 (m, 2H), 1.96 (s, 2H), 1.51 (d, J = 7.0 Hz,
		3H), 1.48-1.38 (m, 1H), 1.37-1.23 (m, 1H), 1.24-1.13 (m, 2H), 0.64-
		0.46 (m, 1H).
493	658.6	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.6 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.94 (s, 3H), 7.45 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.02 (s,
		1H), 6.93 (d, J = 1.2 Hz, 1H), 5.07-4.95 (m, 1H), 4.75-4.64 (m, 1H),
		4.64-4.55 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.84 (d, J = 6.1 Hz, 2H),
		3.76-3.67 (m, 1H), 3.61 (ddd, J = 11.2, 5.4, 3.6 Hz, 1H), 3.57-3.48 (m,
		2H), 3.45 (d, J = 11.4 Hz, 1H), 3.29 (s, 3H), 1.98-1.81 (m, 2H), 1.81-
		1.69 (m, 1H), 1.70-1.48 (m, 4H), 1.43 (d, J = 7.1 Hz, 3H), 1.31-1.16
		(m, 1H), 0.90-0.82 (m, 1H), 0.79-0.57 (m, 2H), 0.53-0.42 (m, 1H).
494	698.7	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.5 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.95 (s, 3H), 7.45 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.02 (s,
		1H), 6.93 (d, J = 1.2 Hz, 1H), 5.08-4.96 (m, 1H), 4.76-4.64 (m, 1H),
		4.64-4.54 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.87-3.75 (m, 2H), 3.71
		(d, J = 11.0 Hz, 1H), 3.64-3.48 (m, 2H), 3.39 (s, 1H), 2.04 (d, J = 2.8 Hz,
		7H), 1.87 (d, J = 7.8 Hz, 2H), 1.76 (s, 1H), 1.70-1.46 (m, 4H), 1.43 (d,
		J = 7.1 Hz, 3H), 1.41-1.34 (m, 1H), 1.30-1.18 (m, 1H), 0.92-0.83 (m,
		1H), 0.77-0.59 (m, 2H), 0.52-0.45 (m, 1H).
495	654.5	1H NMR (400 MHz, Methanol-d4) δ 8.95 (d, J = 7.9 Hz, 1H), 8.11 (dd,
		J = 26.4, 8.1 Hz, 1H), 7.77-7.14 (m, 6H), 7.05 (s, 1H), 7.03-6.97 (m,
		1H), 6.66 (d, J = 15.6 Hz, 1H), 6.35-6.19 (m, 1H), 5.55-5.45 (m, 1H),
		5.04 (d, J = 10.5 Hz, 1H), 4.47 (d, J = 14.2 Hz, 1H), 4.19 (d, J = 4.4 Hz,
		3H), 4.08 (d, J = 2.4 Hz, 3H), 3.82 (s, 2H), 3.68 (d, J = 35.7 Hz, 2H), 3.49
		(d, J = 1.4 Hz, 4H), 2.08 (d, J = 21.0 Hz, 2H), 1.86 (s, 2H), 1.68 (d, J = 6.8
		Hz, 2H), 1.60 (d, J = 6.9 Hz, 3H).
496	648.7	1H NMR (400 MHz, Methanol-d4) δ 8.96 (d, J = 8.0 Hz, 1H), 8.14 (d, J =
		8.1 Hz, 1H), 7.94 (d, J = 1.3 Hz, 1H), 7.82-7.48 (m, 2H), 7.49-7.18 (m,
		6H), 7.04 (d, J = 24.5 Hz, 1H), 6.68 (d, J = 15.7 Hz, 1H), 6.28 (dd, J = 8.8,
		4.1 Hz, 1H), 5.60-5.44 (m, 1H), 4.49 (d, J = 14.2 Hz, 1H), 4.20 (d, J =
		4.5 Hz, 3H), 4.11 (d, J = 2.4 Hz, 3H), 3.61 (d, J = 15.1 Hz, 4H), 2.58 (s,
		2H), 2.40 (d, J = 12.9 Hz, 2H), 1.64 (dd, J = 31.1, 6.9 Hz, 5H).
497	612.2	1H NMR (400 MHz, Methanol-d4) δ 8.15 (t, J = 7.4 Hz, 2H), 7.59 (d, J =
		10.7 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.11 (s, 1H), 5.62 (d, J = 15.4 Hz,
		1H), 5.22 (t, J = 13.5 Hz, 2H), 4.95 (td, J = 9.8, 4.7 Hz, 1H), 4.80 (q, J =
		7.0 Hz, 1H), 4.50 (tt, J = 9.7, 4.8 Hz, 1H), 4.46-4.22 (m, 1H), 4.00 (s,
		3H), 3.70 (dt, J = 12.3, 4.5 Hz, 1H), 3.63-3.46 (m, 1H), 3.25-3.06 (m,
		2H), 2.83 (ddd, J = 13.9, 11.6, 5.1 Hz, 1H), 2.60-2.33 (m, 2H), 2.19-
		1.78 (m, 4H), 1.68 (ddd, J = 15.7, 10.0, 5.4 Hz, 1H), 1.62 (d, J = 7.0 Hz,
		3H), 1.46 (dt, J = 9.5, 5.2 Hz, 1H), 1.01-0.80 (m, 1H).
498	627.1	1H NMR (400 MHz, Methanol-d4) δ 8.43 (dd, J = 4.9, 1.5 Hz, 1H), 8.11
		(dd, J = 7.1, 4.0 Hz, 2H), 7.78 (dd, J = 7.9, 1.6 Hz, 1H), 7.59 (d, J = 10.7
		Hz, 1H), 7.46 (dd, J = 7.8, 4.9 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.09 (s,
		1H), 5.36 (q, J = 7.0 Hz, 1H), 5.08 (dt, J = 14.7, 7.8 Hz, 1H), 4.71-4.36
		(m, 2H), 3.98 (s, 3H), 3.70 (dd, J = 12.9, 4.5 Hz, 1H), 3.55 (d, J = 13.1 Hz,
		1H), 3.17 (ddd, J = 18.3, 13.2, 10.4 Hz, 2H), 2.62-2.28 (m, 5H), 2.22-
		1.99 (m, 2H), 1.65 (d, J = 7.0 Hz, 3H), 1.45 (s, 2H), 1.41-1.04 (m, 1H),
		0.58 (s, 1H).
499	576.2	1H NMR (400 MHz, Methanol-d4) δ 8.15 (d, J = 6.1 Hz, 1H), 8.04 (d, J =
		8.1 Hz, 1H), 7.66 (d, J = 10.5 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.02 (d, J =
		3.2 Hz, 1H), 5.22 (q, J = 7.0 Hz, 1H), 4.54 (qd, J = 9.1, 8.3, 3.4 Hz, 2H),
		4.39 (dd, J = 13.3, 9.2 Hz, 1H), 4.00 (d, J = 4.3 Hz, 3H), 3.67 (dt, J = 11.5,
		4.2 Hz, 1H), 3.60-3.49 (m, 1H), 3.38-3.30 (m, 2H), 3.27-3.06 (m,
		2H), 2.49 (ddt, J = 14.6, 9.9, 4.6 Hz, 1H), 2.28 (dt, J = 10.7, 5.6 Hz, 1H),
		2.17-2.01 (m, 3H), 2.00-1.88 (m, 1H), 1.87-1.68 (m, 2H), 1.60 (d, J =
		7.1 Hz, 4H), 1.54-1.20 (m, 3H), 1.15-1.02 (m, 1H), 1.00-0.89 (m,
		1H), 0.81-0.70 (m, 1H).
500	588.4	1H NMR (400 MHz, Methanol-d4) δ 8.32 (d, J = 1.6 Hz, 1H), 8.21-7.94
		(m, 2H), 7.76 (dd, J = 8.6, 3.8 Hz, 1H), 7.24 (dd, J = 9.8, 8.2 Hz, 1H), 7.06
		(d, J = 21.2 Hz, 1H), 5.41-5.18 (m, 1H), 5.07-4.92 (m, 1H), 4.71-4.29
		(m, 2H), 4.01 (d, J = 7.3 Hz, 3H), 3.68 (d, J = 12.8 Hz, 2H), 3.59-3.43
		(m, 2H), 3.29-3.04 (m, 2H), 2.69-2.36 (m, 1H), 2.10 (dd, J = 24.7, 11.7
		Hz, 1H), 1.97-1.70 (m, 1H), 1.65-1.15 (m, 14H), 1.10 (s, 2H).
501	622.1	1H NMR (400 MHz, Methanol-d4) δ 8.25 (d, J = 1.5 Hz, 1H), 8.09 (dd,
		J = 14.5, 8.1 Hz, 1H), 7.93 (t, J = 1.8 Hz, 1H), 7.24 (dd, J = 9.8, 8.1 Hz,
		1H), 7.04 (d, J = 22.0 Hz, 1H), 5.68-5.17 (m, 1H), 5.18-4.91 (m, 1H),
		4.71 (dtd, J = 48.6, 9.3, 4.5 Hz, 1H), 4.49 (qd, J = 9.3, 4.6 Hz, 1H), 4.39-
		4.03 (m, 4H), 3.66 (d, J = 12.9 Hz, 1H), 3.62-3.38 (m, 2H), 3.32-3.10
		(m, 3H), 2.98 (dd, J = 12.8, 10.2 Hz, 1H), 2.83 (s, 1H), 2.46 (d, J = 36.4
		Hz, 0H), 2.22-1.66 (m, 5H), 1.74-1.18 (m, 10H), 1.10 (s, 3H).
502	686.6	1H NMR (400 MHz, Methanol-d4) δ 8.13 (d, J = 6.3 Hz, 1H), 8.04 (dd,
		J = 16.4, 7.9 Hz, 1H), 7.67 (d, J = 10.8 Hz, 1H), 7.22 (d, J = 8.1 Hz, 1H),
		7.04 (s, 1H), 6.28 (t, J = 74.4 Hz, 1H), 5.39-5.22 (m, 1H), 5.03-4.88
		(m, 6H), 4.83-4.66 (m, 2H), 4.58-4.44 (m, 1H), 4.34 (ddd, J = 14.2,
		9.5, 5.8 Hz, 1H), 4.19 (tdd, J = 11.0, 8.9, 3.8 Hz, 2H), 3.81-3.61 (m, 1H),
		3.60-3.46 (m, 1H), 3.25-3.08 (m, 1H), 2.62-2.39 (m, 1H), 2.07 (t, J =
		11.1 Hz, 1H), 1.97-1.67 (m, 2H), 1.67-1.20 (m, 10H), 1.10 (s, 3H).
503	651.1	NA
504	656.6	1H NMR (400 MHz, Methanol-d4) δ 8.59 (d, J = 2.6 Hz, 1H), 8.50 (d, J =
		2.6 Hz, 1H), 8.16-8.07 (m, 1H), 7.82 (d, J = 1.3 Hz, 1H), 7.54 (d, J = 1.4
		Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.37 (q, J = 7.0 Hz, 1H),
		5.04 (dt, J = 15.2, 7.7 Hz, 1H), 4.54-4.42 (m, 1H), 4.26 (s, 3H), 3.87-
		3.52 (m, 8H), 3.49 (s, 3H), 2.88-2.64 (m, 1H), 2.61-2.39 (m, 1H), 2.19-
		1.94 (m, 2H), 1.85 (s, 1H), 1.65 (d, J = 7.0 Hz, 3H), 1.55-1.40 (m, 3H),
		1.29 (d, J = 12.1 Hz, 1H), 0.67 (s, 1H).
505	618.9	1H NMR (400 MHz, Methanol-d4) δ 8.01 (d, J = 8.0 Hz, 1H), 7.82 (d, J =
		1.3 Hz, 1H), 7.53 (d, J = 1.4 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 6.98 (s,
		1H), 5.11 (q, J = 7.0 Hz, 1H), 4.44 (d, J = 14.4 Hz, 1H), 4.23 (s, 3H),
		3.94-3.54 (m, 7H), 3.49 (m, 4H), 2.20-1.67 (m, 4H), 1.56 (d, J = 7.1 Hz,
		5H), 1.32 (d, J = 9.5 Hz, 1H), 1.09 (dt, J = 8.8, 4.6 Hz, 1H), 0.81 (d, J =
		6.3 Hz, 2H), 0.59 (q, J = 7.7, 5.9 Hz, 1H).
506	588.5	1H NMR (400 MHz, Methanol-d4) δ 8.01 (d, J = 8.1 Hz, 1H), 7.82 (d, J =
		1.4 Hz, 1H), 7.52 (d, J = 1.4 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 6.98 (s,
		1H), 5.11 (q, J = 7.0 Hz, 1H), 4.45 (d, J = 14.5 Hz, 1H), 4.24 (s, 3H), 3.39
		(d, J = 31.6 Hz, 3H), 2.20 (s, 1H), 2.06-1.62 (m, 7H), 1.65-1.22 (m,
		10H), 1.09 (dt, J = 8.8, 4.5 Hz, 1H), 0.86-0.72 (m, 2H), 0.65-0.51 (m,
		1H).
507	606.4	1H NMR (400 MHz, Methanol-d4) δ 8.24 (d, J = 1.5 Hz, 1H), 8.01 (d, J =
		8.1 Hz, 1H), 7.93 (d, J = 1.5 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 6.99 (s,
		1H), 5.11 (q, J = 7.1 Hz, 1H), 4.59-4.32 (m, 3H), 4.24 (s, 3H), 3.66 (d,
		J = 12.8 Hz, 1H), 3.58-3.42 (m, 2H), 3.25-3.05 (m, 3H), 2.63-2.29 (m,
		1H), 2.24-1.89 (m, 1H), 1.74 (s, 1H), 1.65-1.23 (m, 12H), 1.09 (dt, J =
		8.6, 4.5 Hz, 1H), 0.82 (s, 2H), 0.59 (dt, J = 8.0, 4.4 Hz, 1H).
508	610.1	1H NMR (400 MHz, Chloroform-d) δ 8.21 (d, J = 1.3 Hz, 1H), 7.90 (d, J =
		8.0 Hz, 1H), 7.47 (d, J = 1.3 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 6.76 (s,
		1H), 6.68 (d, J = 9.5 Hz, 1H), 5.27 (dq, J = 9.9, 8.0, 7.0 Hz, 1H), 4.79-
		4.61 (m, 2H), 4.14 (d, J = 6.8 Hz, 4H), 4.05 (s, 3H), 3.98 (s, 3H), 2.06 (s,
		2H), 1.99 (ddt, J = 12.7, 5.6, 2.8 Hz, 2H), 1.53 (d, J = 7.1 Hz, 6H), 1.46-
		1.38 (m, 2H), 1.31-1.19 (m, 7H), 0.86 (dt, J = 4.4, 2.0 Hz, 1H), 0.75-
		0.65 (m, 2H), 0.58-0.44 (m, 1H).
509	558.4	1H NMR (400 MHz, Methanol-d4) δ 8.5 (s, 1H), 8.00 (d, J = 8.0 Hz, 1H),
		7.94 (d, J = 1.3 Hz, 1H), 7.46 (d, J = 1.3 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H),
		6.96 (s, 1H), 5.11 (q, J = 7.0 Hz, 1H), 4.64-4.29 (m, 2H), 4.12 (d, J =
		10.4 Hz, 6H), 3.26-2.93 (m, 2H), 1.95 (dd, J = 10.4, 6.6 Hz, 1H), 1.74 (s,
		1H), 1.64-1.20 (m, 13H), 1.13-0.97 (m, 1H), 0.80 (d, J = 12.3 Hz, 2H),
		0.60 (q, J = 6.7, 5.6 Hz, 1H).
510	696.4	1H NMR (400 MHz, Methanol-d4) δ 8.61 (d, J = 2.6 Hz, 1H), 8.51 (d, J =
		2.6 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.60-7.43 (m, 1H), 7.30 (d, J = 8.1
		Hz, 1H), 7.12 (d, J = 7.6 Hz, 1H), 7.05 (d, J = 1.2 Hz, 2H), 5.39 (q, J = 6.8
		Hz, 1H), 5.02 (d, J = 13.4 Hz, 1H), 4.87-4.70 (m, 3H), 4.49 (d, J = 14.2
		Hz, 1H), 4.10 (s, 5H), 3.98-3.55 (m, 5H), 3.50 (d, J = 1.8 Hz, 3H), 3.19
		(s, 4H), 2.89-2.69 (m, 1H), 2.63-2.42 (m, 2H), 1.86 (s, 1H), 1.80-1.37
		(m, 6H), 1.29 (s, 2H), 0.74 (d, J = 12.2 Hz, 1H).
511	650.6	1H NMR (400 MHz, Methanol-d4) δ 8.67 (d, J = 8.4 Hz, 1H), 8.00 (d, J =
		8.0 Hz, 1H), 7.76 (d, J = 1.2 Hz, 1H), 7.41-7.29 (m, 1H), 7.22-7.08 (m,
		2H), 6.97 (d, J = 10.3 Hz, 1H), 5.30-5.06 (m, 1H), 4.46 (d, J = 14.5 Hz,
		1H), 4.13 (s, 3H), 3.90-3.56 (m, 4H), 3.49 (s, 4H), 2.83 (s, 1H), 1.89 (dd,
		J = 81.3, 41.1 Hz, 5H), 1.65-1.25 (m, 8H), 1.12 (dd, J = 29.2, 5.8 Hz,
		1H), 0.81 (s, 2H), 0.59 (s, 1H).
512	602.5	1H NMR (400 MHz, Methanol-d4) δ 8.00 (d, J = 8.0 Hz, 1H), 7.71 (d, J =
		1.2 Hz, 1H), 7.29 (d, J = 11.3 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.00 (s,
		1H), 5.10 (q, J = 7.1 Hz, 1H), 4.52 (d, J = 14.5 Hz, 1H), 4.13 (d, J = 1.0
		Hz, 3H), 3.81 (d, J = 4.5 Hz, 1H), 3.63 (s, 1H), 3.56-3.43 (m, 4H), 2.34-
		1.70 (m, 1H), 1.66-1.22 (m, 16H), 1.11-1.00 (m, 1H), 0.81 (s, 2H),
		0.59 (s, 1H).
513	640.4	NA
514	632.4	1H NMR (400 MHz, DMSO-d6) δ 9.18-8.45 (m, 2H), 8.04 (d, J = 8.1
		Hz, 1H), 7.82 (d, J = 7.4 Hz, 1H), 7.41-7.26 (m, 1H), 7.19 (d, J = 8.1 Hz,
		1H), 7.03 (s, 1H), 6.85 (s, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.86-4.74 (m,
		1H), 4.45-4.19 (m, 2H), 4.12 (s, 3H), 3.99 (s, 3H), 3.54-3.35 (m, 2H),
		3.31-3.18 (m, 2H), 3.09-2.88 (m, 1H), 2.98 (s, 3H), 2.46-2.19 (m,
		1H), 1.92 (t, J = 12.1 Hz, 1H), 1.75-1.53 (m, 2H), 1.45 (d, J = 7.1 Hz,
		3H), 1.53-1.31 (m, 4H), 1.21 (s, 3H), 1.17-0.99 (m, 4H), 0.95 (s, 3H).
515	618.4	1H NMR (400 MHz, DMSO-d6) δ 8.74 (br. s, 2H), 8.63 (d, J = 8.2 Hz,
		1H), 8.05 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H), 7.67-7.58 (m,
		2H), 7.30 (s, 1H), 7.21 (d, J = 8.2 Hz, 1H), 5.16 (p, J = 7.2 Hz, 1H), 4.92-
		4.70 (m, 3H), 4.47-4.34 (m, 1H), 3.86-3.76 (m, 1H), 3.42 (br. dd, J =
		34.5, 12.3 Hz, 2H), 3.13-2.88 (m, 2H), 2.40-2.25 (m, 1H), 1.99-1.63
		(m, 4H), 1.54 (d, J = 7.1 Hz, 3H), 1.63-1.38 (m, 1H), 1.37-1.26 (m,
		1H), 1.21-1.07 (m, 6H), 1.00 (s, 3H), 0.86-0.74 (m, 2H), 0.70-0.64
		(m, 2H).
516	600.3	1H NMR (400 MHz, DMSO-d6) δ 8.90-8.77 (m, 2H), 8.72 (d, J = 8.0
		Hz, 1H), 8.37 (d, J = 6.3 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 8.01 (d, J = 1.2
		Hz, 1H), 7.36 (d, J = 1.2 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.06 (s, 1H),
		5.61 (td, J = 10.8, 4.3 Hz, 1H), 5.32 (td, J = 11.0, 3.3 Hz, 1H), 5.05-4.76
		(m, 2H), 4.65 (td, J = 12.6, 6.2 Hz, 1H), 4.42 (dtd, J = 25.3, 12.7, 11.0, 5.2
		Hz, 2H), 4.17 (s, 3H), 4.02 (s, 3H), 3.49-3.35 (m, 1H), 3.14-2.90 (m,
		3H), 2.74-2.61 (m, 1H), 2.61-2.47 (m, 1H), 2.42-2.29 (m, 1H), 2.20-
		2.08 (m, 1H), 1.98-1.88 (m, 2H), 1.83 (td, J = 8.3, 5.4 Hz, 1H), 1.50 (d,
		J = 7.2 Hz, 3H), 1.15-1.02 (m, 1H), 0.88 (td, J = 8.5, 3.6 Hz, 1H), 0.73-
		0.64 (m, 1H).
517	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J = 6.2 Hz, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 8.01 (br. s, 3H), 7.46 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.03
		(s, 1H), 6.94 (s, 1H), 5.60 (td, J = 10.9, 4.3 Hz, 1H), 5.36-5.25 (m, 1H),
		4.99 (p, J = 7.0 Hz, 1H), 4.62 (td, J = 12.6, 6.2 Hz, 1H), 4.38 (td, J = 12.7,
		3.6 Hz, 1H), 4.15 (s, 3H), 3.99 (s, 3H), 3.95-3.76 (m, 1H), 3.75-3.67
		(m, 1H), 3.62-3.28 (m, 4H), 3.36 (s, 3H), 2.72-2.52 (m, 2H), 2.14-
		1.87 (m, 3H), 1.86-1.69 (m, 2H), 1.50 (d, J = 7.2 Hz, 3H), 1.15-1.01
		(m, 1H), 0.88 (td, J = 8.5, 3.6 Hz, 1H), 0.73-0.64 (m, 1H).
518	602.3	1H NMR (400 MHz, DMSO-d6) δ 8.75 (br. s, 2H), 8.69 (d, J = 7.9 Hz,
		1H), 8.53 (d, J = 5.5 Hz, 1H), 8.03-7.96 (m, 2H), 7.34 (s, 1H), 7.11 (d, J =
		8.0 Hz, 1H), 7.07 (s, 1H), 4.96-4.74 (m, 2H), 4.68-4.60 (m, 1H), 4.50-
		4.36 (m, 1H), 4.11 (s, 3H), 4.02 (s, 3H), 3.70-3.20 (m, 3H), 3.13-2.88
		(m, 2H), 2.42-2.28 (m, 1H), 2.23-2.06 (m, 1H), 1.97-1.87 (m, 1H),
		1.85-1.74 (m, 1H), 1.40 (d, J = 7.1 Hz, 3H), 1.46-1.32 (m, 2H), 1.10-
		0.83 (m, 4H), 0.74-0.60 (m, 3H), 0.39-0.23 (m, 1H).
519	614.3	1H NMR (400 MHz, DMSO-d6) δ 8.88-8.76 (m, 2H), 8.63 (d, J = 7.0
		Hz, 1H), 8.40 (d, J = 6.2 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 6.4
		Hz, 1H), 7.62 (d, J = 10.5 Hz, 1H), 7.31 (s, 1H), 7.18 (d, J = 8.2 Hz, 1H),
		5.61 (td, J = 10.9, 4.2 Hz, 1H), 5.32 (td, J = 10.8, 3.3 Hz, 1H), 4.98 (p, J =
		7.0 Hz, 1H), 4.93-4.83 (m, 2H), 4.76 (td, J = 9.6, 4.6 Hz, 1H), 4.52-
		4.34 (m, 2H), 3.82 (tt, J = 7.1, 3.9 Hz, 1H), 3.46 (br. d, J = 12.4 Hz, 1H),
		3.38 (br. d, J = 12.6 Hz, 1H), 3.12-2.90 (m, 2H), 2.72-2.58 (m, 1H),
		2.48-2.28 (m, 2H), 2.08-1.87 (m, 3H), 1.84 (td, J = 8.3, 5.4 Hz, 1H),
		1.50 (d, J = 7.2 Hz, 3H), 1.29-1.02 (m, 2H), 0.93-0.81 (m, 2H), 0.74-
		0.62 (m, 2H).
520	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.74 (br. s, 2H), 8.62 (d, J = 7.1 Hz,
		1H), 8.56 (d, J = 5.4 Hz, 1H), 7.99 (d, J = 7.9 Hz, 1H), 7.97 (d, J = 6.4 Hz,
		1H), 7.61 (d, J = 10.6 Hz, 1H), 7.29 (s, 1H), 7.11 (d, J = 8.1 Hz, 1H), 5.01-
		4.69 (m, 4H), 4.48-4.33 (m, 1H), 3.86-3.78 (m, 1H), 3.45-3.34 (m,
		1H), 3.12-2.88 (m, 2H), 2.40-2.11 (m, 2H), 2.00-1.82 (m, 1H), 1.79
		(td, J = 8.2, 5.3 Hz, 1H), 1.41 (d, J = 7.0 Hz, 3H), 1.46-1.19 (m, 5H),
		1.14-0.81 (m, 4H), 0.74-0.53 (m, 2H), 0.38-0.12 (m, 4H).
521	588.3	1H NMR (400 MHz, DMSO-d6) δ 8.87-8.70 (m, 2H), 8.65 (d, J = 7.9
		Hz, 1H), 8.38 (d, J = 6.3 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 8.03 (d, J = 6.4
		Hz, 1H), 7.76 (d, J = 10.9 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.14 (s, 1H),
		5.61 (td, J = 11.0, 4.3 Hz, 1H), 5.33 (td, J = 10.9, 3.3 Hz, 1H), 4.99 (p, J =
		7.0 Hz, 1H), 4.93-4.70 (m, 2H), 4.49-4.34 (m, 2H), 3.99 (s, 3H), 3.47
		(d, J = 12.2 Hz, 1H), 3.38 (d, J = 12.8 Hz, 1H), 3.11-2.91 (m, 2H), 2.73-
		2.60 (m, 1H), 2.58-2.41 (m, 1H), 2.40-2.28 (m, 1H), 2.17-2.04 (m,
		1H), 1.93 (d, J = 13.5 Hz, 2H), 1.83 (td, J = 8.2, 5.4 Hz, 1H), 1.50 (d, J =
		7.2 Hz, 3H), 1.15-1.02 (m, 1H), 0.88 (td, J = 8.6, 3.7 Hz, 1H), 0.68 (ddd,
		J = 7.0, 5.3, 3.7 Hz, 1H).
522	590.3	1H NMR (400 MHz, DMSO-d6) δ 8.86-8.70 (m, 2H), 8.64 (d, J = 7.9
		Hz, 1H), 8.55 (d, J = 5.5 Hz, 1H), 8.00 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.4
		Hz, 1H), 7.74 (d, J = 10.8 Hz, 1H), 7.14 (s, 1H), 7.12 (d, J = 8.1 Hz, 1H),
		4.98-4.71 (m, 3H), 4.41 (tq, J = 14.1, 5.0 Hz, 1H), 4.02-3.93 (m, 1H),
		3.95 (s, 3H), 3.46 (d, J = 12.6 Hz, 1H), 3.38 (d, J = 12.7 Hz, 1H), 3.11-
		2.90 (m, 2H), 2.41-2.27 (m, 1H), 2.22-2.08 (m, 1H), 2.00-1.84 (m,
		1H), 1.79 (ddd, J = 9.0, 7.6, 5.3 Hz, 1H), 1.40 (d, J = 7.0 Hz, 3H), 1.44-
		1.34 (m, 3H), 1.10-0.84 (m, 3H), 0.74-0.56 (m, 3H), 0.38-0.22 (m,
		1H).
523	602.3	1H NMR (400 MHz, DMSO-d6) δ 8.76 (br. s, 2H), 8.69 (d, J = 8.0 Hz,
		1H), 8.47 (d, J = 7.5 Hz, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 1.3 Hz,
		1H), 7.34 (d, J = 1.3 Hz, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.08 (s, 1H), 4.97-
		4.74 (m, 2H), 4.70-4.59 (m, 2H), 4.51-4.36 (m, 1H), 4.13 (s, 3H), 4.02
		(s, 3H), 3.49-3.34 (m, 2H), 3.13-2.90 (m, 2H), 2.42-2.29 (m, 1H),
		2.00-1.77 (m, 2H), 1.68 (d, J = 7.0 Hz, 3H), 1.60 (td, J = 8.2, 5.5 Hz,
		1H), 1.50-1.28 (m, 3H), 1.19-0.88 (m, 3H), 0.86-0.61 (m, 3H), 0.48-
		0.33 (m, 1H).
524	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.50 (d, J = 7.4 Hz, 1H), 8.03 (d, J =
		8.2 Hz, 1H), 8.02-7.88 (m, 3H), 7.43 (s, 1H), 7.24 (d, J = 8.3 Hz, 1H),
		7.04 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 4.86-4.73 (m, 1H), 4.68-4.55 (m,
		3H), 4.15-4.06 (m, 1H), 4.10 (s, 3H), 3.98 (s, 3H), 3.74-3.50 (m, 4H),
		3.36 (s, 3H), 2.02-1.82 (m, 2H), 1.81-1.70 (m, 1H), 1.68 (d, J = 7.0 Hz,
		3H), 1.59 (td, J = 8.2, 5.5 Hz, 1H), 1.49-1.20 (m, 3H), 1.18-0.87 (m,
		3H), 0.83-0.62 (m, 3H), 0.43-0.30 (m, 1H).
525	614.4	1H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 5.5 Hz, 1H), 7.99 (d, J =
		8.1 Hz, 1H), 8.08-7.89 (br. s, 3H), 7.42 (s, 1H), 7.11 (d, J = 8.1 Hz, 1H),
		7.03 (s, 1H), 6.92 (d, J = 1.1 Hz, 1H), 4.95-4.77 (m, 2H), 4.66-4.58 (m,
		1H), 4.18-4.03 (m, 2H), 4.09 (s, 3H), 3.98 (s, 3H), 3.74-3.66 (m, 1H),
		3.55-3.50 (m, 2H), 3.44-3.36 (m, 1H), 3.36 (s, 3H), 2.22-2.06 (m,
		1H), 2.04-1.85 (m, 1H), 1.84-1.64 (m, 2H), 1.40 (d, J = 7.1 Hz, 3H),
		1.35 (s, 3H), 1.07-0.84 (m, 3H), 0.76-0.54 (m, 3H), 0.37-0.21 (m,
		1H).
526	616.4	1H NMR (400 MHz, DMSO-d6) δ 8.90-8.82 (m, 1H), 8.79-8.68 (m,
		1H), 8.47 (d, J = 7.8 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.97 (s, 1H), 7.80
		(d, J = 7.4 Hz, 1H), 7.34 (d, J = 1.2 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.06
		(s, 1H), 5.52 (br. s, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.87-4.75 (m, 1H),
		4.63-4.34 (m, 2H), 4.21-4.16 (m, 1H), 4.14 (s, 3H), 4.01 (s, 3H), 3.29
		(br. d, J = 10.8 Hz, 1H), 3.12-2.97 (m, 2H), 2.82 (br. q, J = 11.0 Hz, 1H),
		2.02-1.77 (m, 3H), 1.75-1.58 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.51-
		1.25 (m, 5H), 1.21 (s, 3H), 1.18-0.99 (m, 2H), 0.95 (s, 3H)
527	656.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.93 (br. s,
		3H), 7.82 (d, J = 7.4 Hz, 1H), 7.44 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.03
		(d, J = 1.0 Hz, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.86-
		4.76 (m, 1H), 4.48-4.33 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.94-3.86
		(m, 2H), 3.60-3.30 (m, 3H), 2.10-1.97 (m, 1H), 1.92 (t, J = 12.1 Hz,
		1H), 1.85-1.72 (m, 1H), 1.75-1.53 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H),
		1.49-1.26 (m, 6H), 1.21 (s, 3H), 1.18-0.97 (m, 3H), 0.94 (s, 3H), 0.73-
		0.40 (m, 4H).
528	636.3	1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 7.0 Hz, 1H), 8.60 (d, J =
		2.5 Hz, 1H), 8.49 (d, J = 2.5 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.95 (br. s,
		3H), 7.34 (d, J = 1.1 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.88
		(s, 1H), 5.24 (p, J = 7.0 Hz, 1H), 4.89-4.78 (m, 1H), 4.63-4.54 (m, 1H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.87-3.48 (m, 1H), 3.41-3.29 (m, 1H), 3.26-
		2.81 (m, 2H), 2.73-2.61 (m, 1H), 2.50-2.30 (m, 2H), 1.88-1.64 (m,
		3H), 1.51 (d, J = 7.0 Hz, 3H), 1.64-1.29 (m, 4H), 1.20 (d, J = 6.9 Hz,
		3H), 1.28-1.13 (m, 1H), 0.62 (dd, J = 24.3, 12.2 Hz, 1H).
529	616.4	1H NMR (400 MHz, DMSO-d6) δ 8.90 (br. d, J = 11.5 Hz, 1H), 8.81-
		8.67 (m, 1H), 8.47 (d, J = 7.8 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.97 (d,
		J = 1.3 Hz, 1H), 7.80 (d, J = 7.5 Hz, 1H), 7.35 (d, J = 1.3 Hz, 1H), 7.19 (d,
		J = 8.2 Hz, 1H), 7.06 (s, 1H), 5.69-5.35 (m, 1H), 5.12 (p, J = 7.1 Hz, 1H),
		4.87-4.76 (m, 1H), 4.60-4.49 (m, 1H), 4.46-4.36 (m, 1H), 4.22-4.15
		(m, 1H), 4.14 (s, 3H), 4.01 (s, 3H), 3.29 (d, J = 11.5 Hz, 1H), 3.11-2.95
		(m, 2H), 2.82 (q, J = 10.7 Hz, 1H), 2.02-1.78 (m, 3H), 1.76-1.54 (m,
		3H), 1.45 (d, J = 7.1 Hz, 3H), 1.51-1.25 (m, 4H), 1.21 (s, 3H), 1.17-
		0.98 (m, 3H), 0.95 (s, 3H).
530	616.4	1H NMR (400 MHz, DMSO-d6) δ 8.94 (br. d, J = 11.5 Hz, 1H), 8.79-
		8.71 (m, 1H), 8.48 (d, J = 7.8 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.97 (d,
		J = 1.3 Hz, 1H), 7.80 (d, J = 7.4 Hz, 1H), 7.35 (d, J = 1.3 Hz, 1H), 7.19 (d,
		J = 8.2 Hz, 1H), 7.07 (s, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.87-4.76 (m, 1H),
		4.64-4.48 (m, 1H), 4.46-4.35 (m, 1H), 4.22-4.16 (m, 1H), 4.14 (s,
		3H), 4.02 (s, 3H), 3.29 (d, J = 10.6 Hz, 1H), 3.11-2.98 (m, 2H), 2.83 (q,
		J = 10.9 Hz, 1H), 2.02-1.78 (m, 3H), 1.67 (t, J = 8.7 Hz, 3H), 1.45 (d, J =
		7.1 Hz, 3H), 1.52-1.27 (m, 4H), 1.21 (s, 3H), 1.16-1.00 (m, 3H), 0.95
		(s, 3H).
531	610.4	1H NMR (400 MHz, DMSO-d6) δ 9.08 (br. s, 1H), 8.51 (br. s, 1H), 8.43
		(d, J = 8.6 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.13 (d, J = 8.1
		Hz, 1H), 7.01 (s, 1H), 6.95 (d, J = 1.1 Hz, 1H), 5.01 (p, J = 7.2 Hz, 1H),
		4.77-4.51 (m, 3H), 4.11 (s, 3H), 3.99 (s, 3H), 3.83-3.51 (m, 3H), 3.43-
		3.10 (m, 3H), 2.50-2.41 (m, 1H), 2.18-2.03 (m, 1H), 1.96-1.29 (m,
		9H), 1.43 (d, J = 7.1 Hz, 3H), 1.29-1.16 (m, 1H), 0.92-0.81 (m, 1H),
		0.77-0.57 (m, 3H), 0.52-0.43 (m, 1H).
532	610.4	1H NMR (400 MHz, DMSO-d6) δ 9.12 (br. s, 1H), 8.52 (br. s, 1H), 8.43
		(d, J = 8.6 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H), 7.13 (d, J = 8.1
		Hz, 1H), 7.02 (s, 1H), 6.95 (d, J = 1.1 Hz, 1H), 5.01 (p, J = 7.2 Hz, 1H),
		4.76-4.53 (m, 3H), 4.12 (s, 3H), 3.99 (s, 3H), 3.81-3.55 (m, 3H), 3.43-
		3.10 (m, 3H), 2.50-2.42 (m, 1H), 2.16-2.05 (m, 1H), 1.96-1.30 (m,
		9H), 1.43 (d, J = 7.1 Hz, 3H), 1.29-1.15 (m, 1H), 0.90-0.81 (m, 1H),
		0.77-0.56 (m, 3H), 0.52-0.43 (m, 1H).
533	630.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.85 (br. s,
		3H), 7.81 (d, J = 7.4 Hz, 1H), 7.51 (br. s, 1H), 7.19 (d, J = 8.1 Hz, 1H),
		7.03 (s, 1H), 6.95 (s, 1H), 5.12 (p, J = 7.1 Hz, 1H), 4.86-4.75 (m, 1H),
		4.46-4.33 (m, 1H), 4.11 (s, 3H), 3.98 (s, 3H), 3.64-3.51 (m, 2H), 3.52
		(dd, J = 11.1, 5.7 Hz, 1H), 3.45 (dd, J = 11.1, 7.3 Hz, 1H), 3.32-3.15 (m,
		1H), 3.05 (t, J = 11.7 Hz, 1H), 2.08-1.97 (m, 1H), 1.93 (t, J = 11.8 Hz,
		1H), 1.75-1.49 (m, 4H), 1.45 (d, J = 7.1 Hz, 3H), 1.48-1.26 (m, 5H),
		1.21 (s, 3H), 1.17-0.99 (m, 3H), 0.95 (s, 3H).
534	620.3	1H NMR (400 MHz, DMSO-d6) δ 8.54 (d, J = 9.0 Hz, 1H), 8.12 (d, J =
		8.1 Hz, 1H), 8.10 (brs, 3H), 7.60 (s, 1H), 7.29 (d, J = 8.1 Hz, 1H), 7.16 (s,
		1H), 7.04 (s, 1H), 5.50 (dd, J = 30.1, 14.4 Hz, 1H), 5.38-5.27 (m, 1H),
		5.26-5.10 (m, 1H), 4.62-4.40 (m, 3H), 4.10 (s, 3H), 4.01 (s, 3H), 3.75
		(brs, 1H), 2.40-2.23 (m, 2H), 2.19-2.07 (m, 1H), 1.96-1.50 (m, 5H),
		1.40 (d, J = 7.0 Hz, 3H), 1.38-1.31 (m, 2H), 1.23-1.06 (m, 2H), 1.03-
		0.67 (m, 2H).
535	612.7	NA
536	616.7	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.93 (brs,
		3H), 7.82 (d, J = 7.4 Hz, 1H), 7.42 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.03
		(s, 1H), 6.94 (s, 1H), 5.18-5.08 (m, 1H), 4.87-4.76 (m, 1H), 4.45-4.33
		(m, 1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.74-3.67 (m, 1H), 3.35-3.23 (m,
		1H), 3.0-3.08 (m, 1H), 2.20 (d, J = 12.5 Hz, 1H), 1.98-1.87 m, 2H),
		1.73-1.48 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.43-1.26 (m, 5H), 1.21 (s,
		3H), 1.18-0.98 (m, 3H), 0.95 (s, 3H).
537	602.6	1H NMR (400 MHz, DMSO-d6) δ 8.80 (brs, 2H), 8.62 (d, J = 8.0 Hz,
		1H), 8.05 (d, J = 8.1 Hz, 1H), 7.84 (s, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.59
		(s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.11 (s, 1H), 5.18-5.08 (m, 1H), 4.91-
		4.71 (m, 2H), 4.59-4.34 (m, 2H), 3.96 (s, 3H), 3.48 (d, J = 12.4 Hz, 1H),
		3.37 (d, J = 12.4 Hz, 1H), 3.14-2.89 (m, 2H), 2.54 (s, 3H), 2.41-2.29
		(m, 1H), 1.93 (t, J = 12.3 Hz, 2H), 1.75-1.59 (m, 2H), 1.45 (d, J = 7.1
		Hz, 3H), 1.51-1.28 (m, 4H), 1.21 (s, 3H), 1.18-1.05 (m, 3H), 0.95 (s,
		3H).
538	624.2	1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.79 (brs, 2H), 8.08 (d,
		J = 8.1 Hz, 1H), 7.85 (d, J = 4.7 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.21 (d,
		J = 8.2 Hz, 1H), 7.13 (s, 1H), 5.19-5.08 (m, 1H), 4.95-4.72 (m, 2H), 4.51-
		4.33 (m, 2H), 4.11 (s, 3H), 3.53-3.32 (m, 2H), 3.13-2.91 (m, 2H),
		2.40-2.27 (m, 1H), 2.02-1.84 (m, 2H), 1.76-1.62 (m, 2H), 1.54-1.28
		(m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.22 (s, 3H), 1.18-1.05 (m, 2H), 0.95
		(s, 3H).
539	616.4	1H NMR (400 MHz, DMSO-d6) δ 8.77 (brs, 2H), 8.63 (d, J = 8.0 Hz,
		1H), 8.40 (d, J = 7.2 Hz, 1H), 8.02 (d, J = 8.5 Hz, 1H), 8.00 (d, J = 7.3 Hz,
		2H), 7.63 (d, J = 10.6 Hz, 1H), 7.30 (s, 1H), 7.22 (d, J = 8.2 Hz, 1H), 4.95-
		4.69 (m, 3H), 4.53-4.32 (m, 2H), 3.87-3.78 (m, 1H), 3.47 (d, J = 12.5
		Hz, 1H), 3.38 (d, J = 12.5 Hz, 1H), 3.14-2.93 (m, 2H), 2.40-2.28 (m,
		1H), 1.99-1.78 (m, 1H), 1.74 (d, J = 7.1 Hz, 3H), 1.69-1.06 (m, 5H),
		0.97-0.69 (m, 4H), 0.67-0.58 (m, 4H), 0.58-0.45 (m, 1H).
540	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.77 (brs, 2H), 8.65 (d, J = 7.4 Hz,
		1H), 8.09 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 9.4 Hz, 1H), 8.02 (d, J = 6.5 Hz,
		1H), 7.63 (d, J = 10.5 Hz, 1H), 7.34 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 5.24
		(dq, J = 8.9, 6.8 Hz, 1H), 4.96-4.72 (m, 4H), 4.47-4.36 (m, 1H), 3.88-
		3.78 (m, 1H), 3.52-3.29 (m, 4H), 3.15-2.91 (m, 2H), 2.88-2.76 (m,
		1H), 2.45-2.29 (m, 3H), 1.99-1.83 (m, 1H), 1.46 (d, J = 6.8 Hz, 3H),
		1.34 (s, 3H), 1.22 (s, 3H), 1.20-1.09 (m, 2H), 0.93-0.83 (m, 1H), 0.72
		(brs, 2H), 0.62-0.51 (m, 1H).
541	622.4	1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 7.9 Hz, 1H), 8.75 (brs,
		2H), 8.07 (d, J = 8.1 Hz, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.83 (d, J = 7.4
		Hz, 1H), 7.20 (d, J = 7.4 Hz, 1H), 7.16 (s, 1H), 5.18-5.08 (m, 1H), 4.93-
		4.80 (m, 2H), 4.78-4.67 (m, 1H), 4.60-4.49 (m, 1H), 4.44-4.31 (m,
		1H), 3.99 (s, 3H), 3.57-3.36 (m, 2H), 3.16-2.89 (m, 3H), 2.34 (brs,
		1H), 2.00-1.84 (m, 2H), 1.79-1.59 (m, 2H), 1.46 (d, J = 7.1 Hz, 3H),
		1.43-1.26 (m, 3H), 1.22 (s, 3H), 1.15-1.03 (m, 2H), 0.95 (s, 3H).
542	612.7	1H NMR (400 MHz, DMSO-d6) δ 8.10 (brs, 3H), 8.05 (d, J = 8.1 Hz,
		1H), 7.82 (d, J = 7.4 Hz, 1H), 7.42 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04
		(s, 1H), 6.90 (s, 1H), 5.19-5.06 (m, 1H), 4.89-4.77 (m, 1H), 4.48-4.35
		(m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.93-3.80 (m, 1H), 3.65-3.49 (m,
		2H), 1.98-1.86 (m, 1H), 1.76-1.52 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H),
		1.43-1.22 (m, 6H), 1.21 (s, 3H), 1.18-0.99 (m, 4H), 0.95 (s, 3H), 0.89-
		0.77 (m, 1H), 0.53-0.44 (m, 1H).
543	612.7	1H NMR (400 MHz, DMSO-d6) δ 8.10 (brs, 3H), 8.05 (d, J = 8.1 Hz,
		1H), 7.82 (d, J = 7.4 Hz, 1H), 7.42 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04
		(s, 1H), 6.90 (s, 1H), 5.19-5.06 (m, 1H), 4.89-4.77 (m, 1H), 4.48-4.35
		(m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.93-3.80 (m, 1H), 3.65-3.49 (m,
		2H), 1.98-1.86 (m, 1H), 1.76-1.52 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H),
		1.43-1.22 (m, 6H), 1.21 (s, 3H), 1.18-0.99 (m, 4H), 0.95 (s, 3H), 0.89-
		0.77 (m, 1H), 0.53-0.44 (m, 1H).
544	630.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (brs, 2H), 8.63 (dd, J = 8.1, 1.6
		Hz, 1H), 8.01 (d, J = 1.7 Hz, 1H), 8.00 (s, 1H), 7.62 (d, J = 10.6 Hz, 1H),
		7.56 (d, J = 8.4 Hz, 1H), 7.30 (s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 5.12-5.02
		(m, 1H), 4.94-4.72 (m, 3H), 4.49-4.33 (m, 1H), 3.87-3.75 (m, 1H),
		3.47 (d, J = 11.9 Hz, 1H), 3.39 (d, J = 13.2 Hz, 1H), 3.15-2.93 (m, 2H),
		2.41-2.28 (m, 1H), 2.01-1.82 (m, 1H), 1.74-1.48 (m, 4H), 1.50 (d, J =
		7.2 Hz, 3H), 1.47 (s, 3H), 1.36-1.08 (m, 6H), 0.93-0.86 (m, 1H), 0.75-
		0.49 (m, 2H), 0.19 (dd, J = 6.7, 3.4 Hz, 1H).
545	630.6	1H NMR (400 MHz, DMSO-d6) δ 8.79 (brs, 2H), 8.63 (dd, J = 8.2, 1.5
		Hz, 1H), 8.02 (d, J = 6.2 Hz, 1H), 8.01 (d, J = 4.4 Hz, 1H), 7.62 (d, J =
		10.6 Hz, 1H), 7.28 (s, 1H), 7.25 (d, J = 7.6 Hz, 1H), 7.17 (d, J = 8.2 Hz,
		1H), 4.95-4.73 (m, 3H), 4.66-4.34 (m, 2H), 3.89-3.78 (m, 2H), 3.47
		(d, J = 12.1 Hz, 1H), 3.39 (d, J = 13.1 Hz, 1H), 3.12-2.92 (m, 2H), 2.42-
		2.27 (m, 1H), 2.03-1.82 (m, 2H), 1.76-1.43 (m, 5H), 1.51 (d, J = 7.2
		Hz, 3H), 1.43-1.17 (m, 4H), 1.16 (s, 3H), 0.83-0.70 (m, 2H), 0.37 (dd,
		J = 6.5, 4.3 Hz, 1H).
546	631.6	1H NMR (400 MHz, DMSO-d6) δ 8.79 (brs, 2H), 8.64 (dd, J = 8.0, 1.5
		Hz, 1H), 8.57 (d, J = 6.9 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 6.4
		Hz, 1H), 7.76 (d, J = 10.8 Hz, 1H), 7.25 (d, J = 8.2 Hz, 1H), 7.15 (s, 1H),
		5.20-5.09 (m, 1H), 4.94-4.72 (m, 1H), 4.67-4.58 (m, 1H), 4.51-4.35
		(m, 2H), 4.16 (s, 3H), 3.98 (s, 3H), 3.47 (d, J = 12.3 Hz, 1H), 3.38 (d, J =
		12.8 Hz, 1H), 3.13-2.89 (m, 2H), 2.88-2.63 (m, 2H), 2.42-2.28 (m,
		1H), 1.99-1.81 (m, 2H), 1.76-1.63 (m, 1H), 1.58 (d, J = 7.0 Hz, 3H),
		1.56-1.41 (m, 1H), 1.33-1.13 (m, 1H), 1.10-0.92 (m, 1H).
547	642.2	1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 8.0 Hz, 1H), 8.82 (brs,
		2H), 8.65 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.91-7.84 (m,
		1H), 7.27 (d, J = 8.1 Hz, 1H), 7.25 (s, 1H), 6.41-6.30 (m, 1H), 5.93-
		5.77 (m, 1H), 5.66-5.55 (m, 1H), 5.31-5.17 (m, 1H), 5.07-4.96 (m,
		1H), 4.81 (ddt, J = 49.1, 9.7, 4.9 Hz, 1H), 4.47-4.32 (m, 1H), 4.09 (s,
		3H), 3.49 (d, J = 12.1 Hz, 1H), 3.39 (d, J = 13.1 Hz, 1H), 3.13-2.91 (m,
		2H), 2.61 (dd, J = 18.3, 8.5 Hz, 1H), 2.44-2.34 (m, 1H), 2.06-1.84 (m,
		1H), 1.59-1.38 (m, 2H), 1.43 (d, J = 7.1 Hz, 3H), 0.96-0.86 (m, 1H),
		0.83-0.60 (m, 2H).
548	604.5	1H NMR (400 MHz, DMSO-d6) δ 8.82 (brs, 2H), 8.65 (dd, J = 8.1, 1.5
		Hz, 1H), 8.02 (d, J = 6.4 Hz, 1H), 8.02 (d, J = 8.1 Hz, 1H), 7.76 (d, J =
		10.8 Hz, 1H), 7.54 (d, J = 8.5 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.13 (s,
		1H), 5.14-5.03 (m, 1H), 4.91-4.65 (m, 3H), 4.49-4.34 (m, 2H), 3.97
		(s, 3H), 3.47 (d, J = 12.3 Hz, 1H), 3.44-3.35 (m, 1H), 3.15-2.89 (m,
		2H), 2.42-2.29 (m, 1H), 2.00-1.83 (m, 1H), 1.73-1.51 (m, 3H), 1.49
		(d, J = 7.1 Hz, 3H), 1.47 (s, 3H), 1.44-1.13 (m, 5H), 0.78-0.64 (m, 1H),
		0.18 (dd, J = 6.7, 3.4 Hz, 1H).
549	640.6	1H NMR (400 MHz, DMSO-d6) δ 8.84 (brs, 2H), 8.68 (d, J = 8.0 Hz,
		1H), 8.10 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 6.3 Hz, 1H), 7.77 (d, J = 10.8
		Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.23 (s, 1H), 5.59-5.17 (m, 2H), 4.95-
		4.68 (m, 2H), 4.52-4.34 (m, 1H), 3.94 (s, 3H), 3.47 (d, J = 12.5 Hz, 1H),
		3.38 (d, J = 13.1 Hz, 1H), 3.14-2.90 (m, 2H), 2.42-2.26 (m, 1H), 2.12-
		1.71 (m, 5H), 1.64 (d, J = 7.1 Hz, 3H), 1.59-1.38 (m, 2H), 1.30-0.98
		(m, 3H), 1.18 (s, 3H), 0.32 (dd, J = 6.8, 4.0 Hz, 1H).
550	620.2	1H NMR (400 MHz, DMSO-d6) δ 8.76 (brs, 2H), 8.65 (d, J = 8.0 Hz,
		1H), 8.63 (d, J = 8.8 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.83 (s, 1H), 7.60
		(s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.20 (s, 1H), 6.40-6.28 (m, 1H), 5.94-
		5.70 (m, 2H), 5.22 (dd, J = 28.1, 14.5 Hz, 1H), 5.07-4.96 (m, 1H), 4.92-
		4.67 (m, 1H), 4.48-4.30 (m, 1H), 3.49 (d, J = 12.7 Hz, 1H), 3.38 (d, J =
		12.7 Hz, 1H), 3.11-2.88 (m, 2H), 2.66-2.55 (m, 1H), 2.54 (s, 3H), 2.43-
		2.25 (m, 2H), 2.01-1.85 (m, 1H), 1.59-1.45 (m, 2H), 1.43 (d, J = 7.1
		Hz, 3H), 0.95-0.87 (m, 1H), 0.78-0.59 (m, 2H).
551	622.4	1H NMR (400 MHz, DMSO-d6) δ 8.80 (brs, 2H), 8.65 (d, J = 8.0 Hz,
		1H), 8.55 (d, J = 8.8 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.83 (s, 1H), 7.60
		(s, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.19 (s, 1H), 5.69 (t, J = 13.6 Hz, 1H),
		5.23-5.00 (m, 2H), 4.80 (dtd, J = 49.0, 9.4, 4.5 Hz, 1H), 4.46-4.32 (m,
		1H), 3.93 (s, 3H), 3.49 (d, J = 12.5 Hz, 1H), 3.38 (d, J = 12.8 Hz, 1H),
		3.18-2.86 (m, 2H), 2.54 (s, 3H), 2.42-1.88 (m, 5H), 1.69-1.50 (m,
		2H), 1.45 (d, J = 7.1 Hz, 3H), 1.39-1.22 (m, 1H), 0.90-0.80 (m, 1H),
		0.70-0.44 (m, 3H).
552	638.2	1H NMR (400 MHz, DMSO-d6) δ 8.75 (brs, 2H), 8.69 (d, J = 8.0 Hz,
		1H), 8.09 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 6.3 Hz, 1H), 7.79 (s, 1H), 7.68
		(d, J = 8.4 Hz, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.24 (s, 1H), 6.45-6.35 (m,
		1H), 5.87 (t, J = 17.9 Hz, 1H), 5.69 (t, J = 12.5 Hz, 1H), 5.27 (dd, J = 28.3,
		14.5 Hz, 1H), 5.19-5.08 (m, 1H), 4.96-4.72 (m, 1H), 4.49-4.35 (m,
		1H), 3.92 (s, 3H), 3.48 (d, J = 12.4 Hz, 1H), 3.38 (d, J = 12.9 Hz, 1H),
		3.20-2.91 (m, 3H), 2.41-2.29 (m, 1H), 2.04-1.71 (m, 2H), 1.49 (d, J =
		7.1 Hz, 3H), 1.37 (s, 3H), 1.22 (dd, J = 9.4, 3.7 Hz, 1H), 0.88-0.75 (m,
		1H), 0.38 (dd, J = 6.5, 3.6 Hz, 1H).
