The present invention relates to compounds of Formula (I), or a form thereof wherein ring A 1 , R 1 , R 2 , R 3 , R 3 â€², L, W, and V are as defined herein, useful as FLAP modulators. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention. [structure]

Description

649 parts

›CROSS REFERENCE TO RELATED APPLICATIONS

This application is a national phase of International Application No. PCT/US2014/014111 filed on Jan. 31, 2014, which claims the benefit of U.S. Provisional Application No. 61/760,627 filed on Feb. 4, 2013 and U.S. Provisional Application No. 61/800,353 filed on Mar. 15, 2013, each of which is incorporated herein by reference in its entirety.

›FIELD OF THE INVENTION

The present invention relates to substituted compounds useful as 5-lipoxygenase-activating protein (FLAP) modulators, pharmaceutical compositions of such compounds, methods of preparation and use thereof. More particularly, FLAP modulators are useful for preventing, treating or ameliorating FLAP-mediated diseases and/or disorders, including those inflammation diseases and/or disorders associated with dermatological and respiratory disorders, allergic disorders, autoimmunity, cancer, cardiovascular and metabolic disorders.

›BACKGROUND OF THE INVENTION

FLAP is a key initiator of the leukotriene synthesis pathway that binds and then transfers arachidonic acid to 5-lipoxygenase (M. Abramovitz et al., “5-lipoxygenase-activating protein stimulates the utilization of arachidonic acid by 5-lipoxygenase,” Eur. J. Biochem., 1993, 215, 105-11). FLAP has been demonstrated to interact with LTC 4 synthase, and could putatively modulate the production of LTC 4 (T. Strid et al., “Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein,” Biochem. Biophys. Res. Comm., 2009, 381(4), 518-22). Modulation (including without limitation inhibition) or genetic deletion of FLAP blocks leukotriene production, specifically LTB 4 , the cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) as well as 5-oxo-ETE (J. Z. Haeggström et al., “Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease,” Chem Rev., 2011, 111(10), 5866-98).

Leukotrienes are immune-modulating lipids formed from arachidonic acid (reviewed in Samuelsson, “Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation,” Science, 1983, 220, 568-75). They are synthesized primarily by eosinophils, neutrophils, mast cells, basophils, dendritic cells, macrophages and monocytes. Leukotrienes mediate multiple biological effects including, by way of example only, smooth muscle contraction, leukocyte recruitment and activation, cytokine secretion, fibrosis, mucous secretion, and vascular function (J. Z. Haeggström, at 5866-98).

FLAP-deficient mice are healthy and reproduce normally. They do not produce leukotrienes and have decreased susceptibility in mouse models of arthritis (R. J. Griffiths et al., “Collagen-induced arthritis is reduced in 5-lipoxygenase-activating protein-deficient mice,” J. Exp. Med., 1997, 185, 1123-29). In humans, FLAP itself has been linked by genetic studies to respiratory disorders and cardiovascular disease, including myocardial infarction, atherosclerosis, cerebral infarctions, coronary artery disease and stroke (A. Helgadottir et al., “The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction, atherosclerosis and stroke,” Nat. Genet., 2004, 36, 233-39; A. S. Tulah et al., “The role of ALOX5AP, LTA4H and LTB4R polymorphisms in determining baseline lung function and COPD susceptibility in UK smokers,” BMC Med. Genet., 2011, 29(12), 173; R. Ji et al., “Genetic variants in the promoter region of the ALOX5AP gene and susceptibility of ischemic stroke,” Cerebrovasc. Dis., 2011, 32(3), 261-68; J. W. Holloway et al., “The role of LTA4H and ALOX5AP polymorphism in asthma and allergy susceptibility,” Allergy. 2008, 63(8), 1046-53; J. Nair et al., “Expression analysis of leukotriene-inflammatory gene interaction network in patients with coronary artery disease,” J Atheroscler. Thromb., 2013; L. F. Chi et al., “Interaction between ALOX5AP and CYP3A5 gene variants significantly increases the risk for cerebral infarctions in Chinese,” Neuroreport., 2013). In addition, studies using animal models support a causative role for leukotrienes in aortic aneurisms, atherosclerosis, pulmonary arterial hypertension, myocardial infarction, atherosclerosis, and stroke (reviewed in J. Z. Haeggström, at 5866-98).

Leukotrienes also play a role in autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease, nephritis, spondyloarthritis, polymyositis, dermatomyositis, gouty effusions, systemic lupus erythematosus, systemic sclerosis, Alzheimer's disease and multiple sclerosis (S. Chwieśko-Minarowska et al., “The role of leukotrienes in the pathogenesis of systemic sclerosis,” Folia Histochem. Cytobiol., 2012, 50(2), 180-85; M. Rosnowska et al., “Leukotrienes C4 and B4 in cerebrospinal fluid of patients with multiple sclerosis,” Pol. Merkuriusz Lek., 1997, 2, 254-55; and reviewed in J. Z. Haeggström, at 5866-98; I. Loell et al., “Activated LTB4 pathway in muscle tissue of patients with polymyositis or dermatomyositis,” Ann. Rheum. Dis., 2013, 72(2), 293-99; J. Chu et al., “Involvement of 5-lipoxygenase activating protein in the amyloidotic phenotype of an Alzheimer's disease mouse model,” J. Neuroinflammation, 2012, 9, 127). Leukotrienes have also been implicated in several aspects of carcinogenesis including tumor cell proliferation, differentiation, and apoptosis, tumor-associated angiogenesis, as well as the migration and invasion of carcinoma cells (D. Wang and R. N. Dubois, “Eicosanoids and cancer,” Nat. Rev. Cancer, 2010, 10(3), 181-93).

Leukotrienes play a key role in allergic disorders such as allergic rhinitis, allergic dermatitis and asthma, as well as respiratory disorders such as exacerbations, non-allergic asthma, aspirin exacerbated respiratory disease, fibrotic lung diseases, acute respiratory distress syndrome and chronic obstructive pulmonary disease (reviewed in J. Z. Haeggström at 5866-98). Approved antagonists of the LTC 4 receptor and leukotriene synthesis modulators such as zileuton have shown clinical efficacy in a variety of respiratory disorders (reviewed in M. E. Krawiec and S. E. Wenzel, “Leukotriene modulators and non-steroidal therapies in the treatment of asthma,” Expert. Opin. Pharmacotherapy, 2001, 2(1), 47-65).

All the above evidence supports a key role of leukotrienes in a variety of human diseases and/or disorders, and FLAP modulation would be effective for the prevention, treatment, or amelioration of these immune-mediated inflammatory diseases and/or disorders. Furthermore, there still remains a need for FLAP modulator compounds that have pharmacokinetic and pharmacodynamic properties suitable for use as human pharmaceuticals.

›SUMMARY OF THE INVENTION · 1 of 2

In its many embodiments, the present invention provides novel compounds useful as, for example, FLAP modulators (including without limitation novel compounds that inhibit FLAP), methods of preparing such compounds, pharmaceutical compositions comprising one or more such compounds, methods of preparing pharmaceutical compositions comprising one or more such compounds, and methods of prophylaxis, treatment, amelioration, including without limitation inhibition, of one or more diseases and/or disorders associated with FLAP using such compounds or pharmaceutical compositions.

One aspect of the present invention is directed to compounds, methods, and compositions for the treatment or prophylaxis or amelioration of a variety of diseases and/or disorders that are mediated or sustained through the activity of leukotrienes, including pulmonary, allergic, fibrotic, neurological, inflammatory, autoimmune and cardiovascular diseases and cancer or associated symptoms or complications thereof. More specifically, this invention is directed to a method of treating exacerbations, non-allergic asthma, fibrotic lung diseases, acute respiratory distress syndrome and chronic obstructive pulmonary disease, or associated symptoms or complications thereof, in a subject afflicted with such a disease and/or disorder, wherein the method comprises administering a FLAP modulator.

Another aspect of the present invention is directed to compounds, methods, and compositions for the treatment or prophylaxis or amelioration of cardiac and cardiovascular diseases and/or disorders, or associated symptoms or complications thereof, that include but are not limited to myocardial infarction, atherosclerosis and stroke aortic aneurisms, atherosclerosis, or associated symptoms or complications thereof, in a subject afflicted with such a disease and/or disorder, wherein the method comprises administering a FLAP modulator.

Yet another aspect of the present invention is directed to compounds, methods, and compositions for the prophylaxis, treatment, or amelioration of autoimmune diseases and/or disorders, or associated symptoms or complications thereof, that include but are not limited to rheumatoid arthritis, inflammatory bowel disease, nephritis, spondyloarthritis, polymyositis, dermatomyositis, gouty effusions, systemic lupus erythematosus, systemic sclerosis, Alzheimer's disease, multiple sclerosis or allergic disorders that include but are not limited to allergic rhinitis, allergic dermatitis and asthma, or associated symptoms or complications thereof, in a subject afflicted with such a disease and/or disorder, wherein the method comprises administering a FLAP modulator.

Finally, one aspect of the present invention is directed to compounds, methods, and compositions for the prophylaxis, treatment, or amelioration of carcinogenesis including but not limited to tumor cell proliferation, differentiation, and apoptosis, tumor-associated angiogenesis, as well as the migration and invasion of carcinoma cells, or associated symptoms or complications thereof, in a subject afflicted with such a disease and/or disorder, wherein the method comprises administering a FLAP modulator.

Another aspect of the present invention features a compound of Formula (I)

wherein

L is a bond, —CH 2 —, —SO 2 —, —CH 2 —SO 2 —, —SO 2 —CH 2 —, —SO 2 —NR—,

—SO 2 —NR—CH 2 —, —CH 2 —SO 2 —NR—, —NR—, —NR—SO 2 —, —NR—SO 2 —NR—, —S—, —S—CH 2 —, —CH 2 —S—,

—C(═O)—, —C(═O)—O—, —O—, —O—CH 2 —, —NR—C(═O)—, —NR—C(═O)—NR—, or —C(═O)—NR—, wherein R is H,

C 1-2 alkyl, C 1-2 alkyl-OH or cyclopropyl;

R 1 is H, halo, methyl, CF 3 , —O—CF 3 , or —O— CH 3 ; R 2 is H, cyano, halo, —SO 2 —CH 3 , 2-(trimethylsilyl)ethoxy, phenyl, C 1-6 alkyl, heteroaryl, heterocyclyl, C 3-9 cycloalkyl, provided R 2 is not H if L is a bond, and wherein said phenyl, C 1-6 alkyl, heteroaryl, heterocycyl or C 3-9 cycloalkyl is optionally and independently substituted with 1-4 substituents selected from the group consisting of: methyl, ethyl, oxo, fluoro, hydroxyl, cyano, amino, methoxy, tert-butoxy, acetyl, cyclopropyl, cyclobutyl, cyclohexyl, phenyl, azetidin-1-yl, azetidin-3-yl, pyrrolidin-1-yl, 2,4-dihydro-3H-1,2,4-triazol-3-one-4-yl, 1H-imidazol-4-yl, pyrazin-2-yl, pyrimidin-2-yl, 1,3-oxazolidin-2-one-5-yl, N-benzamide, benzo[d]imidazol-2(3H)-one, 4-methylpiperazin-1-yl, morpholin-4-yl, CF 3 , —SO 2 —CH 3 , —C(═O)-cyclopropyl, —SO 2 -cyclohexyl, —NHCH 3 , —N(CH 3 ) 2 , —NHAc, —NHCO 2 t-Bu, —CH 2 —NH 2 , —C(═O)—NH 2 , —C(═O)—N(ethyl) 2 , —NH—C(═O)—NH 2 , —NH—C(═O)—CH 3 , —C(═O)—(C 1 -C 4 alkyl), —C(═O—OH, —C(═O)—NH(C 1 -C 4 alkyl)-(CH 2 ) n —OH, and —(CH 2 ) n —CN, wherein n is 1 or 2; V is CH, CR′, or N, wherein R′ is methyl or F; W is CR″ or N, wherein R″ is H, F, hydroxyl, amino, CH 3 or —O—CH 3 ; ring A is selected from the group consisting of:

R 3 is H, F, methyl, or —O—CH 3 ;

R 3 ′ is H or F;

R 4 is H, methyl, cyano, amino, halo, —COOH, or —O—CH 3 ;

R 5 is H, methyl, cyano, or —CF 3 ;

R 6 is H, cyano, amino, halo, or —CF 3 ; and

R 7 is halo, amino, —CONH 2 , cyano, —O—CH 3 , —CF 3 , or —COO-ethyl;

or an optical isomer, hydrate, metabolite, enantiomer, diastereomer, cis-trans isomer, racemate, prodrug or pharmaceutically acceptable salt thereof.

Another aspect of the present invention features a pharmaceutical composition comprising at least one compound of Formula (I) and at least one pharmaceutically acceptable carrier. The invention is also directed towards providing a process for formulating a pharmaceutical composition, comprising formulating a pharmaceutical composition of at least one compound of Formula (I) and at lease one pharmaceutically acceptable carrier. The present invention further relates to a process for making a pharmaceutical composition comprising mixing any of the compounds according to Formula (I) and a pharmaceutically acceptable carrier.

The present invention also features a method of treating a subject suffering from or diagnosed with a disease and/or disorder mediated by FLAP activity, comprising administering to the subject a therapeutically effective amount of at least one compound of Formula (I). Such a disease and/or disorder can include, but is not limited to respiratory disorders, cardiac and cardiovascular diseases, autoimmune disorders, carcinogenesis or associated symptoms or complications. More specifically, this invention is directed to a method of treating exacerbations, non-allergic asthma, fibrotic lung diseases, acute respiratory distress syndrome, chronic obstructive pulmonary disease myocardial infarction, atherosclerosis and stroke aortic aneurisms, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, nephritis, spondyloarthritis, polymyositis, dermatomyositis, gouty effusions, systemic lupus erythematosus, systemic sclerosis, Alzheimer's disease, multiple sclerosis, allergic rhinitis, allergic dermatitis and asthma, tumor cell proliferation, differentiation, and apoptosis, tumor-associated angiogenesis, as well as the migration and invasion of carcinoma cells, or associated symptoms or complications thereof, in a subject afflicted with such a disease and/or disorder, or associated symptoms or complications thereof, wherein the method comprises administering a FLAP modulator to a subject in need thereof, a therapeutically effective amount of at least one compound of Formula (I), preferably in a pharmaceutical composition comprising at least one compound of Formula (I).

›SUMMARY OF THE INVENTION · 2 of 2

Additional embodiments and advantages of the invention will become apparent from the detailed discussion, schemes, examples, and claims below.

›DETAILED DESCRIPTION OF THE INVENTION · 1 of 8

This invention relates to novel FLAP modulators and compositions thereof for the prophylaxis, treatment, or amelioration of numerous diseases and/or disorders, including but not limited to respiratory diseases and/or disorders, cardiac and cardiovascular diseases and/or disorders, autoimmune diseases and/or disorders, carcinogenesis, and associated symptoms or complications thereof.

One aspect of the present invention features a compound of Formula (I)

wherein

L is a bond, —CH 2 —, —SO 2 —, —CH 2 —SO 2 —, —SO 2 —CH 2 —, —SO 2 —NR—,

—SO 2 —NR—CH 2 —, —CH 2 —SO 2 —NR—, —NR—, —NR—SO 2 —, —NR—SO 2 —NR—, —S—, —S—CH 2 —, —CH 2 —S—,

—C(═O)—, —C(═O)—O—, —O—, —O—CH 2 —, —NR—C(═O)—, —NR—C(═O)—NR—, or —C(═O)—NR—, wherein R is H,

C 1-2 alkyl, C 1-2 alkyl-OH or cyclopropyl;

R 1 is H, halo, methyl, CF 3 , —O—CF 3 , or —O— CH 3 ; R 2 is H, cyano, halo, —SO 2 —CH 3 , 2-(trimethylsilyl)ethoxy, phenyl, C 1-6 alkyl, heteroaryl, heterocyclyl, C 3-9 cycloalkyl, provided R 2 is not H if L is a bond, and wherein said phenyl, C 1-6 alkyl, heteroaryl, heterocyclyl or C 3-9 cycloalkyl is optionally and independently substituted with 1-4 substituents selected from the group consisting of: methyl, ethyl, oxo, fluoro, hydroxyl, cyano, amino, methoxy, tert-butoxy, acetyl, cyclopropyl, cyclobutyl, cyclohexyl, phenyl, azetidin-1-yl, azetidin-3-yl, pyrrolidin-1-yl, 2,4-dihydro-3H-1,2,4-triazol-3-one-4-yl, 1H-imidazol-4-yl, pyrazin-2-yl, pyrimidin-2-yl, 1,3-oxazolidin-2-one-5-yl, N-benzamide, benzo[d]imidazol-2(3H)-one, 4-methylpiperazin-1-yl, morpholin-4-yl, CF 3 , —SO 2 —CH 3 , —C(═O)-cyclopropyl, —SO 2 -cyclohexyl, —NHCH 3 , —N(CH 3 ) 2 , —NHAc, —NHCO 2 t-Bu, —CH 2 —NH 2 , —C(═O)—NH 2 , —C(═O)—N(ethyl) 2 , —NH—C(═O)—NH 2 , —NH—C(═O)—CH 3 , —C(═O)—(C 1 -C 4 alkyl), —C(═O)—OH, —C(═O)—NH(C 1 -C 4 alkyl)-(CH 2 ) n —OH, and —(CH 2 ) n —CN, wherein n is 1 or 2; V is CH, CR′, or N, wherein R′ is methyl or F; W is CR″ or N, wherein R″ is H, F, hydroxyl, amino, CH 3 or —O—CH 3 ; ring A is selected from the group consisting of:

R 3 is H, F, methyl, or —O—CH 3 ;

R 3 ′ is H or F;

R 4 is H, methyl, cyano, amino, halo, —COOH, or —O—CH;

R 5 is H, methyl, cyano, or —CF 3 ;

R 6 is H, cyano, amino, halo, or —CF 3 ; and

R 7 is halo, amino, —CONH 2 , cyano, —O—CH 3 , —CF 3 , or —COO-ethyl.

Some embodiments are given by compounds of Formula (I), wherein ring A is

In some of these embodiments, wherein ring A is

R 4 is H or cyano.

In some of these embodiments, wherein ring A is

R 5 is H or —CF 3 .

In some of these embodiments, wherein ring A is

R 6 is H, fluoro, chloro, or cyano.

Some embodiments are given by compounds of Formula (I), wherein ring A is

Some embodiments are given by compounds of Formula (I), wherein V is CH and R 1 is H, halo, methyl, or CF 3 .

Some embodiments are given by compounds of Formula (I), wherein R 3 ′ is H.

In some of these embodiments, wherein V is CH and R 1 is H, halo, methyl, or CF 3 , the attachment point of R 1 to the phenyl ring is in the ortho position with regard to V.

Some embodiments are given by compounds of Formula (I), wherein W is CF, R 3 is H, and R 3 ′ is H.

Some embodiments are given by compounds of Formula (I), wherein L is a bond, —CH 2 —, —SO 2 —, —SO 2 —NH—, —SO 2 —NR—CH 2 —, —CH 2 —SO 2 —NR—, —S—, —CH 2 —S—, —O—, or

—O—CH 2 —.

In another embodiment, the present invention includes a compound of Formula (I) wherein

L is a bond, —O—, —SO 2 —NH—, —NH—SO 2 —, —SO 2 —, —S—, —C(═O)—, fluoro or —C(═O)—NH—;

R 1 is H, bromo or CF 3 ;

R 2 is H, methyl, ethyl, propyl, isopropyl, tert-butyl, cyclopropyl, cyclohexyl, pyrrolidin-1-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazin-1-yl, tetrahydro-2H-thiopyran-4-yl, morpholin-2-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrazin-2-yl, pyrimidin-2-yl, or pyrimidin-4-yl, provided R 2 is not H if L is a bond, and wherein R 2 is optionally substituted with hydroxyl, fluoro, amino, oxo, methyl, or —CH 2 —NH 2 ;

V is CH or N;

W is CR″ or N, wherein R″ is H or F;

ring A is

R 3 ′ is H;

R 4 is H or cyano; and

R 5 is H or cyano.

In yet another embodiment, the present invention includes a compound of Formula (I) wherein

L is a bond, —O—, —SO 2 —NH—, —NH—SO 2 —, —SO 2 —, —S—, or —C(═O)—;

R 1 is H or CF 3 ;

V is CH or N;

W is CR″ or N, wherein R″ is H or F;

ring A is

R 3 is H, and R 3 ′ is H.

The embodiments of the present invention also include the optical isomers, hydrates, metabolites, enantiomers, diastereomers, cis-trans isomers, racemates, prodrugs or pharmaceutically acceptable salts thereof.

It is an embodiment of the present invention to provide a compound selected from the compounds listed in Table 1.

Particularly, an embodiment of the present invention comprises a compound selected from the compounds listed in Table 2.

Further, an embodiment of the present invention comprises a compound selected from the compounds listed in Table 1A.

Additionally, an embodiment of the present invention comprises a compound selected from the compounds listed in Table 1, Table 2 and Table 1A.

The invention is also directed to a pharmaceutical composition which include, without limitation, one or more of the disclosed compounds, and pharmaceutically acceptable carriers or excipients.

Another embodiment of the present invention is a pharmaceutical composition of the present invention that comprises at least a compound selected from the compounds listed in Table 1. Another embodiment of the present invention is a pharmaceutical composition of the present invention that comprises at least a compound selected from the compounds listed in Table 3.

›DETAILED DESCRIPTION OF THE INVENTION · 2 of 8

Particularly, an embodiment of the present invention is a pharmaceutical composition of the present invention that comprises at least a compound selected from the compounds listed in Table 2.

The present invention also features a method for preventing, treating, ameliorating, including without limitation inhibiting, the progression of an FLAP-mediated disease and/or disorder in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of at least one compound of Formula (I). Such a disease and/or disorder includes, but is not limited to diabetes, respiratory disorders, and associated symptoms or complications thereof. More specifically, this invention is directed to a method of treating, but not limited to, exacerbations, non-allergic asthma, fibrotic lung diseases, acute respiratory distress syndrome and chronic obstructive pulmonary disease, and their associated symptoms or complications, in a subject afflicted with such a disease and/or disorder.

In another embodiment, the compounds of the present invention are useful for the amelioration of symptoms associated with and/or the treatment of the following cardiac and cardiovascular diseases and/or disorders: myocardial infarction, atherosclerosis and stroke aortic aneurisms, atherosclerosis, or associated symptoms or complications thereof, in a subject afflicted with such a disease and/or disorder.

In another embodiment, the compounds of the present invention are useful for the amelioration of symptoms associated with and/or the treatment of autoimmune or allergic diseases and/or disorders, wherein said autoimmune or allergic diseases and/or disorders include, but are not limited to, rheumatoid arthritis, inflammatory bowel disease, nephritis, spondyloarthritis, polymyositis, dermatomyositis, gouty effusions, systemic lupus erythematosus, systemic sclerosis, Alzheimer's disease, multiple sclerosis, allergic rhinitis, allergic dermatitis and asthma, or associated symptoms or complications thereof, in a subject afflicted with such a disease and/or disorder. In a further embodiment, the compounds of the present invention are useful for the amelioration of symptoms associated with and/or the prophylaxis or treatment of carcinogenesis, wherein said carcinogenesis include, but is not limited to, tumor cell proliferation, differentiation, and apoptosis, tumor-associated angiogenesis, as well as the migration and invasion of carcinoma cells.

It is a further embodiment of the invention to provide a process for making a pharmaceutical composition comprising admixing any of the compounds according to Formula (I) and a pharmaceutically acceptable carrier.

In a further embodiment of the invention, a method for treating or ameliorating an FLAP-mediated disease and/or disorder in a subject in need thereof comprises administering to the subject a therapeutically effective amount of at least one compound of Formula (I), wherein the therapeutically effective amount of the compound of Formula (I) is from about 0.1 mg/dose to about 5 g/dose. In particular, the therapeutically effective amount of the compound of Formula (I) is from about 0.5 mg/dose to about 1000 mg/dose.