553	640.5	1H NMR (400 MHz, DMSO-d6) δ 8.80 (brs, 2H), 8.68 (d, J = 8.0 Hz,
		1H), 8.07 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 6.4 Hz, 1H), 7.77 (d, J = 10.8
		Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.22 (s, 1H),
		5.67-5.51 (m, 1H), 5.25 (dd, J = 26.9, 14.6 Hz, 1H), 5.18-5.05 (m,
		1H), 4.97-4.72 (m, 1H), 4.50-4.35 (m, 1H), 3.94 (s, 3H), 3.48 (d, J =
		12.3 Hz, 1H), 3.44-3.34 (m, 1H), 3.13-2.90 (m, 2H), 2.44-2.30 (m,
		1H), 2.16-1.52 (m, 5H), 1.48 (d, J = 7.1 Hz, 3H), 1.43 (s, 3H), 1.39-
		1.03 (m, 3H), 0.54-0.42 (m, 1H), 0.21 (dd, J = 6.9, 3.6 Hz, 1H).
554	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.16 (brs, 2H), 8.07 (d, J = 8.1 Hz,
		1H), 8.03 (brs, 1H), 7.88 (brs, 1H), 7.78 (d, J = 9.8 Hz, 1H), 7.64 (d, J =
		8.4 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.20 (s, 1H), 5.55 (t, J = 13.5 Hz,
		1H), 5.25 (dd, J = 26.9, 14.6 Hz, 1H), 5.18-5.04 (m, 1H), 4.69 (d, J =
		35.9 Hz, 1H), 3.99 (s, 1H), 3.94 (s, 3H), 3.66 (brs, 1H), 2.36-2.24 (m,
		1H), 2.17-1.55 (m, 6H), 1.48 (d, J = 7.1 Hz, 3H), 1.43 (s, 3H), 1.40-
		1.07 (m, 4H), 0.56-0.45 (m, 1H), 0.21 (dd, J = 6.9, 3.6 Hz, 1H).
555	618.3	1H NMR (400 MHz, DMSO-d6) δ 8.16 (brs, 2H), 8.08 (d, J = 8.1 Hz,
		1H), 8.05 (brs, 1H), 7.83 (d, J = 7.4 Hz, 1H), 7.72 (d, J = 14.5 Hz, 1H),
		7.21 (d, J = 8.1 Hz, 1H), 7.11 (s, 1H), 5.18-5.08 (m, 1H), 4.94-4.63 (m,
		2H), 4.50-4.36 (m, 1H), 4.10 (s, 3H), 4.06-3.95 (m, 1H), 3.76-3.63
		(m, 1H), 2.27 (brs, 1H), 2.13-1.59 (m, 7H), 1.54-1.26 (m, 4H), 1.45 (d,
		J = 7.1 Hz, 3H), 1.25-1.05 (m, 3H), 1.22 (s, 3H), 0.95 (s, 3H).
556	596.5	1H NMR (400 MHz, DMSO-d6) δ 8.18 (brs, 2H), 8.05 (d, J = 8.1 Hz,
		1H), 8.02 (s, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.72 (d, J = 16.4 Hz, 1H), 7.61
		(s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 5.18-5.07 (m, 1H), 4.90-
		4.47 (m, 4H), 3.94 (s, 3H), 3.85-3.61 (m, 2H), 2.45 (s, 3H), 2.35-2.19
		(m, 1H), 2.00-1.54 (m, 7H), 1.52-1.26 (m, 5H), 1.45 (d, J = 7.1 Hz,
		3H), 1.22 (s, 3H), 1.17-1.01 (m, 1H), 0.95 (s, 3H).
557	610.5	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.5 Hz, 1H), 8.17 (brs,
		1H), 8.05 (s, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.83 (brs, 1H), 7.63 (d, J = 9.8
		Hz, 1H), 7.28 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 5.08-4.97 (m, 1H), 4.88-
		4.58 (m, 4H), 3.95 (d, J = 17.6 Hz, 1H), 3.86-3.76 (m, 1H), 3.74-3.59
		(m, 1H), 2.43-2.17 (m, 1H), 1.95-1.46 (m, 9H), 1.44 (d, J = 7.1 Hz,
		3H), 1.41-1.08 (m, 4H), 0.96-0.85 (m, 2H), 0.82-0.56 (m, 4H), 0.52-
		0.45 (m, 1H).
558	668.6	1H NMR (400 MHz, DMSO-d6) δ 8.87 (brs, 1H), 8.83 (d, J = 8.1 Hz,
		1H), 8.07 (d, J = 8.1 Hz, 1H), 7.86 (dd, J = 5.2, 1.2 Hz, 1H), 7.83 (d, J =
		7.5 Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.17 (s, 1H), 5.20-5.07 (m, 1H),
		4.91-4.59 (m, 5H), 4.46-4.34 (m, 2H), 3.71-3.57 (m, 2H), 3.48 (d, J =
		12.0 Hz, 1H), 3.39 (d, J = 12.4 Hz, 1H), 3.06 (s, 3H), 3.03-2.88 (m, 1H),
		2.42-2.30 (m, 1H), 2.00-1.84 (m, 2H), 1.76-1.54 (m, 2H), 1.53-1.25
		(m, 4H), 1.45 (d, J = 7.1 Hz, 3H), 1.21 (s, 3H), 1.15-1.00 (m, 2H), 0.95
		(s, 3H).
559	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J = 8.0 Hz, 1H), 8.81 (brs,
		1H), 8.44 (d, J = 8.5 Hz, 1H), 8.01 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 4.9 Hz,
		1H), 7.15 (d, J = 8.1 Hz, 1H), 7.13 (s, 1H), 5.07-4.96 (m, 1H), 4.94-
		4.32 (m, 7H), 3.48 (d, J = 12.3 Hz, 1H), 3.39 (d, J = 13.2 Hz, 1H), 3.13-
		2.91 (m, 2H), 3.05 (s, 3H), 2.42-2.26 (m, 1H), 2.03-1.77 (m, 3H), 1.74-
		1.33 (m, 7H), 1.43 (d, J = 7.1 Hz, 3H), 1.30-1.16 (m, 1H), 0.92-0.84
		(m, 1H), 0.81-0.58 (m, 2H), 0.56-0.46 (m, 1H).
560	644.5	1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 8.1 Hz, 1H), 8.82 (brs,
		2H), 8.57 (d, J = 8.8 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 4.8 Hz,
		1H), 7.27 (s, 1H), 7.23 (s, 1H), 5.54 (t, J = 13.5 Hz, 1H), 5.18 (dd, J =
		27.7, 14.6 Hz, 1H), 5.10-4.99 (m, 1H), 4.95-4.69 (m, 1H), 4.48-4.32
		(m, 1H), 4.09 (s, 3H), 3.54-3.43 (m, 1H), 3.39 (d, J = 13.3 Hz, 1H), 3.14-
		2.90 (m, 2H), 2.42-2.31 (m, 1H), 2.25-1.84 (m, 4H), 1.71-1.51 (m,
		2H), 1.45 (d, J = 7.0 Hz, 3H), 1.39-1.25 (m, 1H), 0.90-0.80 (m, 1H),
		0.73-0.57 (m, 1H), 0.55-0.42 (m, 2H).
561	638.6	1H NMR (400 MHz, DMSO-d6) δ 8.98 (d, J = 7.8 Hz, 1H), 8.81 (brs,
		2H), 8.70 (s, 1H), 8.52 (d, J = 8.2 Hz, 1H), 8.27 (s, 1H), 8.06 (d, J = 8.0
		Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.19 (s, 1H), 5.78-5.70 (m, 1H), 5.59
		(d, J = 15.9 Hz, 1H), 5.16-4.77 (m, 2H), 4.77-4.58 (m, 2H), 4.56-4.48
		(m, 1H), 4.04 (s, 3H), 3.49 (d, J = 12.2 Hz, 1H), 3.41 (d, J = 12.9 Hz, 1H),
		3.15-2.90 (m, 2H), 2.75-2.60 (m, 1H), 2.49-2.33 (m, 2H), 2.02-1.85
		(m, 1H), 1.56-1.45 (m, 1H), 1.42 (d, J = 7.1 Hz, 3H), 1.41-1.28 (m,
		2H), 0.95-0.79 (m, 1H), 0.64-0.54 (m, 1H).
562	640.5	1H NMR (400 MHz, DMSO-d6) δ 8.98 (d, J = 7.8 Hz, 1H), 8.83 (brs,
		2H), 8.71 (s, 1H), 8.45 (d, J = 8.5 Hz, 1H), 8.27 (s, 1H), 8.03 (d, J = 8.0
		Hz, 1H), 7.17 (d, J = 8.2 Hz, 1H), 7.15 (s, 1H), 5.13-5.02 (m, 1H), 5.00-
		4.80 (m, 1H), 4.76-4.66 (m, 1H), 4.63-4.38 (m, 2H), 4.03 (s, 3H), 3.54-
		3.47 (m, 1H), 3.47-3.37 (m, 1H), 3.19-2.89 (m, 2H), 2.47-2.32 (m,
		1H), 2.06-1.55 (m, 6H), 1.54-1.34 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H),
		1.35-1.16 (m, 1H), 0.93-0.82 (m, 1H), 0.80-0.62 (m, 2H), 0.56-0.44
		(m, 1H).
563	567.5	1H NMR (400 MHz, DMSO-d6) δ 8.69 (d, J = 1.9 Hz, 1H), 8.45 (d, J =
		8.5 Hz, 1H), 8.36 (s, 1H), 8.10 (brs, 3H), 8.04 (d, J = 8.0 Hz, 1H), 7.25 (s,
		1H), 7.17 (d, J = 8.1 Hz, 1H), 5.08-4.97 (m, 1H), 4.90-4.72 (m, 2H),
		4.04 (s, 3H), 2.43-2.23 (m, 1H), 1.92-1.52 (m, 10H), 1.44 (d, J = 7.1
		Hz, 3H), 1.40-1.18 (m, 4H), 0.93-0.62 (m, 4H), 0.53-0.46 (m, 1H).
564	589.6	1H NMR (400 MHz, DMSO-d6) δ 8.80 (brs, 2H), 8.68 (d, J = 8.8 Hz,
		1H), 8.64 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H), 7.74 (d, J = 10.8
		Hz, 1H), 7.62 (s, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.11 (s, 1H), 7.03 (d, J =
		8.3 Hz, 1H), 5.03-4.74 (m, 3H), 4.52-4.35 (m, 1H), 4.24-4.12 (m,
		1H), 3.95 (s, 3H), 3.47 (d, J = 12.2 Hz, 1H), 3.38 (d, J = 13.1 Hz, 1H),
		3.17-2.91 (m, 2H), 2.42-2.28 (m, 1H), 2.04-1.73 (m, 3H), 1.73-1.53
		(m, 2H), 1.43 (d, J = 7.0 Hz, 3H), 1.43-1.28 (m, 3H), 1.01-0.68 (m,
		3H), 0.59-0.51 (m, 1H).
565	605.5	1H NMR (400 MHz, DMSO-d6) δ 8.81 (brs, 2H), 8.65 (d, J = 8.1 Hz,
		1H), 8.05 (d, J = 7.7 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H), 7.74 (d, J = 10.8
		Hz, 1H), 7.62 (d, J = 8.2 Hz, 1H), 7.35 (s, 1H), 7.11 (s, 1H), 7.08 (dd, J =
		8.3, 1.2 Hz, 1H), 5.13-5.02 (m, 1H), 4.95-4.74 (m, 2H), 4.48-4.35 (m,
		1H), 4.20 (t, J = 11.8 Hz, 1H), 3.96 (s, 3H), 3.47 (d, J = 12.6 Hz, 1H),
		3.38 (d, J = 13.0 Hz, 1H), 3.13-2.89 (m, 2H), 2.43-2.31 (m, 1H), 2.16-
		1.58 (m, 5H), 1.54-1.36 (m, 3H), 1.46 (d, J = 7.1 Hz, 3H), 1.25 (s, 3H),
		1.20-1.04 (m, 3H), 0.95 (s, 3H).
566	638.3	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.8 Hz, 1H), 8.18 (s, 1H),
		8.08 (dd, J = 8.0, 2.2 Hz, 1H), 8.03 (brs, 3H), 7.68 (dd, J = 16.8, 4.6 Hz,
		1H), 7.31-7.24 (m, 1H), 7.20 (d, J = 2.5 Hz, 1H), 5.57-5.44 (m, 1H),
		5.18 (ddd, J = 27.6, 14.6, 3.2 Hz, 1H), 5.11-5.00 (m, 1H), 4.08 (s, 3H),
		3.27 (d, J = 11.0 Hz, 1H), 2.74-2.57 (m, 1H), 2.27-1.75 (m, 8H), 1.72-
		1.53 (m, 3H), 1.44 (d, J = 7.1 Hz, 3H), 1.40-1.20 (m, 1H), 0.92-0.79
		(m, 1H), 0.71-0.56 (m, 1H), 0.55-0.43 (m, 2H).
567	670.5	1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 8.0 Hz, 1H), 8.80 (brs,
		2H), 8.58 (d, J = 8.8 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.82 (dd, J = 5.2,
		1.2 Hz, 1H), 7.40 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.85-5.73 (m, 1H),
		5.26-5.16 (m, 1H), 5.12-5.00 (m, 1H), 4.94-4.69 (m, 1H), 4.46-4.35
		(m, 1H), 4.12-4.01 (m, 1H), 3.43 (dd, J = 37.5, 12.5 Hz, 2H), 3.28-2.86
		(m, 2H), 2.43-2.28 (m, 1H), 2.23-2.02 (m, 2H), 2.01-1.87 (m, 2H),
		1.70-1.50 (m, 2H), 1.44 (d, J = 7.0 Hz, 3H), 1.38-1.18 (m, 2H), 1.15-
		0.99 (m, 2H), 0.90-0.81 (m, 1H), 0.73-0.57 (m, 1H), 0.54-0.44 (m,
		3H).
568	598.7	1H NMR (400 MHz, DMSO-d6) δ 8.62 (brs, 3H), 8.45 (d, J = 4.1 Hz,
		1H), 8.43 (s, 1H), 8.00 (d, J = 1.2 Hz, 1H), −7.98 (s, 1H), 7.60 (d, J = 8.0
		Hz, 1H), 7.30 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 5.07-4.95 (m, 1H), 4.88-
		4.68 (m, 2H), 4.22-4.10 (m, 1H), 3.87-3.77 (m, 2H), 3.44-3.32 (m,
		2H), 3.27-3.17 (m, 2H), 2.96-2.80 (m, 2H), 2.01-1.81 (m, 3H), 1.80-
		1.48 (m, 5H), 1.44 (d, J = 7.1 Hz, 3H), 1.42-1.11 (m, 3H), 0.92-0.80
		(m, 2H), 0.77-0.44 (m, 3H).
569	624.8	1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.49 (s, 1H), 8.45 (d, J =
		8.5 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 6.1 Hz, 1H), 7.61 (d, J =
		10.1 Hz, 1H), 7.28 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 5.07-4.95 (m, 1H),
		4.92-4.72 (m, 2H), 4.02-3.85 (m, 2H), 3.86-3.74 (m, 2H), 3.29 (brs,
		2H), 2.96 (brs, 2H), 1.90-1.47 (m, 10H), 1.52-1.31 (m, 1H), 1.44 (d, J =
		7.1 Hz, 3H), 1.27-1.07 (m, 3H), 0.98-0.53 (m, 5H), 0.53-0.38 (m,
		1H).
570	655.7	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 6.9 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 7.97 (brs, 3H), 7.44 (s, 1H), 7.25 (d, J = 8.2 Hz, 1H), 7.04 (s,
		1H), 6.93 (d, J = 1.1 Hz, 1H), 5.19-5.09 (m, 1H), 4.56-4.35 (m, 2H),
		4.16 (s, 3H), 4.13 (s, 3H), 3.99 (s, 3H), 3.75-3.68 (m, 3H), 3.37 (s, 3H),
		2.82-2.64 (m, 2H), 2.02-1.87 (m, 1H), 1.86-1.64 (m, 3H), 1.61-1.51
		(m, 1H), 1.58 (d, J = 7.0 Hz, 3H), 1.50-1.35 (m, 1H), 1.29-1.11 (m,
		1H), 1.08-0.90 (m, 1H).
571	642.7	1H NMR (400 MHz, DMSO-d6) δ 8.77 (brs, 2H), 8.69-8.59 (m, 1H),
		8.51-8.42 (m, 1H), 8.05-7.96 (m, 2H), 7.75-7.59 (m, 1H), 7.58-7.34
		(m, 1H), 7.19-7.09 (m, 2H), 5.17 (d, J = 13.3 Hz, 1H), 5.09-4.63 (m,
		3H), 4.54-4.28 (m, 2H), 3.47 (d, J = 12.3 Hz, 1H), 3.39 (d, J = 13.0 Hz,
		1H), 3.14-2.91 (m, 1H), 2.40-2.29 (m, 1H), 2.02-1.50 (m, 8H), 1.45
		(d, J = 7.1 Hz, 1.5H), 1.43 (d, J = 7.2 Hz, 1.5H), 1.36-1.14 (m, 2H), 1.01-
		0.45 (m, 8H), −0.17 (dd, J = 9.3, 4.9 Hz, 0.5H), −0.38 (dd, J = 9.2, 4.9
		Hz, 0.5H).
572	628.3	1H NMR (400 MHz, DMSO-d6) δ 8.46 (s, 1H), 8.07 (s, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.87 (brs, 3H), 7.63 (d, J = 8.0 Hz, 1H), 7.28 (s, 1H), 7.14 (d,
		J = 8.1 Hz, 1H), 5.07-4.96 (m, 1H), 4.90-4.69 (m, 2H), 3.84-3.76 (m,
		1H), 3.75-3.67 (m, 1H), 3.62-3.47 (m, 1H), 3.41-3.37 (m, 1H), 3.37
		(s, 3H), 3.31-3.18 (m, 1H), 1.93-1.79 (m, 1H), 1.73-1.53 (m, 5H),
		1.44 (d, J = 7.1 Hz, 3H), 1.42-1.31 (m, 2H), 1.31-1.03 (m, 4H), 0.92-
		0.82 (m, 2H), 0.77-0.55 (m, 3H), 0.53-0.42 (m, 1H).
573	599.7	1H NMR (400 MHz, DMSO-d6) δ 8.92 (d, J = 2.0 Hz, 1H), 8.85 (d, J =
		7.8 Hz, 1H), 8.78 (brs, 2H), 8.63 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 8.5 Hz,
		1H), 8.02 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.16 (d, J = 8.1 Hz, 1H), 5.08-
		4.96 (m, 1H), 4.95-4.72 (m, 3H), 4.49-4.35 (m, 1H), 3.86-3.79 (m,
		1H), 3.51-3.38 (m, 3H), 3.18-2.92 (m, 2H), 2.42-2.32 (m, 1H), 2.02-
		1.81 (m, 2H), 1.77-1.61 (m, 3H), 1.62-1.52 (m, 1H), 1.45 (d, J = 7.1
		Hz, 3H), 1.44-1.35 (m, 1H), 1.33-1.13 (m, 3H), 1.08-0.97 (m, 1H),
		0.93-0.80 (m, 2H), 0.78-0.60 (m, 2H), 0.55-0.45 (m, 1H).
574	611.6	1H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 1.9 Hz, 1H), 8.46 (d, J =
		8.5 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.97 (brs,
		3H), 7.38 (s, 1H), 7.16 (d, J = 8.1 Hz, 1H), 5.09-4.96 (m, 1H), 4.92-
		4.74 (m, 2H), 3.84-3.76 (m, 2H), 3.62-3.50 (m, 2H), 3.50-3.37 (m,
		1H), 3.37 (s, 3H), 2.04-1.73 (m, 4H), 1.73-1.49 (m, 4H), 1.45 (d, J =
		7.1 Hz, 3H), 1.45-1.35 (m, 1H), 1.31-1.03 (m, 4H), 0.92-0.82 (m,
		1H), 0.83-0.58 (m, 3H), 0.55-0.42 (m, 1H).
575	610.5	1H NMR (400 MHz, DMSO-d6) δ 8.55 (brs, 2H), 8.45 (d, J = 8.5 Hz,
		1H), 8.35 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 8.1 Hz, 1H), 7.98-7.96 (m,
		1H), 7.60 (d, J = 10.5 Hz, 1H), 7.30 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H),
		5.05-4.95 (m, 1H), 4.93-4.70 (m, 3H), 3.64-3.50 (m, 2H), 3.30-3.20 (m,
		1H), 3.00-2.89 (m, 1H), 2.50-2.40 (m, 1H), 1.92-1.79 (m, 1H), 1.75-
		1.42 (m, 6H), 1.45 (d, J = 7.0 Hz, 3H), 1.41-1.33 (m, 1H), 1.29-1.11
		(m, 3H), 0.92-0.72 (m, 5H), 0.71-0.53 (m, 3H), 0.53-0.43 (m, 1H).
576	651.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 7.9 Hz, 1H), 8.68 (d, J =
		2.6 Hz, 1H), 8.55 (d, J = 2.6 Hz, 1H), 7.98 (brs, 3H), 7.65 (d, J = 8.1 Hz,
		1H), 7.60 (s, 1H), 7.42 (s, 1H), 7.17 (dd, J = 8.3, 1.2 Hz, 1H), 7.06 (s, 1H),
		6.93 (d, J = 1.1 Hz, 1H), 5.29-5.16 (m, 1H), 4.81-4.66 (m, 1H), 4.30-
		4.15 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.75-3.67 (m, 1H), 3.60-3.48
		(m, 2H), 3.46-3.34 (m, 1H), 3.37 (s, 3H), 2.76-2.62 (m, 1H), 2.49-
		2.41 (m, 1H), 2.03-1.84 (m, 2H), 1.83-1.62 (m, 2H), 1.62-1.47 (m,
		2H), 1.53 (d, J = 7.0 Hz, 3H), 1.42-1.27 (m, 1H), 0.89-0.71 (m, 1H).
577	687.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 7.9 Hz, 1H), 8.68 (d, J =
		2.6 Hz, 1H), 8.55 (d, J = 2.6 Hz, 1H), 8.19 (brs, 3H), 7.66 (d, J = 8.2 Hz,
		1H), 7.60 (s, 1H), 7.44 (s, 1H), 7.17 (dd, J = 8.3, 1.2 Hz, 1H), 7.07 (s, 1H),
		6.94 (d, J = 1.2 Hz, 1H), 6.86 (t, J = 74.7 Hz, 1H), 5.28-5.16 (m, 1H),
		4.79-4.71 (m, 1H), 4.70-4.65 (m, 1H), 4.23-4.14 (m, 1H), 4.12 (s,
		3H), 4.00 (s, 3H), 3.98-3.89 (m, 2H), 3.68-3.34 (m, 4H), 2.77-2.64
		(m, 1H), 2.50-2.41 (m, 1H), 2.04-1.84 (m, 2H), 1.76-1.49 (m, 2H),
		1.53 (d, J = 6.2 Hz, 3H), 1.42-1.28 (m, 1H), 0.86-0.73 (m, 1H).
578	666.4	1H NMR (400 MHz, DMSO-d6) δ 9.26 (d, J = 6.8 Hz, 1H), 8.61 (d, J =
		2.6 Hz, 1H), 8.50 (d, J = 2.6 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.98 (brs,
		3H), 7.68 (s, 1H), 7.33 (s, 1H), 7.32-7.27 (m, 2H), 5.29-5.18 (m, 1H),
		5.01-4.74 (m, 2H), 4.08-3.98 (m, 2H), 3.74-3.69 (m, 2H), 3.63-
		3.39 (m, 4H), 3.37 (s, 3H), 2.73-2.64 (m, 1H), 2.46-2.32 (m, 1H), 2.01-
		1.88 (m, 1H), 1.82-1.69 (m, 1H), 1.63-1.34 (m, 2H), 1.52 (d, J = 7.1
		Hz, 3H), 1.29-0.98 (m, 4H), 0.67-0.44 (m, 2H).
579	628.3	1H NMR (400 MHz, DMSO-d6) δ 8.46 (d, J = 8.5 Hz, 1H), 8.00 (d, J =
		8.1 Hz, 1H), 7.95 (brs, 3H), 7.68 (s, 1H), 7.28 (dd, J = 11.6, 1.2 Hz, 1H),
		7.25 (s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 5.07-4.96 (m, 1H), 4.86-4.71 (m,
		2H), 4.05-3.96 (m, 1H), 3.61-3.48 (m, 2H), 3.48-3.37 (m, 2H), 3.37
		(s, 3H), 2.02-1.46 (m, 8H), 1.44 (d, J = 7.1 Hz, 3H), 1.42-1.01 (m, 6H),
		0.99-0.82 (m, 2H), 0.80-0.55 (m, 3H), 0.53-0.46 (m, 1H).
580	616.7	1H NMR (400 MHz, DMSO-d6) δ 8.91 (d, J = 8.0 Hz, 1H), 8.83 (brs,
		3H), 8.80 (d, J = 5.7 Hz, 1H), 8.39 (d, J = 8.6 Hz, 1H), 7.99 (d, J = 6.6 Hz,
		1H), 7.90 (d, J = 8.0 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.82 (s, 1H), 5.04-
		4.93 (m, 1H), 4.93-4.82 (td, J = 9.6, 4.6 Hz, 1H), 4.81-4.64 (m, 3H),
		4.46-4.33 (m, 1H), 3.48 (d, J = 12.5 Hz, 1H), 3.39 (d, J = 13.1 Hz, 1H),
		3.14-2.91 (m, 2H), 2.43-2.28 (m, 2H), 2.21-2.07 (m, 1H), 2.01-
		1.79 (m, 2H), 1.70-1.47 (m, 2H), 1.43 (d, J = 7.0 Hz, 3H), 1.47-1.29
		(m, 1H), 1.27-1.05 (m, 3H), 0.92-0.80 (m, 1H), 0.76-0.56 (m, 2H),
		0.51-0.34 (m, 3H).
581	676.6	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.6 Hz, 1H), 8.31 (s, 3H),
		7.99 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 1.5 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H),
		7.02 (s, 1H), 6.98 (s, 1H), 6.76 (t, J = 76.3 Hz, 1H), 5.07-4.93 (m, 1H),
		4.81-4.52 (m, 3H), 4.12 (s, 3H), 4.01 (s, 3H), 3.69-3.61 (m, 2H), 2.40-
		2.19 (m, 2H), 2.10-1.79 (m, 5H), 1.77-1.31 (m, 6H), 1.43 (d, J = 7.1
		Hz, 3H), 1.32-1.14 (m, 2H), 0.94-0.80 (m, 1H), 0.80-0.56 (m, 2H),
		0.55-0.42 (m, 1H).
582	668.4	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.6 Hz, 1H), 8.36 (brs,
		3H), 7.99 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.02
		(s, 1H), 6.95 (d, J = 1.1 Hz, 1H), 5.08-4.95 (m, 2H), 4.76-4.64 (m, 1H),
		4.64-4.54 (m, 1H), 4.12 (s, 3H), 4.03-3.89 (m, 1H), 4.00 (s, 3H), 3.80-
		3.41 (m, 4H), 2.13-1.94 (m, 2H), 1.93-1.83 (m, 1H), 1.72-1.48 (m,
		5H), 1.48-1.32 (m, 1H), 1.43 (d, J = 7.1 Hz, 3H), 1.31-1.16 (m, 1H),
		0.97-0.80 (m, 1H), 0.79-0.58 (m, 2H), 0.54-0.44 (m, 1H).
583	628.9	1H NMR (400 MHz, DMSO-d6) δ 8.00 (d, J = 8.1 Hz, 1H), 7.99 (brs,
		3H), 7.54 (d, J = 8.4 Hz, 1H), 7.44 (s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 7.02
		(s, 1H), 6.93 (d, J = 1.1 Hz, 1H), 5.13-5.01 (m, 1H), 4.77-4.70 (m, 1H),
		4.60-4.53 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.75-3.68 (m, 1H), 3.65-
		3.52 (m, 3H), 3.45-3.33 (m, 1H), 3.37 (s, 3H), 2.02-1.88 (m, 1H),
		1.83-1.51 (m, 5H), 1.49 (s, 3H), 1.47 (s, 3H), 1.42-1.12 (m, 5H), 0.74-
		0.65 (m, 1H), 0.18 (dd, J = 6.7, 3.4 Hz, 1H).
584	640.7	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.6 Hz, 1H), 8.11 (brs,
		3H), 7.99 (d, J = 8.0 Hz, 1H), 7.47 (d, J = 1.2 Hz, 1H), 7.14 (d, J = 8.1 Hz,
		1H), 6.97 (d, J = 1.2 Hz, 1H), 5.09-4.92 (m, 1H), 4.79-4.55 (m, 3H),
		4.12 (s, 3H), 4.00 (s, 3H), 3.69-3.61 (m, 2H), 3.32 (s, 3H), 2.34-1.70
		(m, 8H), 1.70-1.47 (m, 4H), 1.43 (d, J = 7.1 Hz, 3H), 1.46-1.35 (m,
		1H), 1.30-1.17 (m, 2H), 0.91-0.84 (m, 1H), 0.78-0.58 (m, 3H), 0.54-
		0.42 (m, 1H).
585	664.5	1H NMR (400 MHz, DMSO-d6) δ 8.06 (d, J = 8.0 Hz, 1H), 7.98 (brs,
		3H), 7.64 (d, J = 8.5 Hz, 1H), 7.44 (s, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.13
		(s, 1H), 6.95 (d, J = 1.2 Hz, 1H), 5.45 (t, J = 13.5 Hz, 1H), 5.34-5.03 (m,
		2H), 4.10 (s, 3H), 4.00 (s, 3H), 3.73-3.68 (m, 1H), 3.59-3.49 (m, 2H),
		3.47-3.36 (m, 1H), 3.37 (s, 3H), 2.22-1.66 (m, 6H), 1.66-1.52 (m,
		1H), 1.48 (d, J = 7.1 Hz, 3H), 1.43 (s, 3H), 1.40-1.23 (m, 1H), 1.23-
		1.05 (m, 2H), 0.56-0.45 (m, 1H), 0.21 (dd, J = 6.9, 3.6 Hz, 1H).
586	628.6	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.8 Hz, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 7.98 (s, 3H), 7.45 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.04 (s,
		1H), 6.94 (d, J = 1.2 Hz, 1H), 5.27-5.12 (m, 1H), 4.94-4.83 (m, 1H),
		4.61-4.50 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.74-3.68 (m, 2H), 3.55
		(s, 2H), 3.60-3.48 (m, 1H), 3.47-3.35 (m, 1H), 3.37 (s, 3H), 2.02-1.90
		(m, 2H), 1.82-1.66 (m, 2H), 1.61-1.48 (m, 2H), 1.47 (d, J = 6.9 Hz,
		3H), 1.45-1.33 (m, 2H), 1.32-1.16 (m, 2H), 1.15-1.04 (m, 1H), 1.03-
		0.93 (m, 1H), 0.91-0.79 (m, 2H), 0.68-0.56 (m, 1H), 0.50-0.41 (m,
		1H).
587	652.6	1H NMR (400 MHz, DMSO-d6) δ 8.12 (d, J = 8.1 Hz, 1H), 7.98 (brs,
		3H), 7.75 (d, J = 7.9 Hz, 1H), 7.46 (s, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.15
		(s, 1H), 6.94 (d, J = 1.2 Hz, 1H), 5.38-5.07 (m, 3H), 4.08 (s, 3H), 3.99
		(s, 3H), 3.76-3.50 (m, 3H), 3.37 (s, 3H), 2.10-1.70 (m, 4H), 1.54 (d, J =
		7.1 Hz, 3H), 1.42-1.18 (m, 4H), 1.18 (s, 3H), 1.01 (s, 3H).
588	668.4	1H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 8.0 Hz, 1H), 8.09 (d, J =
		9.4 Hz, 1H), 7.99 (brs, 3H), 7.45 (s, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.18 (s,
		1H), 6.95 (d, J = 1.2 Hz, 1H), 5.46-5.22 (m, 3H), 4.09 (s, 3H), 3.99 (s,
		3H), 3.74-3.68 (m, 2H), 3.59-3.48 (m, 2H), 3.47-3.33 (m, 2H), 3.37
		(s, 3H), 2.61-2.53 (m, 2H), 2.02-1.88 (m, 1H), 1.82-1.60 (m, 3H),
		1.45 (d, J = 6.9 Hz, 3H), 1.34 (s, 3H), 1.20 (s, 3H), 1.18-1.02 (m, 1H).
589	666.4	1H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J = 9.4 Hz, 1H), 8.16 (d, J =
		8.0 Hz, 1H), 8.00 (brs, 3H), 7.45 (s, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.19 (s,
		1H), 6.95 (d, J = 1.2 Hz, 1H), 5.56-5.29 (m, 3H), 4.10 (s, 3H), 4.00 (s,
		3H), 3.73-3.68 (m, 1H), 3.57-3.48 (m, 3H), 3.47-3.39 (m, 1H), 3.48-
		3.36 (m, 3H), 3.37 (s, 3H), 3.13-3.00 (m, 1H), 2.03-1.69 (m, 5H),
		1.48 (d, J = 6.9 Hz, 3H), 1.17-0.94 (m, 4H).
590	638.6	1H NMR (400 MHz, DMSO-d6) δ 8.89 (s, 2H), 8.70 (d, J = 7.9 Hz, 1H),
		8.10 (d, J = 8.2 Hz, 1H), 8.05 (s, 2H), 7.95 (s, 1H), 7.37 (d, J = 1.3 Hz,
		1H), 7.25-7.18 (m, 2H), 7.04 (dt, J = 14.6, 7.4 Hz, 2H), 6.81 (s, 1H),
		6.41 (s, 1H), 6.10 (d, J = 15.7 Hz, 1H), 5.86 (d, J = 15.7 Hz, 1H), 5.05 (p,
		J = 7.1 Hz, 1H), 4.94-4.68 (m, 1H), 4.54-4.35 (m, 1H), 4.16 (s, 3H),
		4.03 (s, 3H), 3.47-3.27 (m, 2H), 3.15-2.86 (m, 2H), 2.86-2.64 (m,
		2H), 2.41-2.25 (m, 2H), 2.18-2.06 (m, 1H), 2.01-1.78 (m, 2H), 1.73-
		1.49 (m, 2H), 1.45 (d, J = 7.2 Hz, 3H).
591	606.4	1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 3H), 8.66 (d, J = 8.1 Hz, 1H),
		8.06 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 6.4 Hz, 1H), 7.82 (d, J = 7.4 Hz, 1H),
		7.76 (d, J = 10.9 Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.15 (s, 1H), 5.13 (p,
		J = 7.1 Hz, 1H), 4.95-4.72 (m, 2H), 4.62-4.49 (m, 1H), 4.42 (s, 1H), 3.97
		(s, 3H), 3.48-3.27 (m, 1H), 3.15-2.88 (m, 3H), 2.03-1.84 (m, 2H),
		1.79-1.58 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.43-1.29 (m, 3H), 1.22 (s,
		3H), 1.19-1.02 (m, 3H), 0.95 (s, 3H).
592	618.5	1H NMR (400 MHz, DMSO-d6) δ 8.79 (s, 3H), 8.45 (d, J = 8.1 Hz, 1H),
		8.14-7.97 (m, 2H), 7.83 (d, J = 7.4 Hz, 1H), 7.42 (s, 1H), 7.19 (d, J = 8.2
		Hz, 1H), 7.11 (s, 1H), 5.17-5.06 (m, 1H), 5.01-4.79 (m, 2H), 4.62-
		4.51 (m, 1H), 4.50-4.38 (m, 1H), 4.00 (s, 3H), 3.98 (s, 3H), 3.54-3.32
		(m, 2H), 3.10-2.92 (m, 2H), 2.44-2.29 (m, 1H), 2.03-1.86 (m, 2H),
		1.74-1.56 (m, 1H), 1.45 (d, J = 7.1 Hz, 3H), 1.43-1.28 (m, 4H), 1.21 (s,
		3H), 1.16-1.00 (m, 4H), 0.95 (s, 3H).
593	626.5	1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 7.0 Hz, 1H), 8.81 (s, 3H),
		8.65 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 6.4 Hz, 1H),
		7.77 (d, J = 10.8 Hz, 1H), 7.38-7.28 (m, 2H), 7.28-7.16 (m, 4H), 5.19
		(p, J = 7.0 Hz, 1H), 5.00-4.83 (m, 2H), 4.83-4.66 (m, 2H), 4.51-4.34
		(m, 1H), 3.98 (s, 3H), 3.43 (dd, J = 35.0, 12.5 Hz, 2H), 3.17-2.88 (m,
		2H), 2.46-2.29 (m, 2H), 2.30-2.14 (m, 1H), 2.00-1.83 (m, 1H), 1.64-
		1.52 (m, 1H), 1.49 (d, J = 7.1 Hz, 3H), 1.47-1.37 (m, 1H), 1.34-1.06
		(m, 2H), 0.66-0.37 (m, 1H).
594	654.5	1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 2H), 8.72 (d, J = 8.0 Hz, 1H),
		8.10 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 1.2 Hz, 1H), 7.89 (d, J = 7.4 Hz, 1H),
		7.35 (d, J = 1.2 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.19 (s, 1H), 5.46-5.29
		(m, 1H), 5.29-5.18 (m, 1H), 5.18-5.06 (m, 1H), 5.00-4.75 (m, 1H),
		4.74-4.50 (m, 4H), 4.52-4.39 (m, 1H), 4.11 (s, 3H), 4.02 (s, 3H), 3.53.
		3.35 (m, 2H), 3.17-2.91 (m, 2H), 2.44-2.28 (m, 1H), 2.02-1.78 (m,
		3H), 1.78-1.59 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H), 1.42-1.33 (m, 0H),
		1.19 (s, 3H), 0.91 (s, 3H), 0.88-0.67 (m, 1H).
595	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.79 (s, 2H), 8.71-8.61 (m, 1H), 8.56
		(d, J = 8.8 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 6.4 Hz, 1H), 7.78
		(d, J = 10.7 Hz, 1H), 7.25 (d, J = 8.0 Hz, 1H), 7.23 (s, 1H), 5.66 (t, J =
		13.6 Hz, 1H), 5.16 (dd, J = 27.7, 14.5 Hz, 1H), 5.10-4.98 (m, 1H), 4.83
		(dtd, J = 49.1, 9.4, 4.5 Hz, 1H), 4.51-4.27 (m, 1H), 3.94 (s, 3H), 3.80-
		3.50 (m, 1H), 3.52-3.32 (m, 1H), 3.16-2.90 (m, 3H), 2.41-2.26 (m,
		1H), 2.25-1.99 (m, 1H), 2.00-1.83 (m, 2H), 1.69-1.50 (m, 2H), 1.45
		(d, J = 7.0 Hz, 3H), 1.38-1.19 (m, 1H), 0.95-0.77 (m, 1H), 0.74-0.56
		(m, 1H), 0.56-0.38 (m, 2H).
596	613.6	1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 2H), 8.45 (s, 1H), 8.26 (s, 1H),
		8.09 (d, J = 8.2 Hz, 1H), 7.86 (d, J = 7.4 Hz, 1H), 7.26 (d, J = 1.8 Hz, 1H),
		7.22 (d, J = 8.2 Hz, 1H), 5.13 (t, J = 7.2 Hz, 1H), 4.89 (s, 1H), 4.71-4.48
		(m, 2H), 4.11 (s, 3H), 3.69-3.42 (m, 3H), 3.19 (s, 3H), 2.02-1.86 (m,
		2H), 1.84-1.54 (m, 1H), 1.46 (d, J = 7.1, 2.3 Hz, 3H), 1.42-1.28 (m,
		5H), 1.22 (s, 3H), 1.19-1.02 (m, 3H), 0.95 (s, 3H), 0.93-0.83 (m, 1H).
597	662.3	1H NMR (400 MHz, DMSO-d6) δ 8.93 (d, J = 7.2 Hz, 1H), 8.77 (s, 2H),
		8.68 (d, J = 8.0 Hz, 1H), 8.17 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H),
		7.78 (d, J = 10.7 Hz, 1H), 7.39-7.31 (m, 3H), 7.31-7.19 (m, 3H), 5.44-
		5.32 (m, 1H), 5.32-5.26 (m, 1H), 5.25-5.09 (m, 1H), 4.82 (dtd, J =
		49.0, 9.4, 4.6 Hz, 1H), 4.69-4.46 (m, 4H), 4.48-4.30 (m, 1H), 3.96 (s,
		3H), 3.54-3.43 (m, 1H), 3.44-3.32 (m, 1H), 3.12-2.86 (m, 2H), 2.41-
		2.18 (m, 1H), 2.04-1.83 (m, 1H), 1.74-1.54 (m, 1H), 1.47 (d, J = 7.1
		Hz, 3H), 1.27-0.83 (m, 1H).
598	634.3	1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 7.0 Hz, 1H), 8.55 (dd, J =
		41.6, 2.6 Hz, 2H), 8.12-8.09 (m, 1H), 8.08 (s, 3H), 7.59 (s, 1H), 7.28 (d,
		J = 8.1 Hz, 1H), 7.10 (s, 1H), 7.04 (d, J = 1.2 Hz, 1H), 5.25 (p, J = 7.1 Hz,
		1H), 4.92-4.77 (m, 1H), 4.67-4.54 (m, 1H), 4.54-4.34 (m, 3H), 4.13
		(s, 3H), 4.02 (s, 3H), 3.84-3.63 (m, 1H), 2.72-2.64 (m, 1H), 2.48-2.22
		(m, 3H), 1.95-1.72 (m, 3H), 1.69-1.58 (m, 1H), 1.52 (d, J = 7.1 Hz,
		3H), 1.50-1.37 (m, 2H), 1.34 (dd, J = 12.8, 4.4 Hz, 1H), 1.29-1.12 (m,
		1H), 0.69-0.56 (m, 1H).
599	688.7	1H NMR (400 MHz, DMSO-d6) δ 8.71 (s, 2H), 8.69 (d, J = 8.2 Hz, 1H),
		8.44 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 6.4 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H),
		7.88 (d, J = 10.8 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.08-
		4.97 (m, 1H), 4.97-4.64 (m, 3H), 4.59-4.48 (m, 1H), 4.49-4.26 (m,
		3H), 3.60-3.14 (m, 2H), 3.15-2.86 (m, 3H), 2.42-2.26 (m, 1H), 1.90
		(dd, J = 28.1, 9.1 Hz, 2H), 1.74-1.46 (m, 5H), 1.43 (d, J = 7.1 Hz, 3H),
		1.41-1.13 (m, 2H), 0.91-0.81 (m, 1H), 0.78-0.57 (m, 2H), 0.55-0.41
		(m, 1H).
600	660.7	1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 3H), 8.66 (d, J = 8.0 Hz, 1H),
		8.43 (d, J = 8.6 Hz, 1H), 8.02 (d, J = 6.5 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H),
		7.79 (d, J = 10.9 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.00 (p,
		1H), 4.95-4.71 (m, 1H), 4.71-4.52 (m, 3H), 4.50-4.29 (m, 1H), 3.83-
		3.66 (m, 2H), 3.67-3.19 (m, 1H), 3.15-2.89 (m, 4H), 2.41-2.28 (m,
		1H), 2.02-1.79 (m, 2H), 1.74-1.60 (m, 2H), 1.61-1.47 (m, 2H), 1.43
		(d, J = 7.1 Hz, 3H), 1.41-1.31 (m, 1H), 1.24 (s, 2H), 0.91-0.80 (m, 1H),
		0.79-0.57 (m, 2H), 0.52-0.44 (m, 1H), 0.33-0.23 (m, 2H), 0.22-0.08
		(m, 2H).
601	620.6	1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 2H), 8.64 (d, J = 8.1 Hz, 1H),
		8.43 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 10.9 Hz, 1H), 7.13 (t, J = 4.0 Hz,
		2H), 5.00 (p, J = 7.5 Hz, 1H), 4.94-4.72 (m, 1H), 4.73-4.30 (m, 5H),
		3.83-3.64 (m, 2H), 3.12-2.86 (m, 4H), 2.01-1.80 (m, 3H), 1.74-1.59
		(m, 3H), 1.60-1.46 (m, 2H), 1.44 (d, J = 7.1 Hz, 3H), 1.40-1.29 (m,
		1H), 1.32-1.08 (m, 2H), 0.91-0.82 (m, 1H), 0.78-0.56 (m, 3H), 0.53-
		0.43 (m, 1H).
602	650.6	1H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 7.9 Hz, 1H), 8.19 (s, 1H),
		8.02 (t, J = 7.3 Hz, 2H), 7.83 (d, J = 7.1 Hz, 1H), 7.65 (d, J = 10.5 Hz,
		1H), 7.35 (s, 1H), 7.18 (d, J = 8.1 Hz, 1H), 5.22-4.98 (m, 1H), 4.98-
		4.66 (m, 4H), 4.47-4.26 (m, 1H), 4.08-3.85 (m, 1H), 3.71-3.55 (m,
		1H), 3.53-3.40 (m, 3H), 3.21-3.09 (m, 1H), 3.09-2.91 (m, 1H), 2.03-
		1.85 (m, 2H), 1.85-1.61 (m, 2H), 1.45 (d, J = 7.0 Hz, 3H), 1.30-1.24
		(m, 6H), 1.24-1.19 (m, 2H), 1.22 (s, 3H), 0.93 (s, 3H).
603	646.7	1H NMR (400 MHz, DMSO-d6) δ 8.46 (s, 1H), 8.18 (d, J = 7.1 Hz, 1H),
		8.06 (d, J = 8.1 Hz, 1H), 7.60 (d, J = 10.5 Hz, 1H), 7.30 (s, 1H), 7.21 (d,
		J = 8.2 Hz, 1H), 6.53 (s, 1H), 5.17 (p, J = 7.1 Hz, 1H), 4.88-4.70 (m, 1H),
		4.81 (d, J = 5.5 Hz, 1H), 4.74 (d, J = 6.3 Hz, 1H), 4.68 (d, J = 22.1 Hz,
		2H), 4.41 (d, J = 6.3 Hz, 1H), 4.19 (d, J = 5.6 Hz, 1H), 4.17-4.05 (m,
		1H), 3.91-3.70 (m, 1H), 3.61-3.28 (m, 7H), 3.24-2.98 (m, 1H), 2.83-
		2.56 (m, 1H), 2.28-2.10 (m, 2H), 2.10-1.89 (m, 1H), 1.84-1.53 (m,
		3H), 1.49 (d, J = 7.1 Hz, 3H), 1.45-1.27 (m, 2H), 1.27-1.17 (m, 1H),
		1.19-1.00 (m, 1H), 0.95-0.79 (m, 1H), 0.66-0.43 (m, 1H).
604	634.4	1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 7.0 Hz, 1H), 8.60 (d, J =
		2.6 Hz, 1H), 8.50 (d, J = 2.6 Hz, 1H), 8.10 (d, J = 8.0 Hz, 2H), 7.95 (s,
		2H), 7.48 (d, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.98 (d, J = 15.9
		Hz, 1H), 5.25 (p, J = 7.0 Hz, 1H), 4.83 (d, J = 13.5 Hz, 1H), 4.65-4.54
		(m, 1H), 4.27-4.19 (m, 1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.86-3.70 (m,
		1H), 3.70-3.48 (m, 2H), 3.26-3.08 (m, 1H), 2.74-2.62 (m, 2H), 2.48-
		2.26 (m, 2H), 2.11-1.79 (m, 3H), 1.76-1.58 (m, 1H), 1.52 (d, J = 7.1
		Hz, 3H), 1.49-1.31 (m, 3H), 1.30-1.09 (m, 1H), 0.75-0.45 (m, 1H).
624	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.74 (br s, 3H), 8.67 (d, J = 7.1 Hz,
		1H), 8.64 (d, J = 8.2 Hz, 1H), 8.06 (d, J = 1.8 Hz, 1H), 8.04 (s, 1H), 7.76
		(d, J = 10.8 Hz, 1H), 7.25 (d, J = 8.2 Hz, 1H), 7.18 (s, 1H), 4.93-4.70 (m,
		2H), 4.64-4.55 (m, 1H), 4.49-4.35 (m, 2H), 3.99 (s, 3H), 3.51-3.42 (m,
		1H), 3.41-3.33 (m, 1H), 3.11-2.91 (m, 2H), 2.40-2.29 (m, 2H), 2.26-
		1.85 (m, 2H), 1.76 (d, J = 7.1 Hz, 3H), 1.55 (dt, J = 8.9, 4.6 Hz, 1H), 1.45-
		1.27 (m, 1H), 0.96-0.78 (m, 2H), 0.69-0.60 (m, 1H).
625	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.73 (br s, 3H), 8.65 (d, J = 8.1 Hz,
		1H), 8.61 (d, J = 8.6 Hz, 1H), 8.06 (d, J = 6.4 Hz, 1H), 8.02 (d, J = 8.0 Hz,
		1H), 7.76 (d, J = 10.8 Hz, 1H), 7.18 (d, J = 8.1 Hz, 1H), 7.17 (s, 1H), 5.03
		(p, J = 7.2 Hz, 1H), 4.93-4.66 (m, 2H), 4.60-4.51 (m, 1H), 4.46-4.35
		(m, 1H), 3.99 (s, 3H), 3.51-3.42 (m, 1H), 3.41-3.33 (m, 1H), 3.02 (d, J =
		27.1 Hz, 2H), 2.45-2.27 (m, 2H), 2.14-2.01 (m, 2H), 1.98-1.86 (m,
		1H), 1.82-1.73 (m, 1H), 1.43 (d, J = 7.1 Hz, 3H), 0.95-0.88 (m, 1H),
		0.70-0.62 (m, 2H).
626	642.3	1H NMR (400 MHz, DMSO-d6) δ 8.82-8.67 (m, 4H), 8.21-7.90 (m,
		3H), 7.826-7.79 (m, 2H), 7.23 (d, J = 8.2 Hz, 1H), 7.00 (s, 1H), 5.12 (p,
		J = 7.1 Hz, 1H), 4.92-4.70 (m, 2H), 4.46-4.32 (m, 2H), 3.52-3.43 (m,
		1H), 3.42-3.33 (m, 1H), 3.12-2.89 (m, 2H), 1.99-1.86 (m, 2H), 1.76-
		1.62 (m, 2H), 1.52-1.29 (m, 7H), 1.21 (s, 3H), 1.17-1.04 (s, 2H), 0.94
		(s, 3H).
627	622.3	1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 7.0 Hz, 1H), 8.60 (d, J =
		2.6 Hz, 1H), 8.49 (d, J = 2.6 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.97 (s,
		4H), 7.40 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.92 (d, J = 1.2
		Hz, 1H), 5.25 (p, J = 7.0 Hz, 1H), 4.90-4.75 (m, 1H), 4.63-4.51 (m,
		1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.32-3.04 (m, 2H), 2.74-2.62 (m, 1H),
		2.48-2.30 (m, 1H), 2.06-2.97 (m, 1H), 1.81-1.71 (m, 1H), 1.66-1.31
		(m, 6H), 1.298-1.14 (m, 1H), 0.69-0.56 (m, 1H).
628	632.4	1H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 8.4 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.97 (s, 3H), 7.44 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.05 (s,
		1H), 6.93 (d, J = 1.2 Hz, 1H), 5.34-5.24 (m, 1H), 4.96-4.86 (m, 1H),
		4.59-4.49 (m, 1H), 4.11 (s, 3H), 4.01-3.92 (m, 4H), 3.73-3.68 (m, 1H),
		3.54 (s, 2H), 3.43-3.34 (m, 4H), 3.23 (s, 3H), 2.03-1.89 (m, 2H), 1.81-
		1.71 (m, 1H), 1.63-1.54 (m, 2H), 1.52-1.35 (m, 4H), 1.35-1.22 (m,
		1H), 1.17-1.00 (m, 2H), 0.91-0.78 (m, 1H), 0.64-0.52 (m, 1H).
629	668.3	1H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 8.4 Hz, 1H), 8.18 (br s,
		3H), 8.06 (d, J = 8.1 Hz, 1H), 7.45 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.05
		(s, 1H), 6.94 (d, J = 1.2 Hz, 1H), 6.85 (t, J = 74.9 Hz, 1H), 5.29 (p, J = 7.1
		Hz, 1H), 4.97-4.87 (m, 1H), 4.69-4.64 (m, 1H), 4.59-4.48 (m, 1H),
		4.11 (s, 3H), 3.99 (s, 3H), 3.95 (dd, J = 9.0, 5.8 Hz, 1H), 3.61 (br s, 2H),
		3.45 (br s, 1H), 3.23 (s, 3H), 2.03-1.88 (m, 4H), 1.62-1.52 (m, 2H), 1.47
		(d, J = 7.0 Hz, 3H), 1.51-1.38 (m, 1H), 1.35-1.18 (m, 1H), 1.18-0.98
		(m, 1H), 0.91-0.78 (m, 1H), 0.65-0.53 (m, 1H).
630	681.5	1H NMR (400 MHz, DMSO-d6) δ 9.27 (br s, 1H), 8.69 (br s, 1H), 8.10
		(d, J = 8.0 Hz, 1H), 7.98 (br s, 3H), 7.47 (br s, 1H), 7.42 (s, 1H), 7.27 (d,
		J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.94 (d, J = 1.1 Hz, 1H), 5.29 (p, J = 7.4 Hz,
		1H), 4.92-4.81 (m, 1H), 4.65-4.56 (m, 1H), 4.11 (s, 3H), 4.07 (s, 3H),
		3.99 (s, 3H), 3.36 (s, 3H), 2.29-2.20 m, 1H), 2.00-1.89 (m, 1H), 1.80-
606	666.3	1H NMR (400 MHz, DMSO-d6) δ 9.01 (d, J = 7.8 Hz, 1H), 8.63 (d, J =
		2.6 Hz, 1H), 8.51 (d, J = 2.5 Hz, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.97 (s,
		3H), 7.44 (s, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.05 (s, 1H), 6.93 (d, J = 1.2
		Hz, 1H), 5.39 (p, J = 7.1 Hz, 1H), 4.68-4.57 (m, 1H), 4.57-4.42 (m,
		1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.96-3.44 (m, 8H), 3.37 (s, 3H), 3.21-
		3.00 (m, 1H), 2.65-2.55 (m, 1H), 2.07-1.88 (m, 1H), 1.83-1.70 (m,
		1H), 1.63 (d, J = 7.0 Hz, 3H), 1.60-1.38 (m, 2H), 1.34-1.12 (m, 2H),
		1.11-0.91 (m, 2H).
607	646.5	1H NMR (400 MHz, DMSO-d6) δ 8.75 (s, 3H), 8.69-8.58 (m, 1H), 8.45
		(t, J = 8.3 Hz, 1H), 8.07-7.91 (m, 2H), 7.62-7.44 (m, 1H), 7.30 (d, J =
		11.8 Hz, 1H), 7.22-7.05 (m, 1H), 5.09-4.96 (m, 1H), 4.94-4.82 (m,
		1H), 4.83-4.63 (m, 2H), 4.50-4.26 (m, 1H), 4.06-3.91 (m, 1H), 3.70-
		3.62 (m, 1H), 3.30 (s, 1H), 3.18 (s, 1H), 3.11-2.94 (m, 2H), 2.93 (s, 1H),
		2.42-2.25 (m, 1H), 2.04-1.79 (m, 4H), 1.75-1.48 (m, 4H), 1.44 (dd, J =
		7.1, 2.4 Hz, 3H), 1.41-1.16 (m, 3H), 1.15-0.99 (m, 1H), 0.94-0.80
		(m, 2H), 0.79-0.55 (m, 3H), 0.49 (s, 1H).