More particularly, the therapeutically effective amount of the compound of Formula (I) is from about 1 mg/dose to about 100 mg/dose. In a further embodiment of the invention, the number of doses per day of a compound of Formula (I) is from 1 to 3 doses. In a further embodiment of the invention, the therapeutically effective amount of the compound of Formula (I) is from about 0.001 mg/kg/day to about 30 mg/kg/day. More particularly, the therapeutically effective amount of the compound of Formula (I) is from about 0.01 mg/kg/day to about 2 mg/kg/day.

The invention is further described below.

A) Terms

Some terms are defined below and by their usage throughout this disclosure.

It should also be noted that any atom with unsatisfied valences in the text, schemes, examples, structural formulae and any tables herein is assumed to have the hydrogen atom or atoms to satisfy the valences.

As used herein, the following terms are intended to have the following definitions. The definitions herein may specify that a chemical term has an indicated formula. The particular formula provided is not intended to limit the scope of the invention, but is provided as an illustration of the term. The scope of the per se definition of the term is intended to include the plurality of variations expected to be included by one of ordinary skill in the art.

The term “C 1-6 alkyl” means a saturated branched or straight-chain hydrocarbon radical having from 1 up to 6 carbon atoms in a linear or branched arrangement, selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, and hexyl. Examples include isopropyl, isobutyl, tert-butyl, sec-butyl, n-butyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1,2-dimethylpropyl, butan-2-yl, 2-methylbutyl, 2-methylbutan-2-yl, 1-methyl-3-methylbutyl, 3,3-dimethylbutan-2-yl, and the like, and all that are exemplified in the below examples. An alkyl radical may be attached to a core molecule by any atom where allowed by available valences. The term “C 1-4 alkyl” means a saturated branched or straight-chain hydrocarbon radical having from 1 up to 4 carbon atoms in a linear or branched arrangement,

The term “C 3-9 cycloalkyl” means a saturated or partially unsaturated, monocyclic, polycyclic or benzofused hydrocarbon ring system radical. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[2.2.1]heptan-2-yl, 2,3-dihydro-1H-inden-2-yl, and the like, and all that are exemplified in the below examples. A C 3-9 cycloalkyl radical may be attached to a core molecule by any ring atom where allowed by available valences.

›DETAILED DESCRIPTION OF THE INVENTION · 3 of 8

The term “aryl” means an unsaturated, aromatic monocyclic or polycyclic hydrocarbon ring system radical. Examples include phenyl and the like, and all that are exemplified in the below examples. An aryl radical may be attached to a core molecule by any ring atom where allowed by available valences.

The term “hetero”, when used as a prefix for a ring system, refers to the replacement of at least one carbon atom member in the ring system with a heteroatom selected from N, O, S, S(O), or SO 2 . A hetero ring may have 1, 2, 3 or 4 carbon atom members replaced by a nitrogen atom. Alternatively, a ring may have 1, 2 or 3 nitrogen atom members and 1 oxygen or sulfur atom member. Alternatively, a ring may have 1 oxygen or sulfur atom member. Alternatively, up to two adjacent ring members may be heteroatoms, wherein one heteroatom is nitrogen and the other heteroatom is selected from N, S or O.

The term “heteroaryl” means an unsaturated monocyclic, polycyclic aromatic “hetero” ring system radical, selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzimidazolyl, and tetrazolyl. Examples include pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-4-yl, pyrazin-2-yl, pyrazin-4-yl, pyrimidin-2-yl, pyridazin-3-yl, 1H-benzimidazol-2-yl, 2H-tetrazol-5-yl, and the like, and all that are exemplied in the below examples. A heteroaryl radical may be attached to a core molecule by any ring atom where allowed by available valences.

The term “heterocycyl” means a saturated monocyclic or polycyclic “hetero” ring system radical, selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, pyrazoyl, thiomorpholinyl, azepanyl, hexahydropyrrolo[1,2-a]pyrazinyl, tetrahydropyrazolo[4,3-c]pyridinyl, diazabicyclo[2.2.1]-heptanyl, dihydro-indolyl, tetrahydropyranyl, azabicyclo[3.1.0]hexanyl, oxetanyl, isothiazolidinyl, thiazinanyl, thiopyranyl, thia-azaspiro[3.3]heptanyl, oxa-azaspiro[3.3]heptanyl, tetrahydro-thiopyranyl, dihydroquinazolinyl, oxadiazolyl, oxa-azabicylco[2.2.1]heptanyl, piperazin-2-one-yl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, pyrrolidin-2-one-yl, imidazolidin-2-one-yl, 1,2-thiazinane 1,1-dioxide-yl, isothiazolidine 1,1-dioxide-yl, 1,2,3,6-tetrahydropyridinyl, and imidazolidinyl. Examples include azetidin-1-yl, azetidin-3-yl, pyrrolidin-1-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazin-1-yl, morpholin-2-yl, morpholin-4-yl, thiomorpholin-4-yl, azepan-1-yl, azepan-3-yl, hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl, 1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 2,3-dihydro-1H-indol-2-yl, tetrahydro-2H-pyran-4-yl, 3-azabicyclo[3.1.0]hexan-3-yl, oxetan-3-yl, isothiazolidin-2-yl, 1,2-thiazinan-2-yl, 2H-thiopyran-4-yl, 2-thia-6-azaspiro[3.3]heptan-6-yl, 2-oxa-6-azaspiro[3.3]heptan-6-yl, tetrahydro-2H-thiopyran-4-yl, 3,4-dihydroquinazolin-2-yl, 1,2,3-oxadiazol-5-yl, 2-oxa-5-azabicylco[2.2.1]heptan-5-yl, imidazolidin-1-yl, thiomorpholine 1,1-dioxide-yl, 4-amino-tetrahydro-2H-pyran-yl, tetrahydro-2H-thiopyran 1,1-dioxide-yl, and the like, and all that are exemplied in the below examples. A heterocyclyl radical may be attached to a core molecule by any ring atom where allowed by available valences.

The term “carboxy” means a radical of the formula: —C(O)OH.

The term “halogen” or “halo” means a radical selected from the group consisting of chloro, bromo, fluoro or iodo.

The term “oxo” means a radical of the formula: ═O.

The term “substituted” refers to a radical in which one or more hydrogen atoms are each independently replaced with the same or different substituent(s). In a preferred embodiment, up to three hydrogen atoms are each independently replaced.

With reference to substituents, the term “independently” means that when more than one of such substituent is possible, such substituents may be the same or different from each other.

It is intended that the definition of any substituent or variable at a particular location in a molecule be independent of its definitions elsewhere in that molecule. It is understood that substituents and substitution patterns on the compounds of this invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques known in the art as well as those methods set forth herein.

In general, unless otherwise specified, IUPAC nomenclature rules are used herein.

The term “about,” whether used explicitly or not in reference to a quantitative expression given herein, means that every quantity given herein qualified with the term or otherwise is meant to refer both to the actual given value and the approximation to such given value that would reasonably be inferred based on the ordinary skill in the art, including approximations due to experimental and/or measurement conditions for such given value.

The term “form” means, in reference to compounds of the present invention, such may exist as, without limitation in the following states, a salt, stereoisomer, tautomer, crystalline, polymorph, amorphous, solvate, hydrate, ester, prodrug or metabolite form. The present invention encompasses all such compound forms and mixtures thereof.

The term “isolated form” means, in reference to compounds of the present invention, such may exist in an essentially pure state such as, without limitation, an enantiomer, a racemic mixture, a geometric isomer (such as a cis or trans stereoisomer), a mixture of geometric isomers, and the like. The present invention encompasses all such compound forms and mixtures thereof.

The term “composition” is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combinations of the specified ingredients in the specified amounts.

The term “subject” as used herein, refers to a patient, such as an animal, a mammal or a human, who has been the object of treatment, observation or experiment and is at risk of (or susceptible to) developing an FLAP-mediated disorder.

›DETAILED DESCRIPTION OF THE INVENTION · 4 of 8

The term “administering” further means that the individual ingredients to be combined may be administered at the same time or at different times during the treatment period, either as one preparation or as different preparations. Accordingly, the invention should be so interpreted that it encompasses any and every administration mode at the same time or at different times. The range of the combination of the compound of the invention and the other therapeutic agent useful for the above-mentioned disorders encompasses, in principle, all combinations of the compound of the invention and any and every pharmaceutical agent useful for the above-mentioned disorders.

The term “treating” refers, without limitation, to facilitating the eradication of, preventing, ameliorating or otherwise inhibiting the progression of or promoting stasis of an FLAP-mediated disease and/or disorder, or associated symptoms or complications thereof.

The term “prodrug” means a compound of Formula (I) or a form thereof that is converted in vivo into a functional derivative form that may contribute to therapeutic biological activity, wherein the converted form may be: 1) a relatively active form; 2) a relatively inactive form; 3) a relatively less active form; or, 4) any form which results, directly or indirectly, from such in vivo conversions. Prodrugs are useful when said compound may be either too toxic to administer systemically, absorbed poorly by the digestive tract or broken down by the body before it reaches its target. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described in, for example, “ Design of Prodrugs ”, ed. H. Bundgaard, Elsevier, 1985.

The term “metabolite” means a prodrug form of a compound of Formula (I) or a form thereof converted by in vivo metabolism or a metabolic process to a relatively less active functional derivative of said compound.

The term “medicament” or “medicine” refers to a product containing a compound of Formula (I) or a form thereof. The present invention includes use of such a medicament for treating an FLAP-mediated disorder.

The term “combination form” refers to the use of a combination product comprising a compound of Formula (I) or a form, pharmaceutical composition, medicine or medicament thereof and at least one therapeutic agent for treating an FLAP-mediated disorder.

Methods are known in the art for determining effective doses for therapeutic and prophylactic purposes for the disclosed pharmaceutical compositions or the disclosed drug combinations, whether or not formulated in the same composition.

For therapeutic purposes, the term “therapeutically effective amount” or “effective amount” as used herein, means that amount of each active compound or pharmaceutical agent, alone or in combination, that elicits the biological or medicinal response in a tissue system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which includes alleviation of the symptoms of the disease and/or disorder being treated. For prophylactic purposes (i.e., inhibiting the progression of a disorder), the term “therapeutically effective amount” refers to that amount of each active compound or pharmaceutical agent, alone or in combination, that treats or inhibits in a subject the progression of a disorder as being sought by a researcher, veterinarian, medical doctor or other clinician. Thus, the present invention provides combinations of two or more drugs wherein, for example, (a) each drug is administered in an independently therapeutically or prophylactically effective amount; (b) at least one drug in the combination is administered in an amount that is sub-therapeutic or sub-prophylactic if administered alone, but is therapeutic or prophylactic when administered in combination with the second or additional drugs according to the invention; or (c) both (or more) drugs are administered in an amount that is sub-therapeutic or sub-prophylactic if administered alone, but are therapeutic or prophylactic when administered together. The effective amount of said compound is from about 0.001 mg/kg/day to about 300 mg/kg/day.

Advantageously, the effective amount of a combination product for treating an FLAP-mediated disease and/or disorder, or associated symptoms or complications thereof, may be a reduced amount of either or both, the compound or therapeutic agent, compared to the effective amount of the compound or therapeutic agent otherwise recommended for treating the disease and/or disorder, or associated symptoms or complications thereof. Therefore, it is contemplated that the compound is administered to the subject before, during or after the time the agent is administered.

The term “pharmaceutically acceptable salt” refers to non-toxic pharmaceutically acceptable salts ( Ref. Int'l J. Pharm., 1986, 33: 201-217 ; J. Pharm. Sci., 1997 (January), 66(1): 1). Other salts well known to those in the art may, however, be useful in the preparation of compounds according to this invention or of their pharmaceutically acceptable salts. Representative organic or inorganic acids include, but are not limited to, hydrochloric, hydrobromic, hydriodic, perchloric, sulfuric, nitric, phosphoric, acetic, propionic, glycolic, lactic, succinic, maleic, fumaric, malic, tartaric, citric, benzoic, mandelic, methanesulfonic, hydroxyethanesulfonic, benzenesulfonic, oxalic, pamoic, 2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, salicylic, saccharinic or trifluoroacetic acid. Representative organic or inorganic bases include, but are not limited to, basic or cationic salts such as benzathine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, procaine, aluminum, calcium, lithium, magnesium, potassium, sodium and zinc.

The compounds of the invention may be present in the form of pharmaceutically acceptable salts. For use in medicines, the “pharmaceutically acceptable salts” of the compounds of this invention refer to non-toxic acidic/anionic or basic/cationic salt forms.

›DETAILED DESCRIPTION OF THE INVENTION · 5 of 8

Suitable salt forms include acid addition salts which may, for example, be formed by mixing a solution of the compound according to the invention with a solution of an acid such as acetic acid, adipic acid, benzoic acid, carbonic acid, citric acid, fumaric acid, glycolic acid, hydrochloric acid, maleic acid, malonic acid, phosphoric acid, saccharinic acid, succinic acid, sulphuric acid, tartaric acid, trifluoroacetic acid and the like.

Furthermore when the compounds of the present invention carry an acidic moiety, suitable salts thereof may include alkali metal salts, e.g. sodium or potassium salts; alkaline earth metal salts, e.g. calcium or magnesium salts; and salts formed with suitable organic ligands, e.g. quaternary ammonium salts.

During any of the processes for preparation of the compounds of the present invention, it may be necessary and/or desirable to protect sensitive or reactive groups on any of the molecules concerned. This may be achieved by means of conventional protecting groups, such as those described in Protective Groups in Organic Chemistry , ed. J. F. W. McOmie, Plenum Press, 1973; and T. W. Greene & P. G. M. Wuts, Protective Groups in Organic Synthesis. 3 rd Edition, John Wiley & Sons, 1999. The protecting groups may be removed at a convenient subsequent stage using methods known in the art. The scope of the present invention encompasses all such protected compound forms and mixtures thereof.

The invention includes compounds of various isomers and mixtures thereof. The term “isomer” refers to compounds that have the same composition and molecular weight but differ in physical and/or chemical properties. Such substances have the same number and kind of atoms but differ in structure. The structural difference may be in constitution (geometric isomers) or in an ability to rotate the plane of polarized light (optical isomers).

The term “stereoisomer” refers to isomers that have the same molecular formula and the same sequence of covalently bonded atoms but a different spatial orientation.

The term “optical isomer” means isomers of identical constitution that differ only in the spatial arrangement of their groups. Optical isomers rotate the plane of polarized light in different directions. The term “optical activity” means the degree to which an optical isomer rotates the plane of polarized light.

The term “racemate” or “racemic” means an equimolar mixture of two enantiomeric species, wherein each of the isolated species rotates the plane of polarized light in the opposite direction such that the mixture is devoid of optical activity.

The term “enantiomer” means an isomer having a nonsuperimposable mirror image. The term “diastereomer” means stereoisomers that are not enantiomers.

The term “chiral” means a molecule that, in a given configuration, cannot be superimposed on its mirror image. This is in contrast to achiral molecules that can be superimposed on their mirror images.

The two distinct mirror image versions of the chiral molecule are also known as levo (left-handed), abbreviated L, or dextro (right-handed), abbreviated D, depending on which way they rotate polarized light. The symbols “R” and “S” represent the configuration of groups around a stereogenic carbon atom(s).

The term “geometric isomer” means isomers that differ in the orientation of substituent atoms in relationship to a carbon-carbon double bond, to a cycloalkyl ring, or to a bridged bicyclic system. Substituent atoms (other than hydrogen) on each side of a carbon-carbon double bond may be in an E or Z configuration according to the Cahn-Ingold-Prelog priority rules. In the “E” configuration, the substituents having the highest priorities are on opposite sides in relationship to the carbon-carbon double bond. In the “Z” configuration, the substituents having the highest priorities are oriented on the same side in relationship to the carbon-carbon double bond.

Substituent atoms (other than hydrogen) attached to a ring system may be in a cis or trans configuration. In the “cis” configuration, the substituents are on the same side in relationship to the plane of the ring; in the “trans” configuration, the substituents are on opposite sides in relationship to the plane of the ring. Compounds having a mixture of “cis” and “trans” species are designated “cis/trans”.

The isomeric descriptors (“R,” “S,” “E,” and “Z”) indicate atom configurations and are intended to be used as defined in the literature.

The compounds of the invention may be prepared as individual isomers by either isomer-specific synthesis or resolved from an isomeric mixture. Conventional resolution techniques include combining the free base (or free acid) of each isomer of an isomeric pair using an optically active acid (or base) to form an optically active salt (followed by fractional crystallization and regeneration of the free base), forming an ester or amide of each of the isomers of an isomeric pair by reaction with an appropriate chiral auxiliary (followed by fractional crystallization or chromatographic separation and removal of the chiral auxiliary), or separating an isomeric mixture of either an intermediate or a final product using various well known chromatographic methods.

Furthermore, compounds of the present invention may have one or more polymorph or amorphous crystalline forms and, as such, are intended to be included in the scope of the invention. In addition, some of the compounds may form solvates with water (i.e., hydrates) or common organic solvents (e.g., organic esters such as ethanolate and the like) and, as such, are also intended to be encompassed within the scope of this invention.

B) Compounds

Representative compounds of the present invention are listed in Table 3 below:

C) Synthesis

The invention provides methods of making the disclosed compounds according to traditional organic synthetic methods as well as matrix or combinatorial synthetic methods. Scheme A described suggested synthetic routes. Using the schemes, the guidelines below, and the examples, a person of skill in the art may develop analogous or similar methods for a given compound that is within the invention. These methods are representative of the synthetic schemes, but are not to be construed as limiting the scope of the invention.

›DETAILED DESCRIPTION OF THE INVENTION · 6 of 8

Where the compounds according to this invention have at least one chiral center, they may accordingly exist as enantiomers. Where the compounds possess two or more chiral centers, they may additionally exist as diastereomers. Where the processes for the preparation of the compounds according to the invention give rise to mixtures of stereoisomers, these isomers may be separated by conventional techniques such as preparative chromatography. The compounds may be prepared in racemic form or as individual enantiomers or diasteromers by either stereospecific synthesis or by resolution. The compounds may, for example, be resolved into their component enantiomers or diastereomers by standard techniques, such as the formation of stereoisomeric pairs by salt formation with an optically active base, followed by fractional crystallization and regeneration of the free acid. The compounds may also be resolved by formation of stereoisomeric esters or amides, followed by chromatographic separation and removal of the chiral auxiliary. Alternatively, the compounds may be resolved using a chiral HPLC column. It is to be understood that all stereoisomers, racemic and scalemic mixtures, diastereomers, geometric isomers, and enantiomers thereof are encompassed within the scope of the present invention.

Representative compounds of the present invention can be synthesized in accordance with the general synthetic schemes described below and are illustrated more particularly in the specific synthetic examples that follow. The general schemes are offered by way of illustration; the invention should not be construed as being limited by the chemical reactions and conditions expressed. The methods for preparing the various starting materials used in the schemes and examples are well within the skill of persons versed in the art. No attempt has been made to optimize the yields obtained in any of the example reactions. One skilled in the art would know how to increase such yields through routine variations in reaction times, temperatures, solvents and/or reagents.

General: 1 H and 13 C NMR spectra were measured on a Bruker AC-300 (300 MHz) spectrometer using tetramethylsilane and the deuterated solvent respectively as internal standards. Elemental analyses were obtained by Quantitative Technologies Inc. (Whitehouse, N.J.) and the results were within 0.4% of the calculated values unless otherwise mentioned. Melting points were determined in open capillary tubes with a Mel-Temp II apparatus (Laboratory Devices Inc.) and were uncorrected. Electrospray mass spectra (MS-ESI) were recorded in the positive mode on a Hewlett Packard 59987A spectrometer. High resolution mass spectra (HRMS) were obtained on a Micromass Autospec. E spectrometer by fast atom bombardment (FAB) technique.

Furthermore, some of the crystalline forms for the compounds may exist as polymorphs and as such are intended to be included in the present invention. In addition, some of the compounds may form solvates with water (i.e., hydrates) or common organic solvents, and such solvates are also intended to be encompassed within the scope of this invention.

Examples of the described synthetic routes include Scheme A-G, Intermediates A-HZ. Examples 1-588 and prophetic Examples 1-247. Compounds analogous to the target compounds of these examples can be made according to similar routes. The disclosed compounds are useful as pharmaceutical agents as described herein.

Abbreviations or acronyms useful herein include:

Abbreviation Meaning BOC/boc tert-butyloxycarbonyl BOP benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate Cpd compound DCE dichloroethane DCM dichloromethane DIPEA diisopropyl ethyl amine DMA N,N-dimethylacetamide DMAP N,N-dimethylaminopyridine DMF N,N-dimethylformamide DMSO dimethyl sulfoxide DPBS Dulbecco's phosphate buffered saline EDC 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride ESI electrospray ionization Et 3 N or TEA triethylamine EtOAc ethyl acetate h/hr/hrs hour(s) HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxid hexafluorophosphate HOBT 1-hydroxybenzotriazole hydrate HBTU O-benzotriazol-1-yloxy-N,N,N′,N′-tetramethyluronium hexafluorophosphate I.D. interior diameter LG Leaving group LiOH lithium hydroxide m-CPBA meta-chloroperoxybenzoic acid min minute(s) MS mass spectroscopy NMR nuclear magnetic resonance spectroscopy OTf Triflate PG protecting group RT/rt room temperature TBME tert-butyl methyl ether THF tetrahydrofuran TLC thin layer chromatography Tos p-toluenesulfonyl dppf 1,1′-Bis(diphenylphosphino)ferrocene

General Guidance Representative compounds of the present invention can be synthesized in accordance with the general synthetic methods described below and are illustrated more particularly in the schemes that follow. Since the schemes are illustrations, the invention should not be construed as being limited by the chemical reactions and conditions expressed. The preparation of the various starting materials used in the schemes is well within the skill of persons versed in the art. The substituents for compounds of Formula (I) or a form thereof, represented in the schemes below, are as previously defined herein.

Unless otherwise specified, reaction solutions were stirred at room temperature under a N 2(g) or Ar (g) atmosphere. When solutions were “concentrated to dryness”, they were concentrated using a rotary evaporator under reduced pressure, when solutions were dried, they are typically dried over a drying agent such as MgSO 4 or Na 2 SO 4 .

Normal phase flash column chromatography (FCC) was performed on silica gel with RediSep® silica gel columns using ethyl acetate (EtOAc)/hexanes, CH 2 Cl 2 /MeOH, CH 2 Cl 2 /10% 2 N NH 3 in MeOH, CH 2 Cl 2 /i-PrOH, and the like as eluent, unless otherwise indicated.

Reverse phase high performance liquid chromatography (HPLC) was performed under the following conditions: 1) Instrument, Shimadzu; Column, Waters XBridge C18 10 μm (250×50 mm), Phenomenex Gemini column 5 μm C18 (150×21.2 mm) or Waters Xterra RP18 OBD 5 μm (100×30 mm); Gradient, 95:5 to 0:100 water (0.05% trifluoroacetic acid (TFA))/CH 3 CN (0.05% TFA); Flow rate, 30-80 mL/min; Detection, UV at λ=220-254 nM; 2) Instrument, Gilson; Column, Phenomenex LUNA column 5 μm C18 (250×50 mm) or Waters XBridge Prep C18 OBD 5 μm (30×150 mm); Gradient, 95:5 to 0:100 water (0.05% TFA)/CH 3 CN (0.05% TFA); Flow rate, 30-80 mL/min; Detection, UV at λ=220-254 nM; 3) Instrument. Gilson/Shimadzu: Column, Inertsil ODS-3 column (30×100 mm) or Inertsil ODS-3 (30×50 mm, 5 μm); Gradient, water-acetonitrile with both phases with 0.05% by volume trifluoroacetic acid; 1 min hold at 5% ACN, then 6 min gradient to 99% ACN followed by a hold at that concentration for 3 min. Flow rate, 80 ml/min; heated column at 46° Celsius with detection of UV light at λ=254 nm; and 4) Instrument, Dionex: UVD 170U Diode array detector and ThermoFinnegan Surveyor MSQ plus mass spectrometer for data collection. Waters XBridge C18 5 μm OBD 50×100 mm prep column.