608	666.4	1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 8.0 Hz, 1H), 7.99 (s, 3H),
		7.90 (d, J = 7.5 Hz, 1H), 7.42 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.14 (s,
		1H), 6.94 (d, J = 1.2 Hz, 1H), 5.35 (p, J = 14.9 Hz, 1H), 5.13 (p, J = 7.4
		Hz, 2H), 5.03-4.15 (m, 3H), 4.10 (s, 3H), 3.99 (s, 3H), 3.76-3.68 (m,
		1H), 3.60-3.47 (m, 3H), 3.48-3.39 (m, 1H), 3.37 (s, 3H), 2.00-1.60
		(m, 5H), 1.44 (d, J = 7.1 Hz, 3H), 1.43-1.35 (m, 2H), 1.30-1.21 (m,
		1H), 1.19 (s, 3H), 0.91 (s, 3H).
609	702.3	1H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 3H), 8.09 (d, J = 8.0 Hz, 1H),
		7.90 (d, J = 7.5 Hz, 1H), 7.43 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.15 (s,
		1H), 6.95 (d, J = 1.2 Hz, 1H), 6.86 (t, J = 74.9 Hz, 1H), 5.35 (p, J = 15.2,
		14.7 Hz, 1H), 5.14 (p, J = 7.7, 7.2 Hz, 2H), 4.10 (s, 3H), 4.00 (s, 3H),
		3.93-3.74 (m, 6H), 3.68-3.52 (m, 2H), 3.52-3.28 (m, 1H), 2.06-1.59 (m,
		5H), 1.44 (d, J = 7.1 Hz, 3H), 1.41-1.35 (m, 1H), 1.29-1.21 (m, 1H),
		1.19 (s, 3H), 0.91 (s, 3H).
610	666.7	1H NMR (400 MHz, DMSO-d6) δ 9.23 (d, J = 6.9 Hz, 1H), 8.60 (s, 1H),
		8.09 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 9.0 Hz, 3H), 7.44 (s, 1H), 7.27 (d, J =
		8.1 Hz, 1H), 7.09 (s, 1H), 6.94 (d, J = 1.2 Hz, 1H), 5.23 (p, J = 7.0 Hz,
		1H), 4.92-4.78 (m, 1H), 4.68-4.50 (m, 0H), 4.12 (s, 3H), 4.00 (s, 3H),
		3.97-3.77 (m, 1H), 3.75-3.63 (m, 1H), 3.65-3.42 (m, 2H), 3.37 (s,
		3H), 3.50-3.18 (m, 1H), 2.63 (s, 3H), 2.42-2.17 (m, 2H), 2.06-1.86
		(m, 1H), 1.84-1.70 (m, 1H), 1.54 (s, 2H), 1.50 (d, J = 7.1 Hz, 3H), 1.48-
		1.35 (m, 2H), 1.30-1.12 (m, 3H), 0.62-0.39 (m, 1H).
611	644.6	1H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J = 7.2 Hz, 1H), 8.06 (d, J =
		8.1 Hz, 1H), 7.98 (s, 3H), 7.45 (s, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.03 (s,
		1H), 6.93 (s, 1H), 5.18 (p, J = 7.0 Hz, 1H), 4.82 (d, J = 5.6 Hz, 1H), 4.74
		(d, J = 6.3 Hz, 1H), 4.73-4.62 (m, 1H), 4.41 (d, J = 6.4 Hz, 1H), 4.49-
		4.27 (m, 1H), 4.33-4.26 (m, 2H), 4.20 (d, J = 5.7 Hz, 1H), 4.11 (s, 3H),
		3.99 (s, 3H), 3.98-3.77 (m, 1H), 3.76-3.67 (m, 1H), 3.65-3.46 (m,
		2H), 3.37 (s, 3H), 2.28-2.15 (m, 1H), 2.06-1.88 (m, 2H), 1.83-1.69
		(m, 1H), 1.69-1.53 (m, 2H), 1.49 (d, J = 7.1 Hz, 3H), 1.45-1.28 (m,
		4H), 1.30-1.04 (m, 2H).
612	714.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 6.9 Hz, 1H), 8.60 (d, J =
		2.6 Hz, 1H), 8.50 (d, J = 2.6 Hz, 1H), 8.18 (s, 3H), 8.09 (d, J = 8.1 Hz,
		1H), 7.43 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.23 (s, 1H), 6.96 (d, J = 1.2
		Hz, 1H), 6.86 (t, 1H), 5.23 (t, J = 7.0 Hz, 1H), 4.96-4.73 (m, 3H), 4.70
		4.60 (m, 1H), 4.00 (s, 3H), 3.98-3.84 (m, 1H), 3.70-3.53 (m, 2H), 3.53-
		3.35 (m, 1H), 2.72-2.61 (m, 1H), 2.46-2.31 (m, 1H), 2.06-1.84 (m,
		2H), 1.52 (d, J = 7.0 Hz, 3H), 1.50-1.33 (m, 5H), 1.29-1.12 (m, 2H),
		1.09-0.97 (m, 1H), 0.97-0.82 (m, 1H), 0.73-0.51 (m, 1H), 0.44-0.30
		(m, 1H).
613	680.6	1H NMR (400 MHz, DMSO-d6) δ 8.21 (s, 3H), 8.17 (d, J = 7.2 Hz, 1H),
		8.06 (d, J = 8.1 Hz, 1H), 7.46 (s, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.03 (s,
		1H), 6.95 (d, J = 1.2 Hz, 1H), 6.86 (t, J = 74.9 Hz, 1H), 5.18 (p, J = 7.1
		Hz, 1H), 4.82 (d, J = 5.6 Hz, 1H), 4.74 (d, J = 6.3 Hz, 1H), 4.73-4.64 (m,
		1H), 4.41 (d, J = 6.3 Hz, 1H), 4.49-4.33 (m, 1H), 4.20 (d, J = 5.6 Hz,
		1H), 4.12 (s, 3H), 4.09-4.02 (m, 1H), 3.99 (s, 3H), 3.70-3.34 (m, 4H),
		2.28-2.15 (m, 1H), 2.08-1.86 (m, 4H), 1.69-1.54 (m, 2H), 1.49 (d, J =
		7.1 Hz, 3H), 1.45-1.28 (m, 4H), 1.28-1.04 (m, 2H).
614	678.4	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 8.1 Hz, 1H), 8.02 (s, 3H),
		7.89 (d, J = 7.8 Hz, 1H), 7.42 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.14 (s,
		1H), 6.94 (d, J = 1.2 Hz, 1H), 6.71-5.53 (m, 3H), 5.37 (q, J = 15.2 Hz,
		1H), 5.24 (p, J = 7.4 Hz, 1H), 5.19-5.04 (m, 1H), 4.09 (s, 3H), 3.99 (s,
		3H), 3.76-3.63 (m, 1H), 3.64-3.46 (m, 2H), 3.44-3.37 (m, 1H), 3.37
		(s, 3H), 2.37 (p, J = 8.3, 7.7 Hz, 2H), 2.02-1.81 (m, 5H), 1.81-1.63 (m,
		3H), 1.65-1.54 (m, 2H), 1.47 (d, J = 7.0 Hz, 3H), 1.31-1.08 (m, 2H),
		1.06-0.76 (m, 1H).
615	620.4	1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 3H), 8.70 (d, J = 7.9 Hz, 1H),
		8.08 (d, J = 8.1 Hz, 1H), 8.00 (s, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.35 (s,
		1H), 7.24 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 5.28 (p, J = 7.1 Hz, 1H), 4.92
		(td, J = 9.4, 4.5 Hz, 1H), 4.83-4.70 (m, 2H), 4.59-4.50 (m, 1H), 4.50-
		4.38 (m, 1H), 4.14 (s, 3H), 4.02 (s, 3H), 3.78 (t, J = 4.1 Hz, 1H), 3.48-
		3.34 (m, 1H), 3.37 (s, 3H), 3.14-2.90 (m, 2H), 2.41-2.31 (m, 1H), 2.00-
		1.64 (m, 4H), 1.61-1.38 (m, 6H), 1.26-1.06 (m, 3H), 0.90-0.79 (m,
		1H).
616	604.3	1H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 3H), 8.70 (d, J = 7.9 Hz, 1H),
		8.44 (d, J = 8.8 Hz, 1H), 8.05-7.98 (m, 2H), 7.36 (s, 1H), 7.17 (d, J = 8.0
		Hz, 1H), 7.07 (s, 1H), 5.07 (p, J = 7.3 Hz, 1H), 4.96-4.76 (m, 2H), 4.59-
		4.51 (m, 1H), 4.49-4.39 (m, 1H), 4.16 (s, 3H), 4.02 (s, 3H), 3.90-3.85
		(m, 1H), 3.66-3.56 (m, 1H), 3.52-3.34 (m, 3H), 3.14-2.91 (m, 2H),
		2.82 (t, J = 11.8 Hz, 1H), 2.40-2.30 (m, 1H), 1.99-1.81 (m, 4H), 1.45
		(d, J = 7.1 Hz, 3H), 1.17-1.07 (m, 1H), 0.92 (dt, J = 9.0, 4.4 Hz, 1H),
		0.62-0.56 (m, 1H).
617	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 3H), 8.69 (d, J = 7.9 Hz, 1H),
		8.17 (d, J = 8.2 Hz, 1H), 8.00 (d, J = 1.3 Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H),
		7.35 (s, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.15 (s, 1H), 5.06-4.86 (m, 2H),
		4.83-4.66 (m, 1H), 4.50-4.38 (m, 2H), 4.17 (s, 3H), 4.02 (s, 3H), 3.49-
		3.34 (m, 2H), 3.13-2.92 (m, 2H), 2.41-2.29 (m, 1H), 2.00-1.58 (m,
		4H), 1.51 (d, J = 6.9 Hz, 3H), 1.43-1.21 (m, 1H), 1.19-1.04 (m, 1H),
		0.98-0.81 (m, 2H), 0.74-0.54 (m, 2H), 0.52 (s, 2H), 0.40-0.28 (m, 1H).
618	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.83-8.68 (m, 4H), 8.14 (d, J = 9.7
		Hz, 1H), 8.04-7.99 (m, 2H), 7.37 (d, J = 1.3 Hz, 1H), 7.15 (d, J = 8.0 Hz,
		1H), 7.06 (s, 1H), 5.25-5.15 (m, 1H), 4.96-4.87 (m, 0.5HH), 4.83-
		4.74 (m, 0.5H), 4.66-4.39 (m, 3H), 4.15 (s, 3H), 4.02 (s, 3H), 3.51-3.34
		(m, 2H), 3.13-2.91 (m, 2H), 2.41-2.30 (m, 1H), 2.00-1.56 (m, 5H),
		1.43 (d, J = 7.0 Hz, 3H), 1.41-1.18 (m, 3H), 0.78-0.68 (m, 1H), 0.63 (s,
		3H), 0.53 (dd, J = 8.2, 3.9 Hz, 1H).
619	608.3	1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 6.8 Hz, 3H), 8.70 (d, J =
		7.9 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 8.03 (d, J = 1.3 Hz, 1H), 7.37 (d, J =
		1.3 Hz, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.18 (s, 1H), 5.86 (ddd, J = 19.8,
		10.5, 5.4 Hz, 1H), 5.49 (t, J = 12.6 Hz, 1H), 5.18-5.03 (m, 2H), 4.95-
		4.76 (m, 2H), 4.51-4.38 (m, 1H), 4.22 (s, 3H), 4.18-4.07 (m, 1H), 4.03
		(s, 3H), 3.90-3.77 (m, 1H), 3.49-3.34 (m, 2H), 3.13-2.91 (m, 2H),
		2.68-2.59 (m, 1H), 2.44-2.30 (m, 2H), 1.99-1.85 (m, 1H), 1.44 (d, J =
		6.7 Hz, 3H).
620	590.3	1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 6.8 Hz, 1H), 8.12 (d, J =
		8.1 Hz, 1H), 7.94 (s, 3H), 7.44 (s, 1H), 7.27 (d, J = 8.2 Hz, 1H), 7.15 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 5.75 (ddd, J = 19.6, 10.5, 5.4 Hz, 1H),
		5.54-5.43 (m, 1H), 5.18-5.05 (m, 2H), 4.892-4.76 (m, 1H), 4.20 (s, 3H),
		4.18-4.04 (m, 1H), 4.00 (s, 3H), 3.91-3.75 (m, 3H), 3.33-3.04 (m, 4H),
		2.69-2.58 (m, 1H), 2.39 (ddd, J = 16.2, 7.7, 3.2 Hz, 1H), 2.07-1.98 (m,
		1H), 1.80-1.71 (m, 1H), 1.64-1.51 (m, 2H), 1.44 (d, J = 6.8 Hz, 3H).
621	620.3	1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 3H), 8.70 (d, J = 7.9 Hz, 1H),
		8.64 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 1.3 Hz, 1H),
		7.35 (d, J = 1.3 Hz, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.10 (s, 1H), 5.34-5.24
		(m, 1H), 4.98-4.76 (m, 2H), 4.62-4.51 (m, 1H), 4.50-4.38 (m, 1H),
		4.14 (s, 3H), 4.02 (s, 3H), 3.95 (dd, J = 9.2, 5.6 Hz, 1H), 3.42 (dd, J =
		25.2, 12.7 Hz, 2H), 3.23 (s, 3H), 3.14-2.90 (m, 3H), 2.41-2.30 (m, 1H),
		2.05-1.85 (m, 2H), 1.64-1.50 (m, 2H), 1.47 (d, J = 7.0 Hz, 3H), 1.36-
		1.21 (m, 1H), 1.23-0.99 (m, 2H), 0.93-0.80 (m, 1H), 0.68-0.57 (m,
		1H).
622	618.3	1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 2H), 8.63 (d, J = 8.1 Hz, 1H),
		8.35 (d, J = 7.2 Hz, 1H), 8.06 (dd, J = 8.2, 1.6 Hz, 1H), 8.02 (dd, J = 6.4,
		1.6 Hz, 1H), 7.62 (dd, J = 10.7, 1.6 Hz, 1H), 7.34 (d, J = 1.6 Hz, 1H), 7.19
		(dd, J = 8.2, 1.5 Hz, 1H), 5.10-4.72 (m, 4H), 4.46-4.34 (m, 1H), 3.95-
		3.77 (m, 3H), 3.60 (dd, J = 12.0, 5.3 Hz, 1H), 3.57-3.33 (m, 3H), 3.12-
		2.89 (m, 2H), 2.68-2.57 (m, 1H), 2.39-2.28 (m, 1H), 2.28-2.18 (m,
		1H), 1.998-1.85 (m, 1H), 1.48 (d, J = 7.0 Hz, 3H), 1.30-1.20 (m, 1H),
		1.18-1.10 (m, 1H), 0.95-0.81 (m, 3H), 0.665-0.55 (m, 1H), 0.28-0.20
		(m, 1H), 0.17-0.08 (m, 1H).
623	644.3	1H NMR (400 MHz, DMSO-d6) δ 8.86 (d, J = 9.1 Hz, 1H), 8.72 (s, 3H),
		8.68 (d, J = 8.2 Hz, 1H), 8.15 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.4 Hz, 1H),
		7.76 (d, J = 10.7 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.25 (s, 1H), 5.59-
		5.29 (m, 2H), 4.92-4.72 (m, 1H), 4.46-4.34 (m, 1H), 4.02 (t, J = 8.0 Hz,
		1H), 3.93 (s, 3H), 3.55-3.33 (m, 2H), 3.25 (s, 3H), 3.10-2.90 (m, 2H),
		2.39-2.22 (m, 1H), 1.98-1.86 (m, 1H), 1.63-1.43 (m, 3H), 1.45 (d, J =
		7.0 Hz, 3H), 1.30-1.06 (m, 2H), 0.93-0.73 (m, 1H), 0.68-0.52 (m, 1H).
		1.70 (m, 1H), 1.60-1.33 (m, 3H), 1.46 (d, J = 7.0 Hz, 3H), 1.29-1.17 (m,
		1H), 0.49-0.37 (m, 1H).
631	634.4	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.5 Hz, 1H), 8.19-7.91
		(br-s, 3H), 7.99 (d, J = 8.0 Hz, 1H), 7.43 (d, J = 1.1 Hz, 1H), 7.14 (d, J =
		8.1 Hz, 1H), 7.02 (s, 1H), 6.94 (d, J = 1.1 Hz, 1H), 6.34-5.94 (m, 1H),
		5.09-4.95 (m, 1H), 4.74-4.63 (m, 1H), 4.62-4.51 (m, 1H), 4.13 (s,
		3H), 4.00 (s, 3H), 3.39-3.26 (m, 1H), 2.47-2.34 (m, 1H), 2.23-2.12
		(m, 1H), 1.91-1.80 (m, 1H), 1.71-1.46 (m, 6H), 1.43 (d, J = 7.1 Hz,
		3H), 1.41-1.35 (m, 1H), 1.31-1.15 (m, 1H), 0.95-0.82 (m, 1H), 0.79-
		0.57 (m, 2H), 0.54-0.41 (m, 1H).
632	660.5	1H NMR (400 MHz, DMSO-d6) δ 8.73-8.56 (m, 2H), 8.54 (d, J = 8.8
		Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 1.2 Hz, 1H), 7.24 (d, J = 8.0
		Hz, 1H), 7.15 (s, 2H), 5.59-5.45 (m, 1H), 5.23-4.98 (m, 2H), 4.39-
		4.30 (m, 1H), 4.23-4.15 (m, 1H), 4.10 (s, 3H), 4.01 (s, 3H), 4.00-3.93
		(m, 1H), 3.84-3.79 (m, 1H), 3.48-3.38 (m, 2H), 3.13-3.02 (m, 2H),
		2.23-2.03 (m, 2H), 2.03-1.90 (m, 3H), 1.80-1.69 (m, 2H), 1.69-1.57
		(m, 2H), 1.56-1.48 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H), 1.38-1.21 (m,
		1H), 0.91-0.80 (m, 1H), 0.71-0.57 (m, 1H), 0.56-0.43 (m, 2H).
633	670.5	1H NMR (400 MHz, DMSO-d6) δ 9.12-9.00 (m, 1H), 8.91-8.76 (m,
		1H), 8.59 (d, J = 7.6 Hz, 1H), 8.54 (d, J = 8.8 Hz, 1H), 8.06 (d, J = 8.0 Hz,
		1H), 7.98 (d, J = 1.2 Hz, 1H), 7.35 (d, J = 1.3 Hz, 1H), 7.24 (d, J = 8.1 Hz,
		1H), 7.17 (s, 1H), 6.15 (td, J = 55.6, 3.5 Hz, 1H), 5.61-5.48 (m, 1H),
		5.23-5.00 (m, 2H), 4.38-4.21 (m, 1H), 4.11 (s, 3H), 4.03 (s, 3H), 3.54-
		3.35 (m, 2H), 2.92-2.71 (m, 2H), 2.21-2.01 (m, 3H), 2.00-1.89 (m,
		1H), 1.68-1.49 (m, 3H), 1.44 (d, J = 7.1 Hz, 3H), 1.32 (s, 2H), 0.92-
		0.78 (m, 1H), 0.70-0.56 (m, 1H), 0.55-0.42 (m, 2H).
634	683.3	1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 8.0 Hz, 1H), 8.00 (s, 3H),
		7.55 (d, J = 8.5 Hz, 1H), 7.45 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.08 (s,
		1H), 6.94 (d, J = 1.1 Hz, 1H), 5.27-5.07 (m, 1H), 4.77-4.64 (m, 1H),
		4.63-4.52 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.55 (s, 1H), 3.44-3.39
		(m, 1H), 3.37 (s, 3H), 1.95 (s, 1H), 1.84-1.70 (m, 3H), 1.64 (s, 2H), 1.59-
		1.52 (m, 1H), 1.49 (d, J = 6.9 Hz, 3H), 1.46-1.26 (m, 4H), 1.23-1.08
		(m, 2H).
635	681.0	1H NMR (400 MHz, DMSO-d6) δ 8.08 (d, J = 8.1 Hz, 1H), 7.98 (s, 3H),
		7.47 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.05 (s,
		1H), 6.94 (s, 1H), 5.84-5.73 (m, 1H), 5.26-5.12 (m, 2H), 4.60-4.41
		(m, 2H), 4.13 (s, 3H), 3.99 (s, 3H), 3.94-379 (m, 1H), 3.84 (d, J = 22.0
		Hz, 1H), 3.75-3.68 (m, 1H), 3.37 (s, 3H), 2.31-2.18 (m, 2H), 2.05-
		1.89 (m, 3H), 1.88-1.71 (m, 3H), 1.58 (d, J = 7.0 Hz, 3H), 1.47 (dd, J =
		7.6, 5.2 Hz, 1H).
636	683.2	1H NMR (400 MHz, DMSO-d6) δ 8.06 (d, J = 8.1 Hz, 1H), 7.98 (s, 3H),
		7.53 (d, J = 7.4 Hz, 1H), 7.46 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04 (s,
		1H), 6.93 (d, J = 1.2 Hz, 1H), 5.08 (p, J = 7.2 Hz, 1H), 4.63-4.47 (m,
		2H), 4.14 (s, 3H), 3.99 (s, 3H), 3.92-3.80 (m, 1H), 3.75-3.67 (m, 1H),
		3.57-3.52 (m, 2H), 3.37 (s, 3H), 2.24-2.19 (m, 2H), 1.96-1.91 (m,
		2H), 1.79-1.66 (m, 2H), 1.58-1.51 (m, 4H), 1.47 (d, J = 7.2 Hz, 3H),
		1.46-1.38 (m, 1H), 1.29-1.23 (m, 1H).
637	653.5	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.8 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.97 (d, J = 10.1 Hz, 3H), 7.44 (s, 1H), 7.24 (d, J = 8.1 Hz,
		1H), 7.14 (s, 1H), 6.95 (d, J = 1.1 Hz, 1H), 5.51 (t, J = 13.6 Hz, 1H), 5.14
		(dd, J = 27.8, 14.6 Hz, 1H), 5.08-4.98 (m, 1H), 4.10 (s, 3H), 4.00 (s,
		3H), 3.74-3.67 (m, 1H), 3.60-3.48 (m, 2H), 3.47-3.35 (m, 1H), 2.23-
		2.00 (m, 2H), 2.00-1.89 (m, 2H), 1.82-1.69 (m, 1H), 1.69-1.57 (m,
		1H), 1.57-1.50 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H), 1.39-1.26 (m, 1H),
		0.91-0.78 (m, 1H), 0.72-0.57 (m, 1H), 0.56-0.39 (m, 2H).
638	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.7 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.97 (s, 3H), 7.69 (s, 1H), 7.37 (s, 1H), 7.31 (dd, J = 11.5, 1.2
		Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.90-5.78 (m, 1H), 5.20 (dd, J = 27.8,
		14.5 Hz, 1H), 5.11-5.01 (m, 1H), 4.08-4.00 (m, 1H), 3.74-3.68 (m,
		1H), 3.59-3.51 (m, 1H), 3.48-3.40 (m, 1H), 3.37 (s, 3H), 2.25-2.02
		(m, 2H), 2.01-1.88 (m, 2H), 1.82-1.71 (m, 1H), 1.69-1.58 (m, 1H),
		1.58-1.52 (m, 1H), 1.45 (d, J = 7.1 Hz, 3H), 1.38-1.29 (m, 1H), 1.29-
		1.20 (m, 2H), 1.09-0.96 (m, 2H), 0.90-0.80 (m, 1H), 0.72-0.58 (m,
		1H), 0.58-0.41 (m, 4H).
639	648.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.92 (s, 3H), 7.63 (d, J = 1.1 Hz, 1H), 7.37 (s, 1H), 7.30-
		7.22 (m, 2H), 5.91-5.78 (m, 1H), 5.20 (dd, J = 27.9, 14.6 Hz, 1H), 5.12-
		5.01 (m, 1H), 4.07-3.99 (m, 1H), 3.43-3.32 (m, 1H), 3.14-2.94 (m,
		1H), 2.29-2.03 (m, 2H), 2.02-1.91 (m, 1H), 1.86-1.49 (m, 5H), 1.45
		(d, J = 7.1 Hz, 3H), 1.40-1.28 (m, 1H), 1.28-1.23 (m, 2H), 1.21 (d, J =
		6.9 Hz, 3H), 1.10-0.97 (m, 2H), 0.89-0.81 (m, 1H), 0.75-0.57 (m,
		1H), 0.58-0.41 (m, 3H).
640	652.2	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.8 Hz, 1H), 8.1-7.96 (m,
		3H), 8.08 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 1.2 Hz, 1H), 7.37 (s, 1H), 7.30-
		7.22 (m, 2H), 5.90-5.75 (m, 1H), 5.20 (dd, J = 27.8, 14.6 Hz, 1H), 5.12-
		5.01 (m, 1H), 4.98-4.70 (m, 1H), 4.08-4.00 (m, 1H), 3.47-3.33 (m,
		1H), 3.03-2.83 (m, 1H), 2.42-2.34 (m, 1H), 2.26-2.02 (m, 1H), 2.02-
		1.85 (m, 2H), 1.85-1.74 (m, 1H), 1.71-1.58 (m, 1H), 1.58-1.51 (m,
		1H), 1.45 (d, J = 7.1 Hz, 3H), 1.40-1.18 (m, 3H), 1.11-0.96 (m, 2H),
		0.90-0.80 (m, 1H), 0.72-0.58 (m, 1H), 0.58-0.42 (m, 3H).
641	667.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 8.05-7.86 (m, 3H), 7.69 (s, 1H), 7.37 (s, 1H), 7.31 (dd, J =
		11.6, 1.2 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.90-5.77 (m, 1H), 5.20 (dd,
		J = 27.8, 14.5 Hz, 1H), 5.11-5.01 (m, 1H), 4.08-3.99 (m, 1H), 3.74-
		3.69 (m, 1H), 3.59-3.52 (m, 1H), 3.50-3.34 (m, 1H), 2.25-2.03 (m,
		2H), 2.03-1.87 (m, 2H), 1.82-1.71 (m, 1H), 1.71-1.58 (m, 1H), 1.58-
		1.51 (m, 1H), 1.45 (d, J = 7.1 Hz, 3H), 1.38-1.29 (m, 1H), 1.30-1.20
		(m, 1H), 1.08-0.97 (m, 2H), 0.91-0.82 (m, 1H), 0.72-0.59 (m, 1H),
		0.57-0.42 (m, 3H).
642	632.3	1H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 8.8 Hz, 1H), 8.17-8.01
		(m, 4H), 7.60 (s, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.15 (s, 1H), 7.05 (d, J =
		1.2 Hz, 1H), 5.55-5.44 (m, 1H), 5.14 (dd, J = 27.9, 14.5 Hz, 1H), 5.09-
		5.01 (m, 1H), 4.60-4.37 (m, 1H), 4.10 (s, 3H), 4.02 (s, 3H), 3.79-3.71
		(m, 1H), 2.38-2.26 (m, 1H), 2.24-1.99 (m, 2H), 1.99-1.90 (m, 1H),
		1.90-1.77 (m, 3H), 1.64 (s, 2H), 1.57-1.50 (m, 1H), 1.45 (d, J = 7.1 Hz,
		3H), 1.39-1.28 (m, 2H), 0.90-0.79 (m, 1H), 0.73-0.56 (m, 1H), 0.54-
		0.41 (m, 2H).
643	647.4	1H NMR (400 MHz, DMSO-d6) δ 8.09-7.89 (m, 4H), 7.43 (s, 1H), 7.38
		(d, J = 8.1 Hz, 1H), 7.09 (d, J = 1.5 Hz, 1H), 7.08-7.03 (m, 1H), 6.93 (s,
		1H), 4.95-4.83 (m, 1H), 4.68-4.53 (m, 2H), 4.07 (s, 3H), 3.99 (s, 3H),
		3.73-3.69 (m, 2H), 3.59-3.50 (m, 2H), 3.40 (d, J = 11.5 Hz, 1H), 3.37
		(s, 3H), 2.03-1.88 (m, 1H), 1.76 (t, J = 6.6 Hz, 2H), 1.58 (d, J = 7.2 Hz,
		3H), 1.47-1.20 (m, 3H), 1.22-1.12 (m, 1H), 1.17 (s, 3H), 1.11-1.02
		(m, 1H), 0.98-0.88 (m, 1H), 0.85 (s, 3H), 0.49-0.31 (m, 2H).
644	650.3	1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 2H), 8.10 (s, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 7.82 (d, J = 7.4 Hz, 1H), 7.38 (s, 1H), 7.19 (d, J = 8.1 Hz,
		1H), 7.04 (s, 1H), 6.88 (s, 1H), 6.66 (t, J = 54.3 Hz, 1H), 5.34 (s, 1H), 5.13
		(p, J = 7.1 Hz, 1H), 4.91-4.73 (m, 1H), 4.50-4.33 (m, 2H), 4.13 (s, 3H),
		4.00 (s, 3H), 3.74-3.55 (m, 2H), 3.37-2.83 (m, 1H), 2.01-1.85 (m,
		3H), 1.82-1.56 (m, 3H), 1.45 (d, J = 7.1 Hz, 3H), 1.43-1.28 (m, 3H),
		1.21 (s, 3H), 1.18-1.01 (m, 2H), 0.95 (s, 3H).
645	631.4	NA
646	645.4	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.13-8.03
		(m, 2H), 7.96-7.87 (m, 2H), 7.80 (s, 0.4H), 7.66 (s, 0.6H), 7.40-7.30
		(m, 0.4H), 7.37 (s, 1H), 7.29 (d, J = 11.5 Hz, 0.6H), 7.25 (d, J = 8.2 Hz,
		1H), 5.90-5.76 (m, 1H), 5.20 (dd, J = 27.7, 14.7 Hz, 1H), 5.12-5.01 (m,
		1H), 4.54 (s, 0.5H), 4.15 (s, 1H), 4.07-3.99 (m, 3H), 3.79-3.73 (m,
		0.5H), 3.64-3.51 (m, 2H), 3.28-3.13 (m, 1H), 2.71-2.64 (m, 1H), 2.60-
		2.56 (m, 0.5H), 2.26-2.03 (m, 1H), 2.03-1.82 (m, 4H), 1.74-1.58
		(m, 2H), 1.58-1.52 (m, 1H), 1.45 (d, J = 7.1 Hz, 3H), 1.38-1.29 (m,
		1H), 1.29-1.20 (m, 1H), 1.08-0.94 (m, 2H), 0.89-0.80 (m, 1H), 0.71-
		0.58 (m, 1H), 0.56-0.37 (m, 3H).
647	670.3	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.9 Hz, 1H), 8.28 (s, 2H),
		8.16-8.08 (s, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 1.1 Hz, 1H), 7.24
		(d, J = 8.1 Hz, 1H), 7.15 (s, 1H), 6.97-6.87 (m, 1H), 6.67 (td, J = 54.2,
		5.7 Hz, 1H), 5.58-5.45 (m, 1H), 5.34 (s, 1H), 5.14 (dd, J = 27.8, 14.5 Hz,
		1H), 5.08-5.01 (m, 1H), 4.43 (s, 1H), 4.11 (s, 3H), 4.00 (s, 3H), 3.34-
		3.18 (m, 1H), 2.26-2.00 (m, 2H), 2.00-1.85 (m, 3H), 1.82-1.66 (m,
		1H), 1.68-1.56 (m, 1H), 1.56-1.50 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H),
		1.39-1.24 (m, 1H), 0.90-0.79 (m, 1H), 0.73-0.56 (m, 1H), 0.54-0.42
		(m, 2H).
648	667.2	1H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 8.3 Hz, 1H), 7.96 (s, 3H),
		7.44 (s, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.19 (d, J = 1.8 Hz, 1H), 7.11 (t, J =
		7.3 Hz, 1H), 6.95 (s, 1H), 5.58-5.47 (m, 1H), 5.04-4.88 (m, 1H), 4.87-
		4.78 (m, 1H), 4.09 (s, 3H), 3.99 (s, 3H), 3.73-3.68 (m, 1H), 3.48-3.38
		(m, 1H), 3.37 (s, 3H), 2.01-1.82 (m, 3H), 1.76 (s, 2H), 1.65-1.55 (m,
		1H), 1.59 (d, J = 7.2 Hz, 3H), 1.53-1.44 (m, 1H), 1.40-1.27 (m, 1H),
		0.86-0.77 (m, 1H), 0.74-0.62 (m, 1H), 0.53-0.42 (m, 2H).
649	651.4	1H NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 6.8 Hz, 1H), 8.61 (s, 1H),
		8.55 (d, J = 5.2 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.97 (s, 3H), 7.42 (s,
		1H), 7.40 (d, J = 5.2 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.93
		(s, 1H), 5.20 (p, J = 6.9 Hz, 1H), 4.89-4.74 (m, 1H), 4.65-4.52 (m, 1H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.93-3.77 (m, 1H), 3.76-3.65 (m, 1H), 3.63-
		3.25 (m, 7H), 2.41-2.26 (m, 2H), 2.03-1.85 (m, 1H), 1.83-1.67 (m,
		1H), 1.59-1.35 (m, 6H), 1.35-1.08 (m, 2H), 0.68-0.48 (m, 1H).
650	669.3	1H NMR (400 MHz, DMSO-d6) δ 9.44 (d, J = 7.3 Hz, 1H), 8.48 (s, 1H),
		8.34 (d, J = 1.1 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.96 (s, 3H), 7.43 (s,
		1H), 7.27 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.28
		(p, J = 7.2 Hz, 1H), 4.95-4.80 (m, 1H), 4.67-4.53 (m, 1H), 4.12 (s, 3H),
		3.99 (s, 3H), 3.45-3.32 (m, 4H), 2.43-2.33 (m, 1H), 2.24-2.05 (m,
		1H), 2.03-1.86 (m, 1H), 1.82-1.67 (m, 1H), 1.60-1.36 (m, 5H), 1.36-
		1.08 (m, 3H), 0.56-0.35 (m, 1H).
651	685.3	1H NMR (400 MHz, DMSO-d6) δ 9.40 (d, J = 7.8 Hz, 1H), 8.53 (s, 1H),
		8.42 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.96 (s, 3H), 7.43 (s, 1H), 7.27 (d,
		J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.93 (d, J = 1.1 Hz, 1H), 5.42-5.28 (m, 1H),
		4.95-4.83 (m, 1H), 4.65-4.55 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.74-
		3.66 (m, 2H), 3.63-3.47 (m, 3H), 3.47-3.30 (m, 4H), 2.42-2.33 (m,
		1H), 2.13-1.85 (m, 2H), 1.83-1.65 (m, 1H), 1.65-1.36 (m, 5H), 1.36-
		1.08 (m, 3H), 0.54-0.33 (m, 1H).
652	681.3	1H NMR (400 MHz, DMSO-d6) δ 9.20 (d, J = 6.7 Hz, 1H), 8.37 (s, 1H),
		8.08 (d, J = 8.0 Hz, 1H), 7.97 (s, 3H), 7.83 (s, 1H), 7.77 (d, J = 8.3 Hz,
		1H), 7.48-7.40 (m, 2H), 7.32 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.16 (p,
		J = 7.0 Hz, 1H), 4.96-4.77 (m, 2H), 4.01-3.76 (m, 2H), 3.76-3.65 (m,
		1H), 3.65-3.46 (m, 2H), 3.46-3.28 (m, 5H), 2.40-2.23 (m, 2H), 2.01-
		1.85 (m, 1H), 1.82-1.66 (m, 1H), 1.51 (d, J = 7.0 Hz, 3H), 1.48-1.37
		(m, 2H), 1.37-1.20 (m, 2H), 1.20-1.04 (m, 2H), 1.02-0.89 (m, 1H),
		0.61-0.36 (m, 2H).
653	685.3	1H NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 6.8 Hz, 1H), 8.36 (s, 1H),
		8.08 (d, J = 8.0 Hz, 1H), 7.96 (s, 3H), 7.44 (s, 1H), 7.42 (s, 1H), 7.25 (d,
		J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.17 (p, J = 7.0 Hz,
		1H), 4.88-4.73 (m, 1H), 4.66-4.53 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H),
		3.90-3.81 (m, 2H), 3.74-3.67 (m, 1H), 3.62-3.47 (m, 2H), 3.45-3.28
		(m, 5H), 2.39-2.24 (m, 2H), 2.02-1.85 (m, 1H), 1.81-1.65 (m, 1H),
		1.59-1.34 (m, 5H), 1.34-1.02 (m, 2H), 0.64-0.47 (m, 1H).
654	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 8.1 Hz, 1H), 7.96 (s, 3H),
		7.44 (s, 1H), 7.36-7.22 (m, 5H), 7.07 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H),
		5.89 (q, J = 7.3 Hz, 1H), 4.81-4.67 (m, 1H), 4.59-4.48 (m, 1H), 4.11 (s,
		3H), 3.99 (s, 3H), 3.89-3.81 (m, 1H), 3.74-3.66 (m, 2H), 3.58-3.50
		(m, 2H), 3.47-3.31 (m, 4H), 3.10 (s, 3H), 2.30-2.11 (m, 2H), 2.04-
		1.86 (m, 1H), 1.84-1.70 (m, 1H), 1.70-1.41 (m, 6H), 1.41-1.10 (m,
		2H), 0.76-0.59 (m, 1H).
655	685.2	1H NMR (400 MHz, DMSO-d6) δ 9.33 (d, J = 7.9 Hz, 1H), 8.30 (d, J =
		5.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.96 (s, 3H), 7.43 (s, 1H), 7.31 (d,
		J = 5.1 Hz, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.93 (d, J = 1.1 Hz,
		1H), 5.45-5.27 (m, 1H), 4.96-4.80 (m, 1H), 4.65-4.48 (m, 1H), 4.11
		(s, 3H), 3.99 (s, 3H), 3.73-3.66 (m, 3H), 3.60-3.48 (m, 2H), 3.46-3.27
		(m, 4H), 2.39-2.25 (m, 1H), 2.17-2.01 (m, 1H), 2.01-1.87 (m, 1H),
		1.83-1.67 (m, 1H), 1.64-1.36 (m, 6H), 1.36-1.10 (m, 2H), 0.54-0.34
		(m, 1H).
656	669.3	1H NMR (400 MHz, DMSO-d6) δ 9.35 (d, J = 7.5 Hz, 1H), 8.50 (dd, J =
		8.7, 5.7 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.96 (s, 3H), 7.43 (s, 1H), 7.27
		(d, J = 8.1 Hz, 1H), 7.25 (dd, J = 9.0, 5.7 Hz, 1H), 7.09 (s, 1H), 6.93 (d,
		J = 1.1 Hz, 1H), 5.29 (p, J = 6.9 Hz, 1H), 4.97-4.80 (m, 1H), 4.66-4.51
		(m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.74-3.64 (m, 2H), 3.61-3.46 (m,
		2H), 3.46-3.28 (m, 4H), 2.45-2.36 (m, 2H), 2.02-1.88 (m, 1H), 1.84-
		1.68 (m, 1H), 1.61-1.33 (m, 7H), 1.32-1.13 (m, 1H), 0.61-0.39 (m,
		1H).
657	653.3	1H NMR (400 MHz, DMSO-d6) δ 9.45 (d, J = 7.2 Hz, 1H), 8.48 (s, 1H),
		8.34 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.91 (s, 3H), 7.34 (s, 1H), 7.26 (d,
		J = 8.0 Hz, 1H), 7.09 (s, 1H), 6.88 (s, 1H), 5.28 (p, J = 7.1 Hz, 1H), 4.94-
		4.80 (m, 1H), 4.68-4.53 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.43-3.29
		(m, 2H), 3.18-2.77 (m, 1H), 2.43-2.29 (m, 1H), 2.23-2.09 (m, 1H),
		1.87-1.34 (m, 9H), 1.34-1.09 (m, 5H), 0.53-0.34 (m, 1H).
658	651.3	1H NMR (400 MHz, DMSO-d6) δ 9.44 (d, J = 7.3 Hz, 1H), 8.48 (s, 1H),
		8.33 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 8.07-7.80 (m, 3H), 7.58-7.36 (m,
		1H), 7.27 (d, J = 8.0 Hz, 1H), 7.10 (s, 1H), 7.02-6.91 (m, 1H), 5.28 (p,
		J = 6.9 Hz, 1H), 4.88 (s, 1H), 4.68-4.57 (m, 1H), 4.57-4.16 (m, 1H), 4.12
		(s, 3H), 4.00 (s, 3H), 3.84-3.73 (m, 1H), 3.24-3.11 (m, 1H), 2.72-2.63
		(m, 1H), 2.61-2.53 (m, 1H), 2.37 (dd, J = 16.3, 12.3 Hz, 1H), 2.12 (dd,
		J = 22.6, 11.5 Hz, 1H), 2.04-1.78 (m, 3H), 1.74-1.56 (m, 1H), 1.55-
		1.36 (m, 5H), 1.36-1.10 (m, 2H), 0.57-0.34 (m, 1H).
659	672.3	1H NMR (400 MHz, DMSO-d6) δ 9.44 (d, J = 7.3 Hz, 1H), 8.48 (s, 1H),
		8.34 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.97 (s, 3H), 7.43 (s, 1H), 7.27 (d,
		J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.93 (s, 1H), 5.28 (p, J = 7.0 Hz, 1H), 4.95-
		4.81 (m, 1H), 4.67-4.53 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.94-3.81
		(m, 1H), 3.76-3.66 (m, 2H), 3.65-3.47 (m, 2H), 3.47-3.29 (m, 1H),
		2.43-2.30 (m, 1H), 2.22-2.05 (m, 1H), 2.02-1.84 (m, 1H), 1.83-1.69
		(m, 1H), 1.61-1.36 (m, 5H), 1.36-1.08 (m, 3H), 0.55-0.33 (m, 1H).
660	655.2	1H NMR (400 MHz, DMSO-d6) δ 9.44 (d, J = 7.3 Hz, 1H), 8.48 (s, 1H),
		8.34 (s, 1H), 8.09 (d, J = 7.8 Hz, 1H), 7.89 (s, 3H), 7.42 (s, 1H), 7.27 (d,
		J = 8.0 Hz, 1H), 7.09 (s, 1H), 6.93 (s, 1H), 5.79-5.60 (m, 1H), 5.28 (p, J =
		7.1 Hz, 1H), 4.96-4.79 (m, 1H), 4.69-4.55 (m, 1H), 4.12 (s, 3H), 4.08-
		4.02 (m, 2H), 3.99 (s, 3H), 3.63-3.25 (m, 4H), 2.43-2.29 (m, 1H), 2.22-
		2.08 (m, 1H), 1.88-1.65 (m, 2H), 1.61-1.10 (m, 8H), 0.56-0.37 (m,
		1H).
661	699.3	1H NMR (400 MHz, DMSO-d6) δ 9.42 (d, J = 7.6 Hz, 1H), 8.53 (s, 1H),
		8.42 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.97 (s, 3H), 7.67 (s, 1H), 7.33 (s,
		1H), 7.31-7.22 (m, 2H), 5.41-5.26 (m, 1H), 5.03-4.89 (m, 1H), 4.89-
		4.77 (m, 1H), 4.06-3.94 (m, 1H), 3.94-3.26 (m, 9H), 2.61-2.52 (m,
		1H), 2.44-2.28 (m, 1H), 2.13-1.98 (m, 1H), 1.98-1.84 (m, 1H), 1.83-
		1.69 (m, 1H), 1.60-1.39 (m, 5H), 1.39-0.91 (m, 5H), 0.56-0.31 (m,
		2H).
662	683.3	1H NMR (400 MHz, DMSO-d6) δ 9.47 (d, J = 7.1 Hz, 1H), 8.49 (s, 1H),
		8.34 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.97 (s, 3H), 7.67 (s, 1H), 7.33 (s,
		1H), 7.31-7.22 (m, 2H), 5.27 (p, J = 7.0 Hz, 1H), 5.02-4.90 (m, 1H),
		4.90-4.79 (m, 1H), 4.07-3.97 (m, 1H), 3.97-3.28 (m, 9H), 2.47-2.30
		(m, 2H), 2.22-2.08 (m, 1H), 1.99-1.84 (m, 1H), 1.83-1.68 (m, 1H),
		1.57-1.38 (m, 5H), 1.38-0.96 (m, 5H), 0.52-0.35 (m, 2H).
663	691.3	1H NMR (400 MHz, DMSO-d6) δ 9.26 (d, J = 8.1 Hz, 1H), 8.30 (d, J =
		5.1 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.97 (s, 3H), 7.43 (s, 1H), 7.27 (d,
		J = 8.0 Hz, 1H), 7.08 (s, 1H), 7.07 (s, 1H), 6.93 (s, 1H), 5.42 (p, J = 6.9,
		6.5 Hz, 1H), 4.98-4.82 (m, 1H), 4.63-4.49 (m, 1H), 4.12 (s, 3H), 3.99 (s,
		3H), 3.94-3.82 (m, 1H), 3.76-3.65 (m, 1H), 3.65-3.46 (m, 3H), 3.46-
		3.27 (m, 4H), 2.63-2.53 (m, 1H), 2.31-2.20 (m, 1H), 2.20-2.01 (m,
		2H), 2.01-1.85 (m, 1H), 1.83-1.70 (m, 1H), 1.67-1.37 (m, 5H), 1.37-
		1.15 (m, 2H), 1.15-0.88 (m, 4H), 0.57-0.35 (m, 1H).
664	675.3	1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 8.1 Hz, 1H), 8.31 (d, J =
		5.1 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.93 (s, 3H), 7.35 (d, J = 1.1 Hz,
		1H), 7.27 (d, J = 8.0 Hz, 1H), 7.10 (s, 1H), 7.08 (s, 1H), 6.88 (s, 1H),
		5.49-5.35 (m, 1H), 4.97-4.82 (m, 1H), 4.66-4.50 (m, 1H), 4.11 (s, 3H),
		3.99 (s, 3H), 3.44-3.27 (m, 1H), 3.19-2.84 (m, 1H), 2.61-2.53 (m,
		1H), 2.36-2.21 (m, 1H), 2.21-2.00 (m, 2H), 1.88-1.38 (m, 10H), 1.38-
		1.14 (m, 6H), 1.14-0.88 (m, 4H), 0.56-0.34 (m, 1H).
665	681.3	1H NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 6.8 Hz, 1H), 8.36 (s, 1H),
		8.08 (d, J = 8.0 Hz, 1H), 8.04-7.64 (m, 3H), 7.44 (s, 1H), 7.35 (s, 1H),
		7.25 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.89 (s, 1H), 5.17 (p, J = 7.0 Hz,
		1H), 5.11-4.90 (m, 0.5H), 4.87-4.72 (m, 1H), 4.69-4.44 (m, 1.5H),
		4.27-4.17 (m, 0.5H), 4.11 (s, 3H), 3.99 (s, 3H), 3.88-3.74 (m, 0.5H),
		3.45-3.04 (m, 2H), 2.86-2.70 (m, 1H), 2.39-2.24 (m, 2H), 2.03-1.34
		(m, 12H), 1.34-1.21 (m, 1H), 1.21-1.06 (m, 1H), 0.63-0.45 (m, 1H).
666	618.3	1H NMR (400 MHz, DMSO-d6) δ 8.54 (d, J = 8.8 Hz, 1H), 8.49-8.19
		(m, 3H), 8.06 (d, J = 8.0 Hz, 1H), 7.73 (s, 0.5H), 7.47 (s, 0.5H), 7.23 (d,
		J = 8.0 Hz, 1H), 7.14 (m, 1.5H), 6.99 (s, 0.5H), 5.53 (t, J = 13.6 Hz, 1H),
		5.13 (dd, J = 27.7, 14.4 Hz, 1H), 5.08-4.97 (m, 1H), 4.82-4.64 (m,
		0.5H), 4.58-4.43 (m, 0.5H), 4.10 (s, 3H), 4.01 (s, 3H), 3.51-3.29 (m,
		1H), 3.07-2.87 (m, 1H), 2.82-2.70 (m, 1H), 2.26-1.68 (m, 4H), 1.68-
		1.49 (m, 2H), 1.44 (d, J = 7.1 Hz, 3H), 1.39-1.16 (m, 2H), 0.91-0.77
		(m, 1H), 0.73-0.56 (m, 1H), 0.56-0.39 (m, 2H).
667	598.3	1H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J = 36.4 Hz, 3H), 8.04 (d, J =
		8.1 Hz, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.72 (s, 0.5H), 7.45 (s, 0.5H), 7.19
		(d, J = 8.1 Hz, 1H), 7.12 (s, 0.5H), 7.04 (s, 1H), 6.98 (s, 0.5H), 5.12 (p, J =
		6.7 Hz, 1H), 4.90-4.65 (m, 1.5H), 4.57-4.28 (m, 1.5H), 4.12 (s, 3H),
		4.00 (s, 3H), 3.53-3.30 (m, 1H), 3.08-2.88 (m, 1H), 2.81-2.69 (m,
		1H), 2.00-1.23 (m, 13H), 1.21 (s, 3H), 1.17-0.98 (m, 2H), 0.94 (s, 3H).
668	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 8.8 Hz, 1H), 8.21-7.73
		(m, 4H), 7.47 (s, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.14 (s, 1H), 6.96 (s, 1H),
		5.52 (t, J = 13.6 Hz, 1H), 5.32-4.76 (m, 3H), 4.58-4.20 (m, 1H), 4.10
		(s, 3H), 4.00 (s, 3H), 3.88-3.73 (m, 0.5H), 3.57-3.25 (m, 1H), 3.07 (s,
		0.5H), 2.82-2.67 (m, 1H), 2.27-1.17 (m, 14H), 0.89-0.76 (m, 1H),
		0.73-0.55 (m, 1H), 0.55-0.40 (m, 2H).
669	713.2	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.1 Hz, 1H), 8.30-7.76
		(m, 5H), 7.69 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.38-7.16 (m, 3H), 5.20
		(p, J = 7.0 Hz, 1H), 5.14-4.75 (m, 4H), 4.57-4.12 (m, 1H), 4.07-3.93
		(m, 1H), 3.84-3.58 (m, 0.5H), 3.55-3.27 (m, 1H), 3.17-2.89 (m,
		0.5H), 2.82-2.56 (m, 2H), 2.45-2.26 (m, 2H), 2.19-1.59 (m, 4H), 1.59-
		1.32 (m, 6H), 1.32-0.89 (m, 4H), 0.66-0.39 (m, 2H).
670	675.4	1H NMR (400 MHz, DMSO-d6) δ 9.09 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H),
		8.06-7.50 (m, 5H), 7.41-7.14 (m, 4H), 5.19 (p, J = 6.9 Hz, 1H), 5.05-
		4.76 (m, 3H), 4.57-4.45 (m, 1H), 4.23-4.11 (m, 1H), 4.07-3.96 (m,
		1H), 3.80-3.67 (m, 0.5H), 3.45-3.01 (m, 2H), 2.85-2.71 (m, 0.5H),
		2.70-2.61 (m, 1H), 2.47-2.33 (m, 2H), 2.04-1.31 (m, 14H), 1.27-
		0.96 (m, 4H), 0.64-0.37 (m, 2H).
671	701.3	1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 7.9 Hz, 1H), 8.30 (d, J =
		5.1 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.06-7.50 (m, 4H), 7.37-7.15 (m,
		3H), 7.05 (d, J = 5.1 Hz, 1H), 5.47-5.33 (m, 1H), 5.05-4.88 (m, 2H),
		4.88-4.73 (m, 1H), 4.60-4.41 (m, 1H), 4.27-4.11 (m, 1H), 4.07-3.94
		(m, 1H), 3.85-3.65 (m, 0.5H), 3.46-3.04 (m, 1.5H), 2.84-2.68 (m,
		1H), 2.31-1.38 (m, 14H), 1.38-0.84 (m, 9H), 0.55-0.29 (m, 2H).
672	695.2	1H NMR (400 MHz, DMSO-d6) δ 9.26 (d, J = 6.6 Hz, 1H), 8.29 (s, 1H),
		8.09 (d, J = 8.1 Hz, 1H), 8.04-7.53 (m, 4H), 7.48 (s, 1H), 7.32 (s, 1H),
		7.29-7.15 (m, 2H), 5.21-5.09 (m, 1H), 5.03-4.76 (m, 3H), 4.58-4.44
		(m, 1H), 4.24-4.12 (m, 1H), 4.06-3.94 (m, 1H), 3.81-3.62 (m, 1H),
		3.45-3.13 (m, 2H), 2.85-2.59 (m, 1H), 2.41-2.25 (m, 3H), 2.04-1.36
		(m, 8H), 1.31-0.92 (m, 6H), 0.55-0.36 (m, 2H).
673	672.3	1H NMR (400 MHz, DMSO-d6) δ 8.85 (d, J = 6.8 Hz, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 8.02-7.62 (m, 3H), 7.38-7.27 (m, 3H), 7.26-7.15 (m,
		4H), 6.90 (s, 1H), 5.15 (p, J = 7.0 Hz, 1H), 5.03-4.76 (m, 3H), 4.60-
		4.43 (m, 1H), 4.32-4.15 (m, 1H), 3.99 (s, 3H), 3.91 (tt, J = 7.2, 3.9 Hz,
		1H), 3.87-3.74 (m, 0.5H), 3.48-2.99 (m, 1.5H), 2.87-2.67 (m, 1H),
		2.46-2.29 (m, 1H), 2.21 (td, J = 12.1, 4.5 Hz, 1H), 2.03-1.32 (m, 11H),
		1.32-1.07 (m, 3H), 1.07-0.74 (m, 2H), 0.59-0.42 (m, 1H), 0.42-0.28
		(m, 1H).
674	711.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 6.8 Hz, 1H), 8.61 (s, 1H),
		8.10 (d, J = 8.1 Hz, 1H), 8.06-7.69 (m, 3H), 7.69-7.52 (m, 2H), 7.32 (s,
		1H), 7.30-7.17 (m, 2H), 6.95 (t, J = 54.9 Hz, 1H), 5.20 (p, J = 6.9 Hz,
		1H), 5.10-4.78 (m, 3H), 4.61-4.45 (m, 1H), 4.25-4.11 (m, 1H), 4.07
		3.95 (m, 1H), 3.84-3.66 (m, 1H), 3.45-3.04 (m, 3H), 2.86-2.68 (m,
		1H), 2.45-2.28 (m, 2H), 2.03-1.38 (m, 9H), 1.38-0.89 (m, 5H), 0.62-
		0.35 (m, 2H).
675	637.3	1H NMR (400 MHz, DMSO-d6) δ 8.61 (dd, J = 4.8, 1.6 Hz, 1H), 8.49 (t,
		J = 5.8 Hz, 1H), 8.23 (d, J = 8.1 Hz, 1H), 8.01 (dd, J = 7.8, 1.6 Hz, 1H),
		7.97 (br. s, 3H), 7.60 (dd, J = 7.8, 4.8 Hz, 1H), 7.49-7.42 (m, 2H), 7.14
		(s, 1H), 6.94 (d, J = 1.2 Hz, 1H), 4.65 (t, J = 6.4 Hz, 2H), 4.16 (s, 3H),
		4.00 (s, 3H), 3.94-3.75 (m, 2H), 3.70 (dd, J = 6.2, 3.1 Hz, 1H), 3.58-
		3.49 (m, 2H), 3.47-3.32 (m, 1H), 3.36 (s, 3H), 3.23-3.16 (m, 2H), 2.00-
		1.90 (m, 1H), 1.82-1.69 (m, 1H), 1.52-1.45 (m, 4H), 1.45-1.37 (m,
		2H), 1.16-1.07 (m, 2H).
676	648.3	1H NMR (400 MHz, DMSO-d6) δ 8.55 (dd, J = 8.9, 2.7 Hz, 1H), 8.05 (d,
		J = 8.0 Hz, 1H), 7.98 (br. d, J = 5.9 Hz, 3H), 7.37 (d, J = 3.5 Hz, 1H), 7.23
		(d, J = 8.1 Hz, 1H), 7.13 (d, J = 1.4 Hz, 1H), 6.89 (s, 1H), 5.58-5.44 (m,
		1H), 5.13 (dd, J = 27.7, 14.5 Hz, 1H), 5.09-4.98 (m, 1H), 4.63-4.50 (m,
		1H), 4.09 (s, 3H), 4.00 (s, 3H), 3.87-3.70 (m, 1H), 3.31-3.17 (m, 2H),
		2.30-2.19 (m, 1H), 2.18-1.80 (m, 4H), 1.68-1.49 (m, 2H), 1.53 (q, J =
		5.5 Hz, 1H), 1.44 (d, J = 7.0 Hz, 3H), 1.39-1.16 (m, 1H), 1.29 (t, J = 7.2
		Hz, 3H), 1.12 (d, J = 7.3 Hz, 3H), 0.88-0.80 (m, 1H), 0.71-0.56 (m,
		1H), 0.54-0.43 (m, 2H).
677	644.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.88 (s, 3H),
		7.81 (d, J = 7.5 Hz, 1H), 7.57-7.37 (m, 1H), 7.19 (d, J = 8.1 Hz, 1H),
		7.03 (s, 1H), 6.97-6.88 (m, 1H), 5.18-5.07 (m, 1H), 4.86-4.76 (m,
		1H), 4.47-4.33 (m, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.58-3.49 (m, 1H),
		3.48-3.39 (m, 1H), 3.37 (d, J = 6.5 Hz, 1H), 3.29 (s, 3H), 3.20-2.92 (m,
		3H), 2.26-2.17 (m, 1H), 2.04-1.86 (m, 2H), 1.81-1.49 (m, 4H), 1.45
		(d, J = 7.1 Hz, 3H), 1.42-1.25 (m, 5H), 1.21 (s, 3H), 1.17-0.98 (m, 3H),
		0.94 (s, 3H).
678	654.3	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 8.8 Hz, 1H), 8.10 (br. s,
		3H), 8.05 (d, J = 8.0 Hz, 1H), 7.43-7.38 (m, 1H), 7.23 (d, J = 8.1 Hz,
		1H), 7.13 (s, 1H), 6.91 (dd, J = 3.9, 1.2 Hz, 1H), 6.61-6.16 (m, 1H), 5.50
		(t, J = 13.5 Hz, 1H), 5.14 (dd, J = 27.8, 14.5 Hz, 1H), 5.09-4.99 (m, 1H),
		4.70 (d, J = 44.4 Hz, 1H), 4.94-4.20 (m, 2H), 4.10 (s, 3H), 4.10-4.06
		(m, 1H), 3.99 (s, 3H), 3.72-3.35 (m, 2H), 3.36-3.17 (m, 1H), 2.26-
		1.98 (m, 2H), 1.99-1.90 (m, 1H), 1.66-1.56 (m, 1H), 1.53 (q, J = 5.3
		Hz, 1H), 1.44 (d, J = 7.0 Hz, 3H), 1.38-1.23 (m, 1H), 0.88-0.79 (m,
		1H), 0.72-0.56 (m, 1H), 0.56-0.44 (m, 2H).
679	689.3	1H NMR (400 MHz, DMSO-d6) δ 9.54 (d, J = 7.5 Hz, 1H), 8.52 (s, 1H),
		8.39 (d, J = 1.1 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.96 (br. s, 3H), 7.37 (d,
		J = 8.1 Hz, 1H), 7.35 (d, J = 1.1 Hz, 1H), 7.19 (s, 1H), 6.89 (s, 1H), 5.38
		(p, J = 7.1 Hz, 1H), 5.34-5.22 (m, 1H), 5.17 (dd, J = 31.4, 14.6 Hz, 1H),
		4.12 (s, 3H), 4.00 (s, 3H), 3.42-3.31 (m, 2H), 3.14-2.89 (m, 1H), 2.70-
		2.52 (m, 1H), 2.45 (dd, J = 13.0, 4.4 Hz, 1H), 2.16 (dt, J = 13.5, 6.6 Hz,
		1H), 1.88-1.63 (m, 4H), 1.61-1.48 (m, 3H), 1.46 (d, J = 7.0 Hz, 3H),
		1.21 (d, J = 6.9 Hz, 3H), 1.18-0.98 (m, 1H).
680	636.3	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.8 Hz, 1H), 8.05 (d, J =
		8.0 Hz, 1H), 7.92 (br. s, 3H), 7.43 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.13
		(s, 1H), 6.95 (d, J = 1.2 Hz, 1H), 5.51 (t, J = 13.4 Hz, 1H), 5.13 (dd, J =
		27.7, 14.5 Hz, 1H), 5.09-4.99 (m, 1H), 4.84-4.41 (m, 2H), 4.10 (s, 3H),
		4.08-4.00 (m, 1H), 3.99 (s, 3H), 3.60-3.41 (m, 3H), 3.41-3.28 (m,
		1H), 2.21-1.99 (m, 2H), 1.95 (dt, J = 13.8, 4.5 Hz, 1H), 1.87-1.66 (m,
		2H), 1.66-1.56 (m, 1H), 1.53 (q, J = 5.3 Hz, 1H), 1.44 (d, J = 7.1 Hz,
		3H), 1.39-1.23 (m, 1H), 0.89-0.79 (m, 1H), 0.72-0.56 (m, 1H), 0.54-
		0.44 (m, 2H).
681	668.3	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 8.9 Hz, 1H), 8.05 (d, J =
		8.0 Hz, 1H), 7.36 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H), 7.12 (s, 1H), 6.90 (s,
		1H), 5.51 (t, J = 13.5 Hz, 1H), 5.13 (dd, J = 27.7, 14.5 Hz, 1H), 5.09-
		4.98 (m, 1H), 4.87 (d, J = 47.0 Hz, 1H), 4.09 (s, 3H), 3.98 (s, 3H), 3.80-
		3.68 (m, 1H), 3.49-3.42 (m, 1H), 3.42 (s, 3H), 3.37-3.26 (m, 1H), 3.12-
		3.01 (m, 1H), 2.25-1.99 (m, 2H), 1.94 (dt, J = 13.4, 4.3 Hz, 1H), 1.66-
		1.55 (m, 1H), 1.53 (q, J = 5.3 Hz, 1H), 1.44 (d, J = 7.1 Hz, 3H), 1.39-
		1.24 (m, 1H), 0.88-0.80 (m, 1H), 0.70-0.55 (m, 1H), 0.54-0.45 (m,
		2H).
682	660.3	1H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 5.5 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.88 (d, J = 98.0 Hz, 3H), 7.69-7.55 (m, 1H), 7.33 (s, 1H),
		7.37-7.17 (m, 1H), 7.23 (d, J = 8.1 Hz, 1H), 5.52 (dt, J = 14.3, 6.9 Hz,
		1H), 5.17 (dd, J = 33.0, 14.6 Hz, 1H), 4.89 (p, J = 6.9 Hz, 1H), 5.02-4.45
		(m, 1H), 4.25-4.13 (m, 1H), 4.05-3.95 (m, 1H), 3.44-2.68 (m, 2H),
		2.19-2.05 (m, 1H), 2.03-1.91 (m, 1H), 1.83 (td, J = 8.1, 5.3 Hz, 1H),
		1.90-1.57 (m, 7H), 1.57-1.29 (m, 2H), 1.40 (d, J = 7.1 Hz, 3H), 1.27-
		1.21 (m, 1H), 1.15-0.87 (m, 4H), 0.82-0.70 (m, 2H), 0.70-0.63 (m,
		1H), 0.50-0.39 (m, 1H).
683	674.3	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 8.1 Hz, 1H), 8.07-7.70
		(m, 3H), 7.70-7.60 (m, 1H), 7.32 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.29-
		7.17 (m, 1H), 5.65 (q, J = 7.3 Hz, 1H), 5.48 (dt, J = 14.2, 6.9 Hz, 1H),
		5.18 (dd, J = 33.0, 14.7 Hz, 1H), 5.03-4.43 (m, 1H), 4.24-3.94 (m, 2H),
		3.51 (s, 3H), 3.42-2.68 (m, 2H), 2.17-2.05 (m, 1H), 2.04-1.91 (m,
		2H), 1.91-1.71 (m, 2H), 1.55 (d, J = 7.3 Hz, 3H), 1.71-1.35 (m, 5H),
		1.34-1.18 (m, 3H), 1.05-0.88 (m, 4H), 0.85 (q, J = 5.2 Hz, 1H), 0.77
		(td, J = 8.0, 3.9 Hz, 1H), 0.56-0.38 (m, 2H).
684	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 8.01-7.68
		(m, 3H), 7.64 (d, J = 8.0 Hz, 1H), 7.68-7.53 (m, 1H), 7.33-7.15 (m,
		1H), 7.25 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 5.16 (p, J = 6.9 Hz, 1H), 4.78
		(qd, J = 13.8, 5.2 Hz, 2H), 5.05-4.45 (m, 1H), 3.98 (dq, J = 9.6, 2.9 Hz,
		1H), 4.24-3.69 (m, 1H), 3.46-3.21 (m, 1H), 3.21-2.73 (m, 1H), 2.02-
		1.91 (m, 1H), 1.89-1.39 (m, 7H), 1.54 (d, J = 7.1 Hz, 3H), 1.39-1.27
		(m, 1H), 1.17 (s, 3H), 1.14-1.06 (m, 4H), 1.00 (s, 3H), 0.80 (dt, J = 14.7,
		8.8 Hz, 4H), 0.74-0.65 (m, 2H).
685	691.3	1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 7.0 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 8.06-7.71 (m, 3H), 7.68 (d, J = 8.3 Hz, 1H), 7.70-7.56 (m,
		1H), 7.31 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.33-7.16 (m, 1H), 6.67 (d, J =
		8.3 Hz, 1H), 5.19 (p, J = 7.0 Hz, 1H), 4.91 (dt, J = 14.4, 7.7 Hz, 1H),
		4.85-4.77 (m, 1H), 4.61-4.43 (m, 1H), 4.01 (tt, J = 7.1, 3.9 Hz, 1H),
		4.20-3.67 (m, 1H), 3.84 (s, 3H), 3.46-3.20 (m, 1H), 3.19-2.70 (m,
		1H), 2.68 (dd, J = 12.3, 8.0 Hz, 1H), 2.41-2.28 (m, 2H), 2.03-1.91 (m,
		1H), 1.91-1.39 (m, 8H), 1.49 (d, J = 7.0 Hz, 3H), 1.28-0.89 (m, 5H),
		0.72-0.54 (m, 1H), 0.52-0.43 (m, 1H).
686	658.4	1H NMR (400 MHz, DMSO-d6) δ 8.11 (d, J = 7.0 Hz, 1H), 8.05 (d, J =
		8.1 Hz, 1H), 8.02-7.91 (m, 3H), 7.44 (s, 1H), 7.20 (d, J = 8.2 Hz, 1H),
		7.02 (s, 1H), 6.93 (d, J = 1.1 Hz, 1H), 4.93 (p, J = 7.0 Hz, 1H), 4.72-4.59
		(m, 1H), 4.49-4.36 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.91-3.66 (m,
		5H), 3.66-3.46 (m, 2H), 3.43-3.26 (m, 4H), 2.24-1.07 (m, 19H).
687	658.3	1H NMR (400 MHz, DMSO-d6) δ 8.07 (d, J = 8.1 Hz, 1H), 8.04-7.98
		(m, 4H), 7.44 (s, 1H), 7.23 (d, J = 8.2 Hz, 1H), 7.06 (s, 1H), 6.93 (d, J =
		1.2 Hz, 1H), 5.25 (dq, J = 9.1, 6.9 Hz, 1H), 4.88-4.76 (m, 1H), 4.60-
		4.50 (m, 1H), 4.10 (s, 3H), 4.01-3.94 (m, 4H), 3.89 (q, J = 7.4 Hz, 1H),
		3.74-3.67 (m, 1H), 3.58-3.48 (m, 3H), 3.44-3.32 (m, 4H), 2.26 (ddd,
		J = 12.1, 7.4, 4.5 Hz, 1H), 2.03-1.61 (m, 7H), 1.51-1.28 (m, 6H), 1.14-
		0.92 (m, 4H), 0.66-0.53 (m, 1H).
688	632.3	1H NMR (400 MHz, DMSO-d6) δ 8.76 (d, J = 8.4 Hz, 1H), 8.04 (d, J =
		8.2 Hz, 1H), 8.01-7.90 (m, 3H), 7.44 (s, 1H), 7.26 (d, J = 8.2 Hz, 1H),
		7.03 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 4.63 (p, J = 7.1 Hz, 1H), 4.58-4.50
		(m, 2H), 4.13 (s, 3H), 3.99 (s, 3H), 3.93-3.77 (m, 1H), 3.74-3.66 (m,
		1H), 3.60-3.48 (m, 2H), 3.46-3.29 (m, 5H), 2.02-1.07 (m, 15H), 0.91
		(dt, J = 19.8, 6.8 Hz, 1H).
689	632.3	1H NMR (400 MHz, DMSO-d6) δ 8.41 (d, J = 9.5 Hz, 1H), 8.00 (d, J =
		8.0 Hz, 1H), 7.45 (s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.03 (s, 1H), 6.93 (d,
		J = 1.2 Hz, 1H), 5.19 (dq, J = 9.5, 7.0 Hz, 1H), 4.79-4.69 (m, 1H), 4.69-
		4.57 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.90-3.67 (m, 3H), 3.60-3.47
		(m, 2H), 3.47-3.29 (m, 4H), 2.31-2.19 (m, 1H), 2.08-1.87 (m, 2H),
		1.80-1.07 (m, 12H), 0.94 (ddd, J = 11.1, 9.3, 6.0 Hz, 1H).
690	646.3	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.8 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 8.04-7.90 (m, 3H), 7.86 (s, 1H), 7.78 (d, J = 8.3 Hz, 1H),
		7.46 (dd, J = 8.3, 1.5 Hz, 1H), 7.36 (s, 1H), 7.23 (d, J = 8.0 Hz, 1H),
		5.96-5.84 (m, 1H), 5.18 (dd, J = 27.7, 14.6 Hz, 1H), 5.12-4.99 (m, 1H),
		3.98-3.81 (m, 2H), 3.76-3.67 (m, 1H), 3.65-3.46 (m, 3H), 3.46-3.31 (m,
		4H), 2.30-1.88 (m, 4H), 1.80-1.70 (m, 1H), 1.67-1.50 (m, 2H), 1.44
		(d, J = 7.1 Hz, 3H), 1.39-1.25 (m, 2H), 1.09-0.90 (m, 2H), 0.89-0.81
		(m, 1H), 0.71-0.57 (m, 1H), 0.56-0.39 (m, 3H).
691	610.3	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.5 Hz, 1H), 8.03-7.89
		(m, 4H), 7.84 (s, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.43 (dd, J = 8.4, 1.5 Hz,
		1H), 7.26 (s, 1H), 7.13 (d, J = 8.1 Hz, 1H), 5.00 (p, J = 7.2 Hz, 1H), 4.92-
		4.81 (m, 1H), 4.81-4.71 (m, 1H), 3.99-3.77 (m, 2H), 3.73-3.67 (m,
		1H), 3.64-3.46 (m, 3H), 3.46-3.29 (m, 4H), 2.02-1.08 (m, 15H), 0.94-
		0.82 (m, 2H), 0.76-0.53 (m, 3H), 0.50-0.43 (m, 1H).
692	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.07 (d, J = 8.1 Hz, 1H), 8.02-7.89
		(m, 3H), 7.45 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.12 (s, 1H), 6.94 (s, 1H),
		5.81 (q, J = 7.4 Hz, 1H), 5.44 (t, J = 14.2 Hz, 1H), 5.10 (dd, J = 25.6, 14.8
		Hz, 1H), 4.08 (s, 3H), 3.99 (s, 3H), 3.74-3.67 (m, 1H), 3.59-3.50 (m,
		3H), 3.48 (s, 3H), 3.46-3.38 (m, 2H), 3.36 (s, 3H), 2.33-1.86 (m, 5H),
		1.81-1.72 (m, 1H), 1.64-1.52 (m, 4H), 1.45-1.31 (m, 1H), 0.99 (t, J =
		5.3 Hz, 1H), 0.92-0.75 (m, 1H), 0.68-0.57 (m, 2H).
693	681.2	1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 7.1 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 8.05-7.90 (m, 3H), 7.84 (s, 1H), 7.82 (d, J = 8.1 Hz, 1H),
		7.77 (d, J = 8.4 Hz, 1H), 7.47-7.43 (m, 1H), 7.41 (d, J = 8.0 Hz, 1H),
		7.33 (s, 1H), 7.25 (d, J = 8.0 Hz, 1H), 5.20 (p, J = 6.9 Hz, 1H), 4.96-4.80
		(m, 2H), 3.94-3.80 (m, 3H), 3.74-3.66 (m, 1H), 3.65-3.48 (m, 2H),
		3.47-3.29 (m, 4H), 2.71-2.55 (m, 1H), 2.43-2.29 (m, 2H), 2.03-1.88
		(m, 1H), 1.82-1.69 (m, 1H), 1.56-1.06 (m, 8H), 1.00-0.89 (m, 1H),
		0.63-0.40 (m, 3H).
694	664.3	1H NMR (400 MHz, Chloroform-d) δ 8.08 (d, J = 8.1 Hz, 1H), 8.02-
		7.89 (m, 4H), 7.45 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), 6.93 (s,
		1H), 5.01 (p, J = 6.9 Hz, 1H), 4.61-4.41 (m, 2H), 4.13 (s, 3H), 3.99 (s,
		3H), 3.93-3.77 (m, 1H), 3.74-3.67 (m, 1H), 3.64-3.48 (m, 2H), 3.44-
		3.29 (m, 5H), 2.02-1.68 (m, 5H), 1.62-1.32 (m, 9H), 1.25 (s, 3H).
695	632.3	1H NMR (400 MHz, DMSO-d6) δ 8.36 (dd, J = 8.3, 1.9 Hz, 1H), 8.01 (d,
		J = 8.0 Hz, 1H), 8.00-7.89 (m, 3H), 7.45 (s, 1H), 7.19 (d, J = 8.1 Hz,
		1H), 7.02 (s, 1H), 6.92 (s, 1H), 5.13 (p, J = 7.3 Hz, 1H), 4.59-4.50 (m,
		2H), 4.11 (s, 3H), 3.98 (s, 3H), 3.91-3.75 (m, 1H), 3.74-3.67 (m, 1H),
		3.62-3.48 (m, 2H), 3.47-3.27 (m, 5H), 2.02-1.85 (m, 2H), 1.82-0.88
		(m, 14H).
696	661.3	1H NMR (400 MHz, DMSO-d6) δ 9.35 (d, J = 7.7 Hz, 1H), 8.60 (d, J =
		5.8 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.06-7.90 (m, 3H), 7.83 (s, 1H),
		7.77 (d, J = 8.3 Hz, 1H), 7.58 (d, J = 5.6 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H),
		7.35 (s, 1H), 7.28 (d, J = 8.0 Hz, 1H), 5.36 (p, J = 7.1 Hz, 1H), 4.95-4.84
		(m, 2H), 3.95-3.82 (m, 2H), 3.74-3.65 (m, 1H), 3.65-3.47 (m, 3H),
		3.47-3.30 (m, 4H), 2.69 (s, 3H), 2.68-2.60 (m, 3H), 2.26-2.16 (m,
		1H), 1.99-1.88 (m, 1H), 1.81-1.69 (m, 1H), 1.55-1.06 (m, 9H), 0.99-
		0.91 (m, 1H), 0.50-0.37 (m, 2H).
697	665.3	1H NMR (400 MHz, DMSO-d6) δ 9.31 (d, J = 7.9 Hz, 1H), 8.56 (d, J =
		5.6 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.05-7.85 (m, 3H), 7.51 (s, 1H),
		7.42 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.94 (s, 1H), 5.39 (q,
		J = 7.3 Hz, 1H), 4.91-4.80 (m, 1H), 4.66-4.56 (m, 1H), 4.12 (s, 3H), 3.99
		(s, 3H), 3.91-3.79 (m, 1H), 3.76-3.66 (m, 1H), 3.59-3.44 (m, 2H), 3.45-
		3.29 (m, 5H), 2.72-2.64 (m, 3H), 2.61 (s, 3H), 2.25-2.14 (m, 1H),
		1.99-1.87 (m, 1H), 1.83-1.67 (m, 1H), 1.63-1.18 (m, 7H), 0.56-0.40
		(m, 1H).
698	679.3	1H NMR (400 MHz, DMSO-d6) δ 9.31 (d, J = 7.6 Hz, 1H), 8.55 (d, J =
		5.5 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.07-7.86 (m, 3H), 7.66 (s, 1H),
		7.48 (s, 1H), 7.37-7.22 (m, 3H), 5.36 (p, J = 7.1 Hz, 1H), 5.01-4.80 (m,
		2H), 4.07-3.97 (m, 1H), 3.95-3.75 (m, 1H), 3.75-3.66 (m, 1H), 3.66-
		3.46 (m, 2H), 3.46-3.29 (m, 5H), 2.61 (s, 3H), 2.46-2.36 (m, 2H), 2.28-
		2.16 (m, 1H), 1.99-1.86 (m, 1H), 1.82-1.71 (m, 1H), 1.59-0.91 (m,
		10H), 0.52-0.39 (m, 2H).
699	656.3	1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 8.0 Hz, 1H), 7.97 (br s,
		3H), 7.45 (s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.08 (s, 1H), 6.93 (d, J = 1.2
		Hz, 1H), 4.95-4.84 (m, 1H), 4.61-4.51 (m, 1H), 4.24 (s, 1H), 4.12 (s,
		3H), 3.99 (s, 3H), 3.83-3.66 (m, 3H), 3.58-3.48 (m, 2H), 3.45-3.31
		(m, 4H), 3.07-2.91 (m, 1H), 2.02-1.88 (m, 1H), 1.81-1.70 (m, 1H),
		1.59 (s, 4H), 1.42-0.96 (m, 10H), 0.76-0.62 (m, 1H).
700	682.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 9.6 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.96 (br s, 3H), 7.69 (s, 1H), 7.37 (s, 1H), 7.31 (dd, J = 11.5,
		1.2 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 5.82 (t, J = 13.7 Hz, 1H), 5.35-
		5.18 (m, 2H), 4.07-3.99 (m, 1H), 3.93-3.80 (m, 2H), 3.74-3.67 (m,
		1H), 3.36 (s, 6H), 2.45-1.67 (m, 7H), 1.54-1.40 (m, 5H), 1.30-0.92
		(m, 5H), 0.50-0.40 (m, 1H).
701	666.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 9.6 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.90 (br s, 3H), 7.63 (d, J = 1.1 Hz, 1H), 7.37 (s, 1H), 7.26
		(d, J = 8.0 Hz, 2H), 7.24 (s, 1H), 5.82 (t, J = 13.7 Hz, 1H), 5.33-5.17 (m,
		2H), 4.05-3.98 (m, 1H), 3.37 (s, 1H), 2.45-1.96 (m, 4H), 1.86-1.38
		(m, 9H), 1.29-0.92 (m, 7H), 0.49-0.39 (m, 1H).
702	668.3	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 9.6 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 7.96 (br s, 3H), 7.44 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.15 (s,
		1H), 6.95 (d, J = 1.2 Hz, 1H), 5.52 (t, J = 13.5 Hz, 1H), 5.27-5.13 (m,
		2H), 4.10 (s, 3H), 3.99 (s, 3H), 3.88-3.67 (m, 3H), 3.37 (s, 6H), 2.43-
		1.89 (m, 5H), 1.72 (t, J = 15.9 Hz, 2H), 1.52-1.37 (m, 5H), 1.28-0.90
		(m, 2H).
703	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 9.6 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 7.91 (br s, 3H), 7.37 (d, J = 1.1 Hz, 1H), 7.25 (d, J = 8.0 Hz,
		1H), 7.15 (s, 1H), 6.89 (s, 1H), 5.53 (t, J = 13.5 Hz, 1H), 5.29-5.09 (m,
		2H), 4.10 (s, 3H), 4.00 (s, 3H), 3.43-3.29 (m, 1H), 3.09-2.88 (m, 1H),
		2.44-1.96 (m, 5H), 1.86-1.36 (m, 10H), 1.22 (d, J = 6.9 Hz, 4H), 1.01-
		0.89 (m, 1H).
704	646.3	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 9.5 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.97 (br s, 3H), 7.69 (s, 1H), 7.28 (dd, J = 11.6, 1.2 Hz, 1H),
		7.26 (s, 1H), 7.17 (d, J = 8.1 Hz, 1H), 5.26-5.13 (m, 1H), 4.86-4.77 (m,
		2H), 4.02-3.95 (m, 1H), 3.89-3.66 (m, 2H), 3.60-3.50 (m, 1H), 3.45-
		3.30 (m, 4H), 2.31-2.20 (m, 1H), 2.03 (ddd, J = 11.4, 8.0, 3.7 Hz, 1H),
		1.90 (d, J = 7.7 Hz, 15H), 1.00-0.82 (m, 2H), 0.67-0.59 (m, 1H).
705	630.3	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 9.5 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.92 (br s, 3H), 7.60 (d, J = 1.3 Hz, 1H), 7.26 (s, 1H), 7.23
		(d, J = 11.9 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 5.26-5.14 (m, 1H), 4.87-
		4.77 (m, 2H), 3.99 (tt, J = 7.2, 3.8 Hz, 1H), 3.43-3.31 (m, 1H), 3.17-
		2.86 (m, 1H), 2.31-2.20 (m, 1H), 2.03 (ddd, J = 9.3, 7.6, 3.7 Hz, 1H),
		1.86-0.83 (m, 22H), 0.67-0.57 (m, 1H).
706	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.41 (d, J = 9.5 Hz, 1H), 8.00 (d, J =
		8.0 Hz, 1H), 7.91 (br s, 3H), 7.35 (d, J = 1.1 Hz, 1H), 7.16 (d, J = 8.1 Hz,
		1H), 7.03 (s, 1H), 6.87 (s, 1H), 5.25-5.14 (m, 1H), 4.80-4.59 (m, 2H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.43-3.30 (m, 1H), 2.32-2.20 (m, 1H), 2.07-
		1.98 (m, 1H), 1.87-1.08 (m, 18H), 0.99-0.89 (m, 1H).
707	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.54 (d, J = 8.8 Hz, 1H), 8.37-8.09
		(m, 3H), 8.06 (d, J = 8.0 Hz, 1H), 7.64-7.43 (m, 1H), 7.23 (d, J = 8.0 Hz,
		1H), 7.14 (s, 1H), 7.08-6.93 (m, 1H), 5.58-5.43 (m, 1H), 5.19-5.00
		(m, 2H), 4.87 (br s, 0.5H), 4.65 (br s, 0.5H), 4.59-4.51 (m, 1H), 4.26-
		3.39 (m, 11H), 2.22-1.88 (m, 3H), 1.67-1.48 (m, 2H), 1.44 (d, J = 7.0
		Hz, 3H), 1.37-1.20 (m, 1H), 0.89-0.79 (m, 1H), 0.69-0.55 (m, 1H),
		0.55-0.42 (m, 2H).
708	614.3	1H NMR (400 MHz, DMSO-d6) δ 8.32 (br s, 1.5H), 8.16 (br s, 1.5H),
		8.04 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H), 7.60 (s, 0.5H), 7.47 (s,
		0.5H), 7.19 (d, J = 8.1 Hz, 1H), 7.06-6.92 (m, 2H), 5.12 (p, J = 7.1 Hz,
		1H), 4.90-4.74 (m, 1.5H), 4.68-4.51 (m, 1.5H), 4.47-4.36 (m, 1H),
		4.22-3.69 (m, 10H), 3.50-3.41 (m, 1H), 1.91 (t, J = 12.0 Hz, 1H), 1.74-
		1.52 (m, 2H), 1.50-0.99 (m, 14H), 0.94 (s, 3H).
709	707.2	1H NMR (400 MHz, DMSO-d6) δ 8.97 (d, J = 6.9 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.95 (s, 2H), 7.89 (d, J = 8.0 Hz, 1H), 7.78-7.55 (m, 2H),
		7.46 (d, J = 8.0 Hz, 1H), 7.35 (s, 1H), 7.31-7.16 (m, 2H), 5.27-5.10 (m,
		2H), 5.02-4.90 (m, 0.5H), 4.70 (dd, J = 14.6, 8.6 Hz, 1H), 4.59-4.45
		(m, 0.5H), 4.21-4.14 (m, 1H), 4.08-3.98 (m, 1H), 3.42-3.20 (m, 2H),
		2.81-2.57 (m, 2H), 2.05-1.46 (m, 12H), 1.27-1.06 (m, 3H), 1.04-
		0.88 (m, 2H), 0.68-0.57 (m, 1H), 0.11-0.02 (m, 1H), −0.61-−0.70 (m,
		1H).
710	707.2	1H NMR (400 MHz, DMSO-d6) δ 9.06 (d, J = 7.0 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 7.95 (br s, 2H), 7.81 (d, J = 8.0 Hz, 1H), 7.77-7.53 (m, 2H),
		7.42 (d, J = 8.0 Hz, 1H), 7.35 (s, 1H), 7.31-7.17 (m, 2H), 5.17 (p, J = 6.5
		Hz, 1H), 5.11-4.91 (m, 1.5H), 4.66-4.43 (m, 1.5H), 4.22-4.12 (m,
		0.5H), 4.07-3.96 (m, 1H), 3.83-3.68 (m, 0.5H), 3.46-3.00 (m, 2.5H),
		2.81-2.55 (m, 2.5H), 2.12-1.44 (m, 12H), 1.30-0.91 (m, 3H), 0.84-
		0.43 (m, 4H), −0.07-−0.16 (m, 1H).
711	628.3	1H NMR (400 MHz, DMSO-d6) δ 8.85 (d, J = 5.5 Hz, 1H), 8.00 (d, J =
		8.0 Hz, 1H), 7.96 (br s, 2H), 7.73 (br s, 1H), 7.36 (s, 1H), 7.12 (d, J = 8.1
		Hz, 1H), 7.04 (s, 1H), 6.89 (s, 1H), 5.08-4.79 (m, 2.5H), 4.70-4.61 (m,
		1H), 4.57-4.47 (m, 0.5H), 4.28-4.18 (m, 0.5H), 4.09 (s, 3H), 3.98 (s,
		3H), 3.80-3.60 (m, 0.5H),  3.45-3.06 (m, 1.5H), 2.84-2.70 (m,
		0.5H), 2.37-2.20 (m, 2H), 2.04-1.22 (m, 14H), 1.10-0.88 (m, 3H),
		0.44-0.28 (m, 1H).
712	642.3	1H NMR (400 MHz, DMSO-d6) δ 8.87 (d, J = 5.3 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.96 (br s, 2H), 7.78-7.53 (m, 2H), 7.27 (s, 1H), 7.26-7.15
		(m, 1H), 7.13 (d, J = 8.1 Hz, 1H), 5.03-4.87 (m, 2.5H), 4.83 (p, J = 6.3
		Hz, 1H), 4.57-4.45 (m, 0.5H), 4.22-4.14 (m, 0.5H), 4.05-3.95 (m,
		1H), 3.81-3.68 (m, 0.5H), 3.43-3.07 (m, 1.5H), 2.81-2.70 (m, 0.5H),
		2.35-2.20 (m, 2H), 2.03-0.85 (m, 20H), 0.41-0.22 (m, 2H).
713	681.2	1H NMR (400 MHz, DMSO-d6) δ 9.12-9.05 (m, 1H), 8.09 (d, J = 8.0
		Hz, 1H), 7.97 (br s, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.74 (br s, 1H), 7.40 (d,
		J = 8.1 Hz, 1H), 7.36 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.90
		(s, 1H), 5.22 (p, J = 7.0 Hz, 1H), 5.07-4.92 (m, 0.5H), 4.90-4.77 (m,
		1H), 4.64-4.44 (m, 1.5H), 4.30-4.16 (m, 0.5H), 4.11 (s, 3H), 3.99 (s,
		3H), 3.86-3.66 (m, 0H), 3.48-3.03 (m, 1.5H), 2.84-2.71 (m, 0.5H),
		2.70-2.57 (m, 1H), 2.41-2.26 (m, 2H), 2.05-1.34 (m, 12H), 1.20 (s,
		1H), 0.68-0.50 (m, 1H).
714	735.2	1H NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 7.2 Hz, 1H), 8.12 (d, J =
		8.0 Hz, 1H), 8.05-7.65 (m, 5H), 7.41 (d, J = 8.0 Hz, 1H), 7.38 (s, 1H),
		7.28 (d, J = 8.1 Hz, 1H), 7.18 (s, 1H), 5.23 (p, J = 7.1 Hz, 1H), 5.05-4.77
		(m, 1.5H), 4.68-4.44 (m, 1.5H), 4.19-4.10 (m, 0.5H), 4.08 (s, 3H), 3.81-
		3.68 (m, 0.5H), 3.49-3.10 (m, 1.5H), 2.86-2.71 (m, 0.5H), 2.45-
		2.29 (m, 2H), 2.03-1.36 (m, 11H), 1.28-1.16 (m, 1H), 0.72-0.49 (m,
		1H).
715	682.3	1H NMR (400 MHz, DMSO-d6) δ 8.42 (d, J = 9.5 Hz, 1H), 8.03 (d, J =
		8.0 Hz, 1H), 8.00-7.66 (m, 4H), 7.38 (br s, 1H), 7.18 (d, J = 8.1 Hz, 1H),
		7.12 (s, 1H), 5.28-5.14 (m, 1H), 5.04-4.92 (m, 0.5H), 4.82-4.45 (m,
		2.5H), 4.17-4.11 (m, 0.5H), 4.08 (s, 3H), 3.80-3.66 (m, 0.5H), 3.50-
		3.08 (m, 1.5H), 2.87-2.71 (m, 0.5H), 2.36-2.21 (m, 1H), 2.09-1.08
		(m, 18H), 1.00-0.87 (m, 1H).
716	682.3	1H NMR (400 MHz, DMSO-d6) δ 8.92 (d, J = 7.2 Hz, 1H), 8.15 (d, J =
		8.0 Hz, 1H), 8.03-7.60 (m, 3H), 7.40-7.30 (m, 4H), 7.30-7.20 (m,
		2H), 7.17 (s, 1H), 6.90 (s, 1H), 5.35-5.10 (m, 3H), 5.08-4.90 (m,
		0.5H), 4.58-4.44 (m, 0.5H), 4.31-4.19 (m, 0.5H), 4.11 (s, 3H), 3.99 (s,
		3H), 3.92-3.73 (m, 0.5H), 3.44-3.06 (m, 1.5H), 2.81-2.68 (m, 0.5H),
		2.36-2.23 (m, 2H), 2.05-1.39 (m, 12H), 1.30-1.00 (m, 2H).
717	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.42 (d, J = 9.5 Hz, 1H), 8.03 (d, J =
		8.0 Hz, 1H), 8.00-7.90 (m, 2H), 7.80-7.57 (m, 2H), 7.29-7.20 (m,
		1H), 7.18 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 5.21 (dq, J = 9.4, 7.0 Hz, 1H),
		5.04-4.92 (m, 0.5H), 4.85-4.62 (m, 2H), 4.59-4.46 (m, 0.5H), 4.19-
		4.12 (m, 0.5H), 4.10 (s, 3H), 3.79-3.69 (m, 0.5H), 3.43-3.02 (m, 1.5H),
		2.81-2.70 (m, 0.5H), 2.31-2.22 (m, 1H), 2.07-1.08 (m, 18H), 0.99-
		0.89 (m, 1H).
718	616.3	1H NMR (400 MHz, DMSO-d6) δ 8.42 (d, J = 9.5 Hz, 1H), 8.03 (d, J =
		8.0 Hz, 1H), 8.00-7.90 (m, 2H), 7.80-7.57 (m, 2H), 7.29-7.20 (m,
		1H), 7.18 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 5.21 (dq, J = 9.4, 7.0 Hz, 1H),
		5.04-4.92 (m, 0.5H), 4.85-4.62 (m, 2H), 4.59-4.46 (m, 0.5H), 4.19-
		4.12 (m, 0.5H), 4.10 (s, 3H), 3.79-3.69 (m, 0.5H), 3.43-3.02 (m, 1.5H),
		2.81-2.70 (m, 0.5H), 2.31-2.22 (m, 1H), 2.07-1.08 (m, 18H), 0.99-
		0.89 (m, 1H).
719	684.4	1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 7.8 Hz, 1H), 8.06 (d, J =
		8.1 Hz, 1H), 8.00 (brs, 3H), 7.45 (brs, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.04
		(s, 1H), 6.94 (s, 1H), 5.29-5.17 (m, 1H), 4.98-4.82 (m, 1H), 4.44-4.33
		(m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.76-3.69 (m, 2H), 3.61-3.47 (m,
		2H), 3.46-3.33 (m, 1H), 3.37 (s, 3H), 2.51-2.39 (m, 1H), 2.02-1.55
		(m, 6H), 1.49-1.45 (m, 3H), 1.45-1.29 (m, 3H), 1.16 (s, 3H), 1.11-
		0.97 (m, 2H).
720	684.4	1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 7.4 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 7.98 (s, 3H), 7.44 (s, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.05 (s,
		1H), 6.94 (s, 1H), 5.21-5.11 (m, 1H), 4.85-4.72 (m, 1H), 4.52-4.39
		(m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.88 (brs, 1H), 3.76-3.66 (m, 1H),
		3.37 (s, 3H), 2.51-2.43 (m, 1H), 2.14-1.58 (m, 5H), 2.03-1.52 (m,
		5H), 1.50 (d, J = 7.1 Hz, 3H), 1.46 (s, 3H), 1.43-1.22 (m, 4H), 1.11-
		0.96 (m, 1H).
721	645.7	NA
722	666.2	1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 7.7 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 8.06 (brs, 1H 1st rotamer), 7.91 (brs, 2H 2nd rotamer), 7.55
		(s, 0.4H 1st rotamer), 7.42 (s, 0.6H 2nd rotamer), 7.21 (d, J = 8.1 Hz, 1H),
		7.05 (s, 1H), 7.00 (s, 0.4H 1st rotamer), 6.96 (s, 0.6H 2nd rotamer), 5.28-
		5.18 (m, 1H), 4.97-4.84 (s, 1H), 4.54 (s, 0.4H 1st rotamer), 4.40 (dt, J =
		13.8, 7.6 Hz, 1H), 4.21 (s, 0.6H 2nd rotamer), 4.12 (s, 3H), 4.00 (s, 3H),
		3.85-3.73 (m, 0.4H 1st rotamer), 3.69-3.56 (m, 0.6H 2nd rotamer), 3.24-
		3.13 (m 1H), 2.67 (s, 0.6H 2nd rotamer), 2.50 (s, 0.4H 1st rotamer), 2.48-
		2.37 (m, 1H), 2.04-1.51 (m, 7H), 1.47 (d, J = 7.1 Hz, 3H), 1.44-1.23
		(m, 4H), 1.16 (s, 3H), 1.13-0.91 (m, 2H).
723	720.2	1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J = 7.8 Hz, 1H), 8.18 (brs,
		3H), 8.06 (d, J = 8.1 Hz, 1H), 7.47 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.04
		(s, 1H), 6.95 (s, 1H), 6.86 (t, J = 74.7 Hz, 1H), 5.29-5.17 (m, 1H), 4.97-
		4.84 (m, 1H), 4.71-4.64 (m, 1H), 4.45-4.32 (m, 1H), 4.12 (s, 3H), 4.00
		(s, 3H), 3.62 (brs, 2H), 2.49-2.39 (m, 1H), 2.04-1.54 (m, 7H), 1.47 (d,
		J = 7.1 Hz, 3H), 1.46-1.29 (m, 4H), 1.16 (s, 3H), 1.14-0.95 (m, 2H).
724	666.2	1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 7.3 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 8.06 (brs, 1H 1st rotamer), 7.92 (brs, 2H 2nd rotamer), 7.55
		(s, 0.4H 1st rotamer), 7.41 (s, 0.6H 2nd rotamer), 7.22 (d, J = 8.1 Hz, 1H),
		7.05 (s, 1H), 7.00 (s, 0.4H 1st ortamer), 6.96 (s, 0.6H 2nd rotamer), 5.21-
		5.11 (m, 1H), 4.85-4.71 (m, 1H), 4.54 (s, 0.4H 1st rotamer), 4.52-4.43
		(m, 1H), 4.21 (s, 0.6H 2nd rotamer), 4.12 (s, 3H), 4.00 (d, J = 2.4 Hz, 3H),
		3.84-3.73 (m, 0.4H 1st rotaner), 3.61 (d, J = 12.0 Hz, 0.6H 2nd rotamer),
		3.24-3.13 (m, 1H), 2.68 (s, 0.6H 2nd rotamer), 2.58 (s, 0.4H 1st
		rotamer), 2.11-1.52 (m, 7H), 1.50 (d, J = 7.1 Hz, 3H), 1.46 (s, 3H), 1.44-
		1.21 (m, 4H), 1.08-0.95 (m, 2H).
725	720.2	1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 7.4 Hz, 1H), 8.18 (brs,
		3H), 8.07 (d, J = 8.1 Hz, 1H), 7.46 (s, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.05
		(s, 1H), 6.95 (s, 1H), 6.86 (t, J = 74.7 Hz, 1H), 5.21-5.12 (m, 1H), 4.86-
		4.73 (m, 1H), 4.70-4.63 (m, 1H), 4.53-4.40 (m, 1H), 4.12 (s, 3H), 4.00
		(s, 3H), 3.60 (brs, 2H), 2.06-1.55 (m, 7H), 1.50 (d, J = 7.1 Hz, 3H), 1.46
		(s, 3H), 1.42-1.21 (m, 5H), 1.13-0.97 (m, 2H).
726	676.2	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.8 Hz, 1H), 8.10 (s, 2H),
		8.06 (d, J = 8.0 Hz, 1H), 7.93 (brs, 1H), 7.48 (s, 1H), 7.24 (d, J = 8.1 Hz,
		1H), 7.14 (s, 1H), 6.98 (d, J = 1.2 Hz, 1H), 5.51 (t, J = 13.5 Hz, 1H), 5.27-
		5.02 (m, 2H), 4.69 (brs, 1H), 4.19 (brs, 1H), 4.10 (s, 3H), 4.01 (s, 3H),
		3.66 (brs, 2H), 3.32 (s, 3H), 2.34-1.49 (m, 10H), 1.44 (d, J = 7.1 Hz,
		3H), 1.41-1.15 (m, 1H), 0.89-0.82 (m, 1H), 0.72-0.53 (m, 1H), 0.55-
		0.43 (m, 2H).
727	720.2	1H NMR (400 MHz, DMSO-d6) δ 8.40 (d, J = 7.9 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 7.99 (brs, 3H), 7.41 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.15 (s,
		1H), 6.94 (d, J = 1.1 Hz, 1H), 5.52-5.33 (m, 1H), 5.28-5.10 (m, 2H),
		4.10 (s, 3H), 3.99 (s, 3H), 3.63-3.37 (m, 3H), 3.36 (s, 3H), 2.44-2.29
		(m, 1H), 2.15-1.57 (m, 6H), 1.56-1.39 (m, 1H), 1.46 (d, J = 7.1 Hz,
		3H), 1.30-1.06 (m, 2H), 1.12 (s, 3H), 1.03-0.77 (m, 1H).
728	708.5	1H NMR (400 MHz, DMSO-d6) δ 8.41 (d, J = 7.9 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 8.09 (s, 1H), 8.05 (s, 3H), 7.37 (d, J = 1.1 Hz, 1H), 7.27 (d,
		J = 8.1 Hz, 1H), 7.15 (s, 1H), 6.89 (s, 1H), 5.51-5.32 (m, 1H), 5.34-4.85
		(m, 3H), 4.09 (s, 3H), 3.99 (s, 3H), 3.50-3.29 (m, 3H), 2.90 (brs, 1H),
		2.41-2.30 (m, 2H), 2.15-1.56 (m, 5H), 1.55-1.40 (m, 1H), 1.46 (d, J =
		7.2 Hz, 3H), 1.28-1.14 (m, 2H), 1.12 (s, 3H), 1.04-0.87 (m, 1H).
729	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.6 Hz, 1H), 8.00 (d, J =
		8.1 Hz, 1H), 7.96 (brs, 3H), 7.44 (s, 1H), 7.16 (s, 1H), 7.15 (d, J = 8.5 Hz,
		1H), 6.87 (s, 1H), 5.07-4.96 (m, 2H), 4.88-4.66 (m, 3H), 4.63-4.52
		(m, 2H), 3.84 (brs, 2H), 3.76-3.65 (m, 2H), 3.36 (s, 3H), 2.04-1.47 (m,
		8H), 1.43 (d, J = 7.1 Hz, 3H), 1.33-1.19 (m, 2H), 0.92-0.79 (m, 1H),
		0.79-0.61 (m, 2H), 0.55-0.41 (m, 1H).
730	756.1	1H NMR (400 MHz, DMSO-d6) δ 8.40 (d, J = 7.9 Hz, 1H), 8.20 (brs,
		3H), 8.11 (d, J = 8.0 Hz, 1H), 7.84 (s, 1H), 7.82 (s, 1H), 7.52 (s, 1H), 7.50
		(s, 1H), 7.43 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.15 (s, 1H), 6.95 (d, J =
		1.2 Hz, 1H), 6.86 (t, J = 74.8 Hz, 1H), 5.54-5.32 (m, 1H), 5.26-5.11
		(m, 2H), 4.70-4.63 (m, 1H), 4.10 (s, 3H), 4.00 (s, 3H), 3.52-3.38 (m,
		1H), 2.44 (s, 3H), 2.42-2.27 (m, 1H), 2.20-1.56 (m, 4H), 1.46 (d, J =
		7.1 Hz, 3H), 1.32-1.15 (m, 1H), 1.12 (s, 3H), 1.05-0.82 (m, 1H).
731	701.2	1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 6.6 Hz, 1H), 8.18 (s, 1H),
		8.10 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 8.5 Hz, 1H), 7.98 (s, 3H), 7.91 (dd,
		J = 8.2, 1.3 Hz, 1H), 7.80-7.73 (m, 1H), 7.65-7.59 (m, 1H), 7.44 (s, 1H),
		7.30 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.94 (d, J = 1.1 Hz, 1H), 5.31-5.17
		(m, 1H), 4.97-4.80 (m, 1H), 4.64-4.52 (m, 1H), 4.13 (s, 3H), 4.00 (s,
		3H), 3.96-3.69 (m, 3H), 3.37 (s, 3H), 3.29-3.22 (m, 1H), 2.81-2.55
		(m, 1H), 2.64-2.38 (m, 2H), 2.04-1.84 (m, 1H), 1.82-1.69 (m, 1H),
		1.55 (d, J = 7.1 Hz, 3H), 1.55-1.15 (m, 4H), 0.60-0.45 (m, 1H).
732	737.3	1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 6.6 Hz, 1H), 8.20 (brs,
		3H), 8.18 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.92
		(dd, J = 8.3, 1.3 Hz, 1H), 7.80-7.72 (m, 1H), 7.65-7.59 (m, 1H), 7.46
		(s, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.95 (d, J = 1.2 Hz, 1H),
		6.86 (t, J = 74.8 Hz, 1H), 5.31-5.20 (m, 1H), 4.97-4.82 (m, 1H), 4.73-
		4.52 (m, 2H), 4.13 (s, 3H), 4.00 (s, 3H), 3.68-3.27 (m, 4H), 2.72-2.35
		(m, 2H), 2.10-2.88 (m, 1H), 1.61-1.36 (m, 1H), 1.55 (d, J = 7.1 Hz,
		3H), 1.32-1.12 (m, 3H), 0.66-0.43 (m, 1H).
733	720.2	1H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J = 7.4 Hz, 1H), 8.12 (d, J =
		8.0 Hz, 1H), 7.99 (brs, 3H), 7.41 (s, 1H), 7.29 (d, J = 8.1 Hz, 1H), 7.16 (s,
		1H), 6.96-6.93 (m, 1H), 5.44-5.06 (m, 4H), 4.10 (s, 3H), 3.99 (s, 3H),
		3.58-3.37 (m, 3H), 3.37 (s, 3H), 2.50-2.41 (m, 1H), 2.00-1.59 (m,
		7H), 1.56-1.41 (m, 1H), 1.48 (d, J = 7.4 Hz, 3H), 1.43 (s, 3H), 1.37-
		0.96 (m, 3H).
734	648.3	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.6 Hz, 1H), 8.18 (brs,
		3H), 8.01 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.16 (s, 1H), 7.15 (d, J = 8.5
		Hz, 1H), 6.88 (s, 1H), 6.85 (t, J = 74.8 Hz, 1H), 5.10-4.98 (m, 2H), 4.79-
		4.55 (m, 6H), 3.91 (brs, 1H), 3.46 (brs, 1H), 2.06-1.39 (m, 10H), 1.43
		(d, J = 7.1 Hz, 3H), 1.34-1.18 (m, 1H), 0.99-0.83 (m, 1H), 0.78-0.60
		(m, 2H), 0.53-0.44 (m, 1H).
735	715.2	1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 8.15 (d, J = 8.1 Hz, 1H),
		8.05 (d, J = 8.5 Hz, 1H), 7.99 (brs, 3H), 7.94 (dd, J = 8.3, 1.4 Hz, 1H),
		7.77 (ddd, J = 8.5, 6.8, 1.5 Hz, 1H), 7.64 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H),
		7.45 (s, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.11 (s, 1H), 6.94 (d, J = 1.1 Hz,
		1H), 5.95 (q, J = 7.2 Hz, 1H), 4.86-4.73 (m, 1H), 4.61-4.53 (m, 1H),
		4.13 (s, 3H), 4.00 (s, 3H), 3.55 (brs, 2H), 3.46-3.33 (m, 1H), 3.37 (s,
		3H), 3.14 (s, 3H), 2.74-2.60 (m, 1H), 2.43-2.27 (m, 1H), 2.05-1.88
		(m, 1H), 1.82-1.68 (m, 1H), 1.71 (d, J = 7.3 Hz, 3H), 1.67-1.21 (m,
		8H), 0.79-0.65 (m, 1H).
736	751.3	1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 8.19 (brs, 3H), 8.15 (d,
		J = 8.1 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.94 (dd, J = 8.3, 1.4 Hz, 1H),
		7.77 (ddd, J = 8.5, 6.8, 1.5 Hz, 1H), 7.64 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H),
		7.47 (s, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.11 (s, 1H), 6.95 (d, J = 1.2 Hz,
		1H), 6.84 (t, J = 74.8 Hz, 1H), 5.95 (q, J = 7.3 Hz, 1H), 4.95-4.75 (m,
		1H), 4.73-4.62 (m, 1H), 4.62-4.52 (m, 1H), 4.17-4.13 (m, 1H), 4.13
		(s, 3H), 4.00 (s, 3H), 3.99-3.93 (m, 1H), 3.50-3.34 (m, 3H), 3.13 (s,
		3H), 2.80-2.58 (m, 1H), 2.45-2.27 (m, 1H), 2.12-1.89 (m, 4H), 1.71
		(d, J = 7.3 Hz, 3H), 1.64-1.19 (m, 3H), 0.80-0.62 (m, 1H).
737	646.2	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.6 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.84 (brs, 2H), 7.55 (s, 0.3H 1st rotamer), 7.37 (s, 0.7H 2nd
		rotamer), 7.24 (d, J = 8.1 Hz, 1H), 7.14 (s, 0.3H 1st rotamer), 7.13 (s,
		0.7H 2nd rotamer), 7.00 (s, 0.3 H 1st rotamer), 6.92 (s, 0.7H 2nd rotamer),
		5.59-5.43 (m, 1H), 5.22-5.09 (m, 1H), 5.09-4.97 (m, 1H), 4.57 (s,
		0.3H 1st rotamer), 4.10 (s, 3H), 4.00 (s, 3H), 3.90 (s, 0.7H 2nd rotamer),
		3.51-3.33 (m, 3H), 2.23-1.76 (m, 4H), 1.77-1.50 (m, 3H), 1.48-1.18
		(m, 2H), 1.44 (d, J = 7.1 Hz, 3H), 0.89-0.78 (m, 1H), 0.73-0.56 (m,
		1H), 0.56-0.42 (m, 2H).
738	638.2	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 8.8 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 3H), 7.72 (s, 1H), 7.71 (d, J = 8.3 Hz, 1H), 7.37 (d,
		J = 8.0 Hz, 1H), 7.33 (d, J = 11.8 Hz, 1H), 7.27 (s, 1H), 7.26 (d, J = 8.5
		Hz, 1H), 7.21 (s, 1H), 5.55 (t, J = 13.6 Hz, 1H), 5.18 (dd, J = 27.8, 14.6
		Hz, 1H), 5.11-5.01 (m, 1H), 4.09 (s, 3H), 3.73-3.67 (m, 2H), 3.63-
		3.40 (m, 2H), 3.37 (s, 3H), 2.28-1.87 (m, 4H), 1.82-1.50 (m, 2H), 1.45
		(d, J = 7.1 Hz, 3H), 1.40-1.24 (m, 1H), 0.89-0.83 (m, 1H), 0.73-0.54
		(m, 1H), 0.56-0.44 (m, 2H).
739	636.2	1H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 8.0 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 3H), 7.72 (s, 1H), 7.33 (dd, J = 11.7, 1.2 Hz, 1H),
		7.27 (d, J = 8.1 Hz, 1H), 7.22 (s, 1H), 6.42-6.29 (m, 1H), 5.86 (t, J =
		18.3 Hz, 1H), 5.68-5.57 (m, 1H), 5.25 (dd, J = 28.2, 14.6 Hz, 1H), 5.07-
		4.97 (m 1H), 4.08 (s, 3H), 3.94-3.68 (m, 2H), 3.48-3.38 (m, 2H),
		3.37 (s, 3H), 2.75-2.55 (m, 1H), 2.00-1.73 (m, 2H), 1.60-1.45 (m,
		1H), 1.44 (d, J = 7.1 Hz, 3H), 1.23 (s, 3H), 1.00-0.89 (m, 1H), 0.78-
		0.58 (m, 2H).
740	673.2	1H NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 7.2 Hz, 1H), 8.12 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 3H), 7.83 (d, J = 8.1 Hz, 1H), 7.71 (s, 1H), 7.42 (d,
		J = 8.0 Hz, 1H), 7.30 (d, J = 11.2 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.16
		(s, 1H), 5.30-5.16 (m, 1H), 4.94-4.76 (m, 1H), 4.70-4.57 (m, 1H),
		4.11 (s, 3H), 3.95-3.53 (m, 5H), 3.37 (s, 3H), 2.74-2.58 (m, 1H), 2.43-
		2.29 (m, 2H), 2.02-1.86 (m 1H), 1.82-1.72 (m, 1H), 1.66-1.40 (m,
		2H), 1.50 (d, J = 7.1 Hz, 3H), 1.31-1.13 (m, 1H), 0.73-0.55 (m, 1H).