›DETAILED DESCRIPTION OF THE INVENTION · 7 of 8

All runs on the Dionex utilized water acetonitrile with 20 mM NH 4 OH added to the aqueous phase and a flow rate for all gradients was 80 mL/min using four possible gradients: 1) 5-60% MeCN over 12 min, then ramped to 100% MeCN and held for 6.3 min; 2) 30-70% MeCN over 12 min, then ramped to 100% MeCN and held for 6.3 min; 3) 50-80% MeCN over 12 min, then ramped to 100% MeCN and held for 6.3 min; and 4) 60-100% MeCN over 12 min, and then held for 6.3 min. The total run time for all gradient systems was 18.5 min.

Instances where solutions were filtered through a syringe filter, Pall 0.45 μM GHP membrane 13 mm and 25 mm diameter syringe filters were used

Thin-layer chromatography was performed using Merck silica gel 60 F 254 2.5 cm×7.5 cm 250 μm or 5.0 cm×10.0 cm 250 m pre-coated silica gel plates. Preparative thin-layer chromatography was performed using EM Science silica gel 60 F 254 20 cm×20 cm 0.5 mm pre-coated plates with a 20 cm×4 cm concentrating zone. Microwave reactions were carried out in either a CEM Discover™ or a Biotage Initiator™ or Optimizer™ Microwave at specified temperatures. Mass spectra were obtained on an Agilent series 1100 MSD using electrospray ionization (ESI) in positive mode unless otherwise indicated. Calculated mass corresponds to the exact mass.

NMR spectra were obtained on either a Bruker model DPX400 (400 MHz), DPX500 (500 MHz), DRX600 (600 MHz) spectrometer. The format of the 1 H NMR data below is: chemical shift in ppm down field of the tetramethylsilane reference (multiplicity, coupling constant J in Hz, integration).

Hydrochloride salts were obtained by treating the corresponding free bases with HCl (4 N in dioxane, 2 M in Et 2 O, or 1.25 N in MeOH) at room temperature with mixtures either concentrated to obtain the HCl salt, or the resulting solid being isolated by filtration. Trifluoroacetic acid salts were obtained by purification of the crude reaction product by preparative reverse phase HPLC, whereby the final products were isolated as either mono-, di- or tri-fluoro acetic acid salts.

Chemical names were generated using ChemDraw Ultra 12.0 (CambridgeSoft Corp., Cambridge, Mass.) or ACD/Name Version 10.01 (Advanced Chemistry).

The compounds of Formula (I), wherein ring A, L, V, W, R, R′, n, R 1 , R 2 , R 3 , and R 4 are defined as in Formula (I), may be synthesized as outlined by the general synthetic route illustrated in Scheme A-G.

Referring to Scheme A, compounds of formulae (XI) can be obtained through a series of metal mediated cross coupling reactions starting from compound (XIII). Compounds of formulae (XIV) in which Ar 1 can be an amine substituted or des-amino 5-, 6-membered or 5/6- or 6/6-fused aromatic or heteroaromatic nitrogen containing ring system, can be prepared via Pd mediated cross coupling of either an aryl or heteroaryl boronic acid or ester, Ar 1 —B(OP) 2 , with intermediates of structure (XIII) in which W is bromo or chloro, Y is an alkyl, hetero-alkyl, aryl, or heteroaryl and Z is H, fluoro, alkyl or heteroalkyl. In instances where W is either bromo or chloro, the boronic acid or ester of compound (XIII) can be formed via palladium catalysis using bis(pinacolato)diboron and KOAc in the presence of [1,1′-bis(diphenylphosphino)ferrocene]-dichloro-palladium(II).CH 2 Cl 2 (Pd(dppf)Cl 2 .CH 2 Cl 2 ) or the X-Phos pre-catalyst in solvents such as 1,4-dioxane or DMSO, at temperatures ranging from 0-100° Celsius. Alliteratively, compounds of Formulae (XIII) in which W is B(OP) 2 can be cross-coupled with an aryl or heteroaryl halide, Ar 1− X where X is either bromo or chloro to obtain compounds of formulae (XII). Preferably, in compounds of formulae (XII), Y is t-butyl, cyclobutyl, trifluoromethoxy, or SF 5 , Z is H or -fluoro ortho to Ar 1 , and Ar 1 is either amino-pyrazine, amino-pyrimidine, or amino-pyridine alliteratively substituted with or without CN, CH 3 , OCH 3 , CF 3 , Cl, F, OH, and NH 2 . Preferred solvents for cross coupling reactions include DME, DMSO, 1,4-dioxane, THF, EtOH DMF, water, and toluene or mixtures thereof, in the presence of a base, such as Na 2 CO 3 , K 2 CO 3 , KOAc, KH 2 PO 4 , and K 3 PO 4 using catalysts such as Pd(dppf)Cl 2 .CH 2 Cl 2 , palladium trifluoroacetate and PhP 3 , chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]-palladium(II), 1,1′-bis[di-t-butylphosphino)ferrocene]palladium chloride with temperatures ranging from rt to 100° Celsius.

Compounds of formulae (XI) can be prepared from compounds of formulae (XIII) via sequential (XIII→XIV→XI or XIII→XV→XI) Pd mediated cross-coupling using methods and intermediates, analogous to those described above compounds of formulae (XV) can be obtained via compounds of formulae (XIII), wherein Y is a boronic acid or ester and W is bromo or chloro, Compounds of formulae (XIII) in which Y is the boronic acid or ester can be obtained from the corresponding iodide wherein W is either bromo or chloro. Preferred methods for conversion of the iodo to the corresponding boronic acid or ester are analogous to the methods described above. In some cases, aryl and heteroaryl halides, boronic esters and acids are commercially available or can be prepared by known methods.

Compounds (XIV) in which Y is alkyl or cycloalykyl can be obtained from the corresponding bromide using alkylzinc bromides in solvents such as THF in the presence of palladium acetate and 2-dicyclohexylphosphine-2′,6′-dimethoxy-1,1′-biphenyl at temperatures ranging from rt to 100° Celsius.

In further embodiments, compounds of formulae (XI) containing a pyridine core, where Z is H or -fluoro ortho to Ar 1 , can be prepared using analogous Pd mediated cross coupling reactions described herein.

Referring to Scheme B, substituted aryl and heteroaryl sulfonamides (XVI) possessing from 0 to 3 G groups, where a G group is alkyl, cycloalkyl, heteroalkyl, CF 3 , F, Cl, Br, or combinations thereof, and where X is bromo or chloro, can be prepared by addition of various primary and secondary amines to the aryl or heteroaryl sulfonyl chloride in solvents such as CH 2 Cl 2 , CH 3 CN, THF, and DMF in the presences of bases such as pyridine, Et 3 N and i-Pr 2 EtNH at temperatures ranging from −20° to 1000 Celsius.

›DETAILED DESCRIPTION OF THE INVENTION · 8 of 8

Alliteratively, sulfones (XVI) can be obtained from the corresponding bromo or chloro aryl thiol (XVIII). S N 1 substitution in the presence of a strong acid, such as H 2 SO 4 , with an appropriately reactive alcohol, such as tert-butanol, provides the desired aryl sulfide. Additionally, one can obtain substituted aryl sulfides via S N 2 or S N Ar displacement of alkyl or aryl bromide, chloride, and fluorides (aryl only) under basic conditions using bases such as NaH or i-Pr 2 EtNH and the desired in solvents such as THF, DMSO, and DMF at temperatures ranging from rt to 1000 Celsius. Sulfone (XVI) can then be obtained via oxidation of the sulfide using an appropriate oxidant such as m-CPBA, oxone, or RuCl 3 /NaIO 4 .

Referring to Scheme C, sulfonamides of formulae (XIX) can be prepared from an aniline (XX) possessing from 0 to 3 G groups G, where a G group can be a variety of alky, heteroalkyl, F, Cl, Br, CF 3 , or combinations thereof, and X is bromo, chloro, B(OH) 2 , or B(OP) 2 , by treatment with an appropriate sulfonyl chloride on which R is alkyl, cycloalkyl, substituted aryl, substituted heteroaryl or CF 3 , in a solvent, such as CH 2 Cl 2 , in the presence of a base, such as pyridine, at temperatures ranging from 0° to 100° Celsius.

Referring to Scheme D, methanesulfonamides of formulae (XXI) can be prepared by treatment of a substituted (halomethyl)benzene, where X is bromo or chloro and possessing 0 to 3 G groups, which can be a variety of alkyl, cycloalkyl, heteroalkyl, F, Cl, Br, CF 3 , or combinations thereof, with sodium sulfite to provide the desired arylmethyl sulfonate which can be subsequently treated with phosphorous pentachloride to provide the desired arylmethylsulfonyl chloride (XXIII). Sulfonyl chlorides (XXIII) can then be transformed to the corresponding sulfonamide (XXI) using methods described herein.

Referring to Scheme E, variously substituted amides (XXIV) can be prepared using standard amide coupling reactions. Substituted carboxylic acid (XXV), where X is bromo or chloro, and possessing 0 to 3 G groups, which can be a variety of alkyl, cycloalkyl, heteroalkyl, F, Cl, Br, CF 3 , or combinations thereof, can be treated with various primary and secondary amines using standard carbodiimide peptide coupling reagents, such as HATU or EDCl, in solvents such as DMF and CH 2 Cl 2 , at temperatures ranging from 0-60° Celsius, to provide amide (XXIV).

Referring to Scheme F, phenyl ethers of formulae (XXVI) can be prepared from the corresponding phenol (XXVII), where X is bromo or chloro, and possessing 0 to 3 G groups, which can be a variety of alkyl, cycloalkyl, heteroalkyl, F, Cl, Br, CF 3 , or combinations thereof, and n=0, 1. Treatment of phenol (XXVII) with appropriately substituted halo aromatic heterocycles, where halo refers to F, Cl, and Br, or halomethyl aromatic heterocycles in which halo refers to Cl or Br, a base, such as Cs 2 CO 3 , K 2 CO 3 , or Na 2 CO 3 , In a polar solvent, such as DMSO, CH 3 CN, or DMF at temperatures ranging from rt to 100° Celsius, provides ethers (XXVI).

Referring to Scheme G, instances where Ar 1 in Scheme A is a 5-, 6-membered, or 5/5-, 5/6-fused heterocyle, compounds of formulae (XXVIII) and (XXX) can be obtained starting from methyl ketone (XXIX). Treatment of the ketone with either urea or thiourea in the presence of I 2 in EtOH at temperatures ranging from rt to 80° Celsius results in the corresponding five-membered amino heterocycle (XXVIII). Whereas, treatment of the ketone under analogous conditions with substituted 2-amino pyridines, possessing 0 to 3 G groups, which can be a variety of alkyl, cycloalkyl, heteroalkyl. F, Cl, Br, CF 3 , or combinations thereof, results in a substituted fused 5/6 heterocycle (XXX).

›EXAMPLES

The following examples are offered by way of illustration: the invention should not be construed as being limited by the chemical reactions and conditions expressed.

Intermediate A

Method 1

To a 250 mL round-bottomed flask were added a stirbar, 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (3.07 g, 11.5 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (5.82 g, 22.9 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (512 mg, 0.623 mmol), and KOAc (2.30 g, 23.4 mmol). The flask was then thoroughly sparged with nitrogen and then charged with 1,4-dioxane (114 mL, sparged with N 2 for 30 min). The flask was then heated at 80° Celsius for 19.5 hours before cooling to rt, filtering the reaction mixture through Na 2 SO 4 and concentrating the filtrate to dryness. The residue was purified by FCC to give the title compound. MS (ESI): mass calcd. for C 16 H 19 BFN 3 O 2 , 315.16; m/z found, 316.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.38 (dd, J=2.4, 1.5, 1H), 8.02 (d, J=1.5, 1H), 7.96-7.89 (m, 1H), 7.56 (dd, J=7.7, 1.1, 1H), 7.42 (dd, J=11.8, 1.1, 1H), 6.77 (s, 2H), 1.31 (s, 12H).

Method 2

›Step A: 5-(4-Bromo-2-fluorophenyl)pyrazin-2-amine

To a solution of 5-bromopyrazin-2-amine (1.74 g, 10.0 mmol) in 1,4-dioxane (40 mL) were added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.65 g, 10.5 mmol) and KOAc (1.96 g, 20.0 mmol). The mixture was sparged with N 2 several times before adding Pd(dppf)Cl 2 .CH 2 Cl 2 (0.41 g, 0.5 mmol). The resultant mixture was stirred at 90° Celsius for 60 hours under N 2 . After cooling to rt, 4-bromo-2-fluoro-1-iodobenzene (4.5 g, 15.0 mmol), K 2 CO 3 (2.76 g, 20.0 mmol) and another portion of Pd(dppf)Cl 2 .CH 2 Cl 2 (0.41 g, 0.5 mmol) were added. The resultant mixture was sparged with N 2 again, and stirred at 80° Celsius for 48 hours under N 2 . The mixture was then cooled to rt, diluted with THF (30 mL) and filtered. The filtrate was concentrated to dryness and the residue purified by FCC to give 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (0.4 g, 15%). 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.33 (s, 1H), 8.01 (s, 1H), 7.82 (m, 1H), 7.63 (dd, J=11.1, 2.1, 1H), 7.50 (dd, J=8.4, 2.1, 1H), 6.75 (s, 2H).

›Step B

To a solution of 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (535 mg, 2.0 mmol) in 1,4-dioxane (20 mL) was added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (1.1 g, 4.0 mmol) and KOAc (0.39 g, 4.0 mmol). The mixture was sparged by bubbling N 2 for 10 min. The mixture was treated with Pd(dppf)Cl 2 .CH 2 Cl 2 (82 mg, 0.1 mmol) and then stirred at 80° Celsius for 1 hour under N 2 . After cooling to rt, the reaction mixture was filtered through Na 2 SO 4 and the filtrate concentrated to dryness. The residue was purified by FCC to give the title compound (460 mg, 72%).

Intermediate B

›Step A: 6-Amino-3-(4-chloro-2-fluorophenyl)pyrazine-2-carbonitrile

To a 200 mL round-bottomed flask were added a stirbar, 5-amino-3-cyano-2-bromopyrazine (4.09 g, 20.5 mmol), 4-chloro-2-fluorophenylboronic acid (3.90 g, 22.4 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (839 mg, 1.03 mmol) and K 2 CO 3 (8.36 g, 60.5 mmol). The flask was flushed with nitrogen and then charged with toluene (17.5 mL), water (17.5 mL) and DMF (10.5 mL), all of which were sparged with N 2 . The flask was heated at 80° Celsius for 19 hours before cooling to rt and adding MgSO 4 until the mixture was a thick paste. The reaction mixture was then stirred with EtOAc and filtered through a thick pad of celite. The pad was rinsed with EtOAc until the filtrate was colorless. The filtrate was concentrated to dryness and subjected to FCC to give 6-amino-3-(4-chloro-2-fluorophenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 11 H 6 ClFN 4 , 248.03; m/z found, 249.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d) δ 8.22 (s, 1H), 7.67-7.60 (m, 2H), 7.46 (dd, J=8.4, 2.0, 1H), 7.37 (s, 2H).

›Step B

To a 200 mL round-bottomed flask were added a stirbar, 6-amino-3-(4-chloro-2-fluorophenyl)pyrazine-2-carbonitrile (1.175 g, 4.73 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (1.583 g, 6.23 mmol), chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (194 mg, 0.247 mmol), and KOAc (1.43 g, 14.6 mmol). The flask was fitted with a septum and sparged with nitrogen for 30 min before adding 48 mL of thoroughly N 2 sparged THF via syringe. The mixture was then heated at 80° Celsius for 16.5 hours before cooling the mixture to rt and concentrating to dryness. The dark residue was taken up in DCM, filtered through a plug of celite, and concentrated to dryness. The residue was subjected to FCC to give the title compound. 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.23 (s, 1H), 7.66-7.58 (m, 2H), 7.53-7.46 (d, J=10.2, 1H), 7.40 (s, 2H), 1.34 (s, 12H).

Intermediate C

›Step A: 4-Bromo-2-fluorobenzoyl chloride

A solution of 4-bromo-2-fluorobenzoic acid (10.8 g, 50.0 mmol) in SOCl 2 (50 mL) was stirred at 70° Celsius for 1 hour. After cooling to rt, the resulting mixture was concentrated to give 4-bromo-2-fluorobenzoyl chloride as colorless oil, which was used directly in the next step without purification.

›Step B: 2-(4-Bromo-2-fluorobenzoyl)-hydrazinecarbothioamide

Hydrazinecarbothioamide (6.8 g, 75 mmol) was added to a solution of 4-bromo-2-fluorobenzoyl chloride (11.8 g, 50.0 mmol) in THF (50 mL) at rt and stirred for 1 hour. The reaction mixture was concentrated to give 2-(4-bromo-2-fluorobenzoyl)-hydrazinecarbothioamide as a white solid, which was used directly in the next step without purification. MS (ESI): mass calcd. for C 8 H 7 BFN 3 OS, 290.95, m/z found, 292.1 [M+H] + .

›Step C: 5-(4-Bromo-2-fluorophenyl)-1,3,4-thiadiazol-2-amine

H 2 SO 4 (2 mL) was added to a solution of 2-(4-bromo-2-fluorobenzoyl)-hydrazinecarbothioamide (2.9 g, 10.0 mmol) in pentanoic acid (5 mL) and the resulting mixture was stirred at 110° Celsius for 2 hours. After cooling to rt, the reaction mixture was poured into ice-water (20 mL) and treated with NH 3 .H 2 O (15 mL). 5-(4-Bromo-2-fluorophenyl)-1,3,4-thiadiazol-2-amine was then isolated via vacuum filtration and air dried. MS (ESI): mass calcd. for C 8 H 5 BFN 3 OS, 272.94, m/z found, 274.1 [M+H] + .

›Step D

To a solution of 5-(4-bromo-2-fluorophenyl)-1,3,4-thiadiazol-2-amine (2.73 g, 10.0 mmol) in 1,4-dioxane (20 mL) were added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.54 g, 10.0 mmol) and KOAc (1.5 g, 20.0 mmol). The mixture was sparged with N 2 for 10 min. Pd(dppf)Cl 2 .CH 2 Cl 2 (82 mg, 0.1 mmol) was then added, and the mixture, stirred at 80° Celsius for 1 hour under N 2 . After cooling to rt, the reaction mixture was filtered through a pad of anhydrous Na 2 SO 4 and the filtrate concentrated to dryness. The residue was purified by FCC to give the title compound. MS (ESI): mass calcd. for C 14 H 17 N 3 BO 2 SBr 321.11, m/z found 322.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 8.28-8.19 (m, 1H), 7.65 (dd, J=7.8, 1.0, 1H), 7.57 (d, J=11.3, 1H), 5.39 (s, 2H), 1.36 (s, 12H).

Intermediate D

›Step A: 4′-Bromo-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide · 1 of 6

1-Bromo-2-fluoro-4-iodobenzene (6.30 g, 20.9 mmol) and (2-(N-methyl-sulfamoyl)-phenyl) boronic acid (4.50 g, 20.9 mmol) were added to a 250 mL flask equipped with a stir bar and reflux condenser. 1,4-Dioxane (50 mL) and Na 2 CO 3 (2 M, 50 mL) were added. Argon was bubbled through the solvent while it was rapidly stirred for 10 minutes before Pd(dppf)Cl 2 .CH 2 Cl 2 (766 mg, 1.05 mmol) was added and the reaction was stirred at 80° Celsius for 15 hours. The reaction was then diluted with 50 mL of water and extracted with ethyl acetate (1×50 mL, 3×100 mL). The combined organic extracts were dried with Na 2 CO 3 , filtered and concentrated to dryness. The crude product was purified by FCC to give 4′-bromo-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide. 1 H NMR (500 MHz, CDCl 3 ) δ 8.17-8.11 (m, 1H), 7.66-7.59 (m, 2H), 7.59-7.54 (m, 1H), 7.33-7.29 (m, 1H), 7.28-7.23 (m, 1H), 7.20-7.13 (m, 1H), 3.67-3.56 (dd, J=10.1, 4.5, 1H), 2.46-2.43 (d, J=5.3, 3H).

Step B: 3′-Fluoro-N-methyl-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide

4′-Bromo-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide (2.0 g, 5.8 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.95 g, 11.6 mmol) and anhydrous KOAc (1.71 g, 17.4 mmol) and 1,4-dioxane (50 mL) were added to a flask, equipped with a stir bar and reflux condenser. The reaction mixture was sparged with argon for 10 min, before adding Pd(dppf)Cl 2 .CH 2 Cl 2 (0.425 g, 0.58 mmol) was added. The flask was heated at 80° Celsius for 15 hours before cooling to rt, diluting with ethyl acetate (50 mL), filtering through Na 2 SO 4 and concentrating to dryness. The crude product was purified by FCC to provide the title compound. 1 H NMR (400 MHz, CDCl 3 ) δ 8.19-8.12 (dd, J=7.8, 1.4, 1H), 7.87-7.78 (dd, J=7.6, 6.2, 1H), 7.64-7.59 (dd, J=7.5, 1.5, 1H), 7.58-7.51 (m, 1H), 7.35-7.27 (m, 2H), 7.19-7.11 (dd, J=9.6, 1.5, 1H), 3.57-3.45 (d, J=5.5, 1H), 2.41-2.37 (d, J=5.4, 3H), 1.39 (s, 12H).

Intermediate E

The title compound was prepared in a manner similar to that described for Intermediate D using (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid in Step A. 1 H NMR (400 MHz, CDCl 3 ) δ 8.17 (dd, J=7.9, 1.4, 1H), 7.81 (dd, J=7.6, 6.2, 1H), 7.62-7.53 (m, 1H), 7.53-7.46 (m, 1H), 7.36-7.30 (m, 1H), 7.29-7.27 (m, 1H), 7.19 (dd, J=9.9, 1.5, 1H), 3.61 (s, 1H), 1.39 (s, 12H), 1.04 (s, 9H).

Intermediate F

The title compound was prepared in a manner similar to that described for Intermediate D using 2-bromo-N-(2-hydroxyethyl)benzenesulfonamide in Step A. 1 H NMR (500 MHz, CD 3 OD) δ 8.09-8.03 (dd, J=8.0, 1.3, 1H), 7.76-7.70 (dd, J=7.6, 6.2, 1H), 7.68-7.62 (m, 1H), 7.61-7.54 (dd, J=8.5, 7.1, 1H), 7.37-7.31 (dd, J=7.5, 1.4, 1H), 7.24-7.20 (dd, J=7.6, 1.5, 1H), 7.16-7.11 (dd, J=10.0, 1.5, 1H), 3.48-3.43 (t, J=5.9, 2H), 2.88-2.82 (t, J=5.9, 2H), 1.37 (s, 12H).

Intermediate G

The title compound was prepared using analogous methods described in Intermediate D using 7-amino-5-bromoindole in Step A. MS (ESI): mass calcd. for C 20 H 22 BFN 2 O 2 , 352.18; m/z found, 353.3 [M+H] + .

Intermediate H

To a solution of 3-amino-6-bromopyrazine-2-carbonitrile (2.00 g, 9.55 mmol) in 1,4-dioxane (48 mL), were added (4-chloro-2-fluorophenyl)boronic acid (1.66 g, 9.55 mmol) and aqueous Na 2 CO 3 (2 M, 24 mL, 48 mmol) and the reaction mixture sparged with N 2 gas for 10 min. Pd(dppf)Cl 2 .CH 2 Cl 2 (0.349 g, 0.477 mmol) was then added and the reaction mixture sparged for an additional 10 min with N 2 gas. The reaction vessel was sealed and heated for 3 hours at 80° Celsius. The mixture was cooled to rt, filtered through celite, and the filter cake washed with EtOAc (300 mL). The filtrate was washed with a 1:1 mixture of brine/H 2 O (2×100 mL). The organic phase was concentrated to dryness and subjected to FCC to give the title compound (1.99 g, 84%). MS (ESI): mass calcd. for C 11 H 6 ClFN 4 , 248.03; m/z found 249.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.67 (d, J=2.0, 1H), 7.83 (m, 1H), 7.25-7.08 (m, 2H), 5.36 (s, 2H).