741	657.3	1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 7.2 Hz, 1H), 8.12 (d, J =
		8.0 Hz, 1H), 7.93 (brs, 3H), 7.83 (d, J = 8.0 Hz, 1H), 7.63 (s, 1H), 7.41 (d,
		J = 8.0 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.25 (d, J = 12 Hz, 1H), 7.16 (s,
		1H), 5.31-5.15 (m, 1H), 4.94-4.82 (m, 1H), 4.71-4.59 (m, 1H), 4.11
		(s, 3H), 3.02 (brs, 2H), 2.71-2.57 (m, 1H), 2.44-2.31 (m, 2H), 1.88-
		1.36 (m, 6H), 1.50 (d, J = 7.1 Hz, 3H), 1.29-1.11 (m, 1H), 1.20 (d, J =
		7.0 Hz, 3H), 0.70-0.54 (m, 1H).
742	662.3	1H NMR (400 MHz, DMSO-d6) δ 8.68 (d, J = 8.0 Hz, 1H), 8.09 (d, J =
		8.1 Hz, 1H), 7.97 (s, 3H), 7.70 (s, 1H), 7.38 (s, 1H), 7.32 (dd, J = 11.5, 1.2
		Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 6.43-6.31 (m, 1H), 5.96-5.79 (m,
		2H), 5.27 (dd, J = 28.4, 14.6 Hz, 1H), 5.10-4.97 (m, 1H), 4.07-4.01 (m,
		1H), 3.87 (brs, 2H), 3.74-3.49 (m, 5H), 2.67-2.55 (m, 1H), 2.02-1.88
		(m, 1H), 1.84-1.73 (m, 1H), 1.61-1.46 (m, 2H), 1.43 (d, J = 7.1 Hz,
		3H), 1.29-1.21 (m, 1H), 1.07-0.90 (m, 3H), 0.84-0.70 (m, 1H), 0.70-
		0.59 (m, 1H), 0.51-0.40 (m, 1H).
743	658.2	1H NMR (400 MHz, DMSO-d6) δ 9.20 (d, J = 6.8 Hz, 1H), 8.38 (s, 1H),
		8.11 (d, J = 8.0 Hz, 1H), 7.99 (brs, 3H), 7.70 (s, 1H), 7.45 (s, 1H), 7.30 (d,
		J = 12.3 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.16 (s, 1H), 5.26-5.12 (m,
		1H), 4.92-4.78 (m, 1H), 4.69-4.61 (m, 1H), 4.11 (s, 3H), 3.63-3.59
		(m, 2H), 3.48-3.38 (m, 2H), 3.37 (s, 3H), 2.44-2.26 (m, 2H), 1.97 (brs,
		1H), 1.84-1.68 (m, 4H), 1.67-1.09 (m, 4H), 1.50 (d, J = 7.1 Hz, 3H),
		0.67-0.49 (m, 1H).
744	673.2	1H NMR (400 MHz, DMSO-d6) δ 9.20 (d, J = 6.8 Hz, 1H), 8.38 (s, 1H),
		8.11 (d, J = 8.0 Hz, 1H), 7.99 (brs, 3H), 7.70 (s, 1H), 7.45 (s, 1H), 7.35-
		7.25 (m, 2H), 7.16 (s, 1H), 5.26-5.11 (m, 1H), 4.96-4.81 (m, 1H), 4.75-
		4.62 (m, 1H), 4.11 (s, 3H), 3.64-3.58 (m, 2H), 3.48-3.38 (m, 1H),
		3.37 (s, 3H), 2.41-2.29 (m, 2H), 1.99-1.85 (m, 1H), 1.87-1.72 (m,
		4H), 1.66-1.42 (m, 5H), 1.37-1.12 (m, 2H), 0.68-0.51 (m, 1H).
745	682.3	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.7 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.97 (brs, 3H), 7.72 (s, 1H), 7.32 (dd, J = 11.4, 1.2 Hz, 1H),
		7.28 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.81 (t, J = 13.6 Hz, 1H), 5.33-
		5.00 (m, 3H), 4.10-4.00 (m, 1H), 3.77-3.68 (m, 2H), 3.47-3.38 (m,
		1H), 3.37 (s, 3H), 2.32-1.46 (m, 8H), 1.45 (d, J = 7.1 Hz, 3H), 1.39-
		1.20 (m, 2H), 0.95-0.75 (m, 2H), 0.73-0.56 (m, 1H), 0.57-0.44 (m,
		2H).
746	682.5	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.8 Hz, 1H), 8.05 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 3H), 7.72 (s, 1H), 7.50 (s, 1H), 7.32 (dd, J = 11.6,
		1.2 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.16-6.00 (m, 1H), 5.25-4.84 (m,
		3H), 4.18-4.09 (m, 1H), 3.78-3.68 (m, 2H), 3.63-3.39 (m, 2H), 3.37
		(s, 3H), 2.38-1.48 (m, 9H), 1.44 (d, J = 7.1 Hz, 3H), 1.39-1.21 (m, 1H),
		0.91-0.80 (m, 1H), 0.73-0.58 (m, 1H), 0.56-0.47 (m, 2H).
747	666.3	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.7 Hz, 1H), 8.05 (d, J =
		8.0 Hz, 1H), 7.96 (brs, 3H), 7.66-7.64 (m, 1H), 7.50 (s, 1H), 7.32-7.21
		(m, 2H), 6.19-6.01 (m, 1H), 5.31-4.81 (m, 3H), 4.17-4.05 (m, 1H),
		3.47-3.32 (m, 1H), 3.10 (brs, 1H), 2.40-1.94 (m, 4H), 1.92-1.49 (m,
		8H), 1.44 (d, J = 7.0 Hz, 3H), 1.39-1.21 (m, 1H), 1.21 (d, J = 6.9 Hz,
		3H), 0.89-0.81 (m, 1H), 0.74-0.58 (m, 1H), 0.56-0.43 (m, 2H).
748	699.3	1H NMR (400 MHz, DMSO-d6) δ 9.36 (s, 1H), 9.34 (s, 1H), 8.20 (d, J =
		8.3 Hz, 1H), 8.14 (d, J = 8.2 Hz, 1H), 7.96 (brs, 3H), 7.92 (s, 1H), 7.78-
		7.69 (m, 1H), 7.61 (s, 1H), 7.34 (s, 1H), 7.33 (s, 1H), 7.25 (d, J = 11.3 Hz,
		1H), 5.61-5.49 (m, 1H), 5.08-4.92 (m, 1H), 4.89-4.73 (m, 1H), 4.08-
		4.00 (m, 4H), 3.37 (brs, 2H), 3.03 (brs, 1H), 2.64-2.52 (m, 2H), 1.88-
		1.44 (m, 5H), 1.54 (d, J = 7.0 Hz, 3H), 1.28 (brs, 1H), 1.20 (d, J = 6.9 Hz,
		3H), 1.14-0.93 (m, 2H), 0.67-0.39 (m, 2H).
749	611.3	1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 8.04 (d, J = 8.1 Hz, 1H),
		7.92 (s, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.53 (s, 0.35H minor rotamer), 7.40
		(s, 0.35H minor rotamer), 7.35 (s, 0.65H major rotamer), 7.07 (d, J = 8.3
		Hz, 0.65H major rotamer), 6.99 (s, 0.65H major rotamer), 6.94 (s, 0.35H
		minor rotamer), 5.13-5.01 (m, 1H), 4.77-4.51 (m, 2H), 4.25-4.11 (m,
		2H), 4.10 (s, 3H), 3.99 (s, 3H), 3.67-3.49 (m, 4H), 3.25-3.13 (m, 1H),
		2.67 (brs, 1H), 2.13-1.84 (m, 4H), 1.76-1.56 (m, 3H), 1.51-1.30 (m,
		4H), 1.45 (d, J = 7.3 Hz, 3H), 1.24 (s, 2H), 1.18-0.99 (m, 4H), 0.94 (s,
		2H).
750	701.1	1H NMR (400 MHz, DMSO-d6) δ 8.75 (brs, 2H), 8.64 (d, J = 8.1 Hz,
		1H), 8.14 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 6.2 Hz, 1H), 7.85 (d, J = 8.0 Hz,
		1H), 7.63 (d, J = 10.7 Hz, 1H), 7.47 (d, J = 8.3 Hz, 1H), 7.37 (s, 1H), 7.31
		(d, J = 8.4 Hz, 1H), 5.97-5.86 (m, 1H), 4.96-4.69 (m, 3H), 4.51-4.32
		(m, 1H), 3.42 (dd, J = 35.2, 12.1 Hz, 2H), 3.08 (s, 3H), 3.05-2.91 (m,
		1H), 2.80-2.64 (m, 2H), 2.47-2.26 (m, 2H), 2.13 (brs, 1H), 2.02-1.82
		(m, 1H), 1.68 (d, J = 7.3 Hz, 3H), 1.63-1.49 (m, 3H), 1.35-1.09 (m,
		3H), 0.95-0.72 (m, 2H), 0.61-0.47 (m, 1H).
751	687.2	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.1 Hz, 1H), 8.83 (brs,
		3H), 8.64 (dd, J = 8.2 Hz, 1H), 8.10 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 6.4
		Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 10.5 Hz, 1H), 7.41 (d, J =
		8.0 Hz, 1H), 7.36 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), 5.27-5.16 (m, 1H),
		4.98-4.68 (m, 3H), 4.47-4.33 (m, 1H), 3.88-3.82 (m, 2H), 3.42 (dd, J =
		32.9, 12.5 Hz, 1H), 3.13-2.90 (m, 2H), 2.71-2.55 (m, 1H), 2.45-
		2.27 (m, 2H), 2.01-1.83 (m, 1H), 1.50 (d, J = 7.1 Hz, 3H), 1.48-1.10
		(m, 5H), 1.04-0.90 (m, 1H), 0.62-0.41 (m, 2H).
752	646.2	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.8 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 2H), 7.81 (brs, 1H), 7.48 (s, 1H), 7.24 (d, J = 8.0
		Hz, 1H), 7.14 (s, 1H), 6.98 (s, 1H), 5.51 (t, J = 13.6 Hz, 1H), 5.26-4.99
		(m, 2H), 4.76 (brs, 0.6H major rotamer), 4.21 (brs, 0.4 H, minor rotamer),
		4.10 (s, 3H), 4.01 (s, 3H), 2.26-1.49 (m, 13H), 1.44 (d, J = 7.1 Hz, 3H),
		1.38-1.23 (m, 1H), 0.90-0.81 (m, 1H), 0.73-0.55 (m, 1H), 0.55-0.44
		(m, 2H).
753	610.2	1H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 8.2 Hz, 1H), 8.05 (brs,
		1H), 8.03 (d, J = 8.0 Hz, 1H), 7.82 (brs, 1H), 7.61 (d, J = 7.9 Hz, 1H),
		7.37 (s, 1H), 7.31 (brs, 1H), 7.17 (d, J = 8.0 Hz, 1H), 5.80-5.51 (m, 2H),
		5.16 (brs, 0.6H major rotamer), 5.09-4.94 (m, 1H), 4.87-4.70 (m, 1H),
		4.42 (d, J = 13.4 Hz, 0.4H minor rotamer), 4.05 (brs, 2H), 3.43-3.01 (m,
		2H), 2.93-2.81 (m, 0.4H minor rotamer), 2.47 (brs, 0.6H major rotamer),
		1.92-1.45 (m, 6H), 1.43 (d, J = 7.1 Hz, 3H), 1.35-1.10 (m, 7H), 0.99-
		0.55 (m, 5H).
754	729.2	1H NMR (400 MHz, DMSO-d6) δ 9.29 (d, J = 6.6 Hz, 1H), 8.43 (s, 1H),
		8.12 (d, J = 8.1 Hz, 1H), 8.07 (dd, J = 8.3, 1.4 Hz, 1H), 8.01 (d, J = 5.4
		Hz, 2H), 7.95 (d, J = 8.4 Hz, 1H), 7.82-7.78 (m, 1H), 7.76 (brs, 0.4H
		minor rotamer), 7.67-7.60 (m, 2H), 7.55 (brs, 0.6H major rotamer), 7.35
		(d, J = 5.8 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 5.26-5.17 (m, 1H), 5.06
		(brs, 0.4H minor rotamer), 5.02-4.76 (m, 2H), 4.62 (dd, J = 13.3, 6.0 Hz,
		0.6H major rotamer), 4.03 (s, 2H), 3.44-3.01 (m, 2H), 2.98-2.70 (m,
		2H), 2.64-2.49 (m, 1H), 1.98 (brs, 1H), 1.90-1.31 (m, 8H), 1.55 (d, J =
		7.0 Hz, 3H), 1.31-1.03 (m, 4H), 0.64-0.39 (m, 2H).
755	710.2	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.8 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.99 (s, 2H), 7.76 (brs, 0.6H major rotamer), 7.69 (brs, 0.4H
		minor rotamer), 7.62 (brs, 0.4H minor rotamer), 7.54 (brs, 0.6H major
		rotamer), 7.30 (brs, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.24 (brs, 1H), 5.27-
		4.88 (m, 4H), 4.52 (brs, 0.4H minor rotamer), 4.42 (brs, 1H), 4.18 (brs,
		0.6H major rotamer), 3.41-3.09 (m, 3H), 2.82-2.74 (m, 1H), 2.29-1.49
		(m, 13H), 1.44 (d, J = 7.1 Hz, 3H), 1.37-1.20 (m, 1H), 0.92-0.80 (m,
		1H), 0.76-0.59 (m, 1H), 0.56-0.34 (m, 2H).
756	710.3	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.8 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.97 (brs, 2H), 7.76 (brs, 1H), 7.69 (brs, 0.4H minor
		rotamer), 7.63 (brs, 0.6H major rotamer), 7.32 (brs, 1H), 7.26 (d, J = 8.1
		Hz, 1H), 7.22 (s, 1H), 5.82-5.63 (s, 1H), 5.37-4.90 (m, 4H), 4.53 (brs,
		0.4H minor rotamer), 4.41 (brs, 1H), 4.16 (brs, 0.6H major rotamer), 3.70
		(brs, 1H), 3.16 (brs, 2H), 2.77 (brs, 1H), 2.31-1.47 (m, 13H), 1.44 (d, J =
		7.0 Hz, 3H), 1.41-1.24 (m, 1H), 0.94-0.79 (m, 1H), 0.74-0.69 (m,
		1H), 0.60-0.40 (m, 2H).
757	646.2	1H NMR (400 MHz, DMSO-d6) δ 8.70 (d, J = 7.6 Hz, 1H), 8.01 (d, J =
		8.1 Hz, 1H), 7.99 (brs, 1H), 7.76 (brs, 1H), 7.37 (brs, 1H), 7.16 (d, J = 8.1
		Hz, 1H), 7.02 (s, 1H), 6.89 (s, 1H), 5.03-4.91 (m, 1H), 4.71-4.48 (m,
		3H), 4.24 (brs, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.44-3.02 (m, 3H), 2.77
		(brs, 1H), 2.47-2.42 (m, 1H), 2.03-1.48 (m, 9H), 1.46 (d, J = 7.1 Hz,
		3H), 1.41-1.09 (m, 4H).
758	654.3	1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 9.5 Hz, 1H), 8.00 (s, 2H),
		7.91 (d, J = 8.0 Hz, 1H), 7.78 (s, 1H), 7.64 (d, J = 8.0 Hz, 0.4H minor
		rotamer), 7.29 (d, J = 8.0 Hz, 0.6H major rotamer), 7.23 (brs, 1H), 7.09 (d,
		J = 8.0 Hz, 1H), 6.65 (s, 1H), 6.43 (s, 1H), 5.23-5.10 (m, 1H), 4.98 (brs,
		1H), 4.72 (t, J = 12.0 Hz, 1H), 4.60-4.43 (m, 2H), 4.23 (brs, 1H), 4.12 (s,
		3H), 3.48-3.04 (m, 2H), 2.84-2.65 (m, 1H), 2.42-2.15 (m, 2H), 2.05-
		1.48 (m, 10H), 1.45 (d, J = 7.0 Hz, 3H), 1.39-1.05 (m, 2H), 1.00-0.80
		(m, 3H), 0.42 (brs, 1H), 0.30-0.17 (m, 1H).
759	672.2	1H NMR (400 MHz, DMSO-d6) δ 8.46 (d, J = 8.5 Hz, 1H), 8.04 (brs,
		1H), 8.00 (d, J = 8.0 Hz, 1H), 7.77 (brs, 1H), 7.46 (t, J = 73.8 Hz, 1H),
		7.22 (s, 1H), 7.18 (brs, 1H), 7.14 (d, J = 8.1 Hz, 1H), 5.11-4.96 (m, 1H),
		4.80 (brs, 2H), 4.53 (brs, 1H), 4.20 (brs, 1H), 3.96-3.09 (m, 4H), 2.78 (s,
		1H), 2.05-1.49 (m, 11H), 1.44 (d, J = 7.1 Hz, 3H), 1.41-0.45 (m, 11H).
760	743.2	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.1 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 8.00 (brs, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.76 (brs, 1H), 7.45
		(t, J = 73.9 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.30-7.22 (m, 2H), 7.17
		(brs, 1H), 5.25-5.15 (m, 1H), 5.04-4.77 (m, 2H), 4.53 (brs, 1H), 4.21
		(brs, 1H), 3.99-3.90 (m, 1H), 3.39-3.08 (m, 2H), 2.84-2.56 (m, 2H),
		2.48-2.30 (m, 2H), 2.07-1.34 (m, 8H), 1.50 (d, J = 7.0 Hz, 3H), 1.29-
		0.88 (m, 5H), 0.63-0.34 (m, 2H).
761	662.2	1H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J = 9.4 Hz, 1H), 8.17 (d, J =
		8.0 Hz, 1H), 7.97 (brs, 2H), 7.74 (brs, 1H), 7.41 (brs, 1H), 7.34 (d, J = 8.1
		Hz, 1H), 7.19 (s, 1H), 6.91 (s, 1H), 5.57-5.30 (m, 3H), 5.00 (brs, 1H),
		4.53 (brs, 1H), 4.25 (brs, 1H), 4.10 (s, 3H), 4.00 (s, 3H), 3.14-2.96 (m,
		1H), 2.80 (brs, 1H), 2.03-1.34 (m, 11H), 1.48 (d, J = 6.8 Hz, 3H), 1.30-
		0.92 (m, 4H).
762	712.4	1H NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 7.2 Hz, 1H), 8.12 (d, J =
		8.0 Hz, 1H), 7.97 (s, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.74 (brs, 2H), 7.45 (t,
		J = 73.4 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.18
		(brs, 1H), 7.14 (s, 1H), 5.28-5.16 (m, 1H), 4.99 (brs, 1H), 4.93-4.77
		(m, 1H), 4.68-4.55 (m, 1H), 4.54 (brs, 1H), 4.20 (s, 1H), 4.09 (s, 3H),
		3.45-2.55 (m, 3H), 2.45-2.31 (m, 2H), 2.04-1.37 (m, 9H), 1.50 (d, J =
		7.0 Hz, 3H), 1.23 (brs, 1H), 0.62 (s, 1H).
763	646.3	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.5 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 2H), 7.74 (brs, 2H), 7.68 (brs, 1H), 7.45 (t, J = 73.4
		Hz, 1H), 7.20 (brs, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 5.06-4.95
		(m, 1H), 4.74-4.47 (m, 2H), 4.20 (brs, 1H), 4.09 (s, 3H), 2.78 (brs, 1H),
		2.01-1.51 (m, 13H), 1.44 (d, J = 7.1 Hz, 3H), 1.42-1.17 (m, 2H), 0.90-
		0.81 (m, 1H), 0.77-0.60 (m, 2H), 0.53-0.45 (m, 1H).
764	697.4	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.0 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.97 (brs, 2H), 7.79-7.55 (m, 2H), 7.42 (d, J = 8.0 Hz, 1H),
		7.32 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.25 (brs, 1H), 5.26-5.16 (m, 1H),
		5.04-4.77 (m, 2H), 4.18 (brs, 1H), 4.07-3.97 (m, 1H), 2.72-2.59 (m,
		1H), 2.45-2.31 (m, 2H), 2.01-1.34 (m, 11H), 1.50 (d, J = 7.0 Hz, 3H),
		1.29-0.90 (m, 4H), 0.65-0.38 (m, 2H).
765	648.2	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.8 Hz, 1H), 8.06 (d, J =
		7.9 Hz, 1H), 7.96 (brs, 2H), 7.72 (brs, 1H), 7.39 (s, 1H), 7.24 (d, J = 8.0
		Hz, 1H), 7.14 (s, 1H), 6.91 (s, 1H), 5.52 (t, J = 13.6 Hz, 1H), 5.21-4.98
		(m, 2H), 4.26 (brs, 1H), 4.10 (s, 3H), 4.00 (s, 3H), 2.25-1.49 (m, 11H),
		1.44 (d, J = 7.1 Hz, 3H), 1.39-1.21 (m, 2H), 0.88-0.80 (m, 1H), 0.72-
		0.56 (m, 1H), 0.57-0.46 (m, 2H).
766	672.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.05 (d, J =
		8.0 Hz, 1H), 7.97 (brs, 2H), 7.73 (s, 1H), 7.35 (s, 1H), 7.28 (s, 1H), 7.22
		(d, J = 8.1 Hz, 1H), 6.92 (s, 1H), 5.88 (t, J = 13.7 Hz, 1H), 5.27-4.91 (m,
		2H), 4.53 (s, 1H), 4.26 (s, 1H), 4.00 (s, 3H), 3.97-3.89 (m, 1H), 3.81
		(brs, 1H), 2.77 (brs, 1H), 2.29-1.49 (m, 11H), 1.44 (d, J = 7.1 Hz, 3H),
		1.38-1.16 (m, 2H), 1.00-0.79 (m, 3H), 0.73-0.57 (m, 1H), 0.59-0.38
		(m, 3H).
767	636.3	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.5 Hz, 1H), 7.97 (d, J =
		8.0 Hz, 1H), 7.73 (s, 1H), 7.33 (s, 1H), 7.15 (s, 1H), 7.12 (d, J = 8.1 Hz,
		1H), 6.90 (s, 1H), 5.07-4.93 (m, 1H), 4.78 (brs, 2H), 4.53 (s, 1H), 4.25
		(s, 1H), 3.94-3.85 (m, 1H), 2.76 (brs, 1H), 2.13-1.49 (m, 12H), 1.44 (d,
		J = 7.1 Hz, 3H), 1.39-1.17 (m, 3H), 1.18-0.94 (m, 3H), 0.92-0.59 (m,
		5H), 0.54-0.40 (m, 3H).
768	707.3	1H NMR (400 MHz, DMSO-d6) δ 9.07 (d, J = 7.2 Hz, 1H), 8.01 (brs,
		1H), 7.99 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.79 (brs, 1H),
		7.40 (d, J = 8.0 Hz, 1H), 7.29 (s, 0.4H minor rotamer), 7.22 (brs, 0.6H
		major rotamer), 7.18 (d, J = 8.0 Hz, 1H), 6.71 (s, 1H), 6.43 (s, 1H), 5.25-
		5.15 (m, 1H), 4.98 (s, 1H), 4.87-4.75 (m, 1H), 4.60-4.48 (m, 2H), 4.24
		(s, 1H), 4.12 (s, 3H), 3.84 (brs, 1H), 3.44-3.08 (m, 2H), 2.84-2.54 (m,
		1H), 2.46-2.29 (m, 3H), 2.08-1.55 (m, 6H), 1.49 (d, J = 7.0 Hz, 3H),
		1.45-1.27 (m, 2H), 1.21-1.07 (m, 1H), 1.00-0.80 (m, 2H), 0.62-0.39
		(m, 2H), 0.25-0.16 (m, 1H).
769	690.2	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 9.6 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.96 (brs, 2H), 7.72 (brs, 1H), 7.36 (brs, 1H), 7.28 (s, 1H),
		7.25 (d, J = 8.1 Hz, 1H), 6.92 (s, 1H), 5.87 (t, J = 13.8 Hz, 1H), 5.34-
		5.16 (m, 2H), 4.99 (s, 1H), 4.53 (s, 1H), 4.26 (s, 1H), 4.00 (s, 3H), 3.97-
		3.87 (m, 1H), 3.44-2.80 (m, 3H), 2.45-1.38 (m, 11H), 1.46 (d, J = 7.1
		Hz, 3H), 1.29-1.08 (m, 2H), 1.04-0.81 (m, 3H), 0.44-0.35 (m, 1H).
770	648.2	1H NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 6.9 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.96 (brs, 2H), 7.73 (brs, 1H), 7.37 (brs, 1H), 7.35 (dd, J =
		7.4, 1.6 Hz, 1H), 7.30 (dd, J = 7.5, 1.6 Hz, 1H), 7.24 (d, J = 8.1 Hz, 2H),
		7.20 (d, J = 7.8 Hz, 1H), 7.08 (s, 1H), 6.90 (brs, 1H), 5.25-5.14 (m, 1H),
		5.00 (brs, 1H), 4.93-4.79 (m, 1H), 4.60 (d, J = 13.3 Hz, 1H), 4.23 (s, 1H),
		4.12 (s, 3H), 4.00 (s, 3H), 2.41-2.16 (m, 3H), 2.05-1.37 (m, 7H), 1.49
		(d, J = 7.1 Hz, 3H), 1.29-1.05 (m, 2H), 0.60-0.42 (m, 1H).
771	690.4	1H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 0.6H major rotamer), 8.10 (s,
		1H), 8.08 (s, 0.4H minor rotamer), 8.00 (s, 2H), 7.79 (brs, 1H), 7.37 (brs,
		1H), 7.29 (d, J = 8.2 Hz, 1H), 7.27 (s, 1H), 6.92 (s, 1H), 5.68-5.54 (m,
		1H), 5.50-5.22 (m, 2H), 4.99 (brs, 0.4H minor rotamer), 4.53 (brs, 0.6H
		major rotamer), 4.26 (brs, 0.6H major rotamer), 4.00 (s, 3H), 3.96-3.86
		(m, 1H), 3.44-3.03 (m, 4H), 2.77 (brs, 0.4H minor rotamer), 2.66-2.52
		(m, 1H), 2.05-1.50 (m, 8H), 1.45 (d, J = 6.9 Hz, 3H), 1.35 (s, 3H), 1.21
		(s, 3H), 1.19-1.02 (m, 1H), 0.97-0.80 (m, 2H), 0.45-0.35 (m, 1H).
772	666.2	1H NMR (400 MHz, DMSO-d6) δ 8.51 (d, J = 9.7 Hz, 1H), 8.04 (d, J =
		8.1 Hz, 1H), 8.00 (brs, 1H), 7.77 (brs, 1H), 7.36 (s, 1H), 7.20 (d, J = 8.1
		Hz, 1H), 7.19 (s, 1H), 6.91 (s, 1H), 5.38-5.25 (m, 1H), 5.15-4.82 (m,
		2H), 4.65-4.23 (m, 1H), 4.00 (s, 3H), 3.95-3.84 (m, 3H), 3.46-2.74
		(m, 4H), 2.36-2.15 (m, 2H), 2.10-1.90 (m, 3H), 1.90-1.31 (m, 5H),
		1.46 (d, J = 7.1 Hz, 3H), 1.20-1.04 (m, 2H), 1.02-0.88 (m, 2H), 0.87-
		0.70 (m, 2H), 0.54-0.42 (m, 1H), 0.17-0.05 (m, 1H), 0.05-−0.01 (m,
		1H).
773	676.3	1H NMR (400 MHz, DMSO-d6) δ 8.27 (d, J = 9.5 Hz, 1H), 8.17 (d, J =
		8.0 Hz, 1H), 8.00 (brs, 2H), 7.76 (brs, 1H), 7.72-7.59 (m, 1H), 7.39 (s,
		1H), 7.34 (J = 8.0 Hz, , 1H), 7.32-7.20 (m, 1H), 5.60-5.48 (m, 2H),
		5.44-5.32 (m, 1H), 4.97 (brs, 0.4H minor rotamer), 4.52 (brs, 0.6H major
		rotamer), 4.19 (brs, 1H), 4.06-3.97 (m, 1H), 3.21-3.08 (m, 1H), 2.77
		(brs, 1H), 2.04-1.42 (m, 8H), 1.49 (d, J = 6.8 Hz, 3H), 1.29-0.90 (m,
		7H), 0.99 (h, J = 6.4, 5.8 Hz, 4H), 0.52-0.41 (m, 1H).
774	695.1	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.1 Hz, 1H), 8.10 (d, J =
		8.1 Hz, 1H), 7.90 (brs, 2H), 7.83 (d, J = 8.1 Hz, 1H), 7.71 (brs, 1H), 7.65
		(brs, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.32 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H),
		7.25 (d, J = 11.8 Hz, 1H), 6.52 (brs, 1H), 5.28-5.12 (m, 1H), 5.09 (brs,
		1H), 5.01-4.75 (m, 2H), 4.27 (brs, 1H), 4.06-3.96 (m, 1H), 2.67-2.58
		(m, 1H), 2.42-2.36 (m, 2H), 2.09-1.92 (m, 3H), 1.71 (brs, 2H), 1.50 (d,
		J = 7.0 Hz, 3H), 1.44 (brs, 2H), 1.31-0.94 (m, 4H), 0.69-0.43 (m, 2H)
		0.14-0.03 (m, 1H).
775	660.5	1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J = 7.6 Hz, 1H), 8.02 (d, J =
		8.0 Hz, 1H), 7.99 (s, 2H), 7.75 (s, 1H), 7.68-7.55 (m, 1H), 7.27 (s, 1H),
		7.23 (brs, 1H), 7.17 (d, J = 8.1 Hz, 1H), 5.03-4.92 (p, J = 7.0 Hz, 1H),
		4.84 (brs, 1H), 4.70-4.59 (m, 1H), 4.53 (brs, 0.4H minor rotamer), 4.17
		(brs, 0.6H major rotamer), 4.04-3.96 (m, 1H), 3.73 (brs, 2H), 3.12 (brs,
		1H), 2.77 (brs, 1H), 2.48-2.43 (m, 2H), 2.03-1.50 (m, 10H), 1.46 (d, J =
		7.0 Hz, 3H), 1.42-1.06 (m, 5H), 0.91 (brs, 1H), 0.65 (brs, 1H).
776	729.5	1H NMR (400 MHz, DMSO-d6) δ 9.19 (d, J = 7.1 Hz, 1H), 8.13 (d, J =
		8.0 Hz, 1H), 8.00 (brs, 2H), 7.95 (d, J = 7.8 Hz, 1H), 7.77 (brs, 1H), 7.66
		(brs, 0.4H minor rotamer), 7.60 (d, J = 7.8 Hz, 1H), 7.39 (s, 1H), 7.29 (d,
		J = 8.1 Hz, 1H), 7.24 (brs, 0.6H major rotamer), 6.93 (t, J = 55.0 Hz, 1H),
		5.30-5.18 (m, 1H), 5.05-4.86 (m, 1H), 4.85-4.72 (m, 1H), 4.70-4.43
		(m, 3H), 4.15 (brs, 1H), 3.75 (m, 1H), 3.15 (brs, 1H), 2.84-2.65 (m, 2H),
		2.48-2.30 (m, 2H), 2.03-1.39 (m, 10H), 1.51 (d, J = 7.0 Hz, 3H), 1.32-
		1.16 (m, 1H), 0.73-0.55 (m, 1H).
777	697.2	1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 7.3 Hz, 1H), 7.98 (d, J =
		7.9 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.77 (brs, 1H), 7.58 (d, J = 7.8 Hz,
		1H), 7.35 7.21 (m, 1H), 7.18 (d, J = 8.0 Hz, 1H), 6.92 (t, J = 55.0 Hz, 1H),
		6.65 (brs, 1H), 6.34 (s, 1H), 5.29-5.17 (m, 1H), 4.98 (brs, 0.4H minor
		rotamer), 4.86-4.76 (m, 1H), 4.53 (d, J = 13.0 Hz, 2H), 4.24 (brs, 0.6H
		major rotamer), 4.09 (s, 3H), 3.78 (brs, 2H), 3.15 (brs, 2H), 2.81 (s, 3H),
		2.71-2.59 (m, 1H), 2.47-2.36 (m, 2H), 2.03-1.46 (m, 6H), 1.49 (d, J =
		7.0 Hz, 3H), 1.49-1.33 (m, 2H), 1.27-1.12 (m, 1H), 0.65-0.48 (m,
		1H).
778	656.4	1H NMR (400 MHz, DMSO-d6) δ 8.06 (d, J = 8.1 Hz, 1H), 7.98 (s, 3H),
		7.89 (d, J = 7.7 Hz, 1H), 7.45 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.04 (s,
		1H), 6.94 (d, J = 1.2 Hz, 1H), 4.89-4.72 (m, 1H), 4.52-4.35 (m, 2H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.94-3.84 (m, 5H), 3.77-3.65 (m, 3H), 3.61
		3.46 (m, 2H), 3.37 (s, 3H), 2.04-1.85 (m, 2H), 1.86-1.51 (m, 1H), 1.33
		(dt, J = 35.8, 7.2 Hz, 5H), 1.22 (s, 3H), 1.19-0.99 (m, 1H), 0.96 (s, 3H),
		0.63-0.46 (m, 3H), 0.42-0.29 (m, 1H).
779	644.4	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.99 (s, 3H),
		7.68 (d, J = 8.0 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), 6.93 (s,
		1H), 4.99-4.91 (m, 1H), 4.91-4.74 (m, 1H), 4.49-4.34 (m, 1H), 4.12
		(s, 3H), 3.99 (s, 3H), 3.82-3.44 (m, 5H), 3.37 (s, 4H), 2.07-1.88 (m,
		2H), 1.91-1.66 (m, 3H), 1.65-1.50 (m, 1H), 1.44-1.28 (m, 5H), 1.23
		(s, 3H), 1.10-0.98 (m, 4H), 0.98-0.91 (m, 6H).
780	685.3	1H NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 7.0 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 7.99 (s, 3H), 7.75 (d, J = 8.2 Hz, 1H), 7.49 (d, J = 8.1 Hz,
		1H), 7.43 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.94 (d, J = 1.2
		Hz, 1H), 5.22 (p, J = 7.0 Hz, 1H), 4.96-4.75 (m, 1H), 4.65-4.51 (m,
		1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.84-3.59 (m, 3H), 3.58-3.45 (m, 1H),
		3.37 (s, 3H), 2.46-2.20 (m, 3H), 2.04-1.89 (m, 1H), 1.76 (s, 1H), 1.51
		(d, J = 7.0 Hz, 3H), 1.49-1.32 (m, 3H), 1.33-1.08 (m, 3H), 0.65-0.33
		(m, 1H).
781	685.3	1H NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 7.0 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 7.99 (s, 3H), 7.75 (d, J = 8.2 Hz, 1H), 7.49 (d, J = 8.1 Hz,
		1H), 7.43 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.94 (d, J = 1.2
		Hz, 1H), 5.22 (p, J = 7.0 Hz, 1H), 4.96-4.75 (m, 1H), 4.65-4.51 (m,
		1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.84-3.59 (m, 3H), 3.58-3.45 (m, 1H),
		3.37 (s, 3H), 2.46-2.20 (m, 3H), 2.04-1.89 (m, 1H), 1.76 (s, 1H), 1.51
		(d, J = 7.0 Hz, 3H), 1.49-1.32 (m, 3H), 1.33-1.08 (m, 3H), 0.65-0.33
		(m, 1H).
782	628.3	NA
783	685.3	1H NMR (400 MHz, DMSO-d6) δ 9.06 (d, J = 6.7 Hz, 1H), 8.47 (d, J =
		2.3 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.93 (s, 3H), 7.87 (d, J = 2.3 Hz,
		1H), 7.43 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.93 (s, 1H), 5.20
		(p, J = 6.9 Hz, 1H), 4.93-4.76 (m, 1H), 4.68-4.49 (m, 1H), 4.12 (s, 3H),
		4.00 (s, 3H), 3.96-3.77 (m, 1H), 3.75-3.68 (m, 1H), 3.67-3.46 (m,
		3H), 3.20-3.02 (m, 1H), 2.48-2.38 (m, 1H), 2.39-2.24 (m, 2H), 2.04-
		1.86 (m, 1H), 1.82-1.70 (m, 1H), 1.50 (d, J = 7.0 Hz, 3H), 1.47-1.36
		(m, 1H), 1.35-1.20 (m, 3H), 1.25 (d, 3H), 0.63-0.36 (m, 1H).
784	721.3	1H NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 7.0 Hz, 1H), 8.19 (s, 3H),
		8.09 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H),
		7.45 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.95 (d, J = 1.2 Hz,
		1H), 6.86 (t, J = 74.8 Hz, 1H), 5.22 (p, J = 7.1 Hz, 1H), 4.96-4.78 (m,
		1H), 4.72-4.62 (m, 1H), 4.63-4.53 (m, 1H), 4.12 (s, 3H), 4.00 (s, 3H),
		3.70-3.50 (m, 3H), 3.49-3.35 (m, 1H), 2.42-2.20 (m, 4H), 2.05-1.88
		(m, 2H), 1.51 (d, J = 7.1 Hz, 3H), 1.47-1.33 (m, 1H), 1.32-1.08 (m,
		3H), 0.53 (d, J = 12.0 Hz, 1H).
785	684.3	1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 8.2 Hz, 1H), 8.16 (d, J =
		9.0 Hz, 1H), 7.98 (s, 3H), 7.48 (d, J = 7.7 Hz, 2H), 7.14 (d, J = 0.9 Hz,
		1H), 6.95 (d, J = 1.1 Hz, 1H), 6.26-5.96 (m, 1H), 4.96-4.76 (m, 1H),
		4.59-4.34 (m, 1H), 4.13 (s, 3H), 4.00 (s, 3H), 3.97-3.78 (m, 4H), 3.75-
		3.66 (m, 1H), 3.63-3.46 (m, 2H), 3.37 (s, 3H), 2.24-2.06 (m, 1H), 2.01
		-1.88 (m, 1H), 1.83-1.70 (m, 2H), 1.69-1.53 (m, 1H), 1.52-1.33 (m,
		5H), 1.25 (s, 3H), 1.21-1.06 (m, 1H), 1.04 (s, 3H).
786	630.4	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.93 (s, 4H),
		7.82 (d, J = 7.4 Hz, 1H), 7.36 (d, J = 1.1 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H),
		7.03 (d, J = 1.8 Hz, 1H), 6.88 (d, J = 1.1 Hz, 1H), 5.13 (p, J = 7.1 Hz, 1H),
		4.88-4.74 (m, 1H), 4.49-4.33 (m, 1H), 4.12 (d, J = 1.4 Hz, 3H), 4.00 (s,
		3H), 3.97-3.81 (m, 3H), 3.79-3.71 (m, 1H), 3.38-3.11 (m, 1H), 2.04-
		1.85 (m, 2H), 1.74-1.55 (m, 1H), 1.45 (d, J = 7.1 Hz, 3H), 1.43-1.26
		(m, 3H), 1.21 (s, 3H), 1.13 (d, J = 6.9 Hz, 3H), 1.10-1.00 (m, 3H), 0.95
		(s, 3H).
787	626.5	1H NMR (400 MHz, DMSO-d6) δ 8.88 (s, 1H), 8.02 (s, 3H), 7.96 (d, J =
		8.3 Hz, 1H), 7.45 (s, 1H), 6.99 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 6.84 (d,
		J = 8.4 Hz, 1H), 4.72-4.60 (m, 1H), 4.58-4.41 (m, 1H), 4.13 (s, 3H), 3.99
		(s, 3H), 3.94-3.76 (m, 1H), 3.77-3.66 (m, 1H), 3.62-3.46 (m, 2H),
		3.37 (s, 3H), 2.02-1.83 (m, 3H), 1.83-1.75 (m, 1H), 1.75-1.56 (m,
		4H), 1.56-1.42 (m, 2H), 1.42-1.32 (m, 1H), 1.32-1.22 (m, 1H), 1.23-
		1.14 (m, 1H), 1.01-0.67 (m, 4H), 0.55-0.41 (m, 1H).
788	707.3	1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 7.0 Hz, 1H), 8.48 (s, 1H),
		8.19 (d, J = 5.4 Hz, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.98 (s, 3H), 7.51 (d, J =
		5.5 Hz, 1H), 7.44 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.94 (d,
		J = 1.2 Hz, 1H), 5.23 (p, J = 6.9 Hz, 1H), 4.97-4.76 (m, 1H), 4.13 (s, 3H),
		4.00 (s, 3H), 3.73-3.68 (m, 4H), 3.63-3.48 (m, 5H), 3.37 (s, 3H), 2.83
		(dd, J = 12.5, 7.9 Hz, 1H), 2.03-1.88 (m, 1H), 1.84-1.69 (m, 1H), 1.52
		(d, J = 7.1 Hz, 3H), 1.50-1.33 (m, 1H), 1.29-1.12 (m, 2H), 0.74-0.46
		(m, 1H).
789	699.4	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.1 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 7.98 (s, 3H), 7.83 (d, J = 8.0 Hz, 1H), 7.68 (s, 1H), 7.42 (d,
		J = 8.1 Hz, 1H), 7.32 (d, J = 6.5 Hz, 1H), 7.29 (s, 1H), 5.21 (p, J = 7.0 Hz,
		1H), 4.99-4.87 (m, 1H), 4.86-4.76 (m, 1H), 4.07-3.97 (m, 1H), 3.74-
		3.68 (m, 1H), 3.65-3.40 (m, 7H), 3.37 (s, 3H), 2.71-2.55 (m, 1H), 2.46-
		2.25 (m, 2H), 2.04-1.87 (m, 1H), 1.83-1.69 (m, 1H), 1.50 (d, J = 7.0
		Hz, 3H), 1.48-1.34 (m, 2H), 1.27-1.16 (m, 2H), 1.14-0.96 (m, 2H),
		0.66-0.53 (m, 1H), 0.53-0.38 (m, 1H).
790	683.4	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.1 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 7.92 (s, 3H), 7.83 (d, J = 8.1 Hz, 1H), 7.60 (d, J = 1.1 Hz,
		1H), 7.42 (d, J = 8.0 Hz, 1H), 7.32 (s, 1H), 7.27 (d, J = 8.2 Hz, 1H), 5.32-
		5.10 (m, 1H), 5.00-4.77 (m, 2H), 4.10-3.93 (m, 1H), 3.65-3.24 (m,
		6H), 2.67-2.56 (m, 2H), 2.43-2.34 (m, 2H), 1.87-1.62 (m, 2H), 1.50
		(d, J = 7.0 Hz, 3H), 1.68-1.31 (m, 2H), 1.32-1.13 (m, 1H), 1.20 (d, J =
		6.9 Hz, 4H), 1.08 (d, J = 43.1 Hz, 3H), 0.70-0.32 (m, 2H).
791	687.3	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.1 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 8.06 (s, 3H), 7.82 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 1.2 Hz,
		1H), 7.42 (d, J = 8.0 Hz, 1H), 7.33 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.23
		(d, J = 11.5 Hz, 1H), 5.21 (p, J = 7.0 Hz, 1H), 5.13-4.99 (m, 1H), 5.00-
		4.87 (m, 1H), 4.87-4.77 (m, 1H), 4.08-3.97 (m, 1H), 3.68-3.48 (m,
		1H), 3.45-3.27 (m, 1H), 3.07-2.81 (m, 1H), 2.70-2.58 (m, 1H), 2.45-
		2.25 (m, 4H), 1.96-1.72 (m, 1H), 1.50 (d, J = 7.0 Hz, 3H), 1.66-1.32
		(m, 2H), 1.30-1.14 (m, 3H), 1.15-0.97 (m, 3H), 0.64-0.53 (m, 1H),
		0.53-0.38 (m, 1H).
792	652.2	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.8 Hz, 1H), 8.07 (d, 1H),
		8.03 (s, 3H), 7.42 (dd, J = 2.7, 1.1 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.14
		(d, J = 1.4 Hz, 1H), 6.92 (d, J = 1.1 Hz, 1H), 5.58-5.44 (m, 1H), 5.22-
		5.02 (m, 2H), 5.01-4.82 (m, 1H), 4.10 (s, 3H), 4.08-4.01 (m, 3H), 4.01
		(s, 3H), 3.51-3.21 (m, 1H), 3.11-2.90 (m, 1H), 2.37-2.24 (m, 1H),
		2.18-1.87 (m, 3H), 1.68-1.56 (m, 1H), 1.54 (q, J = 5.3 Hz, 1H), 1.44 (d,
		J = 7.1 Hz, 3H), 1.40-1.28 (m, 1H), 1.22 (dt, J = 6.9, 2.0 Hz, 3H), 0.92-
		0.76 (m, 1H), 0.73-0.56 (m, 1H), 0.54-0.41 (m, 2H).
793	691.5	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.0 Hz, 1H), 8.49 (s, 1H),
		8.20 (d, J = 5.5 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.93 (s, 3H), 7.51 (d, J =
		5.5 Hz, 1H), 7.35 (d, J = 1.1 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s,
		1H), 6.89 (s, 1H), 5.31-5.16 (m, 1H), 4.96-4.77 (m, 1H), 4.66-4.54
		(m, 1H), 4.13 (s, 3H), 4.00 (s, 3H), 3.93-3.44 (m, 7H), 3.44-3.25 (m,
		2H), 2.89-2.76 (m, 1H), 1.87-1.63 (m, 2H), 1.52 (d, J = 7.0 Hz, 3H),
		1.33 (d, J = 5.6 Hz, 2H), 1.21 (d, J = 6.9 Hz, 3H), 1.34-1.05 (m, 1H),
		0.77-0.43 (m, 1H).
794	695.4	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.0 Hz, 1H), 8.48 (s, 1H),
		8.19 (d, J = 5.5 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.02 (s, 3H), 7.51 (d, J =
		5.5 Hz, 1H), 7.38 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.89 (s,
		1H), 5.23 (p, J = 7.0 Hz, 1H), 5.11-4.91 (m, 1H), 4.92-4.78 (m, 1H),
		4.66-4.51 (m, 1H), 4.13 (s, 3H), 3.99 (s, 3H), 3.48-3.29 (m, 2H), 3.01-
		2.87 (m, 1H), 2.89-2.76 (m, 1H), 2.43-2.20 (m, 2H), 2.08-1.71 (m,
		3H), 1.52 (d, J = 7.0 Hz, 3H), 1.50-1.32 (m, 2H), 1.30-1.13 (m, 2H),
		0.71-0.45 (m, 1H).
795	632.4	1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 3H), 8.05 (d, J = 8.1 Hz, 1H),
		7.83 (d, J = 7.4 Hz, 1H), 7.41 (d, J = 1.1 Hz, 1H), 7.19 (d, J = 8.1 Hz, 1H),
		7.04 (d, J = 2.3 Hz, 1H), 6.92 (d, J = 1.1 Hz, 1H), 5.73-5.18 (m, 2H),
		5.20-5.07 (m, 1H), 4.97 (dt, J = 10.9, 5.2 Hz, 1H), 4.82 (ddq, J = 13.6,
		8.8, 4.9, 4.3 Hz, 1H), 4.52-4.33 (m, 1H), 4.12 (d, J = 1.3 Hz, 3H), 4.00
		(s, 3H), 3.48-3.27 (m, 1H), 3.11-2.93 (m, 1H), 2.31 (dt, J = 11.6, 5.8
		Hz, 1H), 2.06-1.84 (m, 2H), 1.74-1.54 (m, 2H), 1.45 (d, J = 7.1 Hz,
		3H), 1.36 (td, J = 12.8, 5.1 Hz, 3H), 1.25-1.19 (m, 6H), 1.16-1.01 (m,
		4H), 0.95 (d, J = 1.9 Hz, 3H).
796	705.4	1H NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 6.8 Hz, 1H), 8.50 (s, 1H),
		8.20 (d, J = 5.5 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.93 (s, 3H), 7.59 (d, J =
		1.2 Hz, 1H), 7.51 (d, J = 5.5 Hz, 1H), 7.33 (s, 1H), 7.29 (d, J = 8.1 Hz,
		1H), 7.25 (d, J = 11.4 Hz, 1H), 5.21 (p, J = 7.0 Hz, 1H), 5.02-4.88 (m,
		1H), 4.88-4.75 (m, 1H), 4.79-4.13 (m, 3H), 4.10-3.91 (m, 1H), 3.44-
		3.29 (m, 1H), 3.19-2.91 (m, 1H), 2.90-2.77 (m, 1H), 1.85-1.63 (m,
		3H), 1.64-1.54 (m, 1H), 1.53 (d, J = 7.0 Hz, 3H), 1.51-1.28 (m, 3H),
		1.34-1.23 (m, 2H), 1.20 (d, J = 6.9 Hz, 3H), 1.16-0.95 (m, 2H), 0.64-
		0.38 (m, 2H).
797	721.3	1H NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 6.8 Hz, 1H), 8.51 (s, 1H),
		8.21 (d, J = 5.5 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.99 (s, 3H), 7.68 (s,
		1H), 7.52 (d, J = 5.5 Hz, 1H), 7.33 (s, 1H), 7.29 (dd, J = 9.7, 3.6 Hz, 2H),
		5.21 (p, J = 6.9 Hz, 1H), 5.00-4.88 (m, 1H), 4.88-4.76 (m, 1H), 4.09-
		3.97 (m, 1H), 3.95-3.75 (m, 1H), 3.75-3.64 (m, 1H), 3.66-3.47 (m,
		4H), 3.46-3.39 (m, 2H), 3.37 (s, 3H), 2.83 (dd, J = 12.6, 7.9 Hz, 1H),
		2.02-1.87 (m, 1H), 1.82-1.66 (m, 1H), 1.53 (d, J = 7.1 Hz, 3H), 1.51-
		1.32 (m, 4H), 1.28-1.16 (m, 2H), 1.16-0.94 (m, 2H), 0.52 (d, J = 32.5
		Hz, 2H).
798	681.4	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 6.9 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 7.99 (s, 3H), 7.64 (s, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.33 (s,
		1H), 7.31-7.23 (m, 2H), 5.21 (p, J = 7.1 Hz, 1H), 5.02-4.76 (m, 2H),
		4.02 (s, 1H), 3.81-3.71 (m, 1H), 3.68-3.31 (m, 2H), 3.26-3.14 (m,
		1H), 2.73-2.56 (m, 2H), 2.44-2.28 (m, 2H), 2.03-1.80 (m, 4H), 1.57
		1.36 (m, 3H), 1.50 (d, J = 7.0 Hz, 3H), 1.28-1.14 (m, 2H), 1.14-0.96
		(m, 2H), 0.86-0.73 (m, 1H), 0.66-0.35 (m, 2H).
799	628.6	1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J = 7.1 Hz, 1H), 8.06 (d, J =
		8.1 Hz, 1H), 7.89 (s, 3H), 7.36 (d, J = 1.2 Hz, 1H), 7.22 (d, J = 8.2 Hz,
		1H), 7.02 (s, 1H), 6.88 (s, 1H), 5.17 (p, J = 6.8 Hz, 1H), 4.81 (d, J = 5.6
		Hz, 1H), 4.74 (d, J = 6.3 Hz, 1H), 4.73-4.61 (m, 1H), 4.50-4.31 (m,
		1H), 4.19 (d, J = 5.6 Hz, 1H), 4.11 (d, J = 2.5 Hz, 3H), 3.99 (s, 3H), 3.89-
		3.73 (m, 2H), 3.44-3.23 (m, 2H), 2.27-2.12 (m, 1H), 2.06-1.93 (m,
		1H), 1.88-1.66 (m, 3H), 1.66-1.52 (m, 3H), 1.49 (d, J = 7.1 Hz, 3H),
		1.41-1.26 (m, 4H), 1.20 (d, J = 6.9 Hz, 3H), 1.17-0.91 (m, 3H).
800	630.6	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.1 Hz, 1H), 7.82 (d, J =
		7.4 Hz, 1H), 7.37 (d, J = 1.2 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.03 (d, J =
		2.1 Hz, 1H), 6.89 (s, 1H), 5.13 (p, J = 7.2 Hz, 1H), 5.07-4.90 (m, 2H),
		4.92-4.75 (m, 1H), 4.53-4.31 (m, 2H), 4.12 (d, J = 1.9 Hz, 3H), 4.00 (s,
		3H), 3.90-3.54 (m, 5H), 3.49-3.28 (m, 4H), 2.09-1.97 (m, 1H), 1.98-
		1.86 (m, 2H), 1.75-1.53 (m, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.44-1.26
		(m, 3H), 1.21 (s, 3H), 1.27-1.15 (m, 2H), 1.15-0.99 (m, 2H), 0.95 (s,
		3H).
801	676.7	1H NMR (400 MHz, DMSO-d6) δ 9.29 (s, 1H), 8.97 (s, 1H), 8.56 (d, J =
		8.8 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 7.39 (d, J = 1.1 Hz, 1H), 7.24 (d, J =
		8.1 Hz, 1H), 7.14 (d, J = 2.0 Hz, 1H), 6.92-6.87 (m, 1H), 5.64-5.41 (m,
		1H), 5.22-4.99 (m, 2H), 4.10 (d, J = 1.4 Hz, 3H), 4.09-3.92 (m, 1H),
		4.00 (s, 3H), 3.65 (d, J = 12.4 Hz, 3H), 3.56-3.48 (m, 4H), 3.45-3.17
		(m, 3H), 3.12-2.95 (m, 1H), 2.28-1.91 (m, 2H), 1.83-1.68 (m, 1H),
		1.67-1.57 (m, 0H), 1.54 (q, J = 5.2 Hz, 1H), 1.44 (d, J = 7.1 Hz, 3H),
		1.33 (d, J = 7.0 Hz, 3H), 1.31-1.18 (m, 1H), 0.90-0.81 (m, 1H), 0.73-
		0.58 (m, 1H), 0.55-0.43 (m, 2H).
802	678.5	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.94 (s, 3H), 7.63 (d, J = 1.2 Hz, 1H), 7.42 (s, 1H), 7.28 (d,
		J = 11.3 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 5.79 (t, J = 13.8 Hz, 1H), 5.19
		(dd, J = 28.0, 14.6 Hz, 1H), 5.07 (p, J = 8.6, 6.8 Hz, 1H), 4.72-4.25 (m,
		4H), 4.23-4.16 (m, 1H), 4.14-3.82 (m, 4H), 3.83-3.74 (m, 1H), 3.44-
		3.33 (m, 1H), 3.31 (d, J = 1.5 Hz, 3H), 2.28-2.02 (m, 1H), 2.03-1.90
		(m, 1H), 1.83-1.59 (m, 3H), 1.55 (q, J = 5.1 Hz, 1H), 1.44 (d, J = 7.1 Hz,
		3H), 1.40-1.26 (m, 1H), 1.21 (d, J = 6.9 Hz, 3H), 0.92-0.78 (m, 1H),
		0.75-0.55 (m, 1H), 0.55-0.45 (m, 2H).