Intermediate I

To a solution of 3-amino-6-(4-chloro-2-fluorophenyl)pyrazine-2-carbonitrile (0.290 g, 1.17 mmol) in 1,4-dioxane (12 mL), were added (4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (0.370 g, 1.46 mmol) and KOAc (0.343 g, 3.50 mmol). The reaction mixture sparged with N 2 gas for 10 min, before adding chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (18 mg, 0.023 mmol) and then sparged for an additional 10 min with N 2 gas. The reaction vessel was sealed, heated 3 hours at 80° Celsius and cooled to rt. The mixture was filtered through celite and the filter cake washed with EtOAc (30 mL). The filtrate was concentrated in vacuo onto silica gel and purified via FCC to give the product which was then triturated with hexanes to give 3-amino-6-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carbonitrile (0.25 g, 63%). MS (ESI): mass calcd. for C 17 H 18 BFN 4 O 2 , 340.15; m/z found 341.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.79 (d, J=1.8, 1H), 7.94 (m, 1H), 7.67 (dd, J=7.7, 1.1, 1H), 7.58 (dd, J=11.8, 1.1, 1H), 5.35 (s, 2H), 1.36 (s, 12H).

Intermediate K

To a 20 mL vial were added a stirbar, 2-bromobenzene-1-sulfonyl chloride (1.053 g, 4.12 mmol), cyclohexylamine (431 mg, 4.34 mmol) and dry pyridine (5 mL). The mixture was stirred for 3 hours before adding it to a separatory funnel containing 1 N HCl and EtOAc. The layers were mixed thoroughly and then separated. The organic layer was then washed with water followed by sat. NaHCO 3 , dried over MgSO 4 , filtered and evaporated to dryness to give the title compound. MS (ESI): mass calcd. for C 12 H 16 NO 2 SBr 317.01, m/z found 318.0 [M+H] + ; 1 H NMR (500 MHz, CDCl 3 ) δ 8.14 (dd, J=7.9, 1.7, 1H), 7.71 (dd, J=7.9, 1.2, 1H), 7.49-7.42 (m, 1H), 7.42-7.35 (m, 1H), 5.05 (d, J=7.7, 1H), 3.19-3.04 (m, 1H), 1.79-1.66 (m, 2H), 1.66-1.57 (m, 2H), 1.52-1.44 (m, 1H), 1.28-1.04 (m, 5H).

Intermediate L

The title compound was prepared using analogous conditions to those described in Intermediate K using cyclopropylamine. 1 H NMR (500 MHz, CDCl 3 ) 8.19 (dd, J=7.8, 1.8, 1H), 7.73 (dd, J=7.8, 1.3, 1H), 7.51-7.45 (m, 1H), 7.44-7.39 (m, 1H), 5.46 (s, 1H), 2.21-2.08 (m, 1H), 0.69-0.60 (m, 2H), 0.60-0.51 (m, 2H).

›Step A: 4′-Bromo-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide · 2 of 6

Intermediate M

The title compound was prepared using analogous conditions to those described in Intermediate K using cyclopentylamine. 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.02 (dd, J=7.7, 1.8, 1H), 7.84 (dd, J=7.8, 1.3, 2H), 7.61-7.55 (m, 1H), 7.55-7.50 (m, 1H), 3.51-3.40 (m, 1H), 1.64-1.49 (m, 4H), 1.45-1.30 (m, 4H).

Intermediate N

The title compound was prepared using analogous conditions to those described in Intermediate K using isobutylamine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.12 (dd, J=7.8, 1.8, 1H), 7.72 (dd, J=7.9, 1.3, 1H), 7.48-7.43 (m, 1H), 7.43-7.37 (m, 1H), 5.18-5.03 (m, 1H), 2.67 (t, J=6.6, 2H), 1.78-1.64 (m, 1H), 0.87 (d, J=6.7, 6H).

Intermediate O

The title compound was prepared using analogous conditions to those described in Intermediate K using 2-phenethylamine. 1 H NMR (600 MHz, CDCl 3 ) δ 8.14-8.09 (dd, J=7.9, 1.7, 1H), 7.69-7.63 (dd, J=7.8, 1.2, 1H), 7.47-7.42 (m, 1H), 7.42-7.36 (m, 1H), 7.29-7.24 (m, 2H), 7.24-7.17 (m, 1H), 7.12-7.06 (m, 2H), 5.16-5.00 (t, J=6.1, 1H), 3.23-3.10 (m, 2H), 2.84-2.73 (t, J=7.0, 2H).

Intermediate P

The title compound was prepared using analogous conditions to those described in Intermediate K using cyclopropylmethylamine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.18 (dd, J=7.8, 1.7, 1H), 7.70 (dd, J=7.9, 1.2, 1H), 7.50-7.43 (m, 1H), 7.42-7.36 (m, 1H), 5.52 (s, 1H), 1.17-1.09 (m, 3H), 0.89-0.76 (m, 2H), 0.50-0.41 (m, 2H).

Intermediate Q

The title compound was prepared using analogous conditions to those described in Intermediate K using 2,3-dihydro-1H-inden-2-amine. 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.34-8.27 (d, J=7.0, 1H), 8.09-8.04 (dd, J=7.7, 1.8, 1H), 7.91-7.85 (dd, J=7.8, 1.3, 1H), 7.64-7.54 (m, 2H), 7.17-7.06 (m, 4H), 4.01-3.92 (m, 1H), 2.98-2.89 (m, 2H), 2.87-2.79 (m, 2H).

Intermediate R

The title compound was prepared using analogous conditions to those described in Intermediate K using racemic 2-amino-1,1,1-trifluoropropane. 1 H NMR (500 MHz, CDCl 3 ) 8.10 (dd, J=7.7, 1.9, 1H), 7.74 (dd, J=7.7, 1.4, 1H), 7.49-7.38 (m, 2H), 5.33 (d, J=9.8, 1H), 4.03-3.88 (m, 1H), 1.29 (d, J=7.0, 3H).

Intermediate S

The title compound was prepared using analogous conditions to those described in Intermediate K using (S)-2-amino-1,1,1-trifluoropropane.

Intermediate T

The title compound was prepared using analogous conditions to those described in Intermediate K using racemic (endo)-bicyclo[2.2.1]heptan-2-amine 1 H NMR (500 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.8, 1H), 7.71 (dd, J=7.9, 1.3, 1H), 7.49-7.42 (m, 1H), 7.42-7.37 (m, 1H), 4.98 (d, J=7.1, 1H), 3.17-3.04 (m, 1H), 2.27-2.14 (m, 1H), 2.05 (d, J=3.7, 1H), 1.62-1.50 (m, 1H), 1.45-1.28 (m, 3H), 1.28-1.17 (m, 1H), 1.17-1.08 (m, 1H), 1.05-0.91 (m, 2H).

Intermediate U

The title compound was prepared using analogous conditions to those described in Intermediate K using cyclobutylmethylamine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.12 (dd, J=7.8, 1.8, 1H), 7.72 (dd, J=7.8, 1.3, 1H), 7.49-7.43 (m, 1H), 7.43-7.36 (m, 1H), 5.04 (d, J=6.0, 1H), 2.89 (dd, J=7.4, 6.1, 2H), 2.45-2.31 (m, 1H), 2.04-1.91 (m, 2H), 1.90-1.71 (m, 2H), 1.64-1.52 (m, 2H).

Intermediate V

The title compound was prepared using analogous conditions to those described in Intermediate K using 1-amino-1-methylcyclobutane. 1 H NMR (500 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.7, 1H), 7.70 (dd, J=7.9, 1.3, 1H), 7.47-7.41 (m, 1H), 7.40-7.34 (m, 1H), 5.26 (s, 1H), 2.26-2.13 (m, 2H), 1.86-1.76 (m, 2H), 1.76-1.59 (m, 2H), 1.32 (t, J=0.8, 3H).

Intermediate W

The title compound was prepared using analogous conditions to those described in Intermediate K using 2-methylbutan-2-amine. 1 H NMR (500 MHz, DMSO-d 6 ) δ 7.81 (dd, J=7.8, 1.7, 1H), 7.58 (dd, J=7.8, 1.3, 1H), 7.35-7.29 (m, 1H), 7.29-7.24 (m, 1H), 1.24 (q, J=7.4, 2H), 0.80 (s, 6H), 0.52 (t, J=7.4, 3H).

Intermediate X

The title compound was prepared using analogous conditions to those described in Intermediate K using 1,1,1-trifluoro-2-methylpropan-2-amine. 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.61 (s, 1H), 8.05 (dd, J=7.7, 1.8, 1H), 7.86 (dd, J=7.7, 1.4, 1H), 7.62-7.57 (m, 1H), 7.57-7.52 (m, 1H), 1.30 (s, 6H).

Intermediate Y

The title compound was prepared using analogous conditions to those described in Intermediate K using (R)-2,2,2-trifluoro-1-phenylethanamine. 1 H NMR (600 MHz, DMSO-d 6 ) δ 9.64-9.53 (d, J=10.2, 1H), 8.03-7.91 (dd, J=7.8, 1.7, 1H), 7.68-7.62 (dd, J=7.8, 1.2, 1H), 7.53-7.39 (m, 4H), 7.34-7.23 (m, 3H), 5.25-5.11 (m, 1H).

Intermediate Z

The title compound was prepared using analogous conditions to those described in Intermediate K using (S)-2,2,2-trifluoro-1-phenylethanamine.

Intermediate AA

The title compound was prepared using analogous conditions to those described in Intermediate K using (R)-1-phenylethanamine 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.46-8.34 (d, J=8.4, 1H), 7.94-7.83 (dd, J=7.7, 1.9, 1H), 7.74-7.65 (dd, J=7.7, 1.4, 1H), 7.50-7.37 (m, 2H), 7.27-7.07 (m, 5H), 4.42-4.29 (m, 1H), 1.37-1.27 (d, J=7.0, 3H).

Intermediate AB

The title compound was prepared using analogous conditions to those described in Intermediate K using (R)-2,3-dihydro-1H-inden-1-amine. 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.47-8.39 (d, J=9.0, 1H), 8.14-8.06 (dd, J=7.7, 1.8, 1H), 7.93-7.87 (dd, J=7.8, 1.3, 1H), 7.64-7.53 (m, 2H), 7.23-7.10 (m, 4H), 4.77-4.64 (m, 1H), 2.91-2.78 (m, 1H), 2.72-2.61 (m, 1H), 2.21-2.10 (m, 1H), 1.91-1.77 (m, 1H).

Intermediate AC

The title compound was prepared using analogous conditions to those described in Intermediate K using (S)-2,3-dihydro-1H-inden-1-amine. NMR spectra as for Intermediate AB.

Intermediate AD

The title compound was prepared using analogous conditions to those described in Intermediate K using (S)-3-amino-1-ethylazepan-2-one. 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.04-7.99 (dd, J=7.8, 1.7, 1H), 7.84-7.80 (dd, J=7.9, 1.3, 1H), 7.58-7.53 (m, 2H), 7.53-7.49 (m, 1H), 4.13-4.04 (m, 1H), 3.40-3.31 (m, 1H), 3.30-3.15 (m, 3H), 1.85-1.73 (m, 2H), 1.73-1.63 (m, 1H), 1.62-1.52 (m, 1H), 1.50-1.40 (m, 1H), 1.28-1.16 (m, 1H), 0.96-0.88 (t, J=7.1, 3H).

Intermediate AE

The title compound was prepared using analogous conditions to those described in Intermediate K using (S)-3-aminoazepan-2-one. 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.05-8.01 (dd, J=7.8, 1.7, 1H), 7.96-7.91 (m, 1H), 7.85-7.81 (dd, J=7.8, 1.3, 1H), 7.60-7.55 (m, 1H), 7.55-7.50 (m, 1H), 7.47-7.43 (d, J=6.0, 1H), 3.95-3.86 (m, 1H), 3.04-2.93 (m, 2H), 1.89-1.79 (m, 2H), 1.71-1.62 (m, 1H), 1.59-1.44 (m, 2H), 1.20-1.07 (m, 1H).

›Step A: 4′-Bromo-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide · 3 of 6

Intermediate AF

The title compound was prepared using analogous conditions to those described in Intermediate K using (S)-3-amino-1-methylazepan-2-one. MS (ESI): mass calcd. for C 13 H 17 BrN 2 O 3 S 360.01, m/z found 361.0 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.03-8.00 (dd, J=7.8, 1.8, 1H), 7.84-7.81 (dd, J=7.8, 1.3, 1H), 7.59-7.50 (m, 3H), 4.17-4.07 (m, 1H), 3.48-3.38 (m, 1H), 3.20-3.09 (m, 1H), 2.87-2.79 (s, 3H), 1.92-1.81 (dd, J=14.4, 3.4, 1H), 1.81-1.70 (m, 1H), 1.67-1.52 (m, 2H), 1.52-1.41 (m, 1H), 1.34-1.21 (m, 1H).

Intermediate AG

The title compound was prepared using analogous conditions to those described in Intermediate K using 1,2,2,6,6-pentamethylpiperidin-4-amine. MS (ESI): mass calcd. for C 16 H 25 BrN 2 O 2 S 388.08, m/z found 389.1 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.07-8.03 (dd. J=7.8, 1.7, 1H), 7.87-7.81 (m, 2H), 7.61-7.56 (m, 1H), 7.56-7.51 (m, 1H), 3.32-3.21 (m, 1H), 2.11-2.02 (s, 3H), 1.46-1.37 (m, 2H), 1.35-1.26 (m, 2H), 1.01-0.92 (s, 6H), 0.83-0.74 (s, 6H).

Intermediate AH

The title compound was prepared using analogous conditions to those described in Intermediate K using aniline. 1 H NMR (600 MHz, DMSO-d 6 ) δ 10.68-10.56 (s, 1H), 8.13-8.02 (dd, J=7.9, 1.7, 1H), 7.85-7.75 (dd, J=7.8, 1.3, 1H), 7.62-7.46 (m, 2H), 7.25-7.16 (m, 2H), 7.12-7.04 (m, 2H), 7.02-6.93 (m, 1H).

Intermediate AI

The title compound was prepared using analogous conditions to those described in Intermediate K using 3-aminopyridine. MS (ESI): mass calcd. for C 11 H 9 BrN 2 O 2 S 311.96, m/z found 312.9 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 11.05-10.87 (s, 1H), 8.40-8.29 (m, 1H), 8.25-8.17 (dd, J=4.7, 1.4, 1H), 8.15-8.06 (dd, J=7.8, 1.8, 1H), 7.93-7.78 (dd, J=7.8, 1.3, 1H), 7.66-7.52 (m, 2H), 7.47-7.44 (dd, J=2.7, 1.4, 1H), 7.32-7.23 (m, 2H).

Intermediate AJ

The title compound was prepared using analogous conditions to those described in Intermediate K using (R)-2-aminopropan-1-ol. MS (ESI): mass calcd. for C 9 H 12 NOSBr 292.97, m/z found 294.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.8, 1H), 7.72 (dd, J=7.9, 1.3, 1H), 7.48-7.43 (m, 1H), 7.43-7.37 (m, 1H), 5.42 (d, J=7.4, 1H), 3.60-3.50 (m, 1H), 3.49-3.40 (m, 1H), 3.38-3.28 (m, 1H), 2.16 (t, J=5.4, 1H), 1.04 (d, J=6.8, 3H).

Intermediate AK

To a 20 mL vial were added a stirbar, 2-bromobenzene-1-sulfonyl chloride (0.995 g, 3.89 mmol), and THF (5 mL). The vial was then charged with EtNH 2 in THF (5 mL, 2.0 M). The mixture was stirred for 24 hours before adding it to a separatory funnel containing 1 N HCl and EtOAc. The layers were mixed thoroughly and then separated. The organic layer was then washed with water followed by sat. NaHCO 3 , dried over MgSO 4 , filtered and concentrated to dryness to give the crude product. Subjecting the oil to FCC yielded the title compound (580 mg, 56%). 1 H NMR (600 MHz, CDCl 3 ) 8.17-8.10 (dd, J=7.8, 1.7, 1H), 7.75-7.69 (dd, J=7.8, 1.2, 1H), 7.48-7.43 (m, 1H), 7.43-7.37 (m, 1H), 5.16-4.91 (t, J=6.7, 1H), 3.06-2.87 (m, 2H), 1.19-1.00 (t, J=7.3, 3H).

Intermediate AL

The title compound was prepared using analogous conditions to those described in Intermediate AK using 0.5 M methylamine in 1,4-dioxane. 1 H NMR (600 MHz, CDCl 3 ) δ 8.15-8.11 (dd, J=7.8, 1.7, 1H), 7.75-7.70 (dd, J=7.8, 1.3, 1H), 7.49-7.45 (m, 1H), 7.44-7.39 (m, 1H), 5.11-5.00 (d, J=6.6, 1H), 2.66-2.55 (d, J=5.4, 3H).

Intermediate AM

To a 500 mL round-bottomed flask were added a stirbar, (S)-2-aminopropan-1-ol (2.151 g, 28.65 mmol), dry DCM (100 mL), and DIPEA (14.0 mL, 81.2 mmol). The mixture was then treated with 2-bromobenzene-1-sulfonyl chloride (6.981 g, 27.32 mmol) and stirred for 66.5 hours before concentrating to dryness and subjecting the residue to FCC to give the title compound. (7.31 g, 91%).

Intermediate AN

The title compound was prepared using analogous conditions to those described in Intermediate AM using 2-amino-2-methylpropan-1-ol. MS (ESI): mass calcd. for C 10 H 14 BrNO 3 S 306.99, m/z found 330.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.14 (dd, J=7.8, 1.7, 1H), 7.72 (dd, J=7.9, 1.2, 1H), 7.50-7.42 (m, 1H), 7.42-7.35 (m, 1H), 5.33 (s, 1H), 3.46 (d, J=6.3, 2H), 1.11 (s, 6H).

Intermediate AO

The title compound was prepared using analogous conditions to those described in Intermediate AM using (R)-2-amino-3-methylbutan-1-ol. MS (ESI): mass calcd. for C 11 H 16 BrNO 3 S 321.00, m/z found 322.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.15-8.06 (m, 1H), 7.78-7.67 (m, 1H), 7.50-7.42 (m, 1H), 7.42-7.34 (m, 1H), 5.39 (s, 1H), 3.65-3.54 (m, 1H), 3.54-3.43 (m, 1H), 3.11-3.01 (m, 1H), 1.82 (d, J=5.7, 1H), 0.95-0.83 (m, 3H), 0.83-0.73 (m, 3H).

Intermediate AP

The title compound was prepared using analogous conditions to those described in Intermediate AM using (S)-3-aminopiperidin-2-one. MS (ESI): mass calcd. for C 11 H 13 BrN 2 O 3 S 331.98, m/z found 333.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.08 (dd, J=7.8, 1.8, 1H), 7.71 (dd, J=7.8, 1.3, 1H), 7.46-7.40 (m, 1H), 7.40-7.36 (m, 1H), 6.77 (s, 1H), 6.52-6.41 (m, 1H), 3.61-3.49 (m, 1H), 3.34-3.18 (m, 2H), 2.43-2.32 (m, 1H), 1.96-1.84 (m, 1H), 1.81-1.69 (m, 2H).

Intermediate AQ

To a 20 mL vial were added a stir-bar, trans-4-aminocyclohexanol (683 mg, 4.50 mmol), DMF (5 mL), and DIPEA (2.0 mL, 12 mmol). The mixture was then treated with 2-bromobenzene-1-sulfonyl chloride (1.00 g, 3.93 mmol) and the mixture stirred for 2 hours before subjecting the vial's content to FCC to give the title compound. (978 mg, 74%). MS (ESI): mass calcd. for C 12 H 16 BrNO 3 S 333.00, m/z found 334.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.12 (dd, J=7.8, 1.7, 1H), 7.70 (dd, J=7.8, 1.2, 1H), 7.49-7.43 (m, 1H), 7.43-7.37 (m, 1H), 5.10 (d, J=7.5, 1H), 3.62-3.47 (m, 1H), 3.11-3.01 (m, 1H), 2.12 (s, 1H), 1.91-1.75 (m, 4H), 1.31-1.15 (m, 4H).

Intermediate AR

The title compound was prepared using analogous conditions to those described in Intermediate AQ using (S)-pyrrolidin-3-ylmethanol. 1 H NMR (600 MHz, CDCl 3 ) δ 8.06 (dd, J=7.9, 1.7, 1H), 7.70 (dd, J=7.9, 1.2, 1H), 7.44-7.38 (m, 1H), 7.38-7.32 (m, 1H), 3.61-3.54 (m, 1H), 3.54-3.45 (m, 3H), 3.39-3.33 (m, 1H), 3.17 (dd, J=9.8, 6.4, 1H), 2.53-2.39 (m, 2H), 2.04-1.94 (m, 1H), 1.74-1.65 (m, 1H).

›Step A: 4′-Bromo-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide · 4 of 6

Intermediate AS

The title compound was prepared using analogous conditions to those described in Intermediate AQ using (R)-pyrrolidin-3-ylmethanol.

Intermediate AT

The title compound was prepared using analogous conditions to those described in Intermediate AQ using (R)-3-aminopiperidin-2-one.

Intermediate AU

To a 20 mL vial were added a stirbar, 3-amino-3-methylbutan-1-ol (428 mg, 4.15 mmol), ACN (5 mL), and DIPEA (2.0 mL, 12 mmol). The mixture was then treated with 2-bromobenzene-1-sulfonyl chloride (994 mg, 3.89 mmol) and stirred for 12.5 hours before concentrating to dryness and subjecting the residue to FCC to give the title compound. (676 mg, 54%). MS (ESI): mass calcd. for C 11 H 16 BrNO 3 S 321.00, m/z found 344.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.15 (dd, J=7.9, 1.7, 1H), 7.70 (dd, J=7.8, 1.2, 1H), 7.46-7.39 (m, 1H), 7.39-7.31 (m, 1H), 6.15 (s, 1H), 3.93-3.81 (m, 2H), 1.76 (t, J=6.0, 2H), 1.20 (s, 6H).

Intermediate AV

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-tert-butyl 3-(methylamino)piperidine-1-carboxylate. MS (ESI): mass calcd. for C 17 H 25 BrN 2 O 4 S 432.07, m/z found 455.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.14 (dd, J=7.9, 1.7, 1H), 7.72 (dd, J=7.9, 1.3, 1H), 7.46-7.40 (m, 1H), 7.40-7.35 (m, 1H), 4.06 (s, 2H), 3.67 (s, 1H), 2.85 (s, 3H), 2.72 (s, 1H), 2.47 (s, 1H), 1.86 (d, J=11.8, 1H), 1.75-1.65 (m, 1H), 1.65-1.55 (m, 1H), 1.54-1.46 (m, 1H), 1.38 (s, 9H).

Intermediate AW

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-tert-butyl 3-(methylamino)piperidine-1-carboxylate.

Intermediate AX

The title compound was prepared using analogous conditions to those described in Intermediate AU using (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol. MS (ESI): mass calcd. for C 15 H 14 BrNO 3 S 366.99, m/z found 389.9 [M+Na] 4 ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.20 (dd, J=7.7, 1.9, 1H), 7.79 (dd, J=7.8, 1.4, 1H), 7.50-7.42 (m, 2H), 7.24-7.16 (m, 4H), 5.85 (d, J=8.2, 1H), 4.70-4.63 (m, 1H), 4.38-4.31 (m, 1H), 3.09-2.97 (m, 1H), 2.95-2.86 (m, 1H), 2.12 (d, J=5.2, 1H).

Intermediate AY

The title compound was prepared using analogous conditions to those described in Intermediate AU using (1S,2R)-2-amino-1-phenylpropane-1,3-diol. MS (ESI): mass calcd. for C 15 H 16 BrNO 4 S 384.00, m/z found 407.9 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 7.88 (dd, J=7.6, 1.9, 1H), 7.54 (dd, J=7.6, 1.5, 1H), 7.34-7.26 (m, 2H), 7.23-7.19 (m, 2H), 7.17-7.09 (m, 3H), 5.89 (d, J=6.4, 1H), 4.97 (dd, J=4.3, 2.4, 1H), 3.83-3.73 (m, 1H), 3.73-3.64 (m, 1H), 3.48-3.38 (m, 1H), 3.05 (d, J=2.6, 1H), 2.37-2.27 (m, 1H).

Intermediate AZ

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-2-amino-3-phenylpropan-1-ol. MS (ESI): mass calcd. for C 15 H 16 BrNO 3 S 369.00, m/z found 392.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.07 (dd, J=7.8, 1.7, 1H), 7.62 (dd, J=7.9, 1.2, 1H), 7.45-7.39 (m, 1H), 7.38-7.32 (m, 1H), 7.20-7.10 (m, 3H), 7.05-6.95 (m, 2H), 5.46 (d, J=6.8, 1H), 3.63-3.54 (m, 1H), 3.54-3.43 (m, 2H), 2.88-2.78 (m, 1H), 2.78-2.68 (m, 1H), 2.14-1.97 (m, 1H).

Intermediate BA

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-2-amino-3-phenylpropan-1-ol. 1 H NMR (600 MHz, CDCl 3 ) δ 8.10 (dd, J=7.8, 1.8, 1H), 7.71 (dd, J=7.8, 1.3, 1H), 7.47-7.42 (m, 1H), 7.42-7.37 (m, 1H), 7.33-7.28 (m, 2H), 7.28-7.25 (m, 3H), 5.68-5.57 (m, 1H), 4.78 (dd, J=8.7, 3.7, 1H), 3.26-3.15 (m, 1H), 3.04-2.94 (m, 1H), 2.41 (s, 1H).

Intermediate BB

The title compound was prepared using analogous conditions to those described in Intermediate AU using (1S,2S)-2-(methylamino)-1-phenylpropan-1-ol. MS (ESI): mass calcd. for C 16 H 18 BrNO 3 S 383.02, m/z found 406.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.19 (dd, J=7.9, 1.7, 1H), 7.73 (dd, J=7.8, 1.3, 1H), 7.49-7.44 (m, 1H), 7.41-7.36 (m, 1H), 7.34-7.29 (m, 2H), 7.29-7.25 (m, 3H), 4.45 (dd, J=9.4, 3.4, 1H), 3.95-3.85 (m, 1H), 3.05 (d, J=3.4, 1H), 2.98 (s, 3H), 0.97-0.86 (d, J=6.7, 3H).

Intermediate BC

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-1-aminoethane-1,2-diol. MS (ESI): mass calcd. for C 9 H 12 BrNO 4 S 308.97, m/z found 310.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.05 (dd, J=7.8, 1.7, 1H), 7.68 (dd, J=7.9, 1.3, 1H), 7.49-7.40 (m, 1H), 7.40-7.32 (m, 1H), 6.18 (t, J=6.3, 1H), 3.95-3.75 (m, 3H), 3.64 (dd, J=11.8, 3.6, 1H), 3.54 (dd, J 11.6, 6.0, 1H), 3.06-2.97 (m, 1H), 2.97-2.85 (m, 1H).

Intermediate BD

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-3-aminopyrrolidin-2-one. MS (ESI): mass calcd. for C 10 H 11 BrN 2 O 3 S 317.97, m/z found 318.9 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.14-8.05 (m, 1H), 7.71 (dd, J=7.8, 1.3, 1H), 7.49-7.36 (m, 2H), 7.06 (s, 1H), 6.22 (d, J=4.7, 1H), 3.81-3.68 (m, 1H), 3.41-3.29 (m, 1H), 3.29-3.18 (m, 1H), 2.47-2.34 (m, 1H), 2.12-2.00 (m, 1H).

Intermediate BE

The title compound was prepared using analogous conditions to those described in Intermediate AU using 1-amino-2-methylpropan-2-ol. MS (ESI): mass calcd. for C 10 H 14 BrNO 3 S 306.99, m/z found 290.0 [M−OH] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.11 (dd, J=7.8, 1.7, 1H), 7.72 (dd, J=7.8, 1.3, 1H), 7.48-7.43 (m, 1H), 7.43-7.38 (m, 1H), 5.53 (t, J=6.0, 1H), 2.79 (d, J=6.6, 2H), 1.22 (s, 6H).

Intermediate BF

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-2-amino-1,1,1-trifluoropropane.

Intermediate BG

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-tert-butyl (pyrrolidin-2-ylmethyl)carbamate. MS (ESI): mass calcd. for C 16 H 23 BrN 2 O 4 S 418.06, m/z found 319.0 [M-Boc+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.10 (dd, J=7.9, 1.7, 1H), 7.73 (dd, J=7.9, 1.3, 1H), 7.46-7.41 (m, 1H), 7.41-7.36 (m, 1H), 4.99 (t, J=6.5, 1H), 4.05-3.95 (m, 1H), 3.50-3.40 (m, 1H), 3.40-3.34 (m, 1H), 3.32-3.17 (m, 2H), 1.98-1.86 (m, 2H), 1.86-1.71 (m, 2H), 1.40 (s, 9H).

›Step A: 4′-Bromo-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide · 5 of 6

Intermediate BH

The title compound was prepared using analogous conditions to those described in Intermediate AU using tert-butyl 4-aminopiperidine-1-carboxylate. MS (ESI): mass calcd. for C 16 H 23 BrN 2 O 4 S 418.06, m/z found 441.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.7, 1H), 7.72 (dd, J=7.8, 1.3, 1H), 7.49-7.43 (m, 1H), 7.43-7.38 (m, 1H), 5.15 (d, J=7.5, 1H), 3.86 (s, 2H), 3.32-3.20 (m, 1H), 2.75 (s, 2H), 1.69 (d, J=12.2, 2H), 1.40 (s, 9H), 1.38-1.29 (m, 2H).

Intermediate BI

The title compound was prepared using analogous conditions to those described in Intermediate AU using azetidin-3-ol. MS (ESI): mass calcd. for C 9 H 10 BrNO 3 S 290.96, m/z found 292.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.02 (dd, J=7.8, 1.8, 1H), 7.72 (dd, J=7.8, 1.3, 1H), 7.44-7.40 (m, 1H), 7.40-7.35 (m, 1H), 4.61-4.51 (m, 1H), 4.18-4.10 (m, 2H), 3.97-3.91 (m, 2H), 2.92 (d, J=6.3, 1H).

Intermediate BJ

The title compound was prepared using analogous conditions to those described in Intermediate AU using racemic-(1,2-trans)-1R-2-aminocyclohexanol. MS (ESI): mass calcd. for C 12 H 16 BrNO 3 S 333.00, m/z found 334.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.15 (dd, J=7.8, 1.7, 1H), 7.73 (dd, J=7.8, 1.3, 1H), 7.50-7.44 (m, 1H), 7.44-7.39 (m, 1H), 5.29 (d, J=7.4, 1H), 3.38-3.28 (m, 1H), 2.88-2.77 (m, 1H), 2.58 (d, J=3.0, 1H), 2.04-1.96 (m, 1H), 1.77-1.69 (m, 1H), 1.59-1.51 (m, 1H), 1.27-1.12 (m, 3H), 1.12-1.01 (m, 1H).

Intermediate BK

The title compound was prepared using analogous conditions to those described in Intermediate AU using racemic-(1,2-trans)-1R-2-aminocyclohexyl)methanol. MS (ESI): mass calcd. for C 13 H 18 BrNO 3 S 347.02, m/z found 348.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.7, 1H), 7.73 (dd, J=7.8, 1.3, 1H), 7.49-7.44 (m, 1H), 7.44-7.38 (m, 1H), 5.19-5.06 (m, 1H), 4.10-4.00 (m, 1H), 3.51-3.41 (m, 1H), 3.08-2.97 (m, 1H), 2.45-2.36 (m, 1H), 1.72-1.66 (m, 1H), 1.66-1.60 (m, 1H), 1.59-1.53 (m, 1H), 1.52-1.46 (m, 1H), 1.41-1.32 (m, 1H), 1.31-1.24 (m, 1H), 1.20-1.07 (m, 2H), 1.05-0.96 (m, 1H).

Intermediate BL

The title compound was prepared using analogous conditions to those described in Intermediate AU using racemic-(1,2-cis)-1R-2-aminocyclohexanol. MS (ESI): mass calcd. for C 12 H 16 BrNO 3 S 333.00, m/z found 334.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.7, 1H), 7.72 (dd, J=7.8, 1.3, 1H), 7.47-7.42 (m, 1H), 7.42-7.38 (m, 1H), 5.52 (d, J=7.7, 1H), 3.80-3.72 (m, 1H), 3.27-3.15 (m, 1H), 1.80 (d, J=4.8, 1H), 1.74-1.63 (m, 1H), 1.63-1.51 (m, 2H), 1.51-1.43 (m, 2H), 1.43-1.36 (m, 1H), 1.36-1.26 (m, 1H), 1.26-1.11 (m, 1H).

Intermediate BM

The title compound was prepared using analogous conditions to those described in Intermediate AU using racemic-(1,2-cis)-1R-2-aminocyclohexyl)methanol. MS (ESI): mass calcd. for C 13 H 18 BrNO 3 S 347.02, m/z found 348.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.8, 1H), 7.73 (dd, J=7.8, 1.3, 1H), 7.49-7.44 (m, 1H), 7.44-7.39 (m, 1H), 5.43 (d, J=9.3, 1H), 3.76-3.65 (m, 1H), 3.65-3.54 (m, 1H), 3.45-3.33 (m, 1H), 2.82 (dd, J=8.9, 5.2, 1H), 1.73-1.60 (m, 2H), 1.58-1.51 (m, 1H), 1.42-1.35 (m, 1H), 1.35-1.16 (m, 4H), 1.10-0.97 (m, 1H).

Intermediate BN

The title compound was prepared using analogous conditions to those described in Intermediate AU using 4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine. MS (ESI): mass calcd. for C 12 H 12 BrN 3 O 2 S 340.98, m/z found 341.9 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.15 (dd, J=7.8, 1.7, 1H), 7.71 (dd, J=7.9, 1.2, 1H), 7.47-7.42 (m, 1H), 7.41-7.36 (m, 1H), 7.33 (s, 1H), 4.45 (s, 2H), 3.66 (t, J=5.8, 2H), 2.83 (t, J=5.8, 2H).

Intermediate BO

The title compound was prepared using analogous conditions to those described in Intermediate AU using tert-butyl (azetidin-3-ylmethyl)carbamate. MS (ESI): mass calcd. for C 15 H 21 BrN 2 O 4 S 404.04, m/z found 349.0 [M-tBu+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.04 (dd. J=7.8, 1.8, 1H), 7.73 (dd, J=7.7, 1.3, 1H), 7.44-7.40 (m, 1H), 7.40-7.35 (m, 1H), 4.71 (s, 1H), 4.13-4.03 (m, 2H), 3.70 (dd, J=7.9, 5.4, 2H), 3.35-3.22 (m, 2H), 2.78-2.64 (m, 1H), 1.40 (s, 9H).

Intermediate BP

The title compound was prepared using analogous conditions to those described in Intermediate AU using tert-butyl 3-(aminomethyl)azetidine-1-carboxylate. 1 H NMR (600 MHz, CDCl 3 ) δ 8.12 (dd. J=7.8, 1.7, 1H), 7.73 (dd, J=7.8, 1.3, 1H), 7.50-7.45 (m, 1H), 7.45-7.39 (m, 1H), 5.42-5.30 (m, 1H), 3.96-3.85 (m, 2H), 3.52 (d, J=9.3, 2H), 3.17-3.02 (m, 2H), 2.69-2.54 (m, 1H), 1.39 (s, 9H).

Intermediate BQ

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-tert-butyl methyl(pyrrolidin-3-yl)carbamate. MS (ESI): mass calcd. for C 16 H 23 BrN 2 O 4 S 418.06, m/z found 441.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.08 (dd. J=7.9, 1.8, 1H), 7.73 (dd, J=7.8, 1.3, 1H), 7.46-7.40 (m, 1H), 7.40-7.34 (m, 1H), 4.80 (s, 1H), 3.61 (s, 1H), 3.51 (s, 1H), 3.38-3.30 (m, 1H), 3.19 (dd, J=9.9, 7.4, 1H), 2.73 (s, 3H), 2.12-2.03 (m, 1H), 2.03-1.93 (m, 1H), 1.41 (s, 9H).

Intermediate BR

The title compound was prepared using analogous conditions to those described in Intermediate AU using tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate. MS (ESI): mass calcd. for C 16 H 21 BrN 2 O 4 S 416.04, m/z found 439.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) 8.10 (dd, J=7.9, 1.8, 1H), 7.73 (dd, J=8.0, 1.2, 1H), 7.46-7.40 (m, 1H), 7.40-7.34 (m, 1H), 4.63-4.39 (m, 2H), 3.59-3.39 (m, 2H), 3.33-3.22 (m, 2H), 1.88-1.76 (m, 2H), 1.42 (d, J=5.0, 9H).

Intermediate BS

The title compound was prepared using analogous conditions to those described in Intermediate AU (1S,4S)-tert-butyl 2,5-diazabicyclo[2.2.]heptane-2-carboxylate.

Intermediate BT

The title compound was prepared using analogous conditions to those described in Intermediate AU using 4-(piperidin-4-yl)-1H-1,2,4-triazol-5(4H)-one. MS (ESI): mass calcd. for C 13 H 15 BrN 4 O 3 S 386.00, m/z found 387.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 9.63 (s, 1H), 8.10 (dd, J=7.8, 1.8, 1H), 7.75 (dd, J=7.9, 1.3, 1H), 7.49-7.43 (m, 1H), 7.43-7.37 (m, 2H), 4.05-3.97 (m, 3H), 2.97-2.89 (m, 2H), 2.09-2.03 (m, 2H), 1.89-1.79 (m, 2H).

›Step A: 4′-Bromo-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide · 6 of 6

Intermediate BU

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-3-aminopropane-1,2-diol.

Intermediate BV

The title compound was prepared using analogous conditions to those described in Intermediate AU using tert-butyl ((cis)-4-aminocyclohexyl)carbamate. MS (ESI): mass calcd. for C 17 H 25 BrN 2 O 4 S 432.07, m/z found 455.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.7, 1H), 7.72 (dd, J=7.8, 1.2, 1H), 7.48-7.43 (m, 1H), 7.43-7.38 (m, 1H), 5.17 (s, 1H), 4.45 (s, 1H), 3.47 (s, 1H), 3.30-3.20 (m, 1H), 1.66 (s, 2H), 1.60-1.49 (m, 4H), 1.45 (d, J=7.3, 1H), 1.41 (s, 9H).

Intermediate BW

The title compound was prepared using analogous conditions to those described in Intermediate AU using 5-aminopentan-1-ol. MS (ESI): mass calcd. for C 11 H 16 BrNO 3 S 321.00, m/z found 322.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) b 8.10 (dd. J=7.8, 1.7, 1H), 7.71 (dd, J=7.9, 1.3, 1H), 7.48-7.42 (m, 1H), 7.42-7.35 (m, 1H), 5.23 (t, J=6.3, 1H), 3.62-3.50 (m, 2H), 2.93-2.83 (m, 2H), 1.55 (s, 1H), 1.52-1.42 (m, 4H), 1.39-1.29 (m, 2H).

Intermediate BX

The title compound was prepared using analogous conditions to those described in Intermediate AU using 6-aminohexan-1-ol. MS (ESI): mass calcd. for C 12 H 18 BrNO 3 S 335.02, m/z found 336.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.11 (dd, J=7.8, 1.8, 1H), 7.71 (dd, J=7.9, 1.3, 1H), 7.48-7.42 (m, 1H), 7.42-7.36 (m, 1H), 5.15 (t, J=6.2, 1H), 3.57 (t, J=6.6, 2H), 2.94-2.81 (m, 2H), 1.56-1.35 (m, 5H), 1.33-1.21 (m, 4H).

Intermediate BY

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-indolin-2-ylmethanol. MS (ESI): mass calcd. for C 15 H 14 BrNO 3 S 366.99, m/z found 389.9 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.12 (dd, J=7.9, 1.7, 1H), 7.65 (dd, J=7.9, 1.3, 1H), 7.42-7.36 (m, 1H), 7.36-7.31 (m, 1H), 7.27 (d, J=8.1, 1H), 7.14-7.09 (m, 1H), 7.09-7.04 (m, 1H), 6.98-6.93 (m, 1H), 4.86-4.78 (m, 1H), 3.81-3.68 (m, 2H), 3.28 (dd, J=16.2, 9.6, 1H), 2.88-2.79 (m, 1H), 2.20 (s, 1H).

Intermediate BZ

The title compound was prepared using analogous conditions to those described in Intermediate AU using 2-(cyclohexylamino)ethanol. MS (ESI): mass calcd. for C 14 H 20 BrNO 3 S 361.03, m/z found 362.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.14 (dd. J=7.9, 1.7, 1H), 7.71 (dd, J=7.8, 1.3, 1H), 7.46-7.40 (m, 1H), 7.40-7.34 (m, 1H), 3.71 (m, 2H), 3.65-3.57 (m, 1H), 3.47 (t, J=6.1, 2H), 2.22 (t, J=5.9, 1H), 1.80-1.67 (m, 4H), 1.62-1.53 (m, 1H), 1.44-1.32 (m, 2H), 1.27-1.15 (m, 2H), 1.07-0.94 (m, 1H).

Intermediate CA

The title compound was prepared using analogous conditions to those described in Intermediate AU using racemic-azetidine-2-carboxamide. MS (ESI): mass calcd. for C 10 H 11 BrN 2 O 3 S 319.97, m/z found 319.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.11-8.07 (m, 1H), 7.83-7.79 (m, 1H), 7.53-7.46 (m, 2H), 6.91 (s, 1H), 5.53 (s, 1H), 4.75 (t, J=8.8, 1H), 4.02-3.94 (m, 1H), 3.75-3.67 (m, 1H), 2.49-2.39 (m, 2H).

Intermediate CB

›Step A: 1-[(2-Bromophenyl)sulfonyl]-4-{1-[(2-bromophenyl)sulfonyl]-1H-imidazol-4-yl}piperidine

To a 20 mL vial were added a stirbar, 4-(1H-imidazol-4-yl)piperidine.HCl (696 mg, 3.71 mmol), ACN (5 mL), and DIPEA (2.0 mL, 12 mmol). The mixture was then treated with 2-bromobenzene-1-sulfonyl chloride (900 mg, 3.52 mmol) and the mixture was stirred for 15.5 hours before concentrating to dryness and subjecting the residue to FCC to give the title compound (950 mg, 92%). MS (ESI): mass calcd. for C 20 H 19 Br 2 N 3 O 4 S 2 586.92 m/z found 587.9 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.20 (dd, J=7.9, 1.8, 1H), 8.08 (dd, J=7.8, 1.7, 1H), 8.06 (d, J=1.3, 1H), 7.75 (dd, J=7.7, 1.3, 1H), 7.72 (dd, J=7.9, 1.2, 1H), 7.58-7.53 (m, 1H), 7.53-7.49 (m, 1H), 7.45-7.40 (m, 1H), 7.39-7.34 (m, 1H), 6.93-6.91 (m, 1H), 3.90-3.82 (m, 2H), 2.93-2.83 (m, 2H), 2.68-2.59 (m, 1H), 2.02 (dd, J=13.9, 3.0, 2H), 1.70-1.59 (m, 2H).

›Step B · 1 of 3

To a 20 mL vial containing 1-[(2-bromophenyl)sulfonyl]-4-{1-[(2-bromophenyl)-sulfonyl]-1H-imidazol-4-yl}piperidine (884 mg, 1.50 mmol) were added a stirbar and DMSO (10 mL). Once the DMSO solution was homogeneous, LiOH (3 mL, 1.0 M) was added slowly. After 30 min the reaction mixture was diluted with EtOAc, washed with water (×4) and brine (×1), dried over MgSO 4 , filtered and concentrated to dryness to give the title compound (522 mg, 94%). MS (ESI): mass calcd. for C 14 H 16 BrN 3 O 2 S 369.01 m/z found 370.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.08 (dd, J=7.9, 1.7, 1H), 7.72 (dd, J=7.8, 1.3, 1H), 7.62 (s, 1H), 7.45-7.41 (m, 1H), 7.40-7.35 (m, 1H), 6.76 (s, 1H), 3.88 (d, J=12.8, 1H), 2.90 (m, 2H), 2.76-2.69 (m, 1H), 2.09-2.01 (m, 2H), 1.77-1.67 (m, 2H).

Intermediate CC

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-tert-butyl piperidin-3-ylcarbamate. MS (ESI): mass calcd. for C 16 H 23 BrN 2 O 4 S 418.06 m/z found 441.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.10-8.06 (m, 1H), 7.73 (dd, J=7.7, 1.3, 1H), 7.46-7.40 (m, 1H), 7.40-7.35 (m, 1H), 4.88 (d, J=8.5, 1H), 3.77 (s, 1H), 3.44 (s, 1H), 3.28 (d, J=11.8, 1H), 3.23-3.03 (m, 2H), 1.85-1.55 (m, 4H), 1.39 (s, 9H).

Intermediate CD

The title compound was prepared using analogous conditions to those described in Intermediate AU using 2,2′-azanediyldiethanol. MS (ESI): mass calcd. for C 10 H 14 BrNO 4 S 322.98 m/z found 324.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.10-8.05 (m, 1H), 7.74 (dd, J=7.8, 1.3, 1H), 7.47-7.42 (m, 1H), 7.42-7.37 (m, 1H), 3.83 (dd, J=7.3, 3.8, 4H), 3.48 (t, J=5.0, 4H), 3.38 (s, 2H).

Intermediate CE

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-tert-butyl 3-methylpiperazine-1-carboxylate. MS (ESI): mass calcd. for C 16 H 23 BrN 2 O 4 S 418.06 m/z found 319.0 [M-Boc+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.14 (dd, J=7.8, 1.8, 1H), 7.72 (dd, J=7.8, 1.3, 1H), 7.45-7.40 (m, 1H), 7.40-7.35 (m, 1H), 4.16-3.73 (m, 3H), 3.63-3.42 (m, 1H), 3.32-3.22 (m, 1H), 3.17-2.68 (m, 2H), 1.42 (s, 9H), 1.25-1.09 (m, 3H).

Intermediate CF

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-tert-butyl 3-methylpiperazine-1-carboxylate.

Intermediate CG

The title compound was prepared using analogous conditions to those described in Intermediate AU using 2-(isopropylamino)ethanol. MS (ESI): mass calcd. for C 11 H 16 BrNO 3 S 321.00 m/z found 322.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.15 (dd. J=7.9, 1.7, 1H), 7.71 (dd, J=7.9, 1.3, 1H), 7.46-7.41 (m, 1H), 7.39-7.34 (m, 1H), 4.01 (hept, J=6.7, 1H), 3.74 (m, 2H), 3.47 (t, J=6.1, 2H), 2.27 (t, J=5.8, 1H), 1.13 (d, J=6.8, 6H).

Intermediate CH

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate. MS (ESI): mass calcd. for C 16 H 23 BrN 2 O 5 S 434.05 m/z found 335.0 [M-Boc+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.16 (dd, J=7.8, 1.8, 1H), 7.73 (dd, J=7.9, 1.3, 1H), 7.47-7.42 (m, 1H), 7.42-7.37 (m, 1H), 4.32-3.43 (m, 6H), 3.27-3.15 (m, 1H), 3.15-2.66 (m, 3H), 1.44 (s, 9H).

Intermediate CI

The title compound was prepared using analogous conditions to those described in Intermediate AU using 2-amino-2-methylpropane-1,3-diol. 1 H NMR (600 MHz, CDCl 3 ) δ 8.14 (dd, J=7.8, 1.7, 1H), 7.73 (dd, J=7.9, 1.3, 1H), 7.48-7.43 (m, 1H), 7.43-7.37 (m, 1H), 5.93 (s, 1H), 3.72-3.56 (m, 4H), 2.53-2.44 (m, 2H), 0.93 (s, 3H).