803	662.3	1H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 8.87 (s, 1H), 8.56 (d, J =
		8.8 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 7.44 (d, J = 1.1 Hz, 1H), 7.24 (d, J =
		8.1 Hz, 1H), 7.14 (s, 1H), 7.01-6.92 (m, 1H), 5.51 (t, J = 13.6 Hz, 1H),
		5.25-5.10 (m, 1H), 5.05 (dq, J = 9.3, 7.1, 6.2 Hz, 1H), 4.10 (s, 3H), 4.01
		(s, 5H), 3.82 (s, 3H), 3.75 (d, J = 11.3 Hz, 3H), 3.63 (s, 2H), 3.38-3.15
		(m, 1H), 3.07 (s, 1H), 2.22-2.01 (m, 1H), 1.99-1.77 (m, 2H), 1.67-
		1.57 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H), 1.38-1.17 (m, 1H), 0.91-0.77
		(m, 1H), 0.72-0.55 (m, 1H), 0.53-0.44 (m, 2H).
804	676.3	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.7 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 7.91 (s, 2H), 7.80 (s, 0H), 7.66 (s, 1H), 7.42 (s, 1H), 7.41-
		7.20 (m, 2H), 5.79 (t, J = 13.8 Hz, 1H), 5.19 (dd, J = 28.0, 14.6 Hz, 1H),
		5.12-4.94 (m, 1H), 4.31-4.09 (m, 1H), 3.84-3.73 (m, 1H), 3.65-3.51
		(m, 2H), 3.47-3.34 (m, 3H), 3.31 (s, 3H), 3.20 (t, J = 8.8 Hz, 1H), 2.71-
		2.62 (m, 1H), 2.62-2.54 (m, 1H), 2.28-2.05 (m, 1H), 2.07-1.79 (m,
		3H), 1.74-1.59 (m, 2H), 1.59-1.49 (m, 1H), 1.44 (d, J = 7.0 Hz, 3H),
		1.40-1.26 (m, 2H), 0.86 (t, J = 5.3 Hz, 1H), 0.74-0.42 (m, 4H).
805	664.5	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.8 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.01 (s, 3H), 7.75 (d, J = 1.4 Hz, 1H), 7.43 (d, J = 1.3 Hz,
		1H), 7.36 (s, 1H), 7.24 (d, J = 8.1 Hz, 1H), 5.95-5.72 (m, 1H), 5.20 (dd,
		J = 28.0, 14.6 Hz, 1H), 5.06 (p, 1H), 4.76-4.15 (m, 2H), 4.10-3.98 (m,
		1H), 3.45-3.27 (m, 1H), 3.26-2.77 (m, 2H), 2.31-2.04 (m, 2H), 2.05-
		1.87 (m, 1H), 1.88-1.51 (m, 4H), 1.44 (d, J = 7.0 Hz, 3H), 1.43-1.24
		(m, 2H), 1.22 (d, J = 6.9 Hz, 3H), 1.12-1.02 (m, 1H), 1.02-0.92 (m,
		2H), 0.92-0.80 (m, 1H), 0.77-0.59 (m, 1H), 0.59-0.41 (m, 3H).
806	680.3	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.8 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.02 (s, 3H), 7.81 (s, 1H), 7.50 (d, J = 1.4 Hz, 1H), 7.36 (s,
		1H), 7.24 (d, J = 8.1 Hz, 1H), 5.94-5.78 (m, 1H), 5.21 (dd, J = 28.0, 14.6
		Hz, 1H), 5.06 (p, 1H), 4.08-4.00 (m, 1H), 3.97-3.75 (m, 3H), 3.71 (dt, J =
		6.5, 3.1 Hz, 1H), 3.66-3.49 (m, 1H), 3.48-3.38 (m, 2H), 3.37 (s, 3H),
		2.33-2.04 (m, 1H), 2.03-1.85 (m, 1H), 1.85-1.70 (m, 1H), 1.70-1.60
		(m, 1H), 1.59-1.51 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H), 1.40-1.18 (m,
		2H), 1.12-0.92 (m, 2H), 0.91-0.79 (m, 1H), 0.75-0.59 (m, 1H), 0.58-
		0.43 (m, 3H).
807	683.4	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.1 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.90 (s, 3H), 7.83 (d, J = 8.0 Hz, 1H), 7.59 (d, J = 1.2 Hz,
		1H), 7.42 (d, J = 8.0 Hz, 1H), 7.32 (s, 1H), 7.27 (d, J = 8.3 Hz, 1H), 7.26
		(d, 1H), 5.21 (p, J = 7.0 Hz, 1H), 4.98-4.85 (m, 1H), 4.86-4.74 (m,
		1H), 4.08-3.98 (m, 1H), 3.95-3.44 (m, 4H), 3.25-3.09 (m, 1H), 3.10-
		2.83 (m, 1H), 2.72-2.57 (m, 1H), 2.47-2.23 (m, 2H), 1.94-1.71 (m,
		3H), 1.66-1.53 (m, 1H), 1.50 (d, J = 7.0 Hz, 3H), 1.50-1.34 (m, 2H),
		1.30-1.14 (m, 1H), 1.20 (d, J = 6.9 Hz, 3H), 1.17-0.94 (m, 2H), 0.69-
		0.34 (m, 2H).
808	681.6	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.1 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 3H), 8.08 (s, 3H), 7.83 (d, J = 8.1 Hz, 1H), 7.81 (s, 1H), 7.42 (d,
		J = 8.0 Hz, 2H), 7.38 (d, 1H), 7.33 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 5.21
		(p, J = 7.1 Hz, 1H), 5.01-4.74 (m, 2H), 4.71-4.24 (m, 2H), 4.08-3.97 (m,
		1H), 3.89-3.09 (m, 1H), 2.70-2.57 (m, 1H), 2.45-2.23 (m, 2H), 1.92-
		1.72 (m, 3H), 1.68-1.56 (m, 1H), 1.51 (d, J = 7.1 Hz, 3H), 1.48-1.45
		(m, 2H), 1.28-1.14 (m, 2H), 1.14-0.95 (m, 2H), 0.65-0.38 (m, 2H).
809	707.3	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.1 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.99 (s, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.76 (s, 1H), 7.41 (d,
		J = 8.1 Hz, 1H), 7.33 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.22 (s, 1H), 6.91
		(s, 1H), 5.20 (p, J = 7.0 Hz, 1H), 5.05-4.70 (m, 2H), 4.61-4.44 (m, 0.5H),
		4.35-4.20 (m, 0.5H), 4.00 (s, 3H), 3.96-3.88 (m, 1H), 3.87-3.63 (m,
		2H), 3.43-3.34 (m, 0.5H), 3.18-3.13 (m, 0.3H), 2.83-2.70 (m, 0.4H),
		2.71-2.56 (m, 1H), 2.44-2.25 (m, 2H), 2.06-1.89 (m, 1H), 1.90-1.73
		(m, 1H), 1.73-1.56 (m, 5H), 1.50 (d, J = 7.1 Hz, 3H), 1.46-1.31 (m,
		3H), 1.28-1.09 (m, 1H), 1.07-0.96 (m, 1H), 0.95-0.76 (m, 1H), 0.63-
		0.47 (m, 1H), 0.46-0.20 (m, 1H).
810	695.5	1H NMR (400 MHz, DMSO-d6) δ 9.22 (d, J = 6.6 Hz, 1H), 8.37 (s, 1H),
		8.10 (d, J = 8.0 Hz, 1H), 7.99 (s, 2H), 7.76 (s, 1H), 7.58 (s, 0.5H), 7.45 (s,
		1H), 7.32 (s, 1H), 7.30 (s, 0.5H), 7.26 (d, J = 8.1 Hz, 1H), 5.16 (p, J = 6.9
		Hz, 1H), 5.05-4.94 (m, 0.4H), 4.95-4.79 (m, 2H), 4.61-4.44 (m,
		0.6H), 4.25-4.13 (m, 1H), 4.07-3.98 (m, 1H), 3.98-3.85 (m, 3H), 3.82-
		3.66 (m, 1H), 3.43-3.21 (m, 1H), 3.21-2.96 (m, 0.5H), 2.85-2.71
		(m, 0.5H), 2.40-2.23 (m, 2H), 2.06-1.89 (m, 1H), 1.89-1.71 (m, 1H),
		1.73-1.56 (m, 3H), 1.51 (d, J = 7.0 Hz, 3H), 1.48-1.35 (m, 3H), 1.39-
		0.90 (m, 4H), 0.63-0.36 (m, 2H).
811	681.3	1H NMR (400 MHz, DMSO-d6) δ 9.04 (d, J = 7.3 Hz, 1H), 7.98 (d, J =
		8.0 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H), 7.76 (s, 2H), 7.40 (d, J = 8.0 Hz,
		1H), 7.35-7.20 (m, 1H), 7.18 (d, J = 8.0 Hz, 1H), 6.65 (s, 1H), 6.35 (s,
		1H), 5.21 (p, J = 7.0 Hz, 1H), 5.07-4.89 (m, 0.6H), 4.85-4.71 (m, 1H),
		4.65-4.43 (m, 1H), 4.30-4.17 (m, 0.7H), 4.09 (s, 3H), 3.68-3.44 (m,
		2H), 2.81 (s, 3H), 2.66-2.55 (m, 0.6H), 2.45-2.30 (m, 3H), 2.03-1.91
		(m, 2H), 1.81-1.73 (m, 4H), 1.55 (s, 3H), 1.48 (d, J = 7.0 Hz, 3H), 1.46-
		1.32 (m, 1H), 1.23-1.07 (m, 1H), 0.70-0.45 (m, 1H).
812	711.3	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.1 Hz, 1H), 8.10 (d, J =
		8.1 Hz, 1H), 7.97 (s, 2H), 7.83 (d, J = 8.1 Hz, 1H), 7.75 (s, 1H), 7.48 (s,
		1H), 7.42 (d, J = 8.0 Hz, 1H), 7.30 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 5.21
		(p, J = 7.0 Hz, 1H), 5.04-4.75 (m, 2H), 4.64-4.43 (m, 0.57H, rotamer),
		4.27-4.11 (m, 0.53H, rotamer), 4.10-3.98 (m, 1H), 3.83-3.63 (m,
		0.56H, rotamer), 3.59-3.14 (m, 4H), 2.82-2.72 (m, 0.56H, rotamer),
		2.70-2.58 (m, 1H), 2.44-2.27 (m, 2H), 2.06-1.89 (m, 1H), 1.91-1.73
		(m, 1H), 1.72-1.56 (m, 1H), 1.50 (d, J = 7.1 Hz, 3H), 1.48-1.38 (m,
		1H), 1.30-1.06 (m, 3H), 1.05-0.87 (m, 1H), 0.66-0.51 (m, 1H), 0.52-
		0.35 (m, 1H).
813	701.3	1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.10 (d, J = 8.1 Hz, 1H),
		7.96 (s, 1H), 7.73 (s, 1H), 7.62 (s, 2H), 7.31 (s, 1H), 7.25 (d, J = 8.1 Hz,
		1H), 7.16 (d, J = 7.9 Hz, 1H), 5.18 (p, J = 6.9 Hz, 1H), 5.03-4.86 (m,
		1H), 4.86-4.71 (m, 1H), 4.62-4.38 (m, 0.48H, rotamer), 4.28-4.11 (m,
		1H), 4.09-3.97 (m, 1H), 3.90-3.32 (m, 3H), 3.21-2.97 (m, 0.34H,
		rotamer), 2.72-2.60 (m, 2H), 2.39-2.26 (m, 2H), 2.17-2.06 (m, 1H),
		2.04-1.91 (m, 1H), 1.90-1.72 (m, 1H), 1.60 (d, J = 39.2 Hz, 1H), 1.49
		(d, J = 7.1 Hz, 3H), 1.59-1.41 (m, 3H), 1.41-1.31 (m, 1H), 1.29-1.13
		(m, 3H), 1.13-1.01 (m, 1H), 1.01-0.83 (m, 5H), 0.63-0.52 (m, 1H),
		0.51-0.40 (m, 1H).
814	731.3	1H NMR (400 MHz, DMSO-d6) δ 9.19 (d, J = 7.4 Hz, 1H), 8.19 (d, J =
		8.1 Hz, 1H), 7.98 (s, 2H), 7.87 (d, J = 8.0 Hz, 1H), 7.75 (s, 1H), 7.61 (s,
		1H), 7.46 (d, J = 8.0 Hz, 1H), 7.39 (s, 1H), 7.38 (d, J = 8.2 Hz, 1H), 7.25
		(s, 1H), 5.63-5.44 (m, 0.62H, rotamer), 5.31 (p, J = 7.0 Hz, 1H), 5.25-
		5.14 (m, 0.42H, rotamer), 4.99 (m, 0.53H, rotamer), 4.60-4.42 (m,
		0.47H, rotamer), 4.29-4.12 (m, 0.59H, rotamer), 4.09-3.97 (m, 1H),
		3.85-3.65 (m, 0H), 3.45-3.03 (m, 1H), 2.86-2.71 (m, 1H), 2.69-2.58
		(m, 1H), 2.55-2.41 (m, 1H), 2.05-1.91 (m, 1H), 1.89-1.72 (m, 2H),
		1.70-1.53 (m, 5H), 1.48 (d, J = 7.1 Hz, 3H), 1.35-1.13 (m, 2H), 1.11-
		0.89 (m, 2H), 0.65-0.33 (m, 1H).
815	628.3	1H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J = 9.5 Hz, 1H), 7.96 (s, 2H),
		7.90 (d, J = 8.0 Hz, 1H), 7.75 (s, 1H), 7.30 (s, 0H), 7.23 (s, 1H), 7.08 (d,
		J = 8.0 Hz, 1H), 6.60 (s, 1H), 6.35 (s, 1H), 5.16 (p, J = 9.4, 6.8 Hz, 1H),
		5.08-4.88 (m, 0.42H, rotamer), 4.74-4.62 (m, 0.62H, rotamer), 4.61-
		4.44 (m, 2H), 4.29-4.18 (m, 1H), 4.09 (s, 3H), 3.91-3.41 (m, 2H), 3.42-
		3.23 (m, 3H), 3.21-3.00 (m, 1H), 2.80 (s, 3H), 2.31-2.20 (m, 1H),
		2.08-1.91 (m, 2H), 1.90-1.78 (m, 1H), 1.74-1.64 (m, 2H), 1.62-1.52
		(m, 3H), 1.44 (d, J = 7.1 Hz, 3H), 1.38-1.29 (m, 1H), 1.29-1.20 (m,
		1H), 1.19-1.07 (m, 1H), 0.99-0.86 (m, 1H).
816	654.6	1H NMR (400 MHz, DMSO-d6) δ 8.95 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H),
		7.97 (s, 2H), 7.74 (s, 1H), 7.66 (s, 1H), 7.59 (s, 1H), 7.32 (s, 1H), 7.26 (d,
		J = 8.1 Hz, 2H), 7.18 (d, J = 8.0 Hz, 1H), 5.18 (p, J = 6.9 Hz, 1H), 5.07-
		4.76 (m, 2H), 4.60-4.46 (m, 0.78H, rotamer), 4.25-4.15 (m, 0.78H,
		rotamer), 4.08-3.98 (m, 1H), 3.80-3.54 (m, 2H), 3.38 (m, 0.23H,
		rotamer), 3.15 (m, 0.25H, rotamer), 2.86-2.72 (m, 0.40H, rotamer), 2.68-
		2.59 (m, 1H), 2.40-2.24 (m, 3H), 2.17-2.06 (m, 1H), 2.03-1.90 (m,
		1H), 1.88-1.72 (m, 1H), 1.65 (s, 1H), 1.49 (d, J = 7.1 Hz, 3H), 1.47-
		1.41 (m, 2H), 1.41 (s, 1H), 1.32-1.14 (m, 3H), 1.13-1.03 (m, 1H), 1.02-
		0.85 (m, 5H), 0.63-0.52 (m, 1H), 0.49-0.39 (m, 1H).
817	654.6	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 8.6 Hz, 1H), 8.02 (s, 1H),
		7.98 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 45.0 Hz, 1H), 7.39 (s, 1H), 7.13 (d,
		J = 8.1 Hz, 1H), 7.02 (s, 1H), 6.93 (s, 1H), 5.09-4.94 (m, 1H), 4.84-4.64
		(m, 2H), 4.64-4.47 (m, 2H), 4.35-4.21 (m, 4H), 4.20-4.02 (m, 3H),
		4.00 (s, 3H), 3.92-3.73 (m, 2H), 3.70-3.50 (m, 2H), 3.48-3.21 (m,
		1H), 3.22-3.07 (m, 0.56H, rotamer), 3.03 (s, 3H), 2.85-2.71 (m, 0.44H,
		rotamer), 2.06-1.92 (m, 1H), 1.91-1.78 (m, 1H), 1.73-1.59 (m, 4H),
		1.58-1.47 (m, 1H), 1.43 (d, J = 7.1 Hz, 3H), 1.39-1.31 (m, 1H), 1.30-
		1.13 (m, 1H), 0.92-0.81 (m, 1H), 0.78-0.57 (m, 2H), 0.52-0.39 (m,
		1H).
818	707.4	1H NMR (400 MHz, DMSO-d6) δ 9.21 (d, J = 6.6 Hz, 1H), 8.37 (s, 1H),
		8.07 (d, J = 8.0 Hz, 1H), 7.98 (s, 2H), 7.75 (s, 1H), 7.45 (s, 1H), 7.32 (s,
		1H), 7.24 (d, J = 8.1 Hz, 1H), 7.22 (s, 1H), 6.91 (s, 1H), 5.16 (p, J = 6.9
		Hz, 1H), 5.08-4.92 (m, 0.58H, rotamer), 4.94-4.78 (m, 2H), 4.61-4.45
		(m, 0.47H, rotamer), 4.38-4.14 (m, 0.61H, rotamer), 4.00 (s, 3H), 3.96-
		3.87 (m, 1H), 3.82-3.38 (m, 4H), 2.87-2.70 (m, 0.60H, rotamer), 2.42-
		2.22 (m, 2H), 2.06-1.92 (m, 1H), 1.89-1.75 (m, 1H), 1.72-1.55 (m,
		1H), 1.51 (d, J = 7.0 Hz, 3H), 1.46-1.36 (m, 2H), 1.33-1.22 (m, 1H),
		1.21-1.09 (m, 2H), 1.08-0.96 (m, 1H), 0.95-0.82 (m, 1H), 0.63-0.45
		(m, 1H), 0.41-0.27 (m, 1H).
819	723.3	1H NMR (400 MHz, DMSO-d6) δ 9.19 (d, J = 7.0 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.96 (s, 2H), 7.95 (d, J = 7.8 Hz, 1H), 7.73 (s, 1H), 7.33 (s,
		1H), 6.93 (t, J = 55.0 Hz, 1H), 6.91 (s, 1H), 5.22 (p, J = 6.9 Hz, 1H), 5.07-
		4.76 (m, 2H), 4.63-4.42 (m, 0.35H, rotamer), 4.32-4.20 (m, 0.33H,
		rotamer), 3.99 (s, 3H), 3.97-3.88 (m, 1H), 3.86-3.56 (m, 5H), 3.45-
		3.04 (m, 0.36H, rotamer), 2.72-2.62 (m, 1H), 2.46-2.40 (m, 3H), 2.05-
		1.90 (m, 1H), 1.91-1.77 (m, 1H), 1.72-1.55 (m, 5H), 1.51 (d, J = 7.1
		Hz, 3H), 1.45-1.30 (m, 2H), 1.31-1.10 (m, 2H), 1.08-0.97 (m, 1H),
		0.96-0.80 (m, 1H), 0.65-0.46 (m, 1H), 0.44-0.24 (m, 1H).
820	761.4	1H NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 7.0 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.98 (s, 2H), 7.81 (d, J = 7.8 Hz, 1H), 7.75 (s, 1H), 7.64-
		7.61 (m, 2H), 7.55 (d, J = 7.8 Hz, 1H), 7.48 (qd, J = 4.5, 1.4 Hz, 3H), 7.33
		(s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.25 (s, 1H), 5.21 (p, J = 7.0 Hz, 1H),
		5.03-4.90 (m, 1H), 4.90-4.76 (m, 1H), 4.61-4.44 (m, 0.52H, rotamer),
		4.25-4.12 (m, 0.80H, rotamer), 4.08-3.99 (m, 1H), 3.96-3.51 (m, 4H),
		3.44-3.23 (m, 0.50H, rotamer), 3.21-2.97 (m, 0.71H, rotamer), 2.84-
		2.70 (m, 1H), 2.71-2.63 (m, 1H), 2.44-2.37 (m, 2H), 2.03-1.93 (m,
		1H), 1.89-1.77 (m, 1H), 1.70-1.55 (m, 2H), 1.52 (d, J = 7.1 Hz, 3H),
		1.30-1.16 (m, 2H), 1.14-0.93 (m, 3H), 0.62-0.52 (m, 1H), 0.51-0.37
		(m, 1H).
821	714.2	1H NMR (400 MHz, DMSO-d6) δ 8.27 (d, J = 7.4 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.42 (s, 1H), 7.29 (d, J = 8.1 Hz, 1H), 7.14 (s, 1H), 6.94 (d,
		J = 1.1 Hz, 1H), 5.38 (q, J = 15.8 Hz, 1H), 5.26-5.08 (m, 2H), 4.09 (s,
		3H), 3.99 (s, 3H), 3.91 (s, 2H), 3.75-3.67 (m, 2H), 3.37 (s, 3H), 3.00 (dq,
		J = 25.9, 13.4 Hz, 3H), 2.64-2.54 (m, 1H), 2.26 (q, J = 13.0 Hz, 2H),
		2.11-2.01 (m, 1H), 1.94 (s, 1H), 1.84 (s, 1H), 1.76 (s, 3H), 1.55-1.41
		(m, 3H), 1.28 (dd, J = 15.0, 9.1 Hz, 2H), 1.17 (d, J = 9.3 Hz, 1H), 1.08 (s,
		1H).
822	750.2	1H NMR (400 MHz, DMSO-d6) δ 8.27 (d, J = 7.3 Hz, 1H), 8.12 (d, J =
		8.1 Hz, 1H), 7.44 (s, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.15 (s, 1H), 6.95 (d,
		J = 1.2 Hz, 1H), 6.86 (s, 1H), 5.38 (q, J = 15.6 Hz, 1H), 5.26-5.06 (m,
		2H), 4.67 (s, 1H), 4.10 (s, 3H), 4.00 (s, 3H), 3.61 (s, 2H), 3.47 (s, 2H),
		3.00 (m, J = 26.0, 13.4 Hz, 2H), 2.58 (s, 1H), 2.25 (d, J = 13.1 Hz, 2H),
		2.12-2.00 (m, 2H), 1.94 (d, J = 16.9 Hz, 2H), 1.85 (s, 1H), 1.76 (s, 2H),
		1.47 (d, J = 7.0 Hz, 3H), 1.25 (d, J = 9.0 Hz, 1H), 1.19 (s, 1H), 1.08 (s,
		1H).
823	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 8.1 Hz, 1H), 7.98 (t, J =
		8.3 Hz, 2H), 7.43 (s, 1H), 7.29 (d, J = 8.1 Hz, 1H), 7.16 (s, 1H), 6.93 (d,
		J = 5.5 Hz, 1H), 5.52 (d, J = 16.1 Hz, 1H), 5.37-5.25 (m, 1H), 5.20 (d, J =
		13.3 Hz, 1H), 4.11 (s, 3H), 4.00 (s, 3H), 3.71 (d, J = 5.9 Hz, 2H), 3.60-
		3.49 (m, 2H), 3.43 (d, J = 10.0 Hz, 1H), 3.37 (s, 3H), 2.03 (s, 2H), 1.96 (d,
		J = 8.7 Hz, 2H), 1.84 (s, 1H), 1.82-1.71 (m, 2H), 1.54 (d, J = 14.5 Hz,
		2H), 1.44 (d, J = 6.9 Hz, 3H), 1.28 (m, J = 15.3, 11.5, 5.8 Hz, 2H), 1.03 (q,
		J = 4.6, 3.5 Hz, 1H), 0.96 (dd, J = 6.1, 3.2 Hz, 1H), 0.59 (m, J = 6.1, 3.9
		Hz, 1H), 0.47-0.36 (m, 1H).
824	738.2	1H NMR (400 MHz, DMSO-d6) δ 9.49 (d, J = 6.9 Hz, 1H), 8.24-8.08
		(m, 4H), 8.05-7.98 (m, 1H), 7.93-7.82 (m, 2H), 7.46 (s, 1H), 7.32 (d, J =
		8.1 Hz, 1H), 7.12 (s, 1H), 6.95 (s, 1H), 6.86 (t, J = 74.9 Hz, 1H), 5.30
		(p, J = 7.0 Hz, 1H), 4.88 (t, J = 11.4 Hz, 1H), 4.67 (m, J = 6.3, 3.2 Hz,
		1H), 4.63-4.52 (m, 1H), 4.14 (s, 3H), 4.00 (s, 3H), 2.84 (dd, J = 12.7, 8.1
		Hz, 1H), 2.60 (d, J = 8.4 Hz, 2H), 2.03-1.85 (m, 2H), 1.76 (s, 1H), 1.56
		(d, J = 7.1 Hz, 3H), 1.52-1.32 (m, 2H), 1.24 (d, J = 30.6 Hz, 1H), 1.17
		(d, J = 7.1 Hz, 1H), 0.60 (d, J = 12.4 Hz, 1H).
825	669.3	1H NMR (400 MHz, DMSO-d6) δ 9.34 (d, J = 7.4 Hz, 1H), 8.17-8.05
		(m, 2H), 7.97 (s, 3H), 7.44 (d, J = 3.0 Hz, 1H), 7.30-7.19 (m, 2H), 7.10
		(s, 1H), 6.94 (s, 1H), 5.76 (s, 1H), 5.29 (p, J = 7.1 Hz, 1H), 4.88 (t, J =
		12.4 Hz, 1H), 4.60 (d, J = 13.5 Hz, 1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.71 (d,
		J = 5.8 Hz, 4H), 3.37 (s, 4H), 2.34 (m, J = 4.5, 3.8, 2.7 Hz, 1H), 2.30-
		2.15 (m, 1H), 1.94 (t, J = 11.3 Hz, 1H), 1.83-1.69 (m, 2H), 1.47 (d, J =
		7.0 Hz, 4H), 1.37-1.14 (m, 3H), 0.48 (d, J = 12.4 Hz, 1H).
826	634.3	1H NMR (400 MHz, DMSO-d6) δ 8.75 (s, 2H), 8.67 (d, J = 8.0 Hz, 1H),
		8.45 (d, J = 8.5 Hz, 1H), 8.01 (dd, J = 10.5, 7.2 Hz, 2H), 7.69 (d, J = 10.3
		Hz, 1H), 7.25 (s, 1H), 7.15 (d, J = 8.1 Hz, 1H), 5.21-5.13 (m, 1H), 5.06-
		4.97 (m, 1H), 4.93-4.82 (m, 1H), 4.75 (m, J = 21.1, 10.8, 5.7 Hz, 1H),
		4.60 (d, J = 13.8 Hz, 1H), 4.41 (s, 1H), 3.89 (m, J = 9.9, 5.5 Hz, 1H), 3.46
		(s, 1H), 2.98 (dd, J = 38.9, 26.4 Hz, 3H), 1.98-1.80 (m, 2H), 1.74-1.60
		(m, 4H), 1.56 (m, J = 8.2, 4.8 Hz, 2H), 1.48-1.39 (m, 3H), 1.30-1.20
		(m, 2H), 1.13 (d, J = 3.5 Hz, 1H), 1.06 (d, J = 2.8 Hz, 1H), 0.86 (q, J = 3.9
		Hz, 1H), 0.70 (d, J = 24.1 Hz, 2H), 0.48 (d, J = 6.3 Hz, 1H).
827	646.3	1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 8.5 Hz, 1H), 8.06 (s, 2H),
		7.99 (d, J = 8.0 Hz, 1H), 7.86 (s, 1H), 7.69 (d, J = 9.4 Hz, 1H), 7.23 (s,
		1H), 7.15 (d, J = 8.0 Hz, 1H), 5.17 (s, 1H), 5.07-4.96 (m, 2H), 4.69 (s,
		1H), 4.60 (s, 1H), 4.04 (q, J = 7.1 Hz, 0H), 3.87 (dt, J = 9.2, 5.5 Hz, 1H),
		3.37 (d, J = 10.6 Hz, 3H), 1.89 (d, J = 12.4 Hz, 2H), 1.69 (dd, J = 32.6,
		15.3 Hz, 6H), 1.57 (dt, J = 8.3, 4.4 Hz, 1H), 1.44 (d, J = 7.1 Hz, 3H), 1.34-
		1.22 (m, 1H), 1.18 (t, J = 7.1 Hz, 0H), 0.87 (p, J = 4.1 Hz, 1H), 0.79-
		0.60 (m, 2H), 0.53-0.44 (m, 1H).
828	716.5	1H NMR (400 MHz, DMSO-d6) δ 9.51 (d, J = 6.8 Hz, 1H), 8.17-8.09
		(m, 1H), 8.06-8.00 (m, 1H), 7.97 (s, 1H), 7.92-7.84 (m, 2H), 7.68 (s,
		1H), 7.38-7.28 (m, 2H), 5.29 (p, J = 7.0 Hz, 1H), 4.95 (q, J = 7.4 Hz,
		1H), 4.84 (d, J = 13.6 Hz, 1H), 4.04 (m, J = 7.1, 3.9 Hz, 1H), 3.41 (s, 2H),
		3.37 (s, 3H), 2.84 (dd, J = 12.7, 8.0 Hz, 1H), 2.61 (d, J = 8.4 Hz, 2H), 1.91
		(s, 2H), 1.77 (dd, J = 6.3, 3.0 Hz, 2H), 1.57 (d, J = 7.0 Hz, 3H), 1.54-
		1.45 (m, 3H), 1.40 (d, J = 9.3 Hz, 2H), 1.33-1.16 (m, 3H), 1.16-0.99
		(m, 2H), 0.56 (s, 1H), 0.48 (s, 1H).
829	715.6	1H NMR (400 MHz, DMSO-d6) δ 9.28 (d, J = 6.6 Hz, 1H), 8.41 (s, 1H),
		8.12 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 8.5 Hz, 2H),
		7.79 (dd, J = 8.4, 6.9 Hz, 1H), 7.64 (dd, J = 16.6, 9.0 Hz, 2H), 7.36-7.25
		(m, 2H), 5.22 (p, J = 7.0 Hz, 1H), 5.01-4.88 (m, 1H), 4.88-4.78 (m,
		1H), 4.03 (td, J = 7.1, 3.6 Hz, 1H), 3.82 (s, 2H), 3.75-3.66 (m, 1H), 2.92
		(dd, J = 12.5, 7.7 Hz, 2H), 2.56 (d, J = 7.8 Hz, 1H), 1.92 (s, 2H), 1.77 (d,
		J = 7.7 Hz, 2H), 1.55 (d, J = 7.1 Hz, 3H), 1.48 (s, 2H), 1.37 (d, J = 9.3 Hz,
		2H), 1.30-1.17 (m, 2H), 1.17-0.99 (m, 2H), 0.54 (s, 1H), 0.47 (s, 1H).
830	699.5	1H NMR (400 MHz, DMSO-d6) δ 9.29 (d, J = 6.6 Hz, 1H), 8.42 (s, 1H),
		8.12 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H),
		7.80 (t, J = 7.7 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.59 (s, 1H), 7.34 (s, 1H),
		7.30 (d, J = 8.1 Hz, 1H), 7.25 (d, J = 11.3 Hz, 1H), 5.22 (p, J = 6.9 Hz,
		1H), 4.93 (s, 2H), 4.89-4.79 (m, 1H), 4.03 (m, J = 7.3, 4.0 Hz, 1H), 2.92
		(dd, J = 12.8, 7.9 Hz, 2H), 2.56 (d, J = 9.1 Hz, 2H), 1.85-1.64 (m, 4H),
		1.55 (d, J = 7.1 Hz, 3H), 1.47 (d, J = 9.2 Hz, 2H), 1.38 (s, 2H), 1.31-1.16
		(m, 5H), 1.09 (dd, J = 20.7, 10.2 Hz, 3H), 0.50 (d, J = 34.4 Hz, 2H).
831	685.2	1H NMR (400 MHz, DMSO-d6) δ 9.34 (d, J = 7.9 Hz, 1H), 8.44 (d, J =
		5.4 Hz, 1H), 8.22 (s, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.98 (s, 2H), 7.45 (d,
		J = 5.3 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.94 (d, J = 1.2 Hz,
		1H), 5.36 (d, J = 7.8 Hz, 1H), 4.91 (t, J = 11.9 Hz, 2H), 4.58 (d, J = 13.7
		Hz, 1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.69 (s, 3H), 3.37 (s, 3H), 3.15 (m, J =
		7.4, 4.3 Hz, 2H), 2.39 (m, J = 11.9, 5.2 Hz, 2H), 1.95 (s, 1H), 1.76 (s, 1H),
		1.48 (d, J = 6.9 Hz, 5H), 0.50 (d, J = 13.6 Hz, 2H).
832	713.4	1H NMR (400 MHz, DMSO-d6) δ 8.39 (s, 1H), 8.16 (d, J = 8.2 Hz, 1H),
		8.02 (d, J = 8.1 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.80 (ddd, J = 8.5, 6.9,
		1.5 Hz, 1H), 7.68-7.59 (m, 2H), 7.38-7.31 (m, 2H), 7.25 (d, J = 11.4
		Hz, 1H), 5.95 (q, J = 7.1 Hz, 1H), 4.84 (d, J = 15.7 Hz, 2H), 4.04 (q, J =
		7.1 Hz, 2H), 3.21 (s, 3H), 2.95 (t, J = 11.7 Hz, 1H), 1.75 (dd, J = 17.1, 8.5
		Hz, 4H), 1.57 (s, 4H), 1.33 (s, 0H), 1.29-1.22 (m, 1H), 1.22-1.14 (m,
		5H), 1.10 (d, J = 6.6 Hz, 0H), 1.00 (s, 1H), 0.75 (s, 1H), 0.51 (s, 1H).
833	729.3	1H NMR (400 MHz, DMSO-d6) δ 8.39 (s, 1H), 8.16 (d, J = 8.1 Hz, 1H),
		8.02 (d, J = 8.1 Hz, 1H), 7.97 (d, J = 8.4 Hz, 2H), 7.80 (m, J = 8.4, 6.8, 1.5
		Hz, 1H), 7.70 (s, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.35 (d, J = 8.7 Hz, 2H),
		7.29 (d, J = 11.6 Hz, 1H), 5.96 (q, J = 7.3 Hz, 1H), 4.90-4.73 (m, 2H),
		3.70 (dd, J = 6.6, 3.3 Hz, 1H), 3.37 (s, 3H), 3.21 (s, 3H), 3.01-2.89 (m,
		1H), 2.61 (m, J = 12.2, 3.9 Hz, 1H), 1.91 (s, 1H), 1.76 (s, 1H), 1.73 (d, J =
		7.3 Hz, 3H), 1.58 (s, 3H), 1.32 (s, 1H), 1.10 (p, J = 8.2, 7.2 Hz, 1H), 1.01
		(d, J = 11.5 Hz, 1H), 0.77 (s, 1H), 0.52 (d, J = 10.2 Hz, 1H).
834	682.3	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.9 Hz, 1H), 8.09 (d, J =
		8.1 Hz, 1H), 7.71 (s, 1H), 7.44 (s, 1H), 7.36 (d, J = 11.3 Hz, 1H), 7.26 (d,
		J = 8.1 Hz, 1H), 5.78 (t, J = 13.8 Hz, 1H), 5.19 (dd, J = 27.6, 14.4 Hz,
		1H), 5.12-5.01 (m, 1H), 4.57 (ddd, J = 15.3, 9.4, 5.6 Hz, 1H), 3.37 (s,
		3H), 2.23-2.01 (m, 1H), 1.96 (d, J = 13.8 Hz, 1H), 1.78 (dt, J = 12.4, 4.7
		Hz, 2H), 1.63 (s, 0H), 1.54 (q, J = 5.3 Hz, 1H), 1.49-1.40 (m, 4H), 1.33
		(s, 1H), 0.86 (t, J = 5.1 Hz, 1H), 0.78 (dt, J = 13.3, 6.9 Hz, 1H), 0.65 (d,
		J = 11.3 Hz, 1H), 0.57-0.46 (m, 2H).
835	666.3	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.8 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 7.64 (s, 1H), 7.44 (s, 1H), 7.31 (d, J = 11.2 Hz, 1H), 7.25 (d,
		J = 8.1 Hz, 1H), 5.84-5.71 (m, 1H), 5.19 (dd, J = 27.7, 14.4 Hz, 1H),
		5.06 (p, J = 7.3 Hz, 1H), 4.57 (ddd, J = 15.3, 9.4, 5.7 Hz, 1H), 2.24-2.01
		(m, 1H), 1.96 (d, J = 13.6 Hz, 1H), 1.76 (dd, J = 16.2, 12.9 Hz, 2H), 1.69-
		1.58 (m, 1H), 1.54 (q, J = 5.3 Hz, 1H), 1.49-1.40 (m, 4H), 1.34 (d, J =
		6.8 Hz, 0H), 1.21 (d, J = 6.9 Hz, 3H), 0.86 (t, J = 5.1 Hz, 1H), 0.79 (dt, J =
		13.4, 6.5 Hz, 0H), 0.65 (d, J = 11.6 Hz, 1H), 0.57-0.46 (m, 2H).
836	733.3	1H NMR (400 MHz, DMSO-d6) δ 9.39 (d, J = 8.1 Hz, 1H), 8.64 (d, J =
		5.0 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.97 (s, 3H), 7.68 (s, 1H), 7.63 (d,
		J = 5.0 Hz, 1H), 7.33 (s, 1H), 7.31-7.25 (m, 2H), 5.41 (t, J = 7.4 Hz, 1H),
		4.96 (t, J = 11.8 Hz, 1H), 4.89-4.79 (m, 1H), 4.02 (m, J = 7.1, 3.7 Hz,
		1H), 3.75-3.67 (m, 1H), 3.37 (s, 3H), 2.61 (d, J = 12.1 Hz, 1H), 2.45-
		2.36 (m, 1H), 2.21-2.10 (m, 2H), 1.91 (d, J = 8.0 Hz, 2H), 1.76 (s, 2H),
		1.52 (s, 2H), 1.47 (d, J = 7.2 Hz, 3H), 1.40-1.22 (m, 3H), 1.19 (d, J = 7.0
		Hz, 2H), 1.10 (q, J = 6.4 Hz, 1H), 1.01 (s, 1H), 0.44 (d, J = 25.2 Hz, 2H).
837	682.3	1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 8.8 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 7.97 (s, 2H), 7.71 (s, 1H), 7.43 (s, 1H), 7.33 (d, J = 11.4 Hz,
		1H), 7.26 (d, J = 8.1 Hz, 1H), 5.77 (t, J = 13.8 Hz, 1H), 5.23 (dd, J = 27.4,
		14.6 Hz, 1H), 5.15-5.04 (m, 1H), 4.60 (m, J = 15.0, 9.7, 5.6 Hz, 1H),
		4.51-4.43 (m, 1H), 4.31 (t, J = 5.3 Hz, 1H), 3.84 (s, 2H), 3.71 (m, J =
		6.4, 3.0 Hz, 1H), 3.37 (s, 3H), 2.23 (d, J = 19.4 Hz, 1H), 2.18-2.04 (m,
		1H), 1.96 (dd, J = 18.7, 9.5 Hz, 3H), 1.76 (s, 2H), 1.68-1.58 (m, 2H),
		1.56 (m, J = 8.3, 4.6 Hz, 1H), 1.45 (d, J = 7.1 Hz, 3H), 1.42-1.31 (m,
		1H), 0.91-0.81 (m, 1H), 0.66 (d, J = 11.0 Hz, 1H), 0.63-0.55 (m, 2H),
		0.51 (m, J = 6.8, 5.8, 3.6 Hz, 1H).
838	717.3	1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 7.0 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 8.04 (d, J = 7.8 Hz, 1H), 7.91 (s, 3H), 7.81 (d, J = 7.9 Hz,
		1H), 7.59 (d, J = 1.2 Hz, 1H), 7.33 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.25
		(d, J = 11.4 Hz, 1H), 5.23 (p, J = 7.0 Hz, 1H), 4.92 (d, J = 10.4 Hz, 1H),
		4.84 (d, J = 13.4 Hz, 1H), 4.02 (m, J = 7.0, 3.9 Hz, 1H), 2.47 (s, 4H), 1.74
		(q, J = 12.9, 11.6 Hz, 4H), 1.51 (d, J = 7.0 Hz, 7H), 1.20 (d, J = 6.9 Hz,
		5H), 1.15-0.98 (m, 3H), 0.60-0.39 (m, 3H).
839	712.2	1H NMR (400 MHz, DMSO-d6) δ 9.52 (d, J = 6.7 Hz, 1H), 8.19-8.09
		(m, 2H), 8.07-8.00 (m, 1H), 7.96 (s, 1H), 7.93-7.83 (m, 2H), 7.73-
		7.62 (m, 1H), 7.39-7.30 (m, 2H), 7.25 (s, 1H), 5.29 (p, J = 7.0 Hz, 1H),
		5.02-4.89 (m, 0.5H), 4.84 (d, J = 13.5 Hz, 1H), 4.52 (s, 0.43H), 4.18 (s,
		0.5H), 4.08-3.98 (m, 1H), 3.85-3.72 (m, 1H), 3.20-3.01 (m, 1H), 2.84
		(dd, J = 12.7, 8.0 Hz, 1H), 2.61 (d, J = 8.3 Hz, 2H), 1.94 (d, J = 20.1 Hz,
		2H), 1.79 (d, J = 22.6 Hz, 2H), 1.65 (s, 2H), 1.57 (d, J = 7.1 Hz, 3H), 1.49
		(d, J = 11.4 Hz, 2H), 1.41 (s, 1H), 1.24 (s, 2H), 1.09 (s, 2H), 0.55 (s, 1H),
		0.47 (s, 1H).
840	714.2	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.0 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.96 (s, 2H), 7.82 (d, J = 8.1 Hz, 1H), 7.73 (s, 1H), 7.61 (s,
		1H), 7.42 (d, J = 8.0 Hz, 1H), 7.38 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 5.31
		(s, 0.36H), 5.20 (q, J = 7.2 Hz, 1H), 4.90 (d, J = 6.9 Hz, 0.27H), 4.85 (s,
		1H), 4.63-4.49 (m, 2H), 4.17 (s, 0.5H), 3.83-3.69 (m, 0.5H), 3.15 (dd,
		J = 7.2, 4.0 Hz, 0.5H), 2.77 (s, 0.28H), 2.66-2.60 (m, 1H), 2.60-2.54 (m,
		1H), 2.38 (d, J = 7.9 Hz, 2H), 2.03-1.90 (m, 2H), 1.76 (s, 3H), 1.74-
		1.57 (m, 3H), 1.50 (d, J = 7.1 Hz, 3H), 1.46-1.42 (m, 2H), 1.33-1.16
		(m, 3H), 0.85 (s, 2H), 0.52 (s, 2H).
841	711.1	1H NMR (400 MHz, DMSO-d6) δ 9.02-8.89 (m, 1H), 8.37 (dd, J = 8.4,
		1.8 Hz, 1H), 8.11 (d, J = 7.9 Hz, 1H), 7.96 (s, 1H), 7.92 (d, J = 8.5 Hz,
		1H), 7.80-7.57 (m, 1H), 7.54 (dd, J = 8.3, 4.2 Hz, 1H), 7.47 (d, J = 8.4
		Hz, 1H), 7.34 (s, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.24 (s, 1H), 5.45 (t, J =
		7.3 Hz, 1H), 5.09-4.92 (m, 2H), 4.83 (d, J = 13.0 Hz, 1H), 4.53 (s,
		0.42H), 4.19 (s, 0.45H), 4.04 (m, J = 8.5, 4.2 Hz, 2H), 3.82-3.72 (m,
		1H), 3.19-3.08 (m, 1H), 2.77 (s, 0.32H), 2.59 (d, J = 13.1 Hz, 0.37H),
		2.42-2.35 (m, 1H), 2.31-2.19 (m, 1H), 2.02-1.89 (m, 2H), 1.76 (s,
		2H), 1.65 (s, 3H), 1.49 (d, J = 7.1 Hz, 3H), 1.32-1.15 (m, 2H), 1.23 (d,
		J = 8.3 Hz, 2H), 1.09 (s, 2H), 0.46 (s, 2H).
842	715.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 7.2 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 8.04 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.37 (s,
		1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.90 (s, 1H), 5.25 (t, J = 7.1
		Hz, 1H), 5.00 (s, 0.48H), 4.86 (m, J = 14.8, 7.8 Hz, 1H), 4.60 (d, J = 13.6
		Hz, 1H), 4.55-4.48 (m, 0.56H) 4.23 (s, 0.41H), 4.12 (s, 3H), 4.00 (s, 3H),
		3.40 (s, 1H), 3.31-3.21 (m, 1H), 3.14 (s, 0.34H), 2.75 (d, J = 10.7 Hz,
		0.62H), 2.68 (m, J = 10.7, 7.5, 4.7 Hz, 1H), 2.46 (s, 1H), 1.98 (dd, J =
		12.5, 7.2 Hz, 2H), 1.90-1.73 (m, 2H), 1.62 (s, 3H), 1.50 (d, J = 7.0 Hz,
		3H), 1.40 (d, J = 10.2 Hz, 1H), 1.24 (s, 1H), 0.56 (s, 1H).
843	711.2	1H NMR (400 MHz, DMSO-d6) δ 9.20 (d, J = 7.0 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 7.94 (s, 1H), 7.74 (s, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.33 (s,
		1H), 7.28 (d, J = 8.1 Hz, 1H), 6.93 (t, J = 55.0 Hz, 1H), 5.22 (p, J = 7.0
		Hz, 1H), 4.94 (dd, J = 16.6, 7.1 Hz, 1H), 4.85 (s, 1H), 4.52 (s, 0.45H),
		4.18 (s, 0.44H), 4.06-3.99 (m, 1H), 3.81-3.71 (m, 0.89H), 3.20-3.10
		(m, 1H), 2.75 (d, J = 9.9 Hz, 0.48H), 2.72-2.62 (m, 1H), 2.44 (d, J = 8.0
		Hz, 3H), 1.98 (d, J = 11.1 Hz, 2H), 1.76 (s, 2H), 1.65 (s, 2H), 1.51 (d, J =
		7.0 Hz, 3H), 1.47 (s, 1H), 1.42 (s, 1H), 1.29-1.14 (m, 3H), 1.03 (d, J =
		41.5 Hz, 3H), 0.53 (s, 1H), 0.46 (s, 1H).
844	729.6	1H NMR (400 MHz, DMSO-d6) δ 9.32 (d, J = 6.8 Hz, 1H), 8.71 (s, 1H),
		8.11 (d, J = 8.1 Hz, 1H), 7.97 (s, 1H), 7.85 (s, 1H), 7.74 (s, 1H), 7.59 (s,
		1H), 7.33 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.24 (s, 1H), 5.22 (p, J = 7.0
		Hz, 1H), 4.96 (s, 0.56H), 4.96-4.80 (m, 2H), 4.52 (s, 0.48H), 4.17 (s,
		1H), 4.02 (m, J = 6.7, 3.5 Hz, 3H), 3.37 (s, 2H), 3.14 (s, 0.50H), 2.76
		(s, 0.65H), 2.43-2.36 (m, 1H), 1.95 (q, J = 10.5 Hz, 1H), 1.79 (d, J = 20.4
		Hz, 1H), 1.72-1.56 (m, 3H), 1.52 (d, J = 7.1 Hz, 3H), 1.47 (s, 2H), 1.32
		(m, J = 11.5, 5.7 Hz, 1H), 1.20 (s, 2H), 1.07 (s, 2H), 0.59-0.39 (m, 2H).
845	681.2	1H NMR (400 MHz, DMSO-d6) δ 9.34 (d, J = 7.9 Hz, 1H), 8.45 (d, J =
		5.4 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.98 (s, 2H), 7.75 (s, 1H), 7.45 (d,
		J = 5.4 Hz, 1H), 7.37 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.10 (s, 1H), 6.90
		(s, 1H), 5.43-5.30 (m, 1H), 5.0 (s, 0.4H) 4.97-4.85 (m, 1H), 4.59 (d, J =
		13.8 Hz, 2H), 4.23 (s, 0.75H), 4.12 (s, 3H), 4.00 (s, 3H), 2.77 (s, 1H),
		2.44-2.26 (m, 3H), 1.96 (d, J = 9.5 Hz, 1H), 1.79 (d, J = 20.2 Hz, 1H),
		1.62 (s, 3H), 1.48 (d, J = 7.1 Hz, 5H), 1.25 (s, 2H), 0.49 (s, 2H).
846	714.1	1H NMR (400 MHz, DMSO-d6) δ 9.14 (d, J = 7.0 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.98 (s, 2H), 7.83 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 8.0 Hz,
		1H), 7.32-7.23 (m, 2H), 5.26-5.13 (m, 1H), 5.03 (s, 0.47H), 4.93 (t, J =
		12.8 Hz, 0.69H), 4.80 (s, 0.27H), 4.51 (s, 2H), 4.18 (s, 0.32H), 4.09 (m,
		J = 10.0, 5.5 Hz, 2H), 3.76 (s, 0.38H), 3.33 (d, J = 34.8 Hz, 2H), 3.16 (s,
		0.42H), 2.76 (d, J = 14.4 Hz, 0.40H), 2.62 (dd, J = 12.5, 7.5 Hz, 1H), 2.38
		(d, J = 7.8 Hz, 1H), 1.96 (d, J = 11.4 Hz, 2H), 1.76 (s, 2H), 1.61 (dd, J =
		16.6, 7.4 Hz, 4H), 1.50 (d, J = 7.0 Hz, 3H), 1.42 (s, 2H), 1.29-1.10 (m,
		2H), 0.81 (d, J = 26.0 Hz, 1H), 0.55 (s, 1H).
847	741.2	1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 7.0 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.96 (s, 1H), 7.81 (d, J = 7.9 Hz,
		1H), 7.73 (s, 1H), 7.33 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.23 (s, 1H), 6.91
		(s, 1H), 5.23 (p, J = 7.1 Hz, 1H), 5.02 (s, 0.66H), 4.90 (m, J = 23.4, 13.2
		Hz, 2H), 4.53 (s, 0.45H), 4.25 (s, 0.52H), 4.00 (s, 3H), 3.93 (m, J = 7.1,
		3.9 Hz, 1H), 3.83 (s, 1H) 2.75 (s, 0.69H), 2.72-2.63 (m, 1H), 2.46 (s,
		2H), 1.96 (d, J = 11.1 Hz, 2H), 1.79 (d, J = 20.0 Hz, 2H), 1.59 (s, 3H),
		1.51 (d, J = 7.1 Hz, 3H), 1.41 (s, 2H), 1.29-1.09 (m, 2H), 1.03 (d, J = 7.8
		Hz, 1H), 0.90 (s, 1H), 0.53 (d, J = 12.2 Hz, 1H), 0.37 (m, 1H).
848	650.4	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.9 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 8.00 (s, 2H), 7.44 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.14 (s,
		1H), 6.96 (s, 1H), 5.51 (t, J = 13.6 Hz, 1H), 5.22-4.99 (m, 2H), 4.10 (s,
		3H), 4.00 (s, 3H), 3.74-3.67 (m, 1H), 3.56-3.51 (m, 2H), 3.46-3.40
		(m, 1H), 3.37 (s, 3H), 2.26-2.01 (m, 2H), 2.01-1.89 (m, 2H), 1.83-
		1.70 (m, 1H), 1.68-1.57 (m, 1H), 1.57-1.51 (m, 1H), 1.44 (d, J = 7.1
		Hz, 3H), 1.38-1.21 (m, 1H), 0.94-0.78 (m, 1H), 0.72-0.59 (m, 1H),
		0.56-0.45 (m, 2H).
849	634.5	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.9 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.92 (s, 2H), 7.36 (s, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.13 (s,
		1H), 6.89 (s, 1H), 5.50 (t, J = 13.6 Hz, 1H), 5.25-4.99 (m, 2H), 4.10 (s,
		3H), 4.00 (s, 3H), 3.27-2.86 (m, 1H), 2.29-1.69 (m, 5H), 1.69-1.49
		(m, 3H), 1.44 (d, J = 7.1 Hz, 3H), 1.38-1.14 (m, 6H), 0.94-0.78 (m,
		1H), 0.64 (d, J = 12.3 Hz, 1H), 0.50 (d, J = 7.4 Hz, 2H).
850	686.6	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.8 Hz, 1H), 8.19 (s, 2H),
		8.06 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.14 (s,
		1H), 7.07-6.56 (m, 2H), 5.52 (t, J = 13.4 Hz, 1H), 5.24-5.00 (m, 2H),
		4.67 (s, 1H), 4.10 (s, 3H), 4.00 (s, 3H), 3.54 (d, J = 53.9 Hz, 3H), 2.96-
		2.69 (m, 1H), 2.03 (d, J = 53.2 Hz, 4H), 1.71-1.50 (m, 2H), 1.44 (d, J =
		7.0 Hz, 3H), 1.37-1.22 (m, 1H), 0.85 (t, J = 5.1 Hz, 1H), 0.72-0.58 (m,
		1H), 0.50 (d, J = 7.3 Hz, 2H).
851	638.4	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 8.9 Hz, 1H), 8.13-7.93
		(m, 3H), 7.40 (s, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.14 (s, 1H), 6.91 (s, 1H),
		5.51 (t, J = 13.6 Hz, 1H), 5.23-4.88 (m, 3H), 4.10 (s, 3H), 3.99 (s, 3H),
		3.40 (s, 2H), 2.35 (d, J = 11.8 Hz, 2H), 2.25-1.74 (m, 4H), 1.70-1.50
		(m, 2H), 1.44 (d, J = 7.1 Hz, 3H), 1.32 (s, 1H), 0.85 (t, J = 5.1 Hz, 1H),
		0.64 (s, 1H), 0.50 (d, J = 7.5 Hz, 2H).
852	634.5	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.8 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.95 (s, 2H), 7.37 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.14 (s,
		1H), 6.90 (s, 1H), 5.52 (t, J = 13.8 Hz, 1H), 5.29-4.96 (m, 2H), 4.10 (s,
		3H), 4.00 (s, 3H), 3.44-3.30 (m, 1H), 2.25-1.90 (m, 2H), 1.86-1.49
		(m, 5H), 1.44 (d, J = 7.1 Hz, 3H), 1.37-1.26 (m, 1H), 1.22 (d, J = 6.9 Hz,
		3H), 0.85 (t, J = 5.1 Hz, 1H), 0.64 (d, J = 11.5 Hz, 1H), 0.50 (d, J = 7.5
		Hz, 2H).
853	632.7	1H NMR (400 MHz, DMSO-d6) δ 8.56 (d, J = 8.7 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.99-7.88 (m, 2H), 7.24 (d, J = 8.0 Hz, 1H), 7.14 (s, 1H),
		7.08-6.94 (m, 1H), 5.59-5.42 (m, 1H), 5.22-4.99 (m, 2H), 4.58-4.15
		(m, 1H), 4.10 (s, 3H), 4.01 (s, 3H), 3.84-3.51 (m, 2H), 3.23-3.14 (m,
		1H), 2.91-2.55 (m, 2H), 2.21-1.86 (m, 6H), 1.78-1.49 (m, 3H), 1.45
		(d, J = 7.0 Hz, 3H), 1.32 (s, 1H), 0.85 (t, J = 5.1 Hz, 1H), 0.70-0.56 (m,
		1H), 0.50 (d, J = 7.3 Hz, 2H).