Intermediate CJ

The title compound was prepared using analogous conditions to those described in Intermediate AU using endo-3-azabicyclo[3.1.0]hexan-6-amine. MS (ESI): mass calcd. for C 11 H 13 BrN 2 O 2 S 315.99 m/z found 317.0 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 7.97 (dd, J=7.7, 1.9, 1H), 7.88 (dd, J=7.7, 1.4, 1H), 7.62-7.58 (m, 1H), 7.58-7.54 (m, 1H), 3.42-3.38 (m, 2H), 3.37-3.29 (m, 4H), 2.02 (t, J=2.2, 1H), 1.46-1.41 (m, 2H).

Intermediate CK

The title compound was prepared using analogous conditions to those described in Intermediate AU using tert-butyl(2-aminoethyl)carbamate. 1 H NMR (600 MHz, CDCl 3 ) δ 8.10 (dd, J=7.7, 1.7, 1H), 7.71 (dd, J=7.9, 1.3, 1H), 7.47-7.43 (m, 1H), 7.43-7.37 (m, 1H), 5.66 (t, J=5.8, 1H), 4.86 (s, 1H), 3.21 (t, J=5.8, 2H), 3.03-2.95 (m, 2H), 1.40 (s, 9H).

Intermediate CL

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-2-amino-3-methylbutan-1-ol. 1 H NMR (600 MHz, CDCl 3 ) δ 8.11 (dd, J=7.8, 1.7, 1H), 7.72 (dd, J=7.9, 1.2, 1H), 7.47-7.42 (m, 1H), 7.41-7.36 (m, 1H), 5.35 (d, J=8.6, 1H), 3.63-3.54 (m, 1H), 3.54-3.43 (m, 1H), 3.11-3.01 (m, 1H), 1.88-1.75 (m, 2H), 0.86 (d, J=6.9, 3H), 0.80 (d, J=6.8, 3H).

Intermediate CM

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-2-amino-3,3-dimethylbutan-1-ol. MS (ESI): mass calcd. for C 12 H 18 BrNO 3 S 335.02 m/z found 336.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.09 (dd, J=7.9, 1.7, 1H), 7.71 (dd, J=7.9, 1.3, 1H), 7.46-7.41 (m, 1H), 7.40-7.35 (m, 1H), 5.40 (d, J=9.4, 1H), 3.66-3.55 (m, 2H), 3.11-3.01 (m, 1H), 1.81 (t, J=5.6, 1H), 0.85 (s, 9H).

Intermediate CN

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-2-amino-3,3-dimethylbutan-1-ol.

Intermediate CO

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-2-aminobutan-1-ol. MS (ESI): mass calcd. for C 10 H 14 BrNO 3 S 306.99 m/z found 308.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.11 (dd. J=7.8, 1.7, 1H), 7.72 (dd, J=7.9, 1.3, 1H), 7.47-7.42 (m, 1H), 7.42-7.37 (m, 1H), 5.41 (d, J=7.9, 1H), 3.59-3.46 (m, 2H), 3.19-3.10 (m, 1H), 2.15-1.99 (m, 1H), 1.56-1.38 (m, 2H), 0.78 (t, J=7.5, 3H).

Intermediate CP

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate. MS (ESI): mass calcd. for C 15 H 21 BrN 2 O 4 S 404.04 m/z found 427.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.17-8.11 (m, 1H), 7.77-7.69 (m, 1H), 7.51-7.45 (m, 1H), 7.45-7.39 (m, 1H), 5.38-5.29 (m, 1H), 3.87-3.75 (m, 1H), 3.46-3.32 (m, 2H), 3.32-3.21 (m, 1H), 3.16-3.05 (m, 1H), 2.05-1.68 (m, 2H), 1.39 (s, 9H).

›Step B · 2 of 3

Intermediate CQ

The title compound was prepared using analogous conditions to those described in Intermediate AU using (1S,2S)-1-amino-2,3-dihydro-1H-inden-2-ol. MS (ESI): mass calcd. for C 15 H 14 BrNO 3 S 366.99 m/z found 390.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.21 (dd, J=7.7, 1.8, 1H), 7.80 (dd, J=7.8, 1.3, 1H), 7.52-7.47 (m, 1H), 7.47-7.43 (m, 1H), 7.25-7.21 (m, 1H), 7.21-7.13 (m, 3H), 5.61 (d, J=6.8, 1H), 4.58-4.47 (m, 1H), 4.44-4.37 (m, 1H), 3.26 (dd, J=15.9, 7.7, 1H), 3.13 (d. J=2.7, 1H), 2.84-2.73 (m, 1H).

Intermediate CR

The title compound was prepared using analogous conditions to those described in Intermediate AU using (1R,2R)-1-amino-2,3-dihydro-1H-inden-2-ol.

Intermediate CS

The title compound was prepared using analogous conditions to those described in Intermediate AU using (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol.

Intermediate CT

The title compound was prepared using analogous conditions to those described in Intermediate AU using N-cyclopropyltetrahydro-2H-pyran-4-amine. MS (ESI): mass calcd. for C 14 H 18 BrNO 3 S 359.02 m/z found 392.0 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.16 (dd, J=7.9, 1.7, 1H), 7.69 (dd, J=7.9, 1.2, 1H), 7.47-7.40 (m, 1H), 7.40-7.34 (m, 1H), 4.40-4.30 (m, 1H), 4.05-3.96 (m, 2H), 3.52-3.39 (m, 2H), 2.34-2.25 (m, 1H), 2.16-2.06 (m, 2H), 1.85-1.75 (m, 2H), 0.64-0.56 (m, 2H), 0.54-0.46 (m, 2H).

Intermediate CU

The title compound was prepared using analogous conditions to those described in Intermediate AU using racemic morpholin-2-ylmethanol. MS (ESI): mass calcd. for C 11 H 14 BrNO 4 S 334.98 m/z found 357.9 [M+Na] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.06 (dd, J=7.8, 1.8, 1H), 7.74 (dd, J=7.8, 1.3, 1H), 7.47-7.42 (m, 1H), 7.42-7.36 (m, 1H), 3.93 (m, 1H), 3.70-3.58 (m, 5H), 3.58-3.51 (m, 1H), 2.94 (m, 1H), 2.77 (m, 1H), 1.96-1.83 (m, 1H).

Intermediate CV

The title compound was prepared using analogous conditions to those described in Intermediate AU using 2-aminopyrazine. MS (ESI): mass calcd. for C 10 H 8 BrN 3 O 2 S 312.95 m/z found 313.9 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 11.94 (s, 1H), 8.34 (s, 1H), 8.25-8.16 (m, 2H), 8.11 (dd, J=2.7, 1.5, 1H), 7.81 (dd, J=7.9, 1.2, 1H), 7.68-7.59 (m, 1H), 7.59-7.51 (m, 1H).

Intermediate CW

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-2-amino-4-methylpentanamide. MS (ESI): mass calcd. for C 12 H 17 BrN 2 O 3 S 348.01 m/z found 349.0 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.01 (dd, J=7.7, 1.8, 1H), 7.92 (d, J=8.3, 1H), 7.82 (dd, J=7.8, 1.3, 1H), 7.58-7.49 (m, 2H), 7.24 (d, J=2.3, 1H), 6.97 (d, J=2.2, 1H), 3.67-3.56 (m, 1H), 1.65-1.53 (m, 1H), 1.51-1.40 (m, 1H), 1.35-1.25 (m, 1H), 0.79 (d, J=6.6, 3H), 0.61 (d, J=6.5, 3H).

Intermediate CX

The title compound was prepared using analogous conditions to those described in Intermediate AU using 2-aminoacetamide. MS (ESI): mass calcd. for C 8 H 9 BrN 2 O 3 S 291.95 m/z found 293.0 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.00 (dd, J=7.7, 1.8, 1H), 7.88 (s, 1H), 7.84 (dd, J=7.8, 1.3, 1H), 7.59-7.54 (m, 1H), 7.54-7.50 (m, 1H), 7.27 (s, 1H), 7.13 (s, 1H), 3.51 (s, 2H).

Intermediate CY

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-2-amino-3-phenylpropanamide. MS (ESI): mass calcd. for C 15 H 15 BrN 2 O 3 S 382.00 m/z found 382.9 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 7.95 (d, J=8.8, 1H), 7.71-7.65 (m, 2H), 7.44-7.35 (m, 3H), 7.20-7.12 (m, 5H), 7.06 (d, J=2.2, 1H), 3.93 (m, 1H), 2.91 (dd, J=13.7, 4.9, 1H), 2.77 (dd, J=13.7, 9.4, 1H).

Intermediate CZ

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-2-aminopropanamide. MS (ESI): mass calcd. for C 9 H 11 BrN 2 O 3 S 305.97 m/z found 307.0 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.01 (dd, J=7.7, 1.8, 1H), 7.86 (d, J=5.2, 1H), 7.84 (dd, J=7.7, 1.3, 1H), 7.60-7.55 (m, 1H), 7.55-7.50 (m, 1H), 7.24 (s, 1H), 7.07 (s, 1H), 3.78-3.69 (m, 1H), 1.17 (d, J=7.1, 3H).

Intermediate DA

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-tert-butyl 3,4-diamino-4-oxobutanoate. MS (ESI): mass calcd. for C 14 H 19 BrN 2 O 5 S 406.02 m/z found 429.0 [M+Na] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.04-7.99 (m, 2H), 7.80 (dd, J=7.7, 1.3, 1H), 7.58-7.53 (m, 1H), 7.53-7.49 (m, 1H), 7.24 (s, 1H), 7.16 (s, 1H), 4.00 (m, 1H), 2.56-2.51 (m, 1H), 2.45-2.39 (m, 1H), 1.32 (s, 9H).

Intermediate DB

The title compound was prepared using analogous conditions to those described in Intermediate AU using (R)-2-amino-2-phenylacetamide. MS (ESI): mass calcd. for C 14 H 13 BrN 2 O 3 S 367.98 m/z found 369.0 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.20 (d, J=8.8, 1H), 7.91-7.86 (m, 1H), 7.76-7.71 (m, 1H), 7.58 (d, J=2.0, 1H), 7.49-7.43 (m, 2H), 7.35-7.29 (m, 2H), 7.26-7.20 (m, 4H), 4.94 (d, J=8.8, 1H).

Intermediate DC

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-tert-butyl-2-amino-3-methylbutanoate. 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.24 (d, J=9.6, 1H), 8.00 (dd, J=7.8, 1.7, 1H), 7.82 (dd, J=7.9, 1.3, 1H), 7.58-7.54 (m, 1H), 7.54-7.48 (m, 1H), 3.45 (dd, J=9.5, 7.1, 1H), 1.97 (h, J=6.8, 1H), 1.22 (s, 9H), 0.87 (d, J=6.7, 3H), 0.82 (d, J=6.8, 3H).

Intermediate DD

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-tert-butyl 2-aminopropanoate. MS (ESI): mass calcd. for C 13 H 18 BrNO 4 S 363.01 m/z found 386.0 [M+Na] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.36 (d, J=8.6, 1H), 7.99 (dd, J=7.8, 1.8, 1H), 7.83 (dd, J=7.8, 1.3, 1H), 7.58-7.53 (m, 1H), 7.53-7.49 (m, 1H), 3.87-3.78 (m, 1H), 1.30-1.21 (m, 12H).

Intermediate DE

The title compound was prepared using analogous conditions to those described in Intermediate AU using (S)-pyrrolidine-3-carboxamide. MS (ESI): mass calcd. for C 11 H 13 BrN 2 O 3 S 331.98, m/z found 333.0 [M+H]+; 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.05-7.97 (dd, J=7.7, 1.9, 1H), 7.92-7.85 (dd, J=7.7, 1.5, 1H), 7.64-7.53 (m, 2H), 7.43 (s, 1H), 6.96 (s, 1H), 3.57-3.50 (dd, J=9.5, 8.0, 1H), 3.46-3.39 (m, 1H), 3.37-3.27 (m, 2H), 3.02-2.94 (p, J=7.8, 1H), 2.12-2.02 (m, 1H), 2.02-1.91 (m, 1H).

›Step B · 3 of 3

Intermediate DF

The title compound was prepared using analogous conditions to those described in Intermediate AU using piperidine-4-carboxamide. MS (ESI): mass calcd. for C 12 H 15 BrN 2 O 3 S 346.00, m/z found 347.0 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.03-7.97 (dd, J=7.8, 1.8, 1H), 7.91-7.86 (dd, J=7.8, 1.3, 1H), 7.63-7.53 (m, 2H), 7.28 (s, 1H), 6.82 (s, 1H), 3.72-3.62 (m, 2H), 2.83-2.73 (m, 2H), 2.27-2.17 (m, 1H), 1.79-1.70 (m, 2H), 1.57-1.44 (m, 2H).

Intermediate DG

The title compound was prepared using analogous conditions to those described in Intermediate AU using 3-(trifluoromethyl)azetidin-3-ol. MS (ESI): mass calcd. for C 10 H 9 BrF 3 NO 3 S 358.94; m/z found 359.9 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.03-8.00 (m, 1H), 7.94-7.91 (dd, J=7.4, 1.7, 1H), 7.65-7.58 (m, 3H), 4.20-4.15 (m, 2H), 4.09-4.04 (m, 2H).

Intermediate DH

The title compound was prepared using analogous conditions to those described in Intermediate AU using N-methylazetidine-3-carboxamide. MS (ESI): mass calcd. for C 11 H 13 BrN 2 O 3 S 331.98; m/z found 333.0 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 ) δ 8.09-8.04 (dd, J=7.8, 1.8, 1H), 7.79-7.74 (dd, J=7.8, 1.3, 1H), 7.49-7.44 (m, 1H), 7.44-7.37 (m, 1H), 5.72 (s, 1H), 4.25-4.13 (m, 4H), 3.29-3.16 (m, 1H), 2.89-2.77 (d, J=4.8, 3H).

Intermediate DI

The title compound was prepared using analogous conditions to those described in Intermediate AU using 2-oxa-6-azaspiro[3.3]heptane. MS (ESI): mass calcd. for C 11 H 12 BrNO 3 S 316.97; m/z found 317.9 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.00-7.96 (m, 1H), 7.91-7.88 (m, 1H), 7.63-7.56 (m, 2H), 4.62 (s, 4H), 4.11 (s, 4H).

Intermediate DJ

The title compound was prepared using analogous conditions to those described in Intermediate AU using 2-thia-6-azaspiro[3.3]heptane 2,2-dioxide. MS (ESI): mass calcd. for C 11 H 12 BrNO 4 S 2 364.94; m/z found 365.9 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.02-7.98 (m, 1H), 7.93-7.89 (m, 1H), 7.64-7.58 (m, 2H), 4.46 (s, 4H), 4.17 (s, 4H).

Intermediate DL

To a solution of 2-bromoaniline (344 mg, 2.0 mmol) in pyridine (5 mL) was slowly added ethyl-sulfonyl chloride (257 mg, 2.0 mmol) at rt and the mixture was stirred at rt for 16 hours. The pyridine was removed under reduced pressure and resulting residue diluted with water (30 mL) and extracted with DCM (10 mL×2). The combined organic extracts were washed with brine, dried over Na 2 SO 4 , filtered and concentrated to dryness. The residue was purified by FCC to give the title compound (240 mg, 45%). MS (ESI): mass calcd. for C 8 H 10 BrNO 2 S 262.96 m/z found 264.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) 7.71 (dd, J=4.8, 1.5, 1H), 7.59 (dd, J=4.8, 1.5, 1H), 7.32-7.28 (m, 1H), 7.08-7.05 (m, 1H), 6.77 (bs, 1H), 3.14 (q, J=7.2, 2H), 1.41 (t, J=7.5, 3H).

Intermediate DM

The title compound was prepared using analogous conditions described for Intermediate DL utilizing n-propylsulfonyl chloride. MS (ESI): mass calcd. for C 9 H 12 BrNO 2 S, 276.98; m/z found, 278.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 7.70 (dd, J=4.8, 1.5, 1H), 7.59 (dd, J=4.8, 1.5, 1H), 7.32-7.28 (m, 1H), 7.08-7.05 (m, 1H), 6.72 (br s, 1H), 3.15-2.94 (m, 2H), 1.93-1.73 (m, 2H), 1.00 (t, J=7.4, 3H).

Intermediate DN

The title compound was prepared using analogous conditions described for Intermediate DL utilizing iso-butylsulfonyl chloride. MS (ESI): mass calcd. for C 10 H 14 BrNO 2 S, 290.99; m/z found, 292.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 7.69 (dd, J=4.8, 1.5, 1H), 7.59 (dd, J=4.8, 1.5, 1H), 7.32-7.28 (m, 1H), 7.08-7.05 (m, 1H), 6.77 (br s, 1H), 2.99 (d, J=4.2, 2H), 2.38-2.25 (m, 1H), 1.07 (d, J=6.9, 6H).

Intermediate DO

›Step A: Sodium (2-bromophenyl)methanesulfonate

A mixture of 1-bromo-2-(bromomethyl)benzene (20 g, 0.08 mol) and Na 2 SO 3 (15 g, 0.12 mol) in methanol/H 2 O (100 mL/100 mL) was stirred at 85° Celsius for 2.5 hours, concentrated to dryness and dried to give sodium (2-bromophenyl)methanesulfonate (34 g, crude). 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.54 (m, 2H), 7.27 (m, 1H), 7.12 (m, 1H), 3.91 (s, 2H).

›Step B: (2-Bromophenyl)methanesulfonyl chloride

To a suspension of crude sodium (2-bromophenyl)methanesulfonate (34 g) in toluene (500 mL) was added PCl 5 (34 g, 0.16 mol). The resulting mixture was stirred at 100° Celsius for 4 hours before concentrating to dryness and pouring the residue onto crushed ice (150 g), stirring for 5 min, and extracting with DCM (3×50 mL). The combined organic extracts were dried over MgSO 4 , filtered and concentrated to dryness to give (2-bromophenyl)methanesulfonyl chloride (16.8 g, 77%). 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.62-7.45 (m, 2H), 7.29 (m, 1H), 7.18-7.01 (m, 1H), 3.97 (s, 2H).

›Step C

To a solution of (2-bromophenyl)methanesulfonyl chloride (2 g, 7 mmol) in THF (15 mL) was added CH 3 NH 2 /H 2 O (25%, 2 g, 20 mmol) at 0° Celsius. The resulting mixture was warmed up to rt, stirred for 16 hours, concentrated to dryness and purified by HPLC to give the title compound (0.8 g, 41%). MS (ESI): mass calcd. for C 8 H 8 BrO 2 S, 262.96; m/z found, 264.0 [M+H] + ; 1 H NMR (300 MHz, CDCl 3 ) δ 7.65-7.54 (m, 2H), 7.35 (m, 1H), 7.22 (dd, J=7.6, 1.7, 1H), 4.53 (s, 2H), 4.10 (s, 1H), 2.72 (s, 3H).

Intermediate DP

The title compound was prepared using analogous conditions described for Intermediate DO utilizing ethylamine. MS (ESI): mass calcd. for C 9 H 12 BrNO 2 S, 276.98; m/z found, 277.9 [M+H] + ; 1 H NMR (300 MHz, CD 3 OD) δ 7.64 (dd, J=8.0, 1.0, 1H), 7.57 (dd, J=7.6, 1.6, 1H), 7.37 (m, 1H), 7.25 (m, 1H), 4.54 (s, 2H), 3.03 (q, J=7.2, 2H), 1.12 (t, J=7.2, 3H).

Intermediate DQ

The title compound was prepared using analogous conditions described for Intermediate DO utilizing ethanolamine. MS (ESI): mass calcd. for C 9 H 12 BrNO 3 S, 292.97; m/z found, 294.0 [M+H] + ; 1 H NMR (300 MHz, CDCl 3 ) δ 7.69-7.52 (m, 2H), 7.35 (m, 1H), 7.26-7.19 (m, 1H), 4.77 (t, J=6, 1H), 4.56 (s, 2H), 3.65 (t, J=6, 2H), 3.12 (t, J=6, 2H), 2.13 (br s, 1H).

Intermediate DR

The title compound was prepared using analogous conditions described for Intermediate DO utilizing (S)-3-amino-2-propanol. The product was isolated as a x. MS (ESI): mass calcd. for C 7 H 4 BrF 3 O 2 S, 306.99; m/z found, 307.9 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 7.69-7.52 (m, 2H), 7.35 (m, 1H), 7.29-7.20 (m, 1H), 4.67 (s, 1H), 3.96-3.76 (m, 1H), 3.17-2.96 (m, 1H), 2.95-2.74 (m, 1H), 1.90-1.63 (m, 2H), 1.15 (d, J=6.3, 3H).

Intermediate DS

The title compound was prepared using analogous conditions described for Intermediate DO utilizing (R)-3-amino-2-propanol.

Intermediate DT

The title compound was prepared using analogous conditions described for Intermediate DO using ammonia. 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.65 (d, J=7.9, 1H), 7.52 (dd, J=7.6, 1.6, 1H), 7.41 (m, 1H), 7.28 (m, 1H), 7.04 (s, 2H), 4.46 (s, 2H).

Intermediate DU

The title compound was prepared using analogous conditions described for Intermediate DO utilizing piperazin-2-one. The product was isolated as a white solid. MS (ESI): mass calcd. for C 11 H 13 BrN 2 O 3 S, 331.98; m/z found, 333.0 [M+H]+; 1 H NMR (300 MHz, CDCl 3 ) δ 7.68-7.57 (m, 2H), 7.37 (m, 1H), 7.29-7.21 (m, 1H), 6.93 (s, 1H), 4.55 (s, 2H), 3.90 (s, J=18.1, 2H), 3.43-3.17 (m, 4H).

Intermediate DV

The title compound was prepared using analogous conditions described for Intermediate DO utilizing trans-4-aminocyclohexanol. The product was isolated as a white solid. MS (ESI): mass calcd. for C 7 H 4 BrF 3 O 2 S, 347.02; m/z found, 348.0 [M+H] + . 1 H NMR (300 MHz, CD 3 OD) δ 7.70-7.56 (m, 2H), 7.37 (m, 1H), 7.26 (m, 1H), 4.55 (s, 2H), 3.54-3.42 (m, 1H), 3.10-2.93 (m, 1H), 2.05-1.82 (m, 4H), 1.40-1.16 (m, 4H).

Intermediate DW

The title compound was prepared using analogous conditions described for Intermediate DO utilizing tert-butyl piperazine-1-carboxylate. The product was isolated as a white solid. MS (ESI): mass calcd. for C 17 H 25 BrN 2 O 4 S, 432.07; m/z found, 454.9 [M+Na] + . 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.67 (dd, J=7.9, 1.2, 1H), 7.52 (dd, J=7.7, 1.7, 1H), 7.41 (m, 1H), 7.36-7.26 (m, 1H), 6.92 (d, J=7.8, 1H), 4.51 (s, 2H), 3.50 (d, J=12.2, 2H), 3.45-3.35 (m, 1H), 2.92 (t, J=11.3, 2H), 1.77 (d, J=12.5, 2H), 1.45-1.30 (m, 11H).

Intermediate DX

›Step A: 1-(2-Bromobenzylsulfonyl)piperidin-4-amine.HCl

A mixture of tert-butyl (1-((2-bromobenzyl)sulfonyl)piperidin-4-yl)carbamate (500 mg, 1.15 mmol) in HCl methanol (6 N, 20 mL) was stirred at rt for 24 hours, and then concentrated to dryness to give 1-(2-bromobenzylsulfonyl)piperidin-4-amine.HCl (400 mg, 94%), which was directly used for next step without any further purification. MS (ESI): mass calcd. for C 14 H 19 BrN 2 O 3 S, 332.02; m/z found, 332.9 [M+H] + .

›Step B

To a mixture of 1-(2-bromobenzylsulfonyl)piperidin-4-amine.HCl (200 mg, 0.54 mmol) and Et 3 N (164 mg, 1.62 mmol) in dry DCM (20 mL) was added acetyl chloride (85 mg, 1.1 mmol) drop-wise at rt. The reaction mixture was stirred at rt for 2 hours before concentrating to dryness and purifying the residue by HPLC to give the title compound (180 mg, 89%). MS (ESI): mass calcd. for C 14 H 19 BrN 2 O 3 S, 374.03; m/z found, 374.8 [M+H] + .

Intermediate DY

To a mixture of 1-(2-bromobenzylsulfonyl)piperidin-4-amine.HCl (200 mg, 0.54 mmol) and Et 3 N (164 mg, 1.62 mmol) in dry THF (20 mL) was added (COCl 2 ) 3 (160 mg, 0.54 mmol) at rt. The reaction mixture was stirred at rt for 1 hour, and then a solution of NH 3 in THF (4 N, 10 mL) was added drop-wise. The resulting mixture was stirred at rt for 5 hours, concentrated to dryness and purified by HPLC to give the title compound (140 mg, 69%). MS (ESI): mass calcd. for C 13 H 18 BrN 3 O 3 S, 375.03; m/z found, 376.0 [M+H] + .

Intermediate DZ

The title compound was prepared using analogous conditions described for Intermediate DO utilizing 3-hydroxyazetidine. The product was isolated as a white solid. MS (ESI): mass calcd. for C 7 H 4 BrF 3 O 2 S, 304.97; m/z found 306.0 [M+H] + ; 1 H NMR (300 MHz, CDCl 3 ) δ 7.59 (dd, J=17.3, 7.8, 2H), 7.33 (m, 1H), 7.24-7.17 (m, 1H), 4.61-4.37 (m, 3H), 4.04-3.90 (m, 2H), 3.87-3.75 (m, 2H), 2.13 (br s, 1H).

Intermediate EA

To a 50 mL round-bottomed flask were added a stirbar, water (3.5 mL) and H 2 SO 4 (5.0 mL, 18 M). The flask was then cooled to approximately −10° Celsius and treated with t-BuOH (0.70 mL, 7.5 mmol) followed by 2-bromo-thiophenol (0.60 mL, 5.0 mmol) (drop-wise over three minutes). The resulting mixture was stirred for 24 hours with gradual warming to rt. The reaction mixture was then added to a separatory funnel containing Et 2 O and sat. NaHCO 3 . The layers were mixed thoroughly and then separated. The organic layer was washed with 1 N NaOH, dried over MgSO 4 , filtered and concentrated to dryness. The resulting residue was subjected to FCC gave the title compound (686 mg, 56%). 1 H NMR (500 MHz, DMSO-d 6 ) δ 7.75 (dd, J=7.8, 1.4, 1H), 7.68 (dd, J=7.6, 1.6, 1H), 7.43-7.37 (m, 1H), 7.36-7.29 (m, 1H), 1.28 (s, 9H).

Intermediate EB

To a 20 mL vial containing 411 mg (1.43 mmol) 2-bromophenyl)(tert-butyl)sulfane were added DCM (6.0 mL) and a stirbar. The vial was cooled to 0° Celsius and then charged with m-CPBA (77%, 922 mg, 4.43 mmol). The resultant mixture was stirred for 22 hours with gradual warming to rt. The mixture was diluted with EtOAc, washed with aq Na 2 S 2 O 3 followed by 1 N NaOH, dried over MgSO 4 , filtered and concentrated to dryness. The residue was subjected to FCC to give the title compound (304 mg, 77%). 1 H NMR (500 MHz, CDCl 3 ) δ 8.09-8.02 (dd, J=7.9, 1.8, 1H), 7.79-7.74 (dd, J=7.9, 1.3, 1H), 7.50-7.45 (m, 1H), 7.45-7.39 (m, 1H), 1.42-1.37 (s, 9H).

Intermediate EC

›Step A: (2-Bromophenyl)(3-(methylthio)propyl)sulfane

To a solution of 1-bromo-3-chloropropane (1.2 mL, 12.0 mmol), DIPEA (2.1 mL, 12.0 mmol) in DCM (50 mL) was added 2-bromobenzenethiol (1.08 mL, 6.0 mmol) at 5° Celsius. The reaction mixture was warmed to rt and stirred for 4 hours. The reaction mixture was concentrated to dryness and the residue dissolved in ethanol (50 mL) and treated with NaSCH 3 (1.26 g, 18.0 mmol). The resulting mixture was stirred at rt for 18 h. The ethanol was then removed under reduced pressure and the residue taken up in DCM (100 mL) and washed with water (3×20 mL). The organic phase was dried over Na 2 SO 4 , filtered and concentrated to dryness to give (2-bromophenyl)(3-(methylthio)propyl)sulfane (2.3 g, crude).

›Step B · 1 of 5

The procedure to make 1-bromo-2-(3-(methylsulfonyl)propylsulfonyl)benzene is analogous to the one used to make Intermediate EB utilizing (2-bromophenyl)(3-(methylthio)propyl)sulfane. MS (ESI): mass calcd. for C 10 H 13 BrO 4 S 2 , 339.94; m/z found, 340.9 [M+H] + ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.19-8.12 (m, 1H), 7.83-7.75 (m, 1H), 7.59-7.46 (m, 2H), 3.65 (t, J=7.1, 2H), 3.34-3.23 (m, 2H), 2.94 (s, 3H), 2.43-2.30 (m, 2H).

Intermediate ED

To a suspension of NaH (135 mg, 3.40 mmol, 60% in mineral oil) in anhydrous DMF (5 mL) was added 2-bromobenzenethiol (580 mg, 3.10 mmol) drop-wise at rt. After the resultant mixture was stirred at 20° Celsius for 10 min, bromoethane (670 mg, 6.10 mmol) was slowly added into the mixture. The reaction mixture was stirred at 30° Celsius for 14 hours in an oil bath. The reaction was diluted with water (60 mL) and extracted with petroleum ether (20 mL×2). The combined organic extracts were washed with brine, dried over Na 2 SO 4 , filtered, and concentrated to dryness. The residue was dissolved in a mixture of methanol (10 mL) and water (15 mL) then treated with oxone (10 g, 15 mmol) portion-wise. The reaction mixture was stirred at 80° Celsius for 16 hours. The mixture was cooled to rt and the methanol removed. The remaining aqueous mixture was further diluted with water (50 mL) and extracted with DCM (20 mL×2). The combined organic extracts were washed with brine, dried over Na 2 SO 4 , filtered, concentrated to dryness and purified by FCC to give the title compound (570 mg, 75%). 1 H NMR (300 MHz, CDCl 3 ) δ 8.18-8.12 (m, 1H), 7.76 (dd, J=7.8, 1.5, 1H), 7.52-7.43 (m, 2H), 3.46 (q, J=7.5, 2H), 1.26 (t, J=7.5, 3H).

Intermediate EE

The title compound was prepared using analogous conditions described for Intermediate ED utilizing 1-bromopropane. MS (ESI): mass calcd. for C 9 H 11 BrO 2 S, 261.97; m/z found, 263.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ8.15 (dd, J=7.8, 2.1, 1H), 7.78-7.74 (m, 1H), 7.54-7.42 (m, 2H), 3.45-3.37 (m, 2H), 1.80-1.67 (m, 2H), 1.02 (t. J=7.5, 3H).

Intermediate EF

The title compound was prepared using analogous conditions described for Intermediate ED utilizing 1-bromohexane. MS (ESI): mass calcd. for C 12 H 17 BrO 2 S, 304.01; m/z found, 305.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 8.20-8.12 (m, 1H), 7.82-7.73 (m, 1H), 7.58-7.44 (m, 2H), 3.49-3.38 (m, 2H), 1.77-1.63 (m, 2H), 1.43-1.24 (m, 6H), 0.86 (t, J=6.6, 3H).

Intermediate EG

The title compound was prepared using analogous conditions described for Intermediate ED utilizing isopropyl bromide. MS (ESI): mass calcd. for C 9 H 11 BrO 2 S, 261.97; m/z found, 263.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 8.14-8.10 (m, 1H), 7.77-7.72 (m, 1H), 7.50-7.43 (m, 2H), 3.93-3.83 (m, 1H), 1.30 (d, J=6.9, 6H).

Intermediate EH

The title compound was prepared using analogous conditions described for Intermediate ED utilizing isobutyl bromide. MS (ESI): mass calcd. for C 10 H 13 BrO 2 S, 275.98; m/z found, 277.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 8.19-8.14 (m, 1H), 7.78-7.73 (m, 1H), 7.55-7.42 (m, 2H), 3.34 (d, J=6.6, 2H), 2.30-2.19 (m, 1H), 1.07 (d, J=6.6, 6H).

Intermediate EI

The title compound was prepared using analogous conditions described for Intermediate ED utilizing bromocyclopropane. MS (ESI): mass calcd. for C 9 H 9 BrO 2 S, 259.95; m/z found, 261.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 8.11-8.04 (m, 1H), 7.76 (dd, J=7.8, 1.5, 1H), 7.52-7.43 (m, 2H), 3.22-3.14 (m, 1H), 1.36-1.31 (m, 2H), 1.08-1.03 (m, 2H).

Intermediate EJ

The title compound was prepared using analogous conditions described for Intermediate ED utilizing bromocyclobutane. MS (ESI): mass calcd. for C 10 H 11 BrO 2 S, 273.97; m/z found, 275.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 2.1, 1H), 7.73 (dd, J=7.8, 1.5, 1H), 7.53-7.38 (m, 2H), 4.46 (p, J=8.1, 1H), 2.65-2.46 (m, 2H), 2.25-2.12 (m, 2H), 2.08-1.98 (m, 2H).

Intermediate EK

The title compound was prepared using analogous conditions described for Intermediate ED utilizing bromocyclopentane. MS (ESI): mass calcd. for C 11 H 13 BrO 2 S, 287.98; m/z found, 289.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 8.20-8.10 (m, 1H), 7.80-7.72 (m, 1H), 7.58-7.39 (m, 2H), 4.27-4.12 (m, 1H), 2.12-1.97 (m, 2H), 1.93-1.75 (m, 4H), 1.70-1.57 (m, 2H).

Intermediate EL

The title compound was prepared using analogous conditions described for Intermediate ED utilizing trifluoroiodomethane. MS (ESI): mass calcd. for C 7 H 4 BrF 3 O 2 S, 287.91; m/z found, 289.1 [M+H] + . 1 H NMR (300 MHz, CDCl 3 ) δ 8.15-8.07 (m, 1H), 7.80-7.72 (m, 1H), 7.52-7.43 (m, 2H).

Intermediate EM

To a solution of 2-aminophenylboronic acid hydrochloride (347 mg, 2.0 mmol) in pyridine (5 mL) was slowly added chlorosulfonylisopropane (300 mg, 2.1 mmol). The mixture was stirred below 20° Celsius for 14 hours, concentrated to dryness and the residue purified by FCC to give the title compound (280 mg, 57% yield). 1 H NMR (300 MHz, D 2 O+DMSO-d 6 ) δ 8.57-8.55 (m, 1H), 7.82-7.79 (m, 1H), 7.49-7.46 (m, 1H), 7.40-7.37 (m, 2H), 7.08-7.05 (m, 1H), 3.31-3.27 (m, 1H), 1.26 (d, J=6.9, 6H).

Intermediate EN

A solution of 2-bromobenzene-1-sulfonyl chloride (0.300 g, 1.17 mmol) and 3,3-difluoropyrrolidine hydrochloride (0.169 g, 1.17 mmol) in pyridine (5 mL) was stirred for 16 hours at 60° Celsius. The reaction was then cooled to rt, diluted with EtOAc (25 mL), washed with 1 N HCl (2×25 mL), and brine (50 mL). The organic layer was isolated, dried over MgSO 4 , filtered and concentrated to dryness to yield the title compound (0.335 g, 86%), The product was used without further purification. 1 H NMR (500 MHz, CDCl 3 ) δ 8.13-8.09 (m, 1H), 7.80-7.76 (m, 1H), 7.50-7.41 (m, 2H), 3.74 (t, J=12.8, 2H), 3.67 (t, J=7.2, 2H), 2.44-2.35 (m, 2H).

Intermediate EO

The title compound was prepared in a manner similar to that described in Intermediate EN using 4,4-difluoropiperidine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.13-8.11 (m, 1H), 7.78-7.75 (m, 1H), 7.50-7.45 (m, 1H), 7.44-7.39 (m, 1H), 3.53-3.44 (m, 4H), 2.12-2.03 (m, 4H).

Intermediate EP

The title compound was prepared in a manner similar to that described in Intermediate EN using piperazine.

›Step B · 2 of 5

Intermediate EQ

The title compound was prepared in a manner similar to that described in Intermediate EN using 3,3-difluoropiperidine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.14-8.11 (m, 1H), 7.77-7.74 (m, 1H), 7.49-7.44 (m, 1H), 7.44-7.39 (m, 1H), 3.54 (t, J=11.2, 2H), 3.32 (t, J=5.5, 2H), 2.04-1.94 (m, 2H), 1.91-1.85 (m, 2H).

Intermediate ER

The title compound was prepared in a manner similar to that described in Intermediate EN using 3,3-difluoroazetidine. 1 H NMR (500 MHz, CDCl 3 ) 8.11-8.06 (m, 1H), 7.80-7.76 (m, 1H), 7.50-7.42 (m, 2H), 4.42 (t, J=12.1, 4H).

Intermediate ES

The title compound was prepared in a manner similar to that described in Intermediate EN using azepane.

Intermediate ET

The title compound was prepared in a manner similar to that described in Intermediate EN using 4-(trifluoromethyl)piperidin-4-ol.

Intermediate EU

A solution of 2-bromobenzene-1-sulfonyl chloride (50 mg, 0.20 mmol), tert-butyl piperidin-4-ylcarbamate (49 mg, 0.25 mmol), and diisopropylethyl amine (0.101 mL, 0.59 mmol) in CH 2 Cl 2 was stirred for 90 min at rt. The reaction mixture was then concentrated to dryness to give the title compound in quantitative yield. The product was used without further purification.

Intermediate EV

The title compound was prepared in a manner similar to that described in Intermediate EU using racemic tert-butyl piperidin-3-ylcarbamate. 1 H NMR (400 MHz, CDCl 3 ) δ 8.12-8.09 (m, 1H), 7.77-7.74 (m, 1H), 7.48-7.38 (m, 2H), 4.91 (d, J=8.0, 1H), 3.79 (s, 1H), 3.45 (s, 1H), 3.32 (d, J=12.4, 1H), 3.23-3.07 (m, 2H), 1.86-1.59 (m, 4H), 1.45 (s, 9H).

Intermediate EW

A solution of racemic tert-butyl (1-((2-bromophenyl)sulfonyl)piperidin-3-yl)carbamate (82 mg, 0.20 mmol) in CH 2 Cl 2 (5 mL) was treated with 2 N HCl/Et 2 O (1 mL, 2 mmol) and stirred 16 hours at rt. The reaction mixture was then concentrated to dryness to give the title compound in quantitative yield. The product was used without further purification.

Intermediate EX

The title compound was prepared in a manner similar to that described in Intermediate EW using tert-butyl (1-((2-bromophenyl)sulfonyl)piperidin-4-yl)carbamate.

Intermediate EY

The title compound was prepared in a manner similar to that described in Intermediate EU using 1-(methylsulfonyl)piperazine.

Intermediate EZ

The title compound was prepared in a manner similar to that described in Intermediate EU using 1-(piperazin-1-yl)ethanone.

Intermediate FA

The title compound was prepared in a manner similar to that described in Intermediate EU using cyclopropyl(piperazin-1-yl)methanone.

Intermediate FB

The title compound was prepared in a manner similar to that described in Intermediate EU using 2-(piperazin-1-yl)ethanol.

Intermediate FC

The title compound was prepared in a manner similar to that described in Intermediate EU using 1-cyclopropylpiperazine.

Intermediate FD

The title compound was prepared in a manner similar to that described in Intermediate EU using racemic-octahydropyrrolo[1,2-a]pyrazine.

Intermediate FE

The title compound was prepared in a manner similar to that described in Intermediate EU using piperazin-2-one.

Intermediate FF

The title compound was prepared in a manner similar to that described in Intermediate EU using racemic-piperidine-3-carbonitrile.

Intermediate FG

The title compound was prepared in a manner similar to that described in Intermediate EU using piperidine-4-carbonitrile.

Intermediate FH

The title compound was prepared in a manner similar to that described in Intermediate EU using 1-methylpiperazine.

Intermediate FI

A solution of 2-bromobenzene-1-sulfonyl chloride (0.500 g, 1.96 mmol), 4-acetamidopiperidine (0.335 g, 2.45 mmol), and diisopropylethyl amine (1.0 mL, 5.8 mmol) in CH 2 Cl 2 (5 mL) was stirred for 15 min at rt. The reaction mixture was then washed with 1 N HCl (2×5 mL) followed by brine (10 mL). The organic layer was isolated, dried over MgSO 4 , filtered, and concentrated to dryness to give the title compound (0.672 g, 95%). The product was used without further purification. 1 H NMR (400 MHz, CDCl 3 ) δ 8.09-8.05 (m, 1H), 7.77-7.74 (m, 1H), 7.49-7.38 (m, 2H), 6.08 (d, J=8.0, 1H), 3.87-3.79 (m, 2H), 2.93-2.85 (m, 2H), 2.00-1.93 (m, 5H), 1.59-1.51 (m, 3H).

Intermediate FJ

The title compound was prepared in a manner similar to that described in Intermediate FI using piperidin-4-ol. 1 H NMR (400 MHz, CDCl 3 ) δ 8.11-8.07 (m, 1H), 7.77-7.73 (m, 1H), 7.48-7.36 (m, 2H), 3.92-3.84 (m, 1H), 3.65-3.55 (m, 2H), 3.18-3.11 (m, 2H), 1.99-1.88 (m, 2H), 1.69-1.59 (m, 2H).

Intermediate FK

The title compound was prepared in a manner similar to that described in Intermediate FI using piperidin-4-ylmethanol. 1 H NMR (400 MHz, CDCl 3 ) δ 8.11-8.07 (m, 1H), 7.76-7.73 (m, 1H), 7.47-7.36 (m, 2H), 3.90-3.84 (m, 2H), 3.50 (d, J=6.4, 2H), 2.82-2.73 (m, 2H), 1.79-1.84 (m, 2H), 1.67-1.56 (m, 1H), 1.37-1.24 (m, 2H).

Intermediate FL

The title compound was prepared in a manner similar to that described in Intermediate FI using 2-(piperidin-4-yl)ethanol. 1 H NMR (400 MHz, CDCl 3 ) δ 8.10-8.06 (m, 1H), 7.76-7.72 (m, 1H), 7.47-7.36 (m, 2H), 3.86-3.79 (m, 2H), 3.68 (t, J=6.3, 2H), 2.80-2.72 (m, 2H), 1.78-1.71 (m, 2H), 1.56-1.51 (m, 3H), 1.37-1.23 (m, 2H).

Intermediate FM

The title compound was prepared in a manner similar to that described in Intermediate FI using racemic piperidin-3-ol. 1 H NMR (400 MHz, CDCl 3 ) δ 8.13-8.09 (m, 1H), 7.77-7.73 (m, 1H), 7.50-7.37 (m, 2H), 3.89-3.82 (m, 1H), 3.57-3.51 (m, 1H), 3.40-3.32 (m, 1H), 3.24-3.16 (m, 1H), 3.06-3.00 (m, 1H), 2.16 (s, 1H), 1.94-1.80 (m, 2H), 1.70-1.50 (m, 2H).

Intermediate FN

The title compound was prepared in a manner similar to that described in Intermediate FI using racemic piperidin-3-ylmethanol. 1 H NMR (400 MHz, CDCl 3 ) δ 8.11-8.07 (m, 1H), 7.76-7.72 (m, 1H), 7.47-7.36 (m, 2H), 3.76-3.51 (m, 4H), 3.02-2.94 (m, 1H), 2.83-2.75 (m, 1H), 1.94-1.84 (m, 1H), 1.82-1.71 (m, 3H), 1.67-1.57 (m, 1H), 1.29-1.17 (m, 1H).

Intermediate FO

The title compound was prepared in a manner similar to that described in Intermediate FI using racemic 2-(piperidin-3-yl)ethanol. 1 H NMR (400 MHz, CDCl 3 ) δ 8.10-8.06 (m, 1H), 7.76-7.72 (m, 1H), 7.47-7.36 (m, 2H), 3.72-3.62 (m, 4H), 2.88-2.80 (m, 1H), 2.60-2.53 (m, 1H), 1.89-1.39 (m, 7H), 1.16-1.03 (m, 1H).

›Step B · 3 of 5

Intermediate FP

The title compound was prepared in a manner similar to that described in Intermediate FI using thiomorpholine 1,1-dioxide. 1 H NMR (400 MHz, CDCl 3 ) δ 8.17-8.11 (m, 1H), 7.81-7.76 (m, 1H), 7.53-7.43 (m, 2H), 3.92-3.86 (m, 4H), 3.24-3.13 (m, 4H).

Intermediate FQ

The title compound was prepared in a manner similar to that described in Intermediate FI using (1S,2S)-2-amino-1-phenylpropane-1,3-diol.

Intermediate FR

The title compound was prepared in a manner similar to that described in Intermediate FI using (S)-2-amino-4-methylpentan-1-ol.

Intermediate FS

The title compound was prepared in a manner similar to that described in Intermediate FI using 3-aminopropan-1-ol

Intermediate FT

The title compound was prepared in a manner similar to that described in Intermediate FI using (S)-2-amino-2-phenylethanol.

Intermediate FU

The title compound was prepared in a manner similar to that described in Intermediate FI using (R)-2-amino-2-phenylethanol

Intermediate FV

The title compound was prepared in a manner similar to that described in Intermediate FI using (1R,2S)-2-amino-1-phenylpropan-1-ol.

Intermediate FW

The title compound was prepared in a manner similar to that described in Intermediate FI using (2S,3S)-2-amino-3-methylpentan-1-ol.

Intermediate FX

The title compound was prepared in a manner similar to that described in Intermediate FI using (1R,2R)-2-aminocyclohexanol.

Intermediate FY

The title compound was prepared in a manner similar to that described in Intermediate FI using (1S,2R)-2-aminocyclohexanol

Intermediate FZ

The title compound was prepared in a manner similar to that described in Intermediate FI using (R)-2-aminobutan-1-ol.

Intermediate GA

A solution of 2-bromobenzene-1-sulfonyl chloride (100 mg, 0.39 mmol), 2,6-dimethylpiperazine (56 mg, 0.49 mmol), and diisopropylethyl amine (0.202 mL, 1.17 mmol) in CH 2 Cl 2 (2.5 mL) was allowed to stir for 15 min at rt. The reaction mixture was then directly subjected to FCC purification to give the title compound (0.105 g, 81%). 1 H NMR (600 MHz, CDCl 3 ) δ 8.09-8.07 (m, 1H), 7.76-7.73 (m, 1H), 7.47-7.44 (m, 1H), 7.43-7.37 (m, 1H), 3.70-3.66 (m, 2H), 2.97-2.91 (m, 2H), 2.38-2.33 (m, 2H), 1.06-1.04 (m, 6H).

Intermediate GB

The title compound was prepared in a manner similar to that described in Intermediate EU using N-methylpiperidin-4-amine.

Intermediate GC

The title compound was prepared in a manner similar to that described in Intermediate EU using N,N-dimethylpiperidin-4-amine.

Intermediate GD

The title compound was prepared using analogous conditions to those described in Intermediate AM using cycloleucinol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.16 (dd, J=7.8, 1.8, 1H), 7.75 (dd, J=7.9, 1.3, 1H), 7.51-7.45 (m, 1H), 7.44-7.39 (m, 1H), 5.25 (s, 1H), 4.23 (s, 1H), 3.59 (d. J=6.4, 2H), 2.36 (t, J=6.5, 1H), 1.90-1.78 (m, 1H), 1.77-1.60 (m, 4H), 1.56-1.49 (m, 2H).

Intermediate GE

The title compound was prepared using analogous conditions to those described in Intermediate AM using 3-phenyl-3-pyrrolidinol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.17 (dd, J=7.8, 1.8, 1H), 7.77 (dd, J=7.8, 1.3, 1H), 7.49-7.43 (m, 3H), 7.43-7.34 (m, 3H), 7.34-7.27 (m, 1H), 3.82-3.75 (m, 3H), 3.71 (d, J=10.8, 1H), 2.46-2.37 (m, 1H), 2.29-2.23 (m, 1H), 2.15 (s, 1H).

Intermediate GF

The title compound was prepared using analogous conditions to those described in Intermediate AM using (R)-3-hydroxypyrrolidine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.13 (dd, J=7.8, 1.7, 1H), 7.75 (dd, J=7.8, 1.3, 1H), 7.48-7.42 (m, 1H), 7.39 (m, 1H), 4.57-4.47 (m, 1H), 3.63-3.51 (m, 3H), 3.48-3.40 (m, 1H), 2.14-2.04 (m, 1H), 2.04-1.94 (m, 1H), 1.94-1.84 (m, 1H).

Intermediate GG

The title compound was prepared using analogous conditions to those described in Intermediate AM using (S)-3-hydroxypyrrolidine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.12 (dd, J=7.8, 1.7, 1H), 7.75 (dd, J=7.8, 1.3, 1H), 7.45 (m, 1H), 7.39 (m, 1H), 4.56-4.46 (m, 1H), 3.65-3.50 (m, 3H), 3.44 (m, 1H), 2.13-2.03 (m, 1H), 2.03-1.87 (m, 2H).

Intermediate GH

The title compound was prepared using analogous conditions to those described in Intermediate AM using (racemic)-[1,3′-bipyrrolidin]-4′-ol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.12 (dd, J=7.8, 1.8, 1H), 7.75 (dd, J=7.8, 1.3, 1H), 7.48-7.34 (m, 2H), 4.42-4.29 (m, 1H), 3.74 (m, 2H), 3.36 (m, 2H), 2.83 (dd, J=10.9, 6.3, 1H), 2.70-2.43 (m, 4H), 1.83-1.66 (m, 4H).

Intermediate GI

The title compound was prepared using analogous conditions to those described in Intermediate AM using Racemic-4-morpholinopyrrolidin-3-ol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.11 (dd, J=7.8, 1.8, 1H), 7.76 (dd, J=7.8, 1.3, 1H), 7.49-7.44 (m, 1H), 7.44-7.38 (m, 1H), 4.35 (t, J=7.4, 1H), 3.78-3.70 (m, 2H), 3.70-3.67 (m, 4H), 3.35-3.26 (m, 2H), 2.89 (m, 1H), 2.65-2.56 (m, 2H), 2.52-2.44 (m, 2H).

Intermediate GJ

The title compound was prepared using analogous conditions to those described in Intermediate AM using Racemic-4-(4-methylpiperazin-1-yl)pyrrolidin-3-ol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.10 (dd, J=7.8, 1.8, 1H), 7.76 (dd, J=7.8, 1.3, 1H), 7.51-7.37 (m, 2H), 4.37 (dd, J=12.1, 5.8, 1H), 3.81-3.65 (m, 2H), 3.29 (m, 2H), 2.99 (dd, J=13.1, 7.3, 1H), 2.91-2.57 (m, 8H), 2.45 (s, 3H).

Intermediate GK

The title compound was prepared using analogous conditions to those described in Intermediate EU using 2-bromobenzene-1-sulfonyl chloride and piperazin-2-one. MS (ESI): mass calcd. for C 10 H 11 BrN 2 O 3 S, 317.96; m/z found, 319.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.12 (s, 1H), 8.09-8.00 (m, 1H), 7.93-7.89 (m, 1H), 7.62 (m, 2H), 3.79 (s, 2H), 3.50-3.43 (m, 2H), 3.18 (m, 2H).

Intermediate GL

The title compound was prepared in a manner similar to that described for Intermediate EU using 2-aminoethanol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.17-8.11 (dd, J=7.8, 1.8, 1H), 7.79-7.72 (dd. J=7.8, 1.3, 1H), 7.52-7.46 (m, 1H), 7.46-7.40 (m, 1H), 5.79-5.66 (t, J=5.7, 1H), 3.73-3.65 (dd, J=5.6, 4.6, 2H), 3.13-3.03 (m, 2H), 2.14 (s, 1H).

Intermediate GM

The title compound was prepared in a manner similar to that described for Intermediate EU using (R)-pyrrolidin-2-ylmethanol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.25-8.04 (m, 1H), 7.86-7.70 (m, 1H), 7.54-7.45 (m, 1H), 7.45-7.39 (m, 1H), 4.11-3.96 (m, 1H), 3.75-3.57 (m, 2H), 3.58-3.46 (dd, J=10.8, 4.5, 1H), 3.46-3.36 (m, 1H), 2.91-2.39 (m, 1H), 2.14-1.85 (m, 3H), 1.85-1.74 (dd, J=10.7, 5.3, 1H).

›Step B · 4 of 5

Intermediate GN

The title compound was prepared in a manner similar to that described for Intermediate EU using (S)-pyrrolidin-2-ylmethanol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.18-8.07 (dd, J=7.9, 1.8, 1H), 7.81-7.70 (dd, J=7.9, 1.3, 1H), 7.52-7.45 (m, 1H), 7.45-7.38 (m, 1H), 4.08-3.92 (m, 1H), 3.70-3.56 (m, 2H), 3.55-3.45 (m, 1H), 3.45-3.35 (m, 1H), 2.76-2.67 (t. J=6.1, 1H), 2.03-1.87 (m, 3H), 1.84-1.74 (m, 1H).

Intermediate GO

The title compound was prepared in a manner similar to that described for Intermediate EU using (R)-1-aminopropan-2-ol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.17-8.09 (dd, J=7.8, 1.8, 1H), 7.81-7.71 (dd, J=7.8, 1.3, 1H), 7.51-7.46 (m, 1H), 7.46-7.40 (m, 1H), 5.65-5.60 (t, J=6.1, 1H), 3.98-3.81 (m, 1H), 3.08-2.96 (m, 1H), 2.85-2.58 (m, 1H), 2.04-2.02 (d, J=4.3, 1H), 1.18-1.14 (d, J=6.3, 3H).

Intermediate GP

The title compound was prepared in a manner similar to that described for Intermediate EU using (S)-1-aminopropan-2-ol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.21-8.04 (dd, J=7.8, 1.8, 1H), 7.78-7.72 (dd, J=7.8, 1.3, 1H), 7.53-7.46 (m, 1H), 7.46-7.38 (m, 1H), 5.71-5.54 (d, J=5.9, 1H), 3.97-3.84 (m, 1H), 3.07-2.96 (m, 1H), 2.80-2.69 (m, 1H), 2.03-1.95 (d, J=4.4, 1H), 1.19-1.07 (d, J=6.3, 3H).

Intermediate GQ

The title compound was prepared in a manner similar to that described for Intermediate EU using 1-(aminomethyl)cyclohexanol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.17-8.09 (dd. J=7.8, 1.8, 1H), 7.78-7.70 (dd, J=7.8, 1.3, 1H), 7.51-7.45 (m, 1H), 7.45-7.39 (m, 1H), 5.56-5.45 (t, J=6.3, 1H), 3.71 (s, 1H), 2.89-2.77 (d, J=6.4, 2H), 1.60-1.28 (m, 10H).

Intermediate GR

The title compound was prepared in a manner similar to that described for Intermediate EU using (S)-tert-butyl pyrrolidin-3-ylcarbamate. 1 H NMR (500 MHz, CDCl 3 ) δ 8.17-8.06 (dd, J=7.8, 1.8, 1H), 7.81-7.67 (dd, J=7.8, 1.3, 1H), 7.49-7.43 (m, 1H), 7.43-7.37 (m, 1H), 4.73 (s, 1H), 4.25 (s, 1H), 3.65-3.51 (d, J=8.8, 2H), 3.51-3.43 (m, 1H), 3.37-3.20 (dd, J=10.0, 3.8, 1H), 2.33-2.12 (m, 1H), 1.98-1.81 (dd, J=12.8, 6.9, 1H), 1.43 (s, 9H).

Intermediate GS

The title compound was prepared in a manner similar to that described for Intermediate EU using (R)-tert-butyl pyrrolidin-3-ylcarbamate. 1 H NMR (500 MHz, CDCl 3 ) δ 8.15-8.10 (dd, J=7.8, 1.8, 1H), 7.79-7.73 (dd, J=7.8, 1.3, 1H), 7.49-7.43 (m, 1H), 7.43-7.37 (m, 1H), 4.73 (s, 1H), 4.25 (s, 1H), 3.65-3.52 (m, 2H), 3.51-3.43 (m, 1H), 3.34-3.22 (m, 1H), 2.25-2.13 (m, 1H), 1.95-1.82 (dd, J=12.6, 7.0, 1H), 1.43 (s, 9H).

Intermediate GT

The title compound was prepared in a manner similar to that described for Intermediate EU using 2-(piperazin-1-yl)pyrazine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.16-8.09 (m, 2H), 8.07-8.02 (dd, J=2.6, 1.5, 1H), 7.90-7.87 (d, J=2.6, 1H), 7.78-7.74 (dd, J=7.9, 1.3, 1H), 7.51-7.45 (m, 1H), 7.44-7.37 (m, 1H), 3.74-3.58 (m, 4H), 3.48-3.38 (m, 4H).

Intermediate GU

The title compound was prepared in a manner similar to that described for Intermediate EU using 2-(piperazin-1-yl)pyrimidine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.33-8.27 (d, J=4.7, 2H), 8.15-8.06 (dd, J=7.9, 1.7, 1H), 7.78-7.71 (dd, J=7.9, 1.3, 1H), 7.50-7.43 (m, 1H), 7.43-7.36 (m, 1H), 6.57-6.43 (t, J=4.7, 1H), 3.98-3.78 (m, 4H), 3.42-3.31 (m, 4H).

Intermediate GV

The title compound was prepared in a manner similar to that described for Intermediate EU using methylamine and 2-bromo-5-(trifluoromethyl)benzene-1-sulfonyl chloride. 1 H NMR (500 MHz, CDCl 3 ) δ 8.46-8.29 (d, J=2.4, 1H), 7.99-7.79 (d, J=8.3, 1H), 7.79-7.59 (dd. J=8.3, 2.3, 1H), 5.20-5.01 (d, J=6.4, 1H), 2.80-2.56 (d, J=5.3, 3H).

Intermediate GW

The title compound was prepared in a manner similar to that described for Intermediate EU using ethylamine and 2-bromo-5-(trifluoromethyl)benzene-1-sulfonyl chloride. 1 H NMR (500 MHz, CDCl 3 ) δ 8.43-8.38 (m, 1H), 7.93-7.86 (dd, J=8.3, 0.9, 1H), 7.70-7.62 (m, 1H), 5.08 (s, 1H), 3.11-2.96 (m, 2H), 1.19-1.09 (t, J=7.2, 3H).

Intermediate GX

The title compound was prepared in a manner similar to that described for Intermediate EU using 2-aminoethanol and 2-bromo-5-(trifluoromethyl)benzene-1-sulfonyl chloride. 1 H NMR (500 MHz, CD 3 OD) δ 8.35-8.30 (m, 1H), 8.07-7.98 (dd, J=8.2, 0.9, 1H), 7.82-7.76 (m, 1H), 3.59-3.50 (t, J=5.9, 2H), 3.10-3.02 (t, J=5.9, 2H).

Intermediate GY

The title compound was prepared in a manner similar to that described for Intermediate EU using 1-methylpiperazine and 2-bromo-5-(trifluoromethyl)benzene-1-sulfonyl chloride. 1 H NMR (500 MHz, CDCl 3 ) δ 8.37-8.28 (d, J=2.2, 1H), 7.98-7.86 (d, J=8.2, 1H), 7.73-7.59 (d, J=8.2, 1H), 3.45-3.31 (t, J=5.0, 4H), 2.60-2.42 (t, J=4.9, 4H), 2.40-2.20 (d, J=1.5, 3H).

Intermediate GZ

The title compound was prepared in a manner similar to that described for Intermediate EU using piperazin-2-one and 2-bromo-5-(trifluoromethyl)benzene-1-sulfonyl chloride. 1 H NMR (400 MHz, CDCl 3 ) δ 8.43-8.35 (d, J=2.3, 1H), 7.99-7.89 (d, J=8.2, 1H), 7.77-7.65 (dd, J=8.3, 2.3, 2H), 6.95 (s, 2H), 3.99 (s, 3H), 3.73-3.58 (t, J=5.3, 3H), 3.51-3.42 (m, 3H), 1.36-1.04 (m, 1H).

Intermediate HA

To a 500 mL round-bottomed flask were added 5-bromo-2-aminopyrimidine (4.0 g, 23 mmol), 4-chloro-2-fluorophenylboronic acid (3.9 g, 23 mmol), palladium(II)trifluoroacetate (240 mg, 0.72 mmol), and triphenylphoshine (373 mg, 1.40 mmol). The reaction vessel was fitted with a rubber septum, sparged with nitrogen and then charged with sparged toluene (75 mL), ethanol (75 mL), and a 2M solution of sodium carbonate (42 mL, 84 mmol) (solvents were sparged individually nitrogen gas for 30 minutes). The resulting mixture was stirred vigorously and heated at 50° Celsius. After 12 hours, the mixture was cooled to rt and treated with 100 mL of water. The precipitate was isolated via vacuum filtration, and the filtrate extracted with EtOAC. The EtOAc solution was dried, filtered and concentrated to dryness. The resultant solids were recrystallized from IPA (80 mL) to afford title compound (3.8 g, 74%). MS (ESI): mass calcd. for C 10 H 7 ClFN 3 , 223.03; m/z found, 224.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.44 (d, J=1.4, 2H), 7.59 (m, 1H), 7.54 (dd, J=10.7, 2.1, 1H), 7.37 (dd, J=8.3, 2.1, 1H), 6.94 (s, 2H).

›Step B · 5 of 5

Intermediate HB

Nitrogen sparged 1,4-dioxane (80 mL) was added to a 250 mL round-bottomed flask containing 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.1 g, 8.4 mmol), 5-(4-chloro-2-fluorophenyl)pyrimidin-2-amine (1.5 g, 6.7 mmol), chloro(2-dicyclohexyl-phosphino-2′,4′,6′-triisopropyl-1-1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (X-Phos pre-catalyst) (0.1 g, 0.13 mmol), and potassium acetate (1.9 g, 20 mmol). The reaction mixture was heated at 80° Celsius for 4 hours before cooling to rt, concentrating to dryness, and the residue subjected to FCC to provide the title compound (1.8 g, 83%). MS (ESI): mass calcd. for C 16 H 19 BFN 3 O 2 , 315.15; m/z found, 316.4 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.53 (d, J=1.3 Hz, 2H), 7.64 (dd. J=7.6, 1.0 Hz, 1H), 7.58 (dd, J=11.0, 0.9 Hz, 1H), 7.38 (m, 1H), 5.23 (s, 2H), 1.36 (s, 12H).

›Example 1

Method 1

To a 100 mL round-bottomed flask were added a stirbar, 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine, (3.639 g, 13.57 mmol) (2-(methylsulfonyl)-phenyl)boronic acid (4.076 g, 20.38 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (1.136 g, 1.391 mmol) and K 2 CO 3 (5.663 g, 40.97 mmol). The flask was flushed with nitrogen and then charged with 56.0 mL thoroughly sparged (1 hour of bubbling N 2 ) DMSO. The flask was heated at 80° Celsius for 5.25 hours before cooling to room temperature, diluting the reaction mixture with EtOAc and filtering the mixture through a pad of celite. The filtrate was washed twice with 1 N NaOH and the organic layer dried over MgSO 4 . Filtering and concentrating the filtrate to dryness gave the crude product. The soluble portion of the residue was then subjected to FCC to give the title compound. (3.80 g, 81%).

Method 2

›Step A: 5-(4-Chloro-2-fluorophenyl)pyrazin-2-amine

To a nitrogen flushed flask containing 4-chloro-2-fluorobenzene boronic acid (40.0 g, 229 mmol), 2-amino-5-bromopyrazine (39.9 g, 229 mmol), palladium(II) trifluoroacetate (1.5 g, 4.6 mmol), and triphenylphosphine (2.4 g, 9.2 mmol) were added sparged toluene (750 mL), ethanol (750 mL), and 2 M Na 2 CO 3(aq) (418 mL, 836 mmol). The mixture was stirred and heated at 50° Celsius for 15 hours and then cooled to rt. Water (750 mL) was added and the layers were separated. The aqueous layer was washed with ethyl acetate (750 mL). The combined organic layers were washed with brine (500 mL), dried over Na 2 SO 4 , filtered, and concentrated to dryness to give 55.4 g of crude product. The crude solid was crystallized from toluene (450 mL) to provide the title compound (40.0 g, 78%). MS (ESI): mass calcd. for C 10 H 7 ClFN 3 , 223.03; m/z found, 224.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.34 (dd, J=2.6, 1.5, 1H), 8.03 (d, J=1.6, 1H), 7.89 (m, 1H), 7.52 (dd, J=11.3, 2.1, 1H), 7.38 (dd, J=8.5, 2.1, 1H), 6.79 (s, 2H).

›Step B: 5-(3-Fluoro-2′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)pyrazin-2-amine

To a nitrogen sparged flask containing 5-(4-chloro-2-fluorophenyl)pyrazin-2-amine (34.0 g, 152 mmol), 2-methylsulfonylphenylboronic acid (38.0 g, 190 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (2.39 g, 3.0 mmol) were added sparged THF (300 mL) and K 3 PO 4(aq) (608 mL, 0.5 M). The mixture was stirred for 15 hours at rt and then concentrated under reduced pressure to remove the THF. The remaining portion was treated with toluene (325 mL) and THF (25 mL). The biphasic slurry was stirred for 20 h at rt and then filtered and the isolated solid washed with water (150 mL) and toluene (150 mL). The filter cake was dried to provide the title compound (47.1 g, 90%). MS (ESI): mass calcd. for C 17 H 14 FN 3 O 2 S, 343.08; m/z found, 344.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.41 (dd, J=2.4, 1.5, 1H), 8.12 (dd, J=7.9, 1.4, 1H), 8.04 (d, J=1.5, 1H), 7.93 (m, 1H), 7.80 (m, 1H), 7.72 (m, 1H), 7.48 (dd, J=7.6, 1.4, 1H), 7.37 (dd, J=12.3, 1.7, 1H), 7.32 (dd, J=8.1, 1.7, 1H), 6.76 (s, 2H), 2.95 (s, 3H).

›Examples4

›Example 2

The title compound was prepared using analogous conditions to those described in Example 1 using (2-(methylsulfonamido)phenyl)boronic acid. MS (ESI): mass calcd. for C 17 H 15 FN 4 O 2 S, 358.09; m/z found, 359.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 9.11 (s, 1H), 8.40 (dd, J=2.3, 1.4, 1H), 8.04 (d, J=1.5, 1H), 7.97-7.89 (m, 1H), 7.50-7.34 (m, 6H), 6.71 (s, 2H), 2.84 (s, 3H).

›Example 3

The title compound was prepared using analogous conditions to those described in Example 1 using 2-(methylsulfonyl)phenylboronic acid and 5-(4-bromo-2-fluorophenyl)-6-cyanopyrazin-2-amine. MS (ESI): mass calcd. for C 18 H 13 FN 4 O 2 S, 368.07; m/z found, 369.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.26 (s, 1H), 8.13 (dd, J=8.0, 1.4, 1H), 7.84-7.77 (m, 1H), 7.76-7.70 (m, 1H), 7.69-7.62 (m, 1H), 7.51 (dd, J=7.6, 1.4, 1H), 7.46 (dd, J=11.0, 1.6, 1H), 7.42-7.35 (m, 3H), 2.97 (s, 3H).

›Example 4

The title compound was prepared using analogous conditions to those described in Example 1 using (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.1 [M+H] + . 1 H NMR (500 MHz, DMSO-de) δ 8.39 (dd. J=2.2, 1.4, 1H), 8.09-8.02 (m, 2H), 7.93-7.87 (m, 1H), 7.68-7.63 (m, 1H), 7.63-7.57 (m, 1H), 7.38 (dd, J=7.5, 1.4, 1H), 7.33-7.26 (m, 2H), 6.94 (s, 1H), 6.71 (s, 2H), 1.02 (s, 9H).

›Example 5

Method 1

To a 50 mL round-bottomed flask were added 1.071 g (2.67 mmol) 4′-(5-aminopyrazin-2-yl)-N-tert-butyl-3′-fluorobiphenyl-2-sulfonamide, a stirbar and 20 mL TFA. The mixture was heated at 50° Celsius for 2 hours and then carefully and slowly added to 300 mL rapidly stirring sat. NaHCO 3 . The resulting mixture was stirred for 30 min and then the solid was isolated via vacuum filtration. The solid was washed with 200 mL deionized water, air dried and then further dried under high vacuum with gentle heating to give the title compound (751 mg, 82%).

Method 2

›Step A: 4′-(5-Aminopyrazin-2-yl)-N-(tert-butyl)-3′-fluoro-[1,1′-biphenyl]-2-sulfonamide

To a nitrogen flushed flask containing 5-(4-chloro-2-fluorophenyl)pyrazin-2-amine (82.8 g, 370 mmol), (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid (100.0 g, 388.9 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (5.83 g, 7.41 mmol) were added N 2 sparged THF (926 mL) and sparged 0.5 M K 3 PO 4(aq) (1.65 L, 825 mmol). The mixture was stirred for 15 hours at room temperature. The layers were separated and the organic layer was washed with 600 mL brine, dried over MgSO 4 , filtered, and concentrated to dryness to give a solid residue. The solid was dissolved in 900 mL DMA, stirred with 60 g activated charcoal at 80° Celsius for 2 hours, and then stirred at room temperature for an additional 16 hours. The charcoal was removed by filtration and then washed with 150 mL DMA. The combined filtrates were treated three times with fresh Silicycle brand SiliaMetS Thiol Pd Scavenger (30 g, 15 g, 7.5 g) in DMA at 80° Celsius for 8 hours to 16 hours. Upon cooling to rt the scavenger was filtered off and the filtrate was concentrated to dryness. The resulting solid was triturated in toluene (1.2 L) at 90° Celsius for 2 hours. Upon cooling to rt the solid was collected by filtration and washed twice with toluene (700 mL) and twice with hexanes (700 mL) yielding the title compound (120.0 g, 80.9%). MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.42-8.37 (m, 1H), 8.10-8.02 (m, 2H), 7.95-7.86 (m, 1H), 7.70-7.63 (m, 1H), 7.63-7.58 (m, 1H), 7.41-7.35 (m, 1H), 7.35-7.26 (m, 2H), 7.00-6.92 (s, 1H), 6.79-6.66 (s, 2H), 1.10-0.95 (s, 9H).

›Step B: 4′-(5-Aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-sulfonamide

A solution of 4′-(5-aminopyrazin-2-yl)-N-(tert-butyl)-3′-fluoro-[1,1′-biphenyl]-2-sulfonamide (130.0 g, 298.0 mmol), anisole (97.4 mL, 894.0 mmol), and TFA (228.0 mL, 2.98 mol) was stirred at 60° Celsius for 16 hours. The reaction was cooled to rt, concentrated to dryness, and partitioned between 600 mL H 2 O and 600 mL acetone. 750 mL sat. NaHCO 3(aq) , was added over 30 min. The resulting precipitate was isolated via filtration and rinsed with 300 mL H 2 O then 300 mL acetone. The precipitate was triturated with 1.5 L acetone at 50° Celsius for 16 hours. After cooling to room temperature the solid was collected by filtration and rinsed twice with 250 mL acetone then dried in a vacuum oven at 50° Celsius for 16 hours yielding the title compound (74.3 g, 72.4%). MS (ESI): mass calcd. for C 16 H 13 FN 4 O 2 S, 344.07; m/z found, 345.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.44-8.36 (s, 1H), 8.10-8.02 (m, 2H), 7.92-7.85 (m, 1H), 7.69-7.59 (m, 2H), 7.43-7.35 (m, 3H), 7.35-7.27 (m, 2H), 6.77-6.69 (s, 