854	680.3	1H NMR (400 MHz, DMSO-d6) δ 8.78 (d, J = 7.6 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.98 (s, 3H), 7.43 (s, 1H), 7.22 (dt, J = 7.9, 3.9 Hz, 2H), 7.07
		(s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 6.87 (d, J = 8.3 Hz, 1H), 6.76 (d, J = 7.5
		Hz, 1H), 5.33-5.23 (m, 1H), 4.91 (t, J = 12.7 Hz, 1H), 4.56 (d, J = 13.4
		Hz, 1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.78 (s, 3H), 3.70 (s, 1H), 3.53 (s, 2H),
		3.36 (s, 3H), 2.19-2.01 (m, 2H), 2.00-1.90 (m, 1H), 1.82-1.70 (m,
		1H), 1.57-1.36 (m, 2H), 1.43 (d, J = 7.1 Hz, 3H), 1.29-1.10 (m, 3H),
		0.42-0.30 (m, 1H)
855	666.3	1H NMR (400 MHz, DMSO-d6) δ 8.63 (d, J = 2.6 Hz, 1H), 8.54 (d, J =
		2.6 Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 7.98 (br s, 4H), 7.45 (s, 1H), 7.33
		(d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.94 (q, J = 7.3
		Hz, 1H), 4.74 (dt, J = 14.9, 7.8 Hz, 1H), 4.57-4.48 (m, 1H), 4.12 (s, 3H),
		3.99 (s, 4H), 3.71 (br s, 1H), 3.54 (br s, 2H), 3.36 (s, 4H), 3.04 (s, 3H),
		2.81 (td, J = 12.9, 4.2 Hz, 1H), 2.24-2.10 (m, 1H), 2.00-1.90 (m, 1H),
		1.80-1.70 (m, 1H), 1.68 (d, J = 7.3 Hz, 3H), 1.64-1.53 (m, 3H), 1.339-
		1.29 (m, 1H), 0.92-0.80 (m, 1H).
856	650.3	1H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 7.0 Hz, 1H), 8.04 (d, J =
		8.2 Hz, 1H), 7.98 (br s, 3H), 7.46 (s, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.06 (s,
		1H), 6.93 (d, J = 1.1 Hz, 1H), 4.70-4.51 (m, 2H), 4.45 (p, J = 7.1 Hz,
		1H), 4.13 (s, 3H), 3.99 (s, 3H), 3.86 (br s, 1H), 3.70 (br s, 1H), 3.54 (br s,
		2H), 3.36 (s, 3H), 2.42-2.06 (m, 3H), 1.96 (br s, 3H), 1.81-1.72 (m,
		1H), 1.75 (d, J = 7.0 Hz, 3H), 1.54 (dt, J = 8.7, 4.7 Hz, 1H), 1.44-1.27
		(m, 1H), 0.95-0.78 (m, 2H), 0.67-0.59 (m, 1H).
857	650.3	1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J = 8.6 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.96 (br s, 3H), 7.48 (s, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.05 (s,
		1H), 6.92 (d, J = 1.1 Hz, 1H), 5.08-4.98 (m, 1H), 4.64-4.46 (m, 2H),
		4.13 (s, 3H), 3.99 (s, 3H), 3.81 (br s, 1H), 3.70 (br s, 1H), 3.56 (br s, 2H),
		3.36 (s, 3H), 2.44-2.24 (m, 2H), 2.06-1.90 (m, 3H), 1.83-1.67 (m,
		3H), 1.43 (d, J = 7.1 Hz, 3H), 0.92 (t, J = 5.4 Hz, 1H), 0.70-−0.62 m, 2H).
858	650.3	1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 7.3 Hz, 1H), 8.07 (d, J =
		8.2 Hz, 1H), 7.98 (br s, 3H), 7.46 (s, 1H), 7.25 (d, J = 8.3 Hz, 1H), 7.06 (s,
		1H), 6.93 (d, J = 1.2 Hz, 1H), 4.74-4.48 (m, 3H), 4.13 (s, 3H), 3.99 (s,
		3H), 3.86 (br s, 1H), 3.71 (br s, 1H), 3.54 (br s, 2H), 3.36 (s, 3H), 2.32-
		1.66 (m, 6H), 1.71 (d, J = 7.0 Hz, 3H), 1.56-1.33 (m, 1H), 1.23-1.11
		(m, 1H), 0.99-0.89 (m, 1H), 0.79-0.72 (m, 1H).
859	650.3	1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J = 6.4 Hz, 1H), 8.03 (d, J =
		8.1 Hz, 1H), 7.97 (br s, 3H), 7.47 (s, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.04 (s,
		1H), 6.92 (d, J = 1.2 Hz, 1H), 4.91 (p, J = 7.0 Hz, 1H), 4.71-4.63 (m,
		1H), 4.52 (t, J = 12.5 Hz, 1H), 4.13 (s, 3H), 3.99 (s, 3H), 3.83 (br s, 1H),
		3.70 (br s, 1H), 3.55 (br s, 2H), 3.36 (s, 3H), 2.19-1.69 (m, 5H), 1.58-
		1.39 (m, 1H), 1.46 (d, J = 7.1 Hz, 3H), 1.22-1.13 (m, 1H), 0.98 (td, J =
		8.7, 3.7 Hz, 1H), 0.62 (q, J = 5.6 Hz, 1H).
860	679.3	1H NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 8.3 Hz, 1H), 8.59 (br s,
		1H), 8.07 (d, J = 8.1 Hz, 1H), 7.98 br (s, 4.5H), 7.72-7.63 (m, 1H), 7.51-
		7.40 (m, 2H), 7.21 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 6.94 (d, J = 1.2 Hz,
		1H), 5.22 (p, J = 7.2 Hz, 1H), 5.13-5.00 (m, 1H), 4.64-4.54 (m, 1H),
		4.24-4.16 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.85 (br s, 1H), 3.71 (brs,
		1H), 3.54 (s, 3H), 3.37 (s, 3H), 2.29-1.89 (m, 3H), 1.83-1.32 (m, 5H),
		1.41 (d, J = 7.1 Hz, 3H), 1.25-0.92 (m, 3H), 0.62-0.47 (m, 1H).
861	693.3	1H NMR (400 MHz, DMSO-d6) δ 8.58 (dt, J = 4.7, 1.5 Hz, 1H), 8.06 (d,
		J = 8.1 Hz, 1H), 8.03-7.90 (m, 5H), 7.83 (td, J = 7.8, 1.9 Hz, 1H), 7.47-
		7.41 (m, 2H), 7.31 (ddd, J = 7.5, 4.8, 1.0 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H),
		7.04 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.15 (p, J = 7.1 Hz, 1H), 4.91-4.81
		(m, 1H), 4.43-4.34 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.87 (br s, 2H),
		3.70 (br s, 1H), 3.54 (br s, 2H), 3.07 (s, 3H), 2.03-1.59 (m, 6H), 1.42 (br
		s, 4H), 1.35 (d, J = 7.0 Hz, 3H), 1.29 (s, 3H), 1.21-1.00 (m, 2H).
862	693.3	1H NMR (400 MHz, DMSO-d6) δ 8.60-8.54 (m, 1H), 8.26 (d, J = 7.2
		Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 8.04-7.85 (m, 4H), 7.54-7.35 (m,
		3H), 7.26 (d, J = 8.2 Hz, 1H), 7.05 (s, 1H), 6.93 (d, J = 1.2 Hz, 1H), 5.23
		(p, J = 7.1 Hz, 1H), 4.80-4.70 (m, 1H), 4.53-4.43 (m, 1H), 4.12 (s, 3H),
		3.99 (s, 3H), 3.87 (s, 1H), 3.71 (br s, 1H), 3.54 (br s, 2H), 3.36 (s, 3H),
		2.15-2.06 (m, 2H), 2.00-1.90 (m, 1H), 1.80-1.51 (m, 4H), 1.65 (s, 3H),
		1.57 (d, J = 7.0 Hz, 3H), 1.50-1.22 (m, 4H), 1.12 (br s, 1H).
863	681.3	1H NMR (400 MHz, DMSO-d6) δ 8.97 (d, J = 7.6 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.04 (d, J = 5.2 Hz, 1H), 7.98 (br s, 3H), 7.43 (s, 1H), 7.23
		(d, J = 8.0 Hz, 1H), 7.08 (s, 1H), 6.93 (d, J = 1.1 Hz, 1H), 6.84 (d, J = 5.3
		Hz, 1H), 5.28 (p, J = 7.1 Hz, 1H), 4.94-4.84 (m, 1H), 4.60-4.52 (m,
		1H), 4.11 (s, 3H), 3.99 (s, 3H), 3.88 (s, 3H), 3.71 (br s, 1H), 3.53 (br s,
		2H), 3.36 (s, 3H), 2.17 (dt, J = 12.4, 6.4 Hz, 1H), 2.12-2.03 (m, 1H),
		1.94 (br s, 1H), 1.81-1.70 (s, 1H), 1.57-1.38 (m, sH), 1.44 (d, J = 7.0
		Hz, 3H), 1.34-1.11 (m, 2H), 0.48-0.34 (m, 1H).
864	658.2	1H NMR (400 MHz, DMSO-d6) δ 8.04-7.90 (m, 3.5H), 7.70 (d, J = 8.2
		Hz, 0.5H), 7.43 (s, 1H), 7.36 (d, J = 8.1 Hz, 0.5H), 7.26 (s, 0.5H), 7.15 (d,
		J = 8.1 Hz, 1H), 7.04 (s, 1H), 6.92 (d, J = 1.1 Hz, 1H), 5.00-4.89 (m,
		2H), 4.65-4.57 (m, 1H), 4.08 (s, 3H), 3.98 (s, 3H), 3.73-3.68 (br s, 1H),
		3.59 (d, J = 10.6 Hz, 1H), 3.53 (br s, 2H), 3.43 (d, J = 10.6 Hz, 1H), 3.38
		(s, 3H), 3.36 (s, 3H), 2.29-2.17 (m, 1H), 1.99-1.90 (m, 1H), 1.81 1.71
		(m, 1H), 1.43 (d, J = 7.0 Hz, 3H), 1.40-1.29 (m, 4H), 1.07-0.86 (m,
		4H), 0.57 (dd, J = 8.6, 3.9 Hz, 1H), 0.41-0.30 (m, 1H), 0.15-0.03 (m,
		1H).
865	658.3	1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J = 8.2 Hz, 1H), 8.03-7.91
		(m, 4H), 7.44 (s, 1H), 7.23 (d, J = 8.2 Hz, 1H), 7.03 (s, 1H), 6.93 (d, J =
		1.1 Hz, 1H), 5.11 (p, J = 7.2 Hz, 1H), 4.70-4.50 (m, 2H), 4.10 (s, 3H),
		3.98 (s, 3H), 3.95 (d, J = 10.1 Hz, 1H), 3.73-3.67 (m, 1H), 3.54 (br s,
		2H), 3.36 (s, 3H), 3.26 (s, 3H), 2.90 (d, J = 10.0 Hz, 1H), 1.94 (br s, 1H),
		1.75 (br s, 1H), 1.58 (d, J = 7.1 Hz, 3H), 1.67-1.26 (m, 5H), 1.22 (t, J =
		5.6 Hz, 1H), 1.08-0.69 (m, 6H).
866	636.3	1H NMR (400 MHz, DMSO-d6) δ 8.10 (d, J = 8.1 Hz, 1H), 8.05 (d, J =
		6.8 Hz, 1H), 7.98 (br s, 4H), 7.50 (s, 1H),  7.48 (s, 1H), 7.32-7.23
		(m, 2H), 7.19-7.12 (m, 2H), 7.05 (s, 1H), 6.94 (s, 1H), 5.10 (p, J = 6.7
		Hz, 1H), 4.39-4.26 (m, 2H), 4.13 (s, 3H), 4.00 (s, 3H), 3.74-3.69 (m,
		1H), 3.67 (d, J = 15.9 Hz, 1H), 3.52 (d, J = 15.7 Hz, 1H), 3.37 (s, 3H),
		2.20-2.10 (m, 1H), 2.02-1.73 (m, 3H), 1.38 (d, J = 6.8 Hz, 3H).
867	714.3	1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 8.1 Hz, 1H), 7.98 (br s,
		4H), 7.45 (s, 1H), 7.27 (d, J = 8.2 Hz, 1H), 7.12 (s, 1H), 6.94 (s, 1H), 6.46-
		6.15 (m, 1H), 5.88 (q, J = 7.5 Hz, 1H), 5.45 (t, J = 14.1 Hz, 1H), 5.11
		(dd, J = 26.2, 14.9 Hz, 1H), 4.79-4.65 (m, 1H), 4.27-4.12 (m, 1H), 4.08
		(s, 3H), 3.99 (s, 3H), 3.70 (br 2, 1H), 3.53 (br s, 3H), 3.45-3.36 (m, 1H),
		3.36 (s, 1H), 2.28-2.05 (m, 1H), 2.01-1.86 (m, 4H), 1.80-1.70 (m, 1H),
		1.63-1.51 (m, 1H), 1.59 (d, J = 7.4 Hz, 3H), 1.40-1.29 (m, 1H), 1.04-
		0.95 (m, 1H), 0.97-0.78 (m, 1H), 0.71-0.60 (m, 1H).
868	704.3	1H NMR (400 MHz, DMSO-d6) δ 8.06 (d, J = 8.1 Hz, 1H), 7.97 (s, 4H),
		7.45 (s, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.11 (s, 1H), 6.94 (s, 1H), 5.89 (q,
		J = 7.4 Hz, 1H), 5.43 (t, J = 14.3 Hz, 1H), 5.06 (dd, J = 25.6, 14.8 Hz, 1H),
		4.20 (dd, J = 16.2, 5.7 Hz, 1H), 4.07 (s, 3H), 3.99 (s, 4H), 3.70 (br s, 1H),
		3.59-3.38 (m, 5H), 3.36 (s, 3H), 2.35-1.83 (m, 5H), 1.81-1.71 (m,
		1H), 1.60 (d, J = 7.5 Hz, 3H), 1.63-1.51 (m, 1H), 1.42-1.28 (m, 1H),
		1.22-1.11 (m, 1H), 0.98 (t, J = 5.3 Hz, 1H), 0.91-0.80 (m, 1H), 0.72-
		0.63 (m, 2H), 0.61-0.55 (m, 2H), 0.47-0.39 (t, J = 5.7 Hz, 2H).
869	697.3	1H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 4.8 Hz, 1H), 8.31 (d, J =
		7.1 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.98 (s, 3H), 7.92 (td, J = 7.8, 1.6
		Hz, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.48-7.42 (m, 2H), 7.21 (d, J = 8.1 Hz,
		1H), 7.05 (s, 1H), 6.93 (s, 1H), 5.08 (p, J = 7.0 Hz, 1H), 4.87-4.78 (m,
		1H), 4.41 (d, J = 10.8 Hz, 1H), 4.13 (s, 3H), 3.99 (s, 3H), 3.71 (brs, 1H),
		3.55 (br s, 2H), 3.37 (s, 3H), 2.81 (dt, J = 41.9, 12.5 Hz, 1H), 2.19-1.90
		(m, 3H), 1.81-1.65 (m, 3H), 1.52-1.35 (m, 2H), 1.43 (d, J = 7.0 Hz, 3H),
		1.33-1.15 (m, 3H).
870	697.3	1H NMR (400 MHz, DMSO-d6) δ 8.70 (dd, J = 8.5, 3.4 Hz, 1H), 8.60 (d,
		J = 4.8 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.98 (s, 3H), 7.90 (td, J = 7.8,
		1.7 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.48-7.40 (m, 2H), 7.24 (d, J = 8.1
		Hz, 1H), 7.07 (s, 1H), 6.94 (s, 1H), 5.27 (p, J = 7.3 Hz, 1H), 4.89 (dt, J =
		14.7, 7.9 Hz, 1H), 4.63-4.54 (m, 1H), 4.12 (s, 3H), 3.99 (s, 3H), 3.70 (br
		s, 1H), 3.54 (br s, 2H), 3.37 (s, 3H), 2.70-2.58 (m, 1H), 2.16-1.89 (m,
		3H), 1.81-1.62 (m, 2H), 1.55 (d, J = 7.1 Hz, 3H), 1.46-1.33 (m, 1H),
		1.32-1.06 (m, 3H).
871	693.4	1H NMR (400 MHz, DMSO-d6) δ 8.91 (d, J = 8.6 Hz, 1H), 8.60-8.56
		(m, 1H), 8.08 (d, J = 8.1 Hz, 1H), 8.05-7.92 (d, J = 7.5 Hz, 4H), 7.69 (s,
		1H), 7.65 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 6.4 Hz, 1H), 7.32-7.27 (m,
		2H), 7.21 (d, J = 8.2 Hz, 1H), 5.27-5.17 (m, 1H), 5.17-5.08 (m, 1H),
		4.85-4.75 (m, 1H), 4.18 (dd, J = 12.7, 3.7 Hz, 1H), 4.05-3.98 (m, 1H),
		3.75-3.67 (m, 1H), 3.55 (br s, 2H), 3.40 (br s, 2H), 3.36 (s, 3H), 2.21 (br
		s, 1H), 2.12-2.03 (m, 1H), 1.92 (br s, 1H), 1.82-1.71 (m, 2H), 1.68-
		1.50 (m, 1H), 1.42 (d, J = 7.1 Hz, 3H), 1.45-1.34 (m, 2H), 1.27-0.95
		(m, 4H), 0.62-0.45 (m, 2H).
872	727.3	1H NMR (400 MHz, DMSO-d6) δ 8.89 (d, J = 8.6 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 7.97 (s, 3H), 7.83 (t, J = 7.8 Hz, 1H), 7.69 (s, 1H), 7.52 (d,
		J = 7.6 Hz, 1H), 7.39 (dd, J = 7.9, 0.8 Hz, 1H), 7.32-7.26 (m, 2H), 7.20
		(d, J = 8.1 Hz, 1H), 5.27-5.07 (m, 2H), 4.84-4.73 (m, 1H), 4.11-3.97 (m,
		2H), 3.70 (br s, 1H), 3.56 (br s, 1H), 3.41 (br s, 1H), 3.36 (s, 3H), 2.20 (br
		s, 1H), 2.07-1.87 (m, 1H), 1.82-1.72 (m, 1H), 1.62-1.49 (m, 2H), 1.45-
		1.31 (m, 2H), 1.42 (d, J = 7.1 Hz, 3H), 1.27-0.90 (m, 7H), 0.60-0.44
		(m, 2H).
873	727.3	1H NMR (400 MHz, DMSO-d6) δ 8.89 (d, J = 8.6 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 7.97 (s, 3H), 7.83 (t, J = 7.8 Hz, 1H), 7.69 (s, 1H), 7.52 (d,
		J = 7.6 Hz, 1H), 7.39 (dd, J = 7.9, 0.8 Hz, 1H), 7.32-7.26 (m, 2H), 7.20
		(d, J = 8.1 Hz, 1H), 5.27-5.07 (m, 2H), 4.84-4.73 (m, 1H), 4.11-3.97 (m,
		2H), 3.70 (br s, 1H), 3.56 (br s, 1H), 3.41 (br s, 1H), 3.36 (s, 3H), 2.20 (br
		s, 1H), 2.07-1.87 (m, 1H), 1.82-1.72 (m, 1H), 1.62-1.49 (m, 2H), 1.45-
		1.31 (m, 2H), 1.42 (d, J = 7.1 Hz, 3H), 1.27-0.90 (m, 7H), 0.60-0.44
		(m, 2H).
874	630.3	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.5 Hz, 1H), 8.00 (d, J =
		8.0 Hz, 1H), 7.98 (br s, 3H), 7.68 (s, 1H), 7.28 (d, J = 11.4 Hz, 1H), 7.25
		(s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 5.05-4.96 (m, 1H), 4.02-3.96 (m, 1H),
		3.81 (br s, 1H), 3.73-3.67 (m, 1H), 3.55 (br s, 1H), 3.38 (br s, 1H), 3.36
		(s, 3H), 1.99-1.46 (m, 7H), 1.44 (d, J = 7.1 Hz, 3H), 1.40-1.04 (m, 3H),
		0.98-0.82 (m, 2H), 0.77-0.55 (m, 2H), 0.52-0.45 (m, 1H).
875	745.2	1H NMR (400 MHz, DMSO-d6) δ 8.81 (dd, J = 8.3, 3.1 Hz, 1H), 8.10 (d,
		J = 8.1 Hz, 1H), 7.98 (t, J = 7.8 Hz, 1H), 7.97 (br s, 3H), 7.70 (s, 1H), 7.64
		(d, J = 7.7 Hz, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.32-7.22 (m, 3H), 5.26 (p,
		J = 7.4 Hz, 1H), 5.00-4.90 (m, 1H), 4.83-4.72 (m, 1H), 4.04-3.98 (m,
		1H), 3.82 (br s, 1H), 3.70 (br s, 1H), 3.56 (br s, 1H), 3.40 (s, 2H), 3.36 (s,
		3H), 2.13-1.87 (m, 2H), 1.76 (s, 1H), 1.55 (d, J = 7.1 Hz, 3H), 1.44-
		1.03 (m, 4H), 0.94 (br s, 1H), 0.82 (br s, 1H), 0.61-0.53 (m, 1H).
876	745.2	1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J = 8.7 Hz, 0H), 8.38 (d, J =
		7.2 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.99 (t, J = 7.8 Hz, 1H), 7.98 (br s,
		3H), 7.70 (s, 1H), 7.59 (d, J = 7.8 Hz, 2H), 7.32-7.20 (m, 3H), 5.10 (p,
		J = 7.0 Hz, 1H), 4.96-4.85 m, 1H), 4.62 (s, 1H), 4.04-3.97 (m, 1H), 3.82
		(br s, 1H), 3.70 (br s, 1H), 3.56 (br s, 1H), 3.40 (br 2s, 1H), 3.36 (s, 3H),
		2.86-2.66 (m, 1H), 2.23-1.85 (m, 3H), 1.73 (d, J = 29.1 Hz, 3H), 1.47
		(d, J = 7.1 Hz, 3H), 1.35-1.03 (m, 3H), 0.91 (br s, 1H), 0.69-0.61 (m,
		1H).
877	680.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 6.9 Hz, 1H), 8.60 (d, J =
		2.5 Hz, 1H), 8.50 (d, J = 2.5 Hz, 1H), 8.11 (dd, J = 8.1, 1.2 Hz, 1H), 7.99
		(br s, 2H), 7.74 (br s, 1H), 7.63 (d, J = 4.8 Hz, 0.3H), 7.55 (br s, 0.7H),
		7.36-7.26 (m, 2H), 5.23 (p, J = 7.0 Hz, 1H), 5.05 (br s, 0.3H), 4.95-4.74
		(m, 2H), 4.61 (dd, J = 13.4, 6.1 Hz, 0.7H), 4.08-3.96 (m, 2H), 3.59 (br s,
		0.3H), 3.37 (br s, 0.7H), 3.25 (br s, 0.3H), 3.06 (t, J = 12.0 Hz, 0.3H), 2.77
		(t, J = 12.3 Hz, 0.7H), 2.72-2.62 (m, 0.7H), 2.46-2.30 (m, 2H), 2.03-
		1.92 (m, 2H), 1.88-1.34 (m, 4H), 1.51 (d, J = 7.1 Hz, 3H), 1.32-1.03
		(m, 4H), 0.66-0.44 (m, 2H).
878	707.3	1H NMR (400 MHz, DMSO-d6) δ 9.01 (d, J = 7.2 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.00 (br s, 2H), 7.77 (br s, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.69-
		7.56 (m, 1H), 7.37-7.18 (m, 3H), 7.19 (s, 1H), 5.18 (p, J = 7.0 Hz, 1H),
		4.98 (br s, 0.5H), 4.75 (dd, J = 14.2, 5.1 Hz, 1H), 4.53 (br s, 0.5H), 4.29
		(dd, J = 14.3, 7.8 Hz, 1H), 4.16 (br s, 0.5H), 3.95 (br s, 1H), 3.75 (br s,
		0.5H), 3.43-3.07 (m, 1H), 2.80 (ddd, J = 14.5, 10.3, 4.1 Hz, 1H), 2.45-
		2.30 (m, 1H), 2.10-1.89 (m, 2H), 1.89-1.44 (m, 5H), 1.64 (d, J = 7.0
		Hz, 3H), 1.17-0.99 (m, 3H), 0.77 (br s, 4H), 0.46-0.36 (m, 2H).
879	707.3	1H NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 6.9 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.99 (br s, 2H), 7.84 (d, J = 8.1 Hz, 1H), 7.79-7.56 (m, 2H),
		7.41 (d, J = 8.0 Hz, 1H), 7.30-7.18 (m, 3H), 5.16 (p, J = 7.0 Hz, 1H),
		4.98 (s, 0.5H), 4.87 (br s, 1H), 4.53 (br s, 0.5H), 4.17 (br s, 0.5H), 4.04-
		3.96 (m, 1H), 3.89 (dd, J = 14.1, 9.1 Hz, 1H), 3.75 (br s, 0.5 H), 3.42-
		3.04 (m, 1H), 2.83-2.55 (m, 2H), 2.06-1.44 (m, 5H), 1.50 (d, J = 7.0
		Hz, 3H), 1.20-0.94 (m, 6H), 0.81 (br s, 2H), 0.41-0.31 (m, 1H), 0.31-
		0.22 (m, 1H).
880	660.3	1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J = 7.1 Hz, 1H), 8.05 (d, J =
		8.2 Hz, 1H), 7.99 (br s, 2H), 7.83-7.55 (m, 2H), 7.33-7.17 (m, 3H),
		4.98 (s, 0.5H), 4.93-4.84 (m, 1H), 4.70-4.60 (m, 1H), 4.57-4.41 (m,
		1H), 4.46 (p, J = 7.2 Hz, 1H), 4.18 (br s, 0.5H), 3.99 (br s, 1H), 3.43-
		3.07 (m, 2H), 2.76 (br s, 0.5H), 2.41-2.29 (m, 1H), 1.76 (d, J = 7.1 Hz,
		3H), 2.22-1.47 (m, 7H), 1.44-1.25 (m, 1H), 1.12 (br s, 2H), 0.95-0.76
		(m, 3H), 0.76-0.60 (m, 2H).
881	660.3	1H NMR (400 MHz, DMSO-d6) δ 8.62 (d, J = 8.5 Hz, 1H), 8.02 (d, J =
		8.0 Hz, 3H), 7.97 (br s, 2H), 7.78-7.57 (m, 2H), 7.29 (s, 1H), 7.23 (br s,
		2H), 7.17 (d, J = 8.1 Hz, 1H), 5.03 (p, J = 7.2 Hz, 1H), 4.96-4.78 (m,
		2H), 4.66-4.56 (m, 1H), 4.56 (br s, 0.5H), 4.16 (br s, 0.5H), 4.04-3.95
		(m, 1H), 2.44-2.29 (m, 1H), 2.06-1.48 (m, 6H), 1.45 (d, J = 7.1 Hz,
		3H), 1.42-1.20 (m, 1H), 1.18-1.06 (m, 2H), 0.97-0.59 (m, 6H).
882	624.4	1H NMR (400 MHz, DMSO-d6) δ 8.46 (d, J = 8.5 Hz, 1H), 8.09-7.53
		(m, 5H), 7.30-7.17 (m, 2H), 7.14 (d, J = 8.0 Hz, 1H), 5.00 (p, J = 7.2 Hz,
		1H), 4.89-4.72 (m, 2H), 4.52 (br s, 0.5H), 4.17 (br s, 0, 5H), 3.99 (tt, J =
		7.2, 3.8 Hz, 1H), 3.75 (br, 0.5H), 3.43-3.02 (m, 2H), 2.77 (br s, 0.5H),
		1.44 (d, J = 7.1 Hz, 3H), 2.03-0.80 (m, 15H), 0.80-0.43 (m, 4H).
883	693.4	1H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 4.8 Hz, 1H), 8.31 (d, J =
		7.1 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.99 (br s, 2H), 7.92 (dd, J = 8.8, 7.1
		Hz, 1H), 7.76 (br s, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.45 (dd, J = 7.6, 4.9
		Hz, 1H), 7.38 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), 6.90 (s, 1H),
		5.07 (p, J = 7.0 Hz, 1H), 5.00 (br s, 0.6H), 4.83 (t, J = 12.0 Hz, 1H), 4.54
		(br s, 0.4H), 4.47-4.36 (m, 1H), 4.24 (br s, 0.4H), 4.13 (s, 3H), 3.99 (s,
		3H), 3.45-3.03 (m, 1H), 2.80 (dt, J = 41.9, 12.7 Hz, 1H), 2.19-1.91 (m,
		2H), 1.89-1.52 (m, 7H), 1.43 (d, J = 7.0 Hz, 3H), 1.52-1.12 (m, 2H).
884	693.4	1H NMR (400 MHz, DMSO-d6) δ 8.70 (dd, J = 9.0, 3.3 Hz, 1H), 8.60 (d,
		J = 4.9 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.98 (br s, 3H), 7.90 (td, J = 7.8,
		1.8 Hz, 1H), 7.76 (br s, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.45-7.35 (m, 2H),
		7.24 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 6.90 (s, 1H), 5.27 (p, J = 7.4 Hz,
		1H), 4.99 (br s, 0.4H), 4.89 (dt, J = 14.5, 7.7 Hz, 1H), 4.66-4.46 (m,
		1.6H), 4.23 (br s, 0.4H), 4.12 (s, 3H), 3.99 (s, 3H), 3.46-3.04 (m, 1.6H),
		2.77 (s, 0.4H), 2.17-1.44 (m, 7H), 1.55 (d, J = 7.1 Hz, 3H), 1.45-1.05
		(m, 4H), 0.76 (br s, 1H).
885	707.4	1H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 4.8 Hz, 1H), 8.33 (d, J =
		7.0 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 8.01 (br s, 2H), 7.95-7.89 (m, 1H),
		7.86-7.55 (m, 2H), 7.45 (dd, J = 7.6, 4.8 Hz, 1H), 7.31-7.17 (m, 3H),
		5.07 (p, J = 7.0 Hz, 1H), 4.92 (t, J = 11.5 Hz, 1H), 4.64 (br s, 1H), 4.53 (br
		s, 0.5H), 4.18 (br s, 1H), 4.04-3.97 m, 1H),  2.81 (dt, J = 42.2, 13.0
		Hz, 1H), 2.20-1.34 (m, 11H), 1.44 (d, J = 7.1 Hz, 3H), 1.34-1.03 (m,
		2H), 0.94 (br s, 1H), 0.62 (br s, 1H).
886	707.4	1H NMR (400 MHz, DMSO-d6) δ 8.76-8.69 (m, 1H), 8.60 (d, J = 4.8
		Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.99 (br s, 2H), 7.90 (td, J = 7.7, 1.6 Hz,
		1H), 7.95-7.58 (m, J = 34.1 Hz, 2H), 7.62 (d, J = 7.9 Hz, 1H), 7.42 (dd,
		J = 7.5, 4.9 Hz, 1H), 7.32-7.18 (m, 3H), 5.27 (p, J = 7.3 Hz, 1H), 5.02-
		4.02 (m, 1.5H), 4.84-4.73 (m, 1H), 4.52 (br s, 0.5H), 4.18 (br s, 0.5H),
		4.05-3.97 (m, 1H), 3.77 (br s, 0.5H), 3.43-3.07 (m, 1.5H), 2.84-2.58
		(m, 1H), 2.18-1.45 (m, 6H), 1.55 (d, J = 7.1 Hz, 3H), 1.43-1.02 (m,
		6H), 0.96 (br s, 1H), 0.78 (br s, 1H), 0.55 (br s, 1H).
887	727.3	1H NMR (400 MHz, DMSO-d6) δ 8.83-8.75 (m, 1H), 8.08 (d, J = 8.0
		Hz, 1H), 7.97 (t, J = 7.8 Hz, 2H), 8.03-7.67 (m, 2H), 7.63 (d, J = 7.7 Hz,
		1H), 7.57 (d, J = 7.9 Hz, 1H), 7.38 (s, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.07
		(s, 1H), 6.90 (s, 1H), 5.27 (p, J = 7.2 Hz, 1H), 4.99 (br s, 0.5H), 4.87 (dt,
		J = 14.4, 7.8 Hz, 1H), 4.65-4.48 (m, 1.5H), 4.23 (br s, 0.5H), 4.12 (s, 3H),
		3.99 (s, 3H), 3.44-3.04 (m, 2H), 2.77 (br s, 0.5H), 2.11-1.45 (m, 5H),
		1.54 (d, J = 7.1 Hz, 3H), 1.43-1.05 (m, 5H), 0.78 (brs, 1H).
888	727.3	1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 7.3 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 7.99 (t, J = 7.9 Hz, 1H), 7.75 (br s, 1H), 7.60 (s, 1H), 7.58 (s,
		1H), 7.38 (br s, 2H), 7.22 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), 6.90 (s, 1H),
		5.10 (p, J = 7.1 Hz, 1H), 5.00 (br s, 0.5H), 4.82 (t, J = 12.0 Hz, 1H), 4.63-
		4.36 (m, 2H), 4.24 (br s, 1H), 4.13 (s, 3H), 3.99 (s, 3H), 3.44-3.04 (m,
		2H), 2.85-2.64 (m, 2H), 2.23-1.33 (m, 6H), 1.46 (d, J = 7.1 Hz, 3H),
		1.33-1.14 (s, 3H).
889	725.3	1H NMR (400 MHz, DMSO-d6) δ 8.53 (ddd, J = 4.9, 1.9, 0.9 Hz, 1H),
		8.44 (d, J = 7.1 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 8.05-7.68 (m, 3H),
		7.73 (td, J = 7.8, 1.9 Hz, 1H), 7.43-7.23 (m, 4H), 7.04 (s, 1H), 6.89 (s,
		1H), 6.69 (t, J = 55.5 Hz, 1H), 5.18 (p, J = 6.9 Hz, 1H), 4.99 (br s, 0.5H),
		4.82-4.72 (m, 1H), 4.60-4.42 (m, 1H), 4.23 (br s, 0.5H), 4.11 (s, 3H),
		3.98 (s, 3H), 3.45-3.05 (m, 1.5H), 2.76 (br s, 0.5H), 2.46-2.22 (m, 2H),
		2.05-1.21 (m, 11H), 1.57 (d, J = 7.0 Hz, 3H), 1.22-0.97 (m, 2H).
890	725.3	1H NMR (400 MHz, DMSO-d6) δ 8.61 (ddd, J = 4.8, 1.9, 0.9 Hz, 1H),
		8.24 (d, J = 7.1 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 8.09-7.71 (m, 3H),
		7.85 (td, J = 7.7, 1.9 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.37 (ddd, J = 7.5,
		4.8, 1.0 Hz, 1H), 7.21 (d, J = 8.2 Hz, 1H), 7.04 (s, 1H), 6.90 (s, 1H), 6.47
		(t, J = 55.2 Hz, 1H), 5.20 (p, J = 7.0 Hz, 1H), 5.00 (s, 0.5H), 4.83 (t, J =
		10.2 Hz, 1H), 4.61-4.35 (m, 1.5H), 4.23 (br s, 0.5H), 4.11 (s, 3H), 3.99
		(s, 3H), 3.45-3.03 (m, 1.5H), 2.77 (br s, 0.5H), 2.55-2.38 (m, 2H), 2.03-
		1.23 (m, 13H), 1.33 (d, J = 7.0 Hz, 3H), 1.00 (br s, 1H).
891	675.3	1H NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 8.6 Hz, 1H), 8.58 (d, J =
		5.1 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 8.03-7.69 (m, 4H), 7.66 (d, J = 8.3
		Hz, 1H), 7.44 (s, 1H), 7.38 (s, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H),
		6.90 (s, 1H), 5.22 (p, J = 7.2 Hz, 1H), 5.11-4.95 (m, 1.5H), 4.66-4.46
		(m, 1.5H), 4.29-4.14 (m, 1.5H), 4.12 (s, 3H), 3.99 (s, 3H), 3.45-3.04 (m,
		1.5H), 2.77 (br s, 0.5H), 2.21 (br s, 0.5H), 2.13-1.30 (m, 9H), 1.41 (d, J =
		7.0 Hz, 3H), 1.21-0.90 (m, 3H), 0.53 (br s, 1H).
892	675.3	1H NMR (400 MHz, DMSO-d6) δ 8.61-8.57 (m, 1H), 8.29 (d, J = 7.4
		Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 8.02-7.65 (m, 5H), 7.53 (d, J = 7.9 Hz,
		1H), 7.41-7.34 m, 2.5H), 7.21 (d, J = 8.1 Hz, 1H), 7.05 (s, 1H), 6.90 (s,
		1.5H), 5.11 (p, J = 7.1 Hz, 1H), 4.98 (brs, 0.5H), 4.85-4.75 (m, 1H), 4.61-
		4.39 (m, 1.5H), 4.24 (br s, 0.5H), 4.13 (s, 3H), 3.99 (s, 3H), 3.65 (dd, J =
		12.6, 3.6 Hz, 1H), 3.45-3.04 (m, 1.5H), 2.76 (br s, 0.5H), 2.37-2.30 (m,
		1H), 2.05-1.29 (m, 15H), 1.46 (d, J = 7.1 Hz, 3H), 1.29-1.15 (m, 2H).
893	658.6	1H NMR (400 MHz, DMSO-d6) δ 8.84 (d, J = 7.1 Hz, 1H), 8.06 (d, J =
		8.1 Hz, 1H), 8.04-7.93 (m, 2H), 7.77 (s, 1H), 7.42-7.33 (m, 1H), 7.33-
		7.24 (m, 3H), 7.20-7.09 (m, 1H), 7.00 (s, 1H), 6.90 (s, 1H), 6.78 (d, J =
		7.8 Hz, 1H), 5.20 (p, J = 7.0 Hz, 1H), 5.07-4.93 (m, 0.4H), 4.66-4.58
		(m, 1H), 4.56-4.48 (m, 0.5H), 4.47-4.34 (m, 1H), 4.29-4.17 (m,
		0.5H), 4.08 (s, 3H), 3.99 (s, 3H), 3.87-3.76 (m, 0.3H), 3.46-3.22 (m,
		1H), 3.21-3.03 (m, 0.4H), 2.81-2.75 (m, 0.5H), 2.61-2.54 (m, 1H),
		2.04-1.92 (m, 1H), 1.89-1.73 (m, 3H), 1.73-1.45 (m, 7H), 1.12-1.01
		(m, 1H), 0.80-0.69 (m, 1H), 0.61-0.47 (m, 1H), 0.36-0.19 (m, 1H).
894	682.6	1H NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 7.1 Hz, 1H), 8.09 (d, J =
		8.0 Hz, 1H), 8.06-7.67 (m, 3H), 7.43-7.33 (m, 1H), 7.31-7.21 (m,
		2H), 7.11 (d, J = 14.7 Hz, 2H), 6.90 (s, 1H), 5.20 (p, J = 7.0 Hz, 1H), 4.99
		(s, 0.2H), 4.92-4.80 (m, 1H), 4.67-4.58 (m, 1H), 4.58-4.48 (m, 0.4H),
		4.27-4.20 (m, 1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.45-3.20 (m, 1H), 3.17-
		3.10 (m, 0.2H), 2.82-2.74 (m, 0.4H), 2.46-2.27 (m, 2H), 2.21-2.12
		(m, 1H), 2.03-1.92 (m, 1H), 1.88-1.73 (m, 1H), 1.63 (s, 5H), 1.52-
		1.38 (m, 4H), 1.30-1.11 (m, 2H), 0.54-0.40 (m, 1H).
895	713.8	1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 6.8 Hz, 1H), 8.04 (d, J =
		10.4 Hz, 1H), 7.99 (s, 2H), 7.85 (d, J = 8.1 Hz, 1H), 7.82-7.71 (m, 1H),
		7.70-7.55 (m, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.32 (s, 1H), 7.30-7.19 (m,
		1H), 5.48-5.35 (m, 1H), 5.02-4.91 (m, 0.5H), 4.93-4.76 (m, 2H), 4.56-
		4.48 (s, 0.5H), 4.23-4.12 (m, 0.5H), 4.08-3.97 (m, 1H), 3.84-3.68
		(m, 0.3H), 3.45-3.21 (m, 1H), 3.20-3.07 (m, 0.3H), 2.82-2.72 (m,
		0.5H), 2.71-2.62 (m, 1H), 2.41-2.29 (m, 2H), 2.03-1.91 (m, 1H), 1.90-
		1.74 (m, 1H), 1.65 (s, 5H), 1.55-1.42 (m, 4H), 1.42-1.30 (m, 1H),
		1.29-1.14 (m, 0H), 1.13-0.99 (m, 2H), 0.61-0.34 (m, 2H).
896	696.2	1H NMR (400 MHz, DMSO-d6) δ 8.97 (d, J = 7.0 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.84 (d, J = 91.2 Hz, 3H), 7.52-7.30 (m, 4H), 7.25 (d, J =
		8.1 Hz, 1H), 7.18-6.98 (m, 2H), 6.89 (s, 1H), 5.20 (p, J = 7.1 Hz, 1H),
		5.06-4.92 (m, 0.5H), 4.92-4.78 (m, 1H), 4.68-4.46 (m, 1.5H), 4.29-
		4.19 (m, 0.5H), 4.11 (s, 3H), 3.99 (s, 3H), 3.44-2.99 (m, 1.5H), 2.86-
		2.66 (m, 0.5H), 2.47-2.23 (m, 3H), 2.06-1.35 (m, 12H), 1.35-1.06 (m,
		2H), 0.62-0.41 (m, 1H).
897	682.2	1H NMR (400 MHz, DMSO-d6) δ 9.32 (d, J = 7.2 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 8.05-7.62 (m, 3H), 7.42-7.29 (m, 2H), 7.26 (d, J = 8.1 Hz,
		1H), 7.09 (s, 1H), 7.05 (dd, J = 8.5, 4.5 Hz, 1H), 6.89 (s, 1H), 5.27 (p, J =
		7.0 Hz, 1H), 5.05-4.95 (m, 0.5H), 4.95-4.81 (m, 1H), 4.68-4.46 (m,
		1.5H), 4.28-4.18 (m, 0.5H), 4.11 (s, 3H), 3.99 (s, 3H), 3.87-3.75 (m,
		0.5H), 3.47-3.01 (m, 1.5H), 2.85-2.68 (m, 0.5H), 2.48-2.38 (m, 1H),
		2.31-2.08 (m, 2H), 2.04-1.33 (m, 12H), 1.33-1.06 (m, 2H), 0.48-
		0.31 (m, 1H).
898	698.2	1H NMR (400 MHz, DMSO-d6) δ 9.05 (d, J = 7.1 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 8.03-7.62 (m, 3H), 7.54-7.43 (m, 1H), 7.36 (s, 1H), 7.28-
		7.20 (m, 2H), 7.08 (s, 1H), 6.89 (s, 1H), 5.20 (p, J = 6.9 Hz, 1H), 5.07-
		4.92 (m, 0.5H), 4.91-4.78 (m, 1H), 4.68-4.45 (m, 1.5H), 4.28-4.17
		(m, 0.5H), 4.12 (s, 3H), 3.99 (s, 3H), 3.87-3.73 (m, 0.5H), 3.46-3.04
		(m, 1.5H), 2.86-2.69 (m, 0.5H), 2.44-2.18 (m, 2H), 2.05-1.36 (m,
		12H), 1.36-1.09 (m, 2H), 0.58-0.40 (m, 1H).
899	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.93 (d, J = 6.8 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.04-7.63 (m, 3H), 7.36 (s, 1H), 7.28-7.19 (m, 2H), 7.19-
		7.11 (m, 2H), 7.07 (s, 1H), 6.89 (s, 1H), 5.16 (p, J = 7.0 Hz, 1H), 5.07-
		4.91 (m, 0.5H), 4.91-4.79 (m, 1H), 4.68-4.45 (m, 1.5H), 4.29-4.17
		(m, 0.5H), 4.11 (s, 3H), 3.99 (s, 3H), 3.87-3.71 (m, 0.5H), 3.48-3.02
		(m, 1.5H), 2.86-2.69 (m, 0.5H), 2.47-2.28 (m, 2H), 2.28-2.16 (m,
		1H), 2.05-1.31 (m, 12H), 1.31-1.06 (m, 2H), 0.58-0.43 (m, 1H).
900	664.3	1H NMR (400 MHz, DMSO-d6) δ 8.86 (d, J = 6.9 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 8.04-7.63 (m, 3H), 7.45-7.31 (m, 2H), 7.24 (d, J = 8.1 Hz,
		1H), 7.11-7.02 (m, 3H), 6.89 (s, 1H), 5.16 (p, J = 7.0 Hz, 1H), 5.03-
		4.92 (m, 0.5H), 4.90-4.78 (m, 1H), 4.68-4.45 (m, 1.5H), 4.27-4.17
		(m, 0.5H), 4.11 (s, 3H), 3.99 (s, 3H), 3.89-3.74 (m, 0.5H), 3.45-3.04
		(m, 1.5H), 2.84-2.69 (m, 0.5H), 2.44-2.18 (m, 2H), 2.04-1.34 (m,
		12H), 1.34-1.07 (m, 2H), 0.61-0.44 (m, 1H).
901	680.2	1H NMR (400 MHz, DMSO-d6) δ 8.92 (d, J = 6.9 Hz, 1H), 8.07 (d, J =
		8.0 Hz, 1H), 8.03-7.63 (m, 3H), 7.42-7.32 (m, 2H), 7.32-7.27 (m,
		2H), 7.24 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H), 6.89 (s, 1H), 5.17 (p, J = 6.9
		Hz, 1H), 5.05-4.92 (m, 0.5H), 4.91-4.79 (m, 1H), 4.68-4.46 (m,
		1.5H), 4.29-4.16 (m, 0.5H), 4.11 (s, 3H), 3.99 (s, 3H), 3.87-3.72 (m,
		0.5H), 3.45-3.03 (m, 1.5H), 2.84-2.69 (m, 0.5H), 2.47-2.18 (m, 3H),
		2.03-1.33 (m, 12H), 1.33-1.06 (m, 2H), 0.62-0.42 (m, 1H).
902	664.3	1H NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 7.4 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 8.04-7.65 (m, 3H), 7.44-7.27 (m, 2H), 7.25 (d, J = 8.1 Hz,
		1H), 7.11-7.00 (m, 3H), 6.90 (s, 1H), 5.27 (p, J = 7.1 Hz, 1H), 5.07-
		4.83 (m, 1.5H), 4.69-4.46 (m, 1.5H), 4.28-4.17 (m, 0.5H), 4.11 (s, 3H),
		3.99 (s, 3H), 3.89-3.74 (m, 0.5H), 3.47-3.00 (m, 1.5H), 2.86-2.67 (m,
		0.5H), 2.31-2.13 (m, 2H), 2.06-1.33 (m, 12H), 1.33-1.10 (m, 2H),
		0.49-0.32 (m, 1H).
903	682.3	1H NMR (400 MHz, DMSO-d6) δ 9.32 (d, J = 7.5 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 8.05-7.64 (m, 3H), 7.36 (br. s, 1H), 7.26 (d, J = 8.1 Hz,
		1H), 7.22 (td, J = 9.1, 4.5 Hz, 1H), 7.15 (ddd, J = 9.0, 8.3, 4.0 Hz, 1H),
		7.09 (s, 1H), 6.90 (s, 1H), 5.29 (p, J = 7.1 Hz, 1H), 5.02-4.97 (m, 0.5H),
		4.95-4.84 (m, 1H), 4.62 (d, J = 13.4 Hz, 1H), 4.56-4.51 (m, 0.5H), 4.31-
		4.15 (m, 0.5H), 4.12 (s, 3H), 3.99 (s, 3H), 3.92-3.68 (m, 0.5H), 3.49-
		2.59 (m, 2H), 2.47-2.35 (m, 3H), 2.04-1.87 (m, 3H), 1.88-1.33 (m,
		6H), 1.46 (d, J = 7.0 Hz, 3H), 1.34-1.10 (m, 2H), 0.47-0.28 (m, 1H).
904	652.3	1H NMR (400 MHz, DMSO-d6) δ 8.38 (d, J = 8.9 Hz, 1H), 8.10 (d, J =
		8.1 Hz, 1H), 8.08-7.70 (m, 3H), 7.35 (br. s, 1H), 7.27 (d, J = 8.1 Hz,
		1H), 7.18 (s, 1H), 6.91 (s, 1H), 5.32 (dq, J = 8.9, 6.8 Hz, 1H), 5.10-4.86
		(m, 0.5H), 4.84-4.64 (m, 2H), 4.63-4.44 (m, 0.5H), 4.32-4.15 (m,
		0.5H), 3.99 (s, 3H), 3.89 (tt, J = 7.3, 3.9 Hz, 1H), 3.86-3.75 (m, 0.5H),
		3.43 (t, J = 8.1 Hz, 2H), 3.51-2.98 (m, 1H), 2.88-2.68 (m, 1H), 2.33-
		2.21 (m, 1H), 2.04-1.93 (m, 1H), 1.92-1.53 (m, 11H), 1.49 (d, J = 6.8
		Hz, 3H), 1.47-1.37 (m, 1H), 1.20-0.93 (m, 6H), 0.85-0.68 (m, 1H),
		0.53 (h, J = 5.0 Hz, 1H).
905	654.3	1H NMR (400 MHz, DMSO-d6) δ 8.06 (d, J = 8.0 Hz, 1H), 8.05 (d, J =
		9.1 Hz, 1H), 8.02-7.62 (m, 3H), 7.34 (br. s, 1H), 7.21 (d, J = 8.1 Hz,
		1H), 7.18 (s, 1H), 6.91 (s, 1H), 5.29-5.16 (m, 1H), 5.06-4.92 (m,
		0.5H), 4.86 (dt, J = 14.1, 7.4 Hz, 1H), 4.83-4.74 (m, 1H), 4.61-4.45 (m,
		0.5H), 4.32-4.17 (m, 0.5H), 3.99 (s, 3H), 3.89 (tt, J = 7.2, 3.9 Hz, 1H),
		3.83-3.75 (m, 0.5H), 3.39-3.28 (m, 1H), 3.51-3.00 (m, 1H), 2.85-
		2.72 (m, 1H), 2.44-2.27 (m, 1H), 2.03-1.90 (m, 1H), 1.88-1.50 (m,
		9H), 1.46 (d, J = 6.9 Hz, 3H), 1.33 (s, 3H), 1.30-1.25 (m, 2H), 1.22 (s,
		3H), 1.14-1.03 (m, 1H), 1.03-0.92 (m, 1H), 0.89-0.76 (m, 1H), 0.75-
		0.62 (m, 1H), 0.48-0.38 (m, 1H).
906	682.2	1H NMR (400 MHz, DMSO-d6) δ 9.02 (d, J = 7.0 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 8.05-7.67 (m, 3H), 7.42-7.27 (m, 2H), 7.24 (d, J = 8.0 Hz,
		1H), 7.27-7.19 (m, 1H), 7.08 (s, 1H), 6.90 (s, 1H), 5.18 (p, J = 7.0 Hz,
		1H), 5.05-4.92 (m, 0.5H), 4.91-4.80 (m, 1H), 4.66-4.58 (m, 1H), 4.58-
		4.46 (m, 0.5H), 4.28-4.16 (m, 0.5H), 4.12 (s, 3H), 3.99 (s, 3H), 3.92-
		3.71 (m, 0.5H), 3.48-3.00 (m, 2H), 2.88-2.68 (m, 1H), 2.59-2.23 (m,
		2H), 2.02-1.92 (m, 1H), 1.90-1.35 (m, 8H), 1.48 (d, J = 7.0 Hz, 3H),
		1.34-1.10 (m, 2H), 0.57-0.43 (m, 1H).
907	612.3	1H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 8.0 Hz, 0.4 of 1H), 8.09 (d,
		J = 8.0 Hz, 0.6 of 1H), 8.03-7.64 (m, 3H), 7.39 (br. s, 1H), 7.32 (d, J =
		8.0 Hz, 0.4 of 1H), 7.14 (s, 0.4 of 1H), 7.13 (s, 0.6 of 1H), 7.11 (d, J = 8.0
		Hz, 0.6 of 1H), 6.90 (s, 1H), 6.12 (q, J = 7.0 Hz, 0.6 of 1H), 5.29 (dd, J =
		13.4, 6.5 Hz, 0.4 of 1H), 5.06-4.94 (m, 1H), 4.64 (br. d, J = 13.4 Hz,
		1H), 4.59-4.14 (m, 2H), 4.12 (s, 3H), 3.99 (s, 3H), 3.87-3.59 (m, 1H),
		3.45-3.35 (m, 0.4 of 1H), 3.35-3.21 (m, 1H), 3.21-3.09 (m, 1H), 2.82-
		2.69 (m, 0.6 of 1H), 2.29 (s, 1H of 3H), 2.02 (s, 2H of 3H), 2.02-1.91
		(m, 2H), 1.90-1.45 (m, 5H), 1.63 (d, J = 6.7 Hz, 1H of 3H), 1.54 (d, J =
		7.0 Hz, 2H of 3H), 1.43-1.03 (m, 6H), 0.98-0.74 (m, 2H), 0.19-−0.30
		(m, 2H).
908	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 8.0 Hz, 0.33H of 1H), 8.09
		(d, J = 8.0 Hz, 0.66H of 1H), 8.03 (br. s, 2H of 3H), 7.81 (br. s, 1H of 3H),
		7.39 (s, 1H), 7.31 (d, J = 8.1 Hz, 0.33H of 1H), 7.12 (s, 0.33 H of 1H),
		7.11 (d, J = 8.1 Hz, 0.66H of 1H), 7.11 (s, 0.66H of 1H), 6.91 (s, 1H), 6.05
		(q, J = 6.9 Hz, 0.66H of 1H), 5.40 (q, J = 6.8 Hz, 0.33H of 1H), 5.05-
		4.94 (m, 1H), 4.73-4.63 (m, 1H), 4.89-4.42 (m, 1H), 4.29-4.18 (m,
		0.66H of 1H), 4.13 (s, 1H of 3H), 4.12 (s, 2H of 3H), 3.99 (s, 3H), 3.92-
		3.69 (m, 0.33H of 1H), 3.45-3.25 (m, 1H), 3.23-3.11 (m, 1H), 2.89-
		2.69 (m, 2H), 2.31 (s, 1H of 3H), 2.04 (s, 2H of 3H), 2.04-1.93 (m, 1H),
		1.92-1.73 (m, 1H), 1.71 (d, J = 6.8 Hz, 1H of 3H), 1.61 (d, J = 6.9 Hz,
		2H of 3H), 1.67-1.49 (m, 7H), 1.48-1.00 (m, 6H), 1.00-0.63 (m, 3H),
		0.62-0.42 (m, 1H).
909	628.3	1H NMR (400 MHz, DMSO-d6) δ 8.08 (d, J = 8.0 Hz, 1H), 8.06 (d, J =
		9.0 Hz, 1H), 7.94-7.75 (m, 3H), 7.41-7.35 (m, 1H), 7.23 (d, J = 8.1 Hz,
		1H), 7.06 (s, 1H), 6.90 (s, 1H), 5.23 (dq, J = 9.0, 6.8 Hz, 1H), 5.02-4.97
		(m, 0.5H), 4.87-4.75 (m, 1H), 4.61-4.50 (m, 2H), 4.27-4.18 (m,
		0.5H), 4.10 (s, 3H), 3.99 (s, 3H), 3.91-3.73 (m, 0.5H), 3.35 (ddd, J =
		10.5, 8.3, 5.5 Hz, 1H), 3.49-3.04 (m, 0.5H), 2.89-2.49 (m, 2H), 2.42-
		2.27 (m, 1H), 2.05-1.93 (m, 1H), 1.92-1.72 (m, 2H), 1.72-1.50 (m,
		7H), 1.45 (d, J = 6.9 Hz, 3H), 1.33 (s, 3H), 1.37-1.20 (m, 1H), 1.22 (s,
		3H), 0.80-0.66 (m, 1H).
910	626.3	1H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J = 8.8 Hz, 1H), 8.13 (d, J =
		8.0 Hz, 1H), 8.08-7.67 (m, 3H), 7.38 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H),
		7.07 (s, 1H), 6.90 (s, 1H), 5.32 (dq, J = 8.6, 6.7 Hz, 1H), 5.06-4.92 (m,
		0.5H), 4.79-4.67 (m, 1H), 4.61-4.49 (m, 2H), 4.29-4.18 (m, 0.5H),
		4.12 (s, 3H), 3.99 (s, 3H), 3.91-3.68 (m, 1H), 3.51-3.37 (m, 1H), 3.37-
		3.06 (m, 1H), 2.86-2.69 (m, 1H), 2.34-2.19 (m, 1H), 2.04-1.92 (m,
		2H), 1.90-1.51 (m, 8H), 1.47 (d, J = 6.8 Hz, 3H), 1.43 (q, J = 6.8 Hz,
		1H), 1.19-0.97 (m, 5H).
911	735.3	1H NMR (400 MHz, DMSO-d6) δ 9.25 (d, J = 8.1 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 7.95 (s, 2H), 7.82-7.54 (m, 2H), 7.32 (s, 1H), 7.27 (d, J =
		8.1 Hz, 1H), 7.24-7.17 (m, 1H), 6.86 (s, 1H), 5.45-5.33 (m, 1H), 5.06-
		4.93 (m, 1.5H), 4.88-4.74 (m, 1H), 4.58-4.47 (m, 0.5H), 4.22-4.12
		(m, 0.5H), 4.05-3.95 (m, 1H), 3.79-3.68 (m, 0.5H), 3.45-3.04 (m,
		1.5H), 2.81-2.70 (m, 0.5H), 2.31-2.16 (m, 2H), 2.05-1.37 (m, 14H),
		1.30-0.83 (m, 8H), 0.54-0.30 (m, 2H).
912	650.3	1H NMR (400 MHz, DMSO-d6) δ 8.98 (d, J = 6.6 Hz, 1H), 8.08 (d, J =
		8.1 Hz, 1H), 7.97 (s, 2H), 7.79-7.52 (m, 3H), 7.50 (d, J = 1.9 Hz, 1H),
		7.29-7.17 (m, 3H), 6.68 (d, J = 1.9 Hz, 1H), 5.08 (p, J = 7.0 Hz, 1H),
		5.03-4.89 (m, 0.5H), 4.86-4.70 (m, 1H), 4.58-4.40 (m, 2.5H), 4.23-
		4.09 (m, 0.5H), 4.09-3.94 (m, 2H), 3.79-3.67 (m, 0.5H), 3.43-3.01
		(m, 1.5H), 2.80-2.68 (m, 0.5H), 2.03-1.34 (m, 12H), 1.19-0.81 (m,
		6H), 0.65-0.55 (m, 1H).
913	606.3	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 8.5 Hz, 1H), 8.02-7.89
		(m, 3H), 7.82-7.66 (m, 3H), 7.39 (d, J = 8.3 Hz, 1H), 7.26 (s, 1H), 7.13
		(d, J = 8.1 Hz, 1H), 5.00 (p, J = 7.1 Hz, 1H), 4.95-4.69 (m, 2.5H), 4.59-
		4.47 (m, 0.5H), 4.27-4.15 (m, 0.5H), 3.87-3.68 (m, 1.5H), 3.46-2.98
		(m, 1.5H), 2.83-2.69 (m, 0.5H), 2.05-1.05 (m, 19H), 0.95-0.80 (m,
		2H), 0.77-0.41 (m, 4H).
914	642.3	1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.8 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 7.97 (s, 2H), 7.85-7.63 (m, 3H), 7.41 (d, J = 8.2 Hz, 1H),
		7.36 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 5.90 (t, J = 13.8 Hz, 1H), 5.18 (dd,
		J = 27.7, 14.6 Hz, 1H), 5.11-4.89 (m, 1.5H), 4.59-4.46 (m, 0.5H), 4.27-
		4.17 (m, 0.5H), 3.91-3.69 (m, 1.5H), 3.46-3.07 (m, 1.5H), 2.83-2.69
		(m, 0.5H), 2.30-1.21 (m, 16H), 1.09-0.80 (m, 3H), 0.71-0.56 (m, 1H),
		0.56-0.37 (m, 3H).
915	642.3	1H NMR (400 MHz, DMSO-d6) δ 8.10 (d, J = 8.1 Hz, 1H), 8.02-7.68
		(m, 3H), 7.69-7.60 (m, 1H), 7.38 (s, 1H), 7.25 (d, J = 8.2 Hz, 1H), 7.04
		(s, 1H), 6.90 (s, 1H), 5.04-4.88 (m, 1.5H), 4.64-4.50 (m, 1.5H), 4.45-
		4.37 (m, 1H), 4.25-4.19 (m, 0.5H), 4.13 (s, 3H), 3.99 (s, 3H), 3.86-3.76
		(m, 0.5H), 3.45-3.00 (m, 1.5H), 2.83-2.70 (m, 0.5H), 2.40-2.28 (m,
		1H), 2.03-1.42 (m, 17H), 1.24 (d, J = 2.0 Hz, 3H), 0.80 (dd, J = 13.1, 6.8
		Hz, 1H).
916	642.3	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.0 Hz, 1H), 7.96 (s, 2H),
		7.82 (d, J = 8.8 Hz, 1H), 7.73 (s, 1H), 7.37 (s, 1H), 7.18 (d, J = 8.1 Hz,
		1H), 7.05 (s, 1H), 6.89 (s, 1H), 5.29-5.19 (m, 1H), 5.05-4.94 (m,
		0.5H), 4.91-4.81 (m, 1H), 4.69-4.60 (m, 1H), 4.60-4.45 (m, 0.5H),
		4.29-4.18 (m, 0.5H), 4.12 (s, 3H), 3.99 (s, 3H), 3.89-3.73 (m, 0.5H),
		3.43-3.03 (m, 1.5H), 2.84-2.70 (m, 0.5H), 2.13-1.31 (m, 21H), 0.58
		(dd, J = 12.7, 6.4 Hz, 1H).
917	624.4	1H NMR (400 MHz, DMSO-d6) δ 8.00 (d, J = 8.1 Hz, 1H), 7.99 (brs,
		1H), 7.76 (s, 1H), 7.54 (d, J = 8.5 Hz, 1H), 7.37 (s, 1H), 7.15 (d, J = 8.1
		Hz, 1H), 7.02 (s, 1H), 6.90 (s, 1H), 5.13-5.03 (m, 1H), 5.00 (brs, 1H),
		4.87-4.52 (m, 4H), 4.11 (s, 3H), 3.99 (s, 3H), 3.42-2.70 (m, 3H), 2.06
		1.51 (m, 10H), 1.49 (s, 3H), 1.47 (s, 3H), 1.39-1.08 (m, 5H), 0.75-0.61
		(m, 1H), 0.25-0.14 (m, 1H).
918	654.5	1H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 9.7 Hz, 1H), 8.07 (d, J =
		8.1 Hz, 1H), 7.97 (brs, 2H), 7.83-7.55 (m, 2H), 7.29 (s, 1H), 7.24 (brs,
		1H), 7.22 (d, J = 8.1 Hz, 1H), 5.41-5.26 (m, 1H), 5.18-4.82 (m, 2H),
		4.53 (brs, 1H), 4.19 (brs, 1H), 4.00 (brs, 2H), 3.31-3.02 (m, 1H), 2.91-
		2.73 (m, 1H), 2.36-2.17 (m, 2H), 2.15-1.50 (m, 8H), 1.46 (d, J = 7.1
		Hz, 3H), 1.40-0.67 (m, 8H), 0.57 (brs, 1H), 0.20-−0.14 (m, 2H).
919	640.5	1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J = 9.3 Hz, 1H), 8.06 (brs,
		2H), 8.02 (d, J = 8.1 Hz, 1H), 7.83 (brs, 2H), 7.70-7.54 (m, 1H), 7.26
		(brs, 1H), 7.24 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 5.85-5.68 (m, 1H), 5.60-
		5.40 (m, 1H), 5.26-5.13 (m, 1H), 5.08-4.84 (m, 1H), 4.72 (brs, 2H),
		4.54 (brs, 1H), 4.17 (brs, 1H), 3.98 (brs, 1H), 3.76 (brs, 1H), 3.49-3.02
		(m, 2H), 2.94-2.58 (m, 2H), 2.47-2.24 (m, 1H), 2.20-1.53 (m, 6H),
		1.56-1.39 (m, 3H), 1.24-0.99 (m, 4H), 0.92-0.65 (m, 2H).
920	666.5	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 9.5 Hz, 1H), 8.04 (d, J =
		8.0 Hz, 1H), 8.03 (brs, 1H), 7.90-7.62 (m, 3H), 7.31 (brs, 1H), 7.19 (d,
		J = 8.1 Hz, 1H), 7.07 (s, 1H), 6.45 (t, J = 56.0 Hz, 1H), 5.29-4.90 (m,
		4H), 4.85-4.44 (m, 3H), 4.17 (brs, 1H), 3.77 (brs, 1H), 3.48-3.09 (m,
		1H), 2.76 (brs, 1H), 2.39-2.20 (m, 1H), 2.13-1.48 (m, 11H), 1.45 (d,
		J = 7.1 Hz, 3H), 1.40-1.09 (m, 3H), 1.01-0.86 (m, 1H)
921	710.2	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.1 Hz, 1H), 8.11 (d, J =
		8.0 Hz, 1H), 7.99 (brs, 2H), 7.83 (d, J = 8.0 Hz, 1H), 7.76-7.61 (m, 3H),
		7.42 (d, J = 8.0 Hz, 1H), 7.32 (brs, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.15 (s,
		1H), 5.29-5.16 (m, 1H), 5.04-4.83 (m, 2H), 4.675-4.48 (m, 1H), 4.46
		(d, J = 7.0 Hz, 2H), 4.20 (brs, 1H), 2.84-2.57 (m, 2H), 2.46-2.30 (m,
		2H), 2.04-1.32 (m, 8H), 1.50 (d, J = 7.1 Hz, 4H), 1.29-1.04 (m, 2H),
		0.60 (brs, 1H), 0.51-0.31 (m, 2H), 0.33-0.20 (m, 1H), 0.09-−0.09 (m,
		1H)
922	684.4	1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 8.8 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 2H), 7.84-7.63 (m, 2H), 7.47-7.28 (m, 1H), 7.26
		(d, J = 8.1 Hz, 1H), 7.22 (s, 1H), 6.44 (t, J = 54.3 Hz, 1H), 5.52-5.31 (m,
		1H), 5.32-4.93 (m, 3H), 4.83 (q, J = 14.6 Hz, 1H), 4.54 (brs, 1H), 4.18
		(brs, 1H), 3.48-3.09 (m, 3H), 2.78 (brs, 1H), 2.23-1.49 (m, 9H), 1.45
		(d, J = 7.0 Hz, 3H), 1.43-1.23 (m, 2H), 0.90-0.80 (m, 1H), 0.71-0.57
		(m, 1H), 0.56-0.45 (m, 2H).
923	624.7	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 9.5 Hz, 1H), 8.01 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 1H), 7.77 (d, J = 8.3 Hz, 2H), 7.76 (brs, 2H), 7.40
		(d, J = 8.3 Hz, 1H), 7.28 (s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 5.24-5.15 (m,
		1H), 5.07-4.73 (m, 2H), 4.54 (brs, 1H), 4.20 (brs, 1H), 3.50-2.71 (m,
		3H), 2.37-2.20 (m, 1H), 2.14-1.90 (m, 3H), 1.89-1.50 (m, 10H), 1.46
		(d, J = 7.0 Hz, 3H), 1.40-1.10 (m, 4H), 1.01-0.80 (m, 2H), 0.61 (brs,
		1H).
924	686.2	1H NMR (400 MHz, DMSO-d6) δ 8.04 (d, J = 8.1 Hz, 1H), 7.96 (brs,
		2H), 7.72 (brs, 2H), 7.66 (d, J = 8.5 Hz, 1H), 7.36 (brs, 1H), 7.26 (s, 1H),
		7.22 (d, J = 8.1 Hz, 1H), 6.92 (s, 1H), 5.86-5.72 (m, 1H), 5.24 (dd, J =
		27.2, 14.6 Hz, 1H), 5.17-5.05 (m, 1H), 4.99 (brs, 1H), 4.53 (brs, 1H),
		4.26 (brs, 1H), 4.00 (s, 3H), 3.96-3.87 (dt, J = 7.1, 4.1 Hz, 1H), 3.44-
		2.66 (m, 3H), 2.20-1.51 (m, 8H), 1.47 (d, J = 7.1 Hz, 3H), 1.44 (s, 3H),
		1.40-1.04 (m, 4H), 1.01-0.82 (m, 2H), 0.62-0.38 (m, 2H), 0.26-0.18
		(m, 1H).
925	720.3	1H NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 7.1 Hz, 1H), 8.12 (d, J =
		8.1 Hz, 1H), 8.02-7.92 (m, 2H), 7.82 (d, J = 8.1 Hz, 1H), 7.80-7.62 (m,
		2H), 7.41 (d, J = 8.0 Hz, 1H), 7.34 (brs, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.15
		(s, 1H), 6.46 (t, J = 54.0 Hz, 1H), 5.27-4.81 (m, 5H), 4.73-4.43 (m,
		1H), 4.17 (brs, 1H), 3.33-3.01 (m, 1H), 2.90-2.58 (m, 2H), 2.44-2.32
		(m, 2H), 2.05-1.34 (m, 10H), 1.49 (d, J = 7.1 Hz, 3H), 1.29-1.09 (m,
		1H), 0.72-0.56 (m, 1H).
926	678.2	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.1 Hz, 1H), 8.10 (d, J =
		8.0 Hz, 1H), 7.98 (brs, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.4 Hz,
		1H), 7.75 (brs, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.33 (s, 1H), 7.26 (d, J = 8.0
		Hz, 1H), 5.26-5.16 (m, 1H), 5.09-4.80 (m, 2H), 4.54 (brs, 1H), 4.21
		(brs, 1H), 3.94-3.81 (m, 1H), 3.46-3.03 (m, 2H), 2.82-2.58 (m, 2H),
		2.47-2.27 (m, 2H), 2.08-1.35 (m, 10H), 1.50 (d, J = 7.1 Hz, 3H), 1.35-
		0.84 (m, 4H), 0.66-0.37 (m, 2H).
927	682.3	1H NMR (400 MHz, DMSO-d6) δ 8.95 (d, J = 6.8 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.97 (brs, 2H), 7.74 (brs, 1H), 7.44 (dd, J = 10.8, 8.3 Hz,
		1H), 7.36 (brs, 1H), 7.32 (dd, J = 11.7, 7.9 Hz, 1H), 7.25 (d, J = 8.1 Hz,
		1H), 7.08 (s, 1H), 6.90 (brs, 1H), 5.22-5.18 (m, 1H), 4.99 (brs, 0.4H
		minor rotamer), 4.91-4.78 (m, 1H), 4.68-4.46 (m, 1H), 4.26 (brs, 0.6H
		major rotamer), 4.12 (s, 3H), 4.00 (s, 3H), 2.77 (brs, 1H), 2.49-2.19 (m,
		2H), 2.04-1.62 (m 9H), 1.49 (d, J = 7.1 Hz, 3H), 1.48-1.34 (m, 1H),
		1.36-1.06 (m, 3H), 0.60-0.42 (m, 1H).
928	626.3	1H NMR (400 MHz, DMSO-d6) δ 7.99 (brs, 2H), 7.95 (d, J = 8.0 Hz,
		1H), 7.78 (d, J = 7.6 Hz, 2H), 7.36-7.24 (m, 1H), 7.12 (d, J = 8.1 Hz,
		1H), 6.61 (s, 1H), 6.40 (s, 1H), 5.11 (p, J = 7.1 Hz, 1H), 4.98 (brs, 0.4H
		minor rotamer), 4.82-4.67 (m, 1H), 4.53 (brs, 0.6H minor rotamer), 4.36-
		4.20 (m, 2H), 4.09 (s, 3H), 3.45-3.03 (m, 2H), 2.79 (s, 3H), 2.10-1.49
		(m, 12H), 1.44 (d, J = 7.1 Hz, 3H), 1.41-1.23 (m, 2H), 1.21 (s, 3H), 1.15-
		0.99 (m, 2H), 0.95 (s, 3H).
929	646.3	1H NMR (400 MHz, DMSO-d6) δ 8.65 (d, J = 7.6 Hz, 1H), 7.98 (brs,
		2H), 7.90 (d, J = 8.0 Hz, 1H), 7.75 (brs, 1H), 7.38-7.19 (m, 2H), 7.08 (d,
		J = 8.0 Hz, 1H), 6.59 (s, 1H), 6.36 (s, 1H), 5.04-4.89 (m, 1H), 4.51 (brs,
		2H), 4.23 (brs, 1H), 4.09 (s, 3H), 3.68-3.54 (m, 2H), 3.36 (brs, 1H), 3.17
		(s, 3H), 2.81 (s, 3H), 2.23-1.52 (m, 9H), 1.44 (d, J = 7.1 Hz, 3H), 1.37-
		0.99 (m, 4H).
930	672.3	1H NMR (400 MHz, DMSO-d6) δ 8.71 (d, J = 7.6 Hz, 1H), 7.99 (d, J =
		8.0 Hz, 1H), 7.97 (brs, 1H), 7.75 (brs, 1H), 7.33 (brs, 1H), 7.16 (s, 1H),
		7.15 (d, J = 7.6 Hz, 1H), 6.90 (s, 1H), 5.05-4.92 (m, 1H), 4.90-4.21
		(m, 4H), 3.99 (s, 3H), 3.93-3.84 (m, 2H), 3.45-3.02 (m, 3H), 2.85-
		2.68 (m, 1H), 2.49-2.40 (m, 2H), 2.06-1.42 (m, 10H), 1.46 (d, J = 7.1
		Hz, 3H), 1.38-0.96 (m, 5H), 0.78 (brs, 1H), 0.53 (brs, 1H).
931	688.3	1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H),
		7.97 (brs, 2H), 7.74 (brs, 1H), 7.37 (brs, 1H), 7.32 (d, J = 8.1 Hz, 1H),
		7.28 (s, 1H), 6.92 (s, 1H), 5.69-5.29 (m, 3H), 4.98 (brs, 1H), 4.53 (brs,
		1H), 4.26 (brs, 1H), 4.00 (s, 3H), 3.95-3.88 (m, 2H), 3.56-3.05 (m,
		4H), 2.77 (brs, 1H), 2.16-1.50 (m, 8H), 1.49 (d, J = 6.9 Hz, 3H), 1.30-
		0.79 (m, 7H), 0.50-0.34 (m, 1H).
932	695.4	1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.10 (d, J = 8.2 Hz, 1H),
		8.02 (s, 2H), 7.80 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.36 (d, J =
		8.3 Hz, 1H), 7.09 (s, 1H), 6.91 (s, 1H), 5.05-4.94 (m, 0.65H, rotamer),
		4.75-4.66 (m, 2H), 4.64-4.34 (m, 3H), 4.28-4.18 (m, 0.32H, rotamer),
		4.13 (s, 3H), 4.00 (s, 3H), 3.70-3.56 (m, 0.31H, rotamer), 3.48-3.21 (m,
		1H), 3.20-3.09 (m, 0.42H, rotamer), 2.87-2.70 (m, 0.33H, rotamer),
		2.66-2.56 (m, 2H), 2.05-1.93 (m, 1H), 1.75 (s, 6H), 1.64 (s, 4H), 1.51-
		1.35 (m, 2H), 1.26 (q, J = 7.2, 6.6 Hz, 3H), 0.98-0.77 (m, 2H).
933	642.6	1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.02 (d, J = 8.2 Hz, 1H),
		7.98 (s, 2H), 7.75 (s, 1H), 7.37 (s, 1H), 7.28 (d, J = 8.2 Hz, 1H), 7.03 (s,
		1H), 6.90 (s, 1H), 5.12-4.91 (m, 0.55H, rotamer), 4.77-4.65 (m, 1H),
		4.65-4.47 (m, 2H), 4.30-4.19 (m, 3H), 4.12 (s, 3H), 3.99 (s, 3H), 3.86-
		3.73 (m, 0.15H, rotamer), 3.69-3.56 (m, 0.14H, rotamer), 3.47-3.22 (m,
		0.59H, rotamer), 3.22-3.06 (m, 0.13H, rotamer), 2.87-2.71 (m, 0.59H,
		rotamer), 2.30-2.18 (m, 1H), 2.09-1.85 (m, 1H), 1.95 (s, 3H), 1.81 (m,
		2H), 1.74-1.57 (m, 3H), 1.53 (s, 3H), 1.44-1.29 (m, 2H), 1.29-1.22
		(m, 2H), 1.23-1.02 (m, 1H), 0.98-0.80 (m, 1H).
934	742.3	1H NMR (400 MHz, DMSO-d6) δ 9.43 (d, J = 7.0 Hz, 1H), 9.04 (s, 1H),
		8.10 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 91.6 Hz, 3H), 7.33 (s, 1H), 7.28 (d,
		J = 8.1 Hz, 1H), 7.23 (s, 1H), 6.91 (s, 1H), 5.25 (p, J = 7.0 Hz, 1H), 5.08-
		4.94 (m, 0.42H, rotamers), 4.93-4.77 (m, 2H), 4.64-4.45 (m, 0.51H,
		rotamers), 4.35-4.18 (m, 0.57H, rotamers), 4.00 (s, 3H), 3.96-3.87 (m,
		1H), 3.85-3.57 (m, 3H), 2.77-2.65 (m, 1H), 2.48-2.32 (m, 1H), 2.05-
		1.89 (m, 1H), 1.88-1.77 (m, 1H), 1.73-1.58 (m, 7H), 1.53 (d, J = 7.1
		Hz, 3H), 1.47 (s, 1H), 1.45-1.34 (m, 1H), 1.33-1.21 (m, 1H), 1.20-
		1.11 (m, 1H), 1.11-0.97 (m, 1H), 0.97-0.82 (m, 1H), 0.72-0.49 (m,
		1H), 0.48-0.30 (m, 1H).
935	682.4	1H NMR (400 MHz, DMSO-d6) δ 9.22 (d, J = 7.3 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 8.03 (s, 2H), 7.79 (s, 1H), 7.37 (s, 1H), 7.25 (d, J = 8.0 Hz,
		1H), 7.13 (dd, J = 9.4, 2.4 Hz, 1H), 7.09 (s, 1H), 6.98 (dd, J = 9.7, 2.4 Hz,
		1H), 6.90 (s, 1H), 5.26 (p, J = 7.1 Hz, 1H), 4.99 (m, 0.17H, rotamer), 4.96-
		4.84 (m, 1H), 4.62 (d, J = 13.6 Hz, 1H), 4.32 (d, J = 72.1 Hz, 7H), 4.12
		(s, 3H), 4.00 (s, 3H), 3.81 (m, 0.17H, rotamer), 3.49-3.02 (m, 1H), 2.77
		(s, 1H), 2.33-2.14 (m, 2H), 2.05-1.91 (m, 1H), 1.90-1.77 (m, 1H),
		1.64 (d, J = 21.7 Hz, 3H), 1.46 (d, J = 7.1 Hz, 3H), 1.43-1.35 (m, 1H),
		1.34-1.23 (m, 1H), 1.21-1.09 (m, 1H), 0.57-0.20 (m, 1H).
936	646.4	1H NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 7.0 Hz, 1H), 8.02 (s, 2H),
		7.98 (d, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.37-7.29 (m, 2H), 7.24 (d, J =
		7.4, 1.3 Hz, 1H), 7.20 (d, 1H), 7.17 (d, J = 8.0 Hz, 1H), 6.66 (s, 1H), 6.40
		(s, 1H), 5.18 (p, J = 7.0 Hz, 1H), 5.05-4.90 (m, 0.43H, rotamer), 4.91-
		4.72 (m, 1H), 4.62-4.41 (m, 1H), 4.33-4.21 (m, 0.50H, rotamer), 4.10
		(s, 3H), 4.08-3.83 (m, 5H), 3.37 (s, 1H), 3.22-3.05 (m, 0.35H,
		rotamer), 2.80 (s, 3H), 2.48-2.31 (m, 2H), 2.29-2.17 (m, 1H), 2.06-
		1.91 (m, 1H), 1.90-1.73 (m, 1H), 1.74-1.59 (m, 2H), 1.48 (d, J = 7.0
		Hz, 3H), 1.42-1.05 (m, 3H), 0.67-0.37 (m, 1H).
937	608.3	1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 8.43 (s, 1H), 8.19 (d, J =
		8.4 Hz, 1H), 7.44 (d, J = 1.1 Hz, 1H), 7.27 (d, J = 8.3 Hz, 1H), 7.15 (s,
		1H), 6.92 (s, 1H), 5.82 (s, 1H), 4.69 (t, J = 6.4 Hz, 2H), 4.19 (s, 1H), 4.13
		(s, 3H), 4.00 (s, 3H), 3.83-3.36 (m, 4H), 3.51 (s, 3H), 3.40-3.21 (m,
		3H), 2.67-2.55 (m, 2H), 1.81-1.64 (m, 3H), 1.56-1.40 (m, 4H), 1.38-
		1.22 (m, 2H), 1.22-1.08 (m, 2H), 1.00-0.71 (m, 2H).
938	630.6	1H NMR (400 MHz, DMSO-d6) δ 8.43 (d, J = 9.5 Hz, 1H), 8.04 (d, J =
		8.0 Hz, 1H), 7.85-7.61 (m, 2H), 7.26 (d, J = 15.0 Hz, 1H), 7.19 (d, J =
		8.0 Hz, 1H), 7.05 (s, 1H), 5.20 (m, J = 9.6, 7.0 Hz, 1H), 4.99 (s, 0.45H),
		4.78 (m, J = 13.8, 9.4 Hz, 1H), 4.56 (d, J = 8.9 Hz, 0.24H), 4.47 (m, J =
		21.7, 7.2 Hz, 3H), 4.18 (s, 0.61H), 3.38 (s, 0.73H), 3.29 (s, 0.69H), 3.14
		(s, 0.45H), 2.76 (d, J = 16.0 Hz, 0.53H), 2.30-2.19 (m, 1H), 2.07-1.91
		(m, 2H), 1.76 (s, 3H), 1.59 (s, 7H), 1.49-1.38 (m, 7H), 1.35 (d, J = 10.0
		Hz, 1H), 1.30-1.20 (m, 1H), 1.15 (m, J = 13.8, 9.4, 3.5 Hz, 1H), 0.95 (m,
		J = 11.3, 9.4, 6.0 Hz, 1H).
939	684.2	1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 7.1 Hz, 1H), 8.13 (d, J =
		8.1 Hz, 1H), 8.00 (s, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.79-7.60 (m, 2H),
		7.41 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H), 7.12 (s, 1H), 5.22 (p, J =
		7.0 Hz, 1H), 4.98 (s, 0.44H), 4.92-4.81 (m, 1H), 4.56 (m, J = 14.2, 6.9
		Hz, 2H), 4.44 (m, J = 14.4, 7.2 Hz, 2H), 4.19 (s, 0.69H), 3.77 (s, 0.35H),
		3.37 (s, 0.71H), 3.29 (s, 1H), 3.15 (s, 0.31H), 2.76 (d, J = 15.7 Hz, 0.63H),
		2.70-2.56 (m, 1H), 2.43-2.29 (m, 2H), 1.97 (q, J = 6.9, 3.7 Hz, 1H),
		1.79 (d, J = 25.5 Hz, 2H), 1.67 (s, 3H), 1.50 (d, J = 7.1 Hz, 3H), 1.47 (s,
		1H), 1.45 (s, 4H), 1.20 (s, 1H), 0.58 (d, J = 12.3 Hz, 1H).
940	686.3	1H NMR (400 MHz, DMSO-d6) δ 8.12 (d, J = 8.1 Hz, 1H), 7.99 (d, J =
		8.5 Hz, 2H), 7.75 (s, 1H), 7.35 (s, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.25 (s,
		1H), 6.91 (s, 1H), 5.57 (q, J = 16.2 Hz, 1H), 5.38 (q, J = 10.7, 9.0 Hz, 1H),
		5.30 (q, J = 7.4 Hz, 1H), 4.99 (s, 0.36H), 4.53 (s, 0.54H), 4.26 (s, 0.59H),
		4.00 (s, 3H), 3.91 (m, J = 7.2, 3.8 Hz, 1H), 3.81 (s, 1H), 2.75 (d, J = 12.1
		Hz, 0.58H), 2.09-1.92 (m, 3H), 1.92-1.75 (m, 3H), 1.66 (s, 4H), 1.48
		(d, J = 9.4 Hz, 2H), 1.44 (d, J = 7.0 Hz, 3H), 1.25 (m, J = 14.2, 13.2, 6.2
		Hz, 2H), 1.20-1.10 (m, 1H), 1.05-0.97 (m, 2H), 0.92 (t, J = 8.1 Hz,
		1H), 0.81 (s, 1H), 0.63-0.55 (m, 1H), 0.49 (q, J = 7.4, 4.6 Hz, 1H), 0.41
		(m, J = 8.6, 3.2 Hz, 1H). 19F NMR Peak Table: 19F NMR (376 MHz,
		DMSO-d6) 8-94.94 (d, J = 241.2 Hz).
941	688.2	1H NMR (400 MHz, DMSO-d6) δ 8.08 (d, J = 8.0 Hz, 1H), 8.00 (s, 1H),
		7.91 (d, J = 7.4 Hz, 1H), 7.77 (s, 1H), 7.33 (s, 1H), 7.24 (t, J = 4.0 Hz,
		2H), 6.90 (s, 1H), 5.39 (t, J = 13.7 Hz, 2H), 5.12 (p, J = 7.1 Hz, 1H), 4.98
		(s, 0.39H), 4.53 (s, 0.54H), 4.26 (s, 0.54H), 3.99 (s, 3H), 3.90 (m, J = 7.3,
		3.9 Hz, 2H), 3.40 (s, 0.41H), 2.75 (d, J = 12.8 Hz, 0.54H), 2.02-1.92 (m,
		2H), 1.83 (m, J = 30.4, 14.8 Hz, 4H), 1.62 (s, 3H), 1.52-1.34 (m, 5H),
		1.19 (s, 6H), 0.91 (s, 5H), 0.81 (s, 1H), 0.49 (dt, J = 8.1, 4.5 Hz, 1H).
942	741.2	1H NMR (400 MHz, DMSO-d6) δ 9.32 (d, J = 6.9 Hz, 1H), 8.70 (s, 1H),
		8.08 (d, J = 8.0 Hz, 1H), 7.99 (s, 2H), 7.85 (s, 1H), 7.76 (s, 1H), 7.32 (s,
		1H), 7.26 (d, J = 8.1 Hz, 1H), 7.22 (s, 1H), 6.91 (s, 1H), 5.22 (t, J = 7.0
		Hz, 1H), 4.99 (s, 0.52H), 4.93-4.77 (m, 2H), 4.53 (s, 0.53H), 4.24 (s,
		0.55H), 4.00 (s, 3H), 3.92 (m, J = 7.3, 3.9 Hz, 1H), 3.82 (s, 0.93H), 2.75
		(d, J = 10.9 Hz, 0.54H), 2.49-2.29 (m, 4H), 1.97 (m, J = 9.5, 9.0, 4.6 Hz,
		2H), 1.78 (d, J = 18.7 Hz, 2H), 1.64 (d, J = 18.4 Hz, 3H), 1.52 (d, J = 7.0
		Hz, 3H), 1.45 (d, J = 19.8 Hz, 2H), 1.33 (m, J = 11.4, 10.8, 6.3 Hz, 1H),
		1.17 (p, J = 7.8, 6.6 Hz, 2H), 1.01 (p, J = 7.1 Hz, 1H), 0.90 (s, 1H), 0.52
		(d, J = 12.4 Hz, 1H), 0.36 (m, J = 13.5, 5.4 Hz, 1H).
943	662.3	1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 8.0 Hz, 1H), 7.96 (s, 1H),
		7.91 (d, J = 7.5 Hz, 1H), 7.74 (s, 1H), 7.37 (s, 1H), 7.25 (d, J = 8.1 Hz,
		1H), 7.14 (s, 1H), 6.89 (s, 1H), 5.35 (q, J = 15.1 Hz, 1H), 5.24-5.09 (m,
		2H), 4.99 (s, 0.62H), 4.53 (s, 0.77H), 4.25 (d, J = 11.1 Hz, 0.88H), 4.09 (s,
		3H), 3.99 (s, 3H), 3.83 (s, 0.84H), 2.77 (s, 1H), 1.96 (d, J = 12.1 Hz, 2H),
		1.84 (t, J = 11.5 Hz, 2H), 1.71 (d, J = 41.5 Hz, 5H), 1.42 (s, 3H), 1.41-
		1.32 (m, 1H), 1.19 (s, 5H), 0.91 (s, 3H), 0.83 (m, 1H).
944	719.3	1H NMR (400 MHz, DMSO-d6) δ 8.71 (dd, J = 8.3, 2.6 Hz, 2H), 8.60 (dt,
		J = 4.8, 1.3 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 7.90 (td, J = 7.8, 1.8 Hz,
		1H), 7.99-7.65 (m, 3H), 7.62 (d, J = 8.0 Hz, 1H), 7.42 (dd, J = 7.6, 4.8
		Hz, 1H), 7.35 (s, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.19 (s, 1H), 6.91 (s, 1H),
		5.27 (p, J = 7.2 Hz, 1H), 5.06-4.86 (m, 1.5H), 4.86-4.69 (m, 1H), 4.63-
		4.41 (m, 0.5H), 4.35-4.18 (m, 0.5H), 3.99 (s, 3H), 3.96-3.73 (m,
		1.5H), 3.50-3.02 (m, 1.5H), 2.88-2.69 (m, 0.5H), 2.22-1.43 (m, 14H),
		1.41-1.19 (m, 3H), 1.19-0.93 (m, 3H), 0.91-0.69 (m, 2H), 0.53-0.36
		(m, 1H).
945	719.3	1H NMR (400 MHz, DMSO-d6) δ 8.70-8.61 (m, 1H), 8.32 (d, J = 7.0
		Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.92 (td, J = 7.8, 1.8 Hz, 1H), 8.00-
		7.63 (m, 3H), 7.58 (d, J = 7.4 Hz, 1H), 7.45 (ddd, J = 7.7, 4.8, 1.0 Hz, 1H),
		7.41-7.28 (m, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.17 (s, 1H), 6.91 (s, 1H),
		5.12-4.82 (m, 2.5H), 4.71-4.43 (m, 1.5H), 4.33-4.19 (m, 0.5H), 3.99
		(s, 3H), 3.95-3.75 (m, 1.5H), 3.47-3.01 (m, 1.5H), 2.94-2.68 (m,
		1.5H), 2.22-0.92 (m, 21H), 0.90-0.70 (m, 1H), 0.57-0.45 (m, 1H).
946	697.2	1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 7.0 Hz, 1H), 8.12 (d, J =
		8.1 Hz, 1H), 8.01-7.89 (m, 2H), 7.82 (d, J = 8.1 Hz, 1H), 7.79-7.65 (m,
		3H), 7.41 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.1 Hz, 1H), 7.00 (s, 1H), 5.20
		(p, J = 7.0 Hz, 1H), 5.05-4.93 (m, 1.5H), 4.89-4.76 (m, 1H), 4.58-
		4.37 (m, 1.5H), 4.25-4.12 (m, 0.5H), 3.82-3.05 (m, 1.5H), 2.83-2.71
		(m, 0.5H), 2.67-2.56 (m, 1H), 2.41-2.31 (m, 2H), 2.04-1.32 (m, 15H),
		1.26-1.16 (m, 0H), 0.68-0.52 (m, 1H).
947	725.3	1H NMR (400 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H),
		8.01-7.88 (m, 2H), 7.83 (d, J = 8.1 Hz, 1H), 7.78-7.56 (m, 3H), 7.42 (d,
		J = 8.0 Hz, 1H), 7.34-7.19 (m, 2H), 5.31-5.17 (m, 1H), 5.05-4.74 (m,
		1.5H), 4.60-4.35 (m, 2H), 4.23-4.13 (m, 0.5H), 3.75-3.08 (m, 5.5H),
		2.83-2.69 (m, 0.5H), 2.01-1.14 (m, 15H), 0.70 (s, 9H).
948	630.3	1H NMR (400 MHz, DMSO-d6) δ 8.22 (d, J = 7.2 Hz, 1H), 8.06 (d, J =
		8.1 Hz, 1H), 8.02-7.66 (m, 3H), 7.37 (s, 1H), 7.22 (d, J = 8.2 Hz, 1H),
		7.03 (s, 1H), 6.89 (s, 1H), 5.07 (p, J = 7.0 Hz, 1H), 5.02-4.94 (m, 0.5H),
		4.79-4.68 (m, 1H), 4.62-4.35 (m, 2H), 4.27-4.19 (m, 0.5H), 4.11 (s,
		3H), 3.99 (s, 3H), 3.86-3.76 (m, 0H), 3.49-3.03 (m, 1H), 2.82-2.70
		(m, 0.5H), 2.19 (dt, J = 39.4, 11.8 Hz, 1H), 2.03-1.27 (m, 18H), 1.26-
		1.07 (m, 2H).
949	630.3	1H NMR (400 MHz, DMSO-d6) δ 8.24 (dd, J = 8.7, 3.6 Hz, 1H), 8.07 (d,
		J = 8.1 Hz, 1H), 8.04-7.64 (m, 3H), 7.37 (s, 1H), 7.23 (d, J = 8.2 Hz,
		1H), 7.05 (s, 1H), 6.89 (s, 1H), 5.28 (p, J = 7.3 Hz, 1H), 5.03-4.94 (m,
		0.5H), 4.82 (dt, J = 14.5, 7.8 Hz, 1H), 4.60-4.47 (m, 2H), 4.27-4.19 (m,
		0.5H), 4.10 (s, 3H), 3.98 (s, 3H), 3.89-3.74 (m, 0.5H), 3.45-3.02 (m,
		1H), 2.84-2.70 (m, 0.5H), 2.03-0.98 (m, 21H), 0.75-0.60 (m, 1H).
950	668.4	1H NMR (400 MHz, DMSO-d6) δ 9.03 (d, J = 7.9 Hz, 1H), 8.59 (brs,
		1H), 8.17 (d, J = 8.1 Hz, 1H), 7.98 (brs, 2H), 7.94 (dd, J = 7.9, 1.6 Hz,
		1H), 7.90 (d, J = 8.5 Hz, 1H), 7.76 (brs, 1H), 7.56-7.48 (m, 2H), 7.40
		(brs, 1H), 7.36 (d, J = 8.2 Hz, 2H), 7.13 (s, 1H), 6.92 (s, 1H), 5.57-5.44
		(m, 1H), 5.01 (brs, 1H), 4.94-4.81 (m, 1H), 4.63-4.44 (m, 1H), 4.26
		(brs, 1H), 4.18 (s, 3H), 4.01 (s, 3H), 3.45-3.05 (m, 4H), 2.89-2.71 (m,
		1H), 2.19-1.56 (m, 8H), 1.53 (d, J = 7.1 Hz, 3H).
951	700.2	1H NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 7.0 Hz, 1H), 8.11 (d, J =
		8.1 Hz, 1H), 7.96 (s, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.73 (s, 1H), 7.59 (s,
		1H), 7.42 (d, J = 8.0 Hz, 1H), 7.32 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 5.21
		(p, J = 7.1 Hz, 1H), 5.01-4.87 (m, 1H), 4.84 (s, 1H), 4.53 (s, 0.49H),
		4.18 (s, 0.63H), 4.02 (m, J = 6.8, 3.1 Hz, 1H), 3.37 (s, 2H), 3.27 (s, 1H),
		3.17 (s, 1H), 2.75 (d, J = 11.8 Hz, 0.51H), 1.95 (d, J = 11.6 Hz, 1H), 1.79
		(d, J = 21.4 Hz, 2H), 1.66 (s, 2H), 1.50 (d, J = 7.0 Hz, 3H), 1.19 (q, J = 6.7
		Hz, 2H), 1.07 (s, 3H), 0.54 (s, 1H), 0.47 (s, 1H).
952	660.5	1H NMR (400 MHz, DMSO-d6) δ 8.42 (d, J = 9.5 Hz, 1H), 8.04 (d, J =
		8.1 Hz, 1H), 7.97 (s, 1H), 7.74 (s, 1H), 7.68 (s, 0.59H), 7.61 (s, 0.52H),
		7.32 (s, 1H), 7.27 (s, 1H), 7.18 (d, J = 8.1 Hz, 1H), 5.22 (m, J = 9.7, 7.0
		Hz, 1H), 4.99 (s, 0.46H), 4.91 (s, 0.47H), 4.76 (s, 3H), 4.55 (t, J = 10.2
		Hz, 2H), 4.14 (s, 0.61H), 3.12 (s, 0.50H), 2.75 (d, J = 12.3 Hz, 0.58H),
		2.29 (s, 0.63H), 2.09-2.00 (m, 1H), 1.94 (d, J = 20.9 Hz, 1H), 1.90-
		1.67 (m, 6H), 1.63 (s, 2H), 1.50 (d, J = 6.7 Hz, 1H), 1.48-1.38 (m, 4H),
		1.38-1.21 (m, 2H), 1.16 (t, J = 12.1 Hz, 1H), 1.01-0.89 (m, 1H).
953	690.3	1H NMR (400 MHz, DMSO-d6) δ 8.95 (d, J = 6.7 Hz, 1H), 8.06 (d, J =
		8.0 Hz, 1H), 8.03-7.62 (m, 3H), 7.32 (s, 1H), 7.27-7.10 (m, 5H), 6.90
		(s, 1H), 5.14 (p, J = 7.0 Hz, 1H), 5.07-4.75 (m, 2.5H), 4.62-4.45 (m,
		0.5H), 4.31-4.14 (m, 0.5H), 3.99 (s, 3H), 3.91 (tt, J = 7.2, 3.9 Hz, 1H),
		3.86-3.75 (m, 0.5H), 3.46-3.02 (m, 1.5H), 2.85-2.68 (m, 0.5H), 2.47-
		2.28 (m, 2H), 2.28-2.14 (m, 1H), 2.03-1.30 (m, 12H), 1.30-1.05 (m,
		3H), 1.06-0.78 (m, 2H), 0.56-0.39 (m, 1H), 0.39-0.27 (m, 1H).
954	681.4	1H NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 7.0 Hz, 1H), 8.08 (d, J =
		8.0 Hz, 1H), 7.97 (s, 2H), 7.75 (d, J = 8.1 Hz, 1H), 7.75 (s, 1H), 7.49 (d,
		J = 8.1 Hz, 1H), 7.37 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.90
		(s, 1H), 5.21 (p, J = 7.0 Hz, 1H), 5.13-4.92 (m, 0.36H, rotamer), 4.93-4.80
		(m, 1H), 4.68-4.43 (m, 1H), 4.35-4.17 (m, 1H), 4.12 (s, 3H), 4.00 (s,
		3H), 3.65-3.57 (m, 0.32H, rotamer), 3.46-3.30 (m, 0.66H, rotamer),
		3.29-3.01 (m, 1H), 2.88-2.70 (m, 1H), 2.42-2.19 (m, 3H), 2.07-1.91
		(m, 1H), 1.91-1.70 (m, 2H), 1.69-1.56 (m, 3H), 1.51 (d, J = 7.0 Hz,
		3H), 1.48-1.32 (m, 2H), 1.34-1.08 (m, 3H), 0.61-0.35 (m, 1H).
955	640.3	1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J = 8.2 Hz, 1H), 8.03-7.63
		(m, 3H), 7.41-7.33 (m, 2H), 7.13 (s, 1H), 6.90 (s, 1H), 5.06-4.86 (m,
		2H), 4.77-4.65 (m, 1H), 4.60-4.46 (m, 0.5H), 4.28-4.18 (m, 0.5H),
		4.13 (s, 3H), 3.99 (s, 3H), 3.85 (ddd, J = 11.7, 7.6, 4.2 Hz, 1H), 3.56 (dt,
		J = 11.7, 7.4 Hz, 1H), 3.44-3.22 (m, 2H), 3.17-3.06 (m, 0.5H), 2.81-
		2.69 (m, 0.5H), 2.66-2.57 (m, 1H), 2.31-2.11 (m, 2H), 2.08-1.40 (m,
		12H), 1.19 (dt, J = 21.7, 7.3 Hz, 1H), 1.00-0.85 (m, 1H), 0.69-0.56 (m,
		1H), 0.36 (q, J = 8.1 Hz, 1H), −0.51 (q, J = 12.9 Hz, 1H).

TABLE 4

Example	PAD4 IC 50 (nM)
1	104
2	75
3	110
4	69
5	76
6	105
7	101
8	71
9	53
10	56
11	251
12	120
13	121
14	121
15	60
16	67
17	74
18	85
19	76
20	62
21	63
22	62
23	40
24	56
25	775
26	86
27	201
28	46
29	70
30	1777
31	81
32	12
33	248
34	54
35	34
36	372
37	553
38	1203
39	23
40	24
41	268
42	108
43	118
44	64
45	4958
46	277
47	458
48	75
49	112
50	10000
51	215
52	424
53	283
54	1380
55	4677
56	193
57	213
58	77
59	161
60	118
61	231
62	150
63	24987
64	315
65	50000
66	1156
67	1301
68	287
69	201
70	137
71	560
72	308
73	125
74	221
75	103
76	87
77	367
78	80
79	76
80	255
81	505
82	8113
83	204
84	89
85	406
86	643
87	83
88	97
89	113
90	497
91	82
92	175
93	161
94	165
95	86
96	3131
97	57
98	122
99	111
100	833
101	7447
102	45
103	166
104	115
105	27425
106	201
107	24
108	150
109	303
110	70
111	49
112	81
113	302
114	61
115	40
116	255
117	54
118	41
119	60
120	22
121	46
122	16
123	12
124	12
125	21
126	25
127	31
128	13
129	13
130	21
131	15
132	28
133	47
134	125
135	37
136	40
137	35
138	18
139	40
140	97
141	68
142	28
143	158
144	31
145	58
146	47
147	365
148	45
149	46
150	107
151	123
152	43
153	116
154	57
155	77
156	56
157	36
158	241
159	62
160	53
161	108
162	55
163	51
164	33
165	235
166	49
167	90
168	39
169	69
170	118
171	804
172	101
173	109
174	80
175	231
176	196
177	30488
178	50
179	62
180	75
181	171
182	31
183	121
184	42
185	66
186	139
187	109
188	49
189	33
190	94
191	140
192	6686
193	66
194	150
195	56
196	116
197	6493
198	5955
199	18388
200	50000
201	737
202	5126
203	114
204	3348
205	50000
206	850
207	187
208	136
209	74
210	39
211	34
212	22
213	385
214	15
215	20
216	33
217	32
218	29
219	72
220	49
221	32
222	64
223	28
224	57
225	73
226	24
227	154
228	131
229	72
230	84
231	84
232	549
233	82
234	622
235	113
236	858
237	62
238	87
239	583
240	137
241	82
242	31
243	68
244	2577
245	411
246	3325
247	18
248	44
249	51
250	44
251	74
252	45
253	103
254	32
255	59
256	48
257	2474
258	39
259	37
260	453
261	106
262	4444
263	69
264	91
265	81
266	153
267	88
268	137
269	36
270	90
271	65
272	69
273	68
274	104
275	24
276	343
277	50000
278	47
279	82
280	64
281	88
282	13
283	13
284	52
285	7
286	9
287	55
288	36
289	25
290	221
291	335
292	53
293	548
294	275
295	3346
296	23734
297	129
298	914
299	58
300	50
301	36
302	67
303	525
304	70
305	65
306	85
307	82
308	72
309	1378
310	135
311	175
312	56
313	85
314	156
315	45
316	14
317	16
318	18
319	266
320	17
321	32
322	15
323	14
324	36
325	16
326	30
327	12
328	25
329	48
330	80
331	69
332	20
333	33
334	39
335	32
336	34
337	32
338	53
339	39
340	61
341	59
342	43
343	371
344	51
345	60
346	97
347	51
348	66
349	34
350	38
351	97
352	53
353	29
354	26
355	18
356	37
357	31
358	83
359	104
360	58
361	74
362	137
363	110
364	203
365	119
366	120
367	82
368	34
369	37
370	163
371	222
372	183
373	254
374	121
375	109
376	82
377	32
378	41
379	2045
380	1269
381	29
382	108
383	28
384	62
385	—
386	24
387	25
388	12
389	31
390	88
391	34
392	22
393	63
394	23
395	29
396	17
397	91
398	74
399	86
400	150
401	90
402	91
403	50000
404	83
405	27
406	22
407	70
408	255
409	83
410	51
411	398
412	42
413	37
414	125
415	52
416	34
417	62
418	122
419	370
420	184
421	304
422	39
423	64
424	111
425	104
426	25
427	54
428	29
429	68
430	44
431	41
432	161
433	46
434	41
435	394
436	93
437	30
438	25
439	32
440	27
441	37
442	32
443	37
444	20
445	72
446	38
447	37
448	26
449	22
450	21
451	19
452	37
453	53
454	31
455	36
456	57
457	38
458	23
459	130
460	71
461	51
462	31
463	29
464	28
465	23
466	55
467	27
468	28
469	21
470	43
471	44
472	42
473	44
474	49
475	62
476	38
477	35
478	50
479	47
480	134
481	231
482	26
483	33
484	44
485	29
486	110
487	82
488	64
489	78
490	86
491	253
492	156
493	76
494	136
495	518
496	125
497	54
498	67
499	163
500	90
501	271
502	128
503	110
504	172
505	97
506	39
507	32
508	57
509	146
510	277
511	95
512	65
513	161
514	371
515	74
516	48
517	128
518	49
519	44
520	35
521	76
522	40
523	205
524	388
525	78
526	65
527	215
528	55
529	409
530	51
531	36
532	239
533	398
534	56
535	384
536	137
537	87
538	90
539	175
540	90
541	123
542	479
543	405
544	40
545	56
546	59
547	50
548	56
549	129
550	60
551	43
552	61
553	47
554	34
555	56
556	69
557	31
558	80
559	47
560	52
561	523
562	466
563	26
564	24
565	41
566	97
567	33
568	33
569	109
570	94
571	31
572	53
573	23
574	117
575	26
576	68
577	84
578	78
579	50
580	24
581	176
582	271
583	69
584	51
585	74
586	88
587	163
588	193
589	145
590	683
591	81
592	175
593	44
594	112
595	37
596	3577
597	42
598	42
599	67
600	46
601	45
602	97
603	44
604	86
606	129
607	51
608	115
609	172
610	190
611	85
612	157
613	108
614	114
615	94
616	71
617	1121
618	69
619	38
620	36
621	43
622	59
623	47
624	70
625	9
626	48
627	49
628	83
629	108
630	122
631	211
632	46
633	57
634	251
635	682
636	52
637	31
638	—
639	15
640	24
641	49
642	23
643	54
644	76
645	36
646	22
647	58
648	41
649	52
650	59
651	59
652	42
653	44
654	51
655	60
656	124
657	14
658	25
659	32
660	16
661	27
662	32
663	71
664	51
665	26
666	86
667	70
668	22
669	45
670	6
671	20
672	28
673	27
674	17
675	559
676	83
677	82
678	15
679	33
680	34
681	39
682	28
683	16
684	20
685	13
686	44
687	64
688	719
689	39
690	54
691	33
692	27
693	18
694	268
695	57
696	48
697	74
698	68
699	640
700	22
701	5
702	21
703	11
704	31
705	20
706	19
707	21
708	91
709	25
710	18
711	19
712	24
713	19
714	40
715	19
716	13
717	11
718	18
719	91
720	65
721	246
722	174
723	309
724	94
725	136
726	23
727	93
728	75
729	307
730	270
731	140
732	214
733	96
734	185
735	143
736	304
737	75
738	48
739	62
740	30
741	33
742	58
743	—
744	96
745	22
746	25
747	10
748	25
749	17
750	28
751	32
752	30
753	113
754	59
755	29
756	31
757	5
758	17
759	17
760	70
761	67
762	26
763	13
764	22
765	16
766	28
767	18
768	59
769	13
770	5
771	28
772	6
773	16
774	33
775	29
776	17
777	17
778	338
779	339
780	53
781	73
782	63
783	109
784	97
785	954
786	237
787	94
788	35
789	22
790	23
791	17
792	342
793	24
794	18
795	661
796	5
797	16
798	17
799	12
800	74
801	334
802	22
803	118
804	27
805	6
806	42
807	31
808	15
809	39
810	25
811	26
812	31
813	26
814	38
815	26
816	19
817	13
818	12
819	10
820	168
821	102
822	205
823	146
824	43
825	38
826	31
827	36
828	24
829	15
830	19
831	75
832	13
833	61
834	126
835	16
836	32
837	30
838	49
839	13
840	61
841	17
842	49
843	18
844	35
845	16
846	27
847	82
848	33
849	15
850	64
851	20
852	16
853	48
854	68
855	65
856	156
857	13
858	459
859	38
860	44
861	39
862	78
863	69
864	68
865	230
866	79
867	44
868	37
869	24
870	83
871	31
872	90
873	120
874	29
875	148
876	122
877	40
878	26
879	34
880	39
881	24
882	22
883	18
884	24
885	11
886	29
887	52
888	37
889	54
890	10
891	13
892	27
893	28
894	72
895	34
896	56
897	40
898	156
899	30
900	28
901	59
902	48
903	55
904	101
905	72
906	55
907	82
908	151
909	52
910	49
911	61
912	17
913	22
914	16
915	47
916	26
917	27
918	31
919	20
920	21
921	30
922	35
923	24
924	46
925	40
926	23
927	49
928	51
929	18
930	22
931	64
932	58
933	27
934	103
935	29
936	39
937	187
938	28
939	44
940	80
941	68
942	72
943	48
944	64
945	34
946	69
947	92
948	28
949	31
950	38
951	24
952	21
953	68
954	32
955	81

description truncated at 500,000 characters

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Claims as granted

15 claims

Classifications

17 codes

IPC · International Patent Classification

Section A — Human necessities

A61K31/4184
A61K31/4188
A61K31/437
A61K45/06
A61P3/10
A61P7/02
A61P19/02
A61P35/00

Section C — Chemistry; metallurgy

C07D471/18
C07D471/12
C07D471/14
C07D487/08
C07D491/22
C07D498/18
C07D498/22
C07D513/18
C07D519/00

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art unit 1624 · TC 1600

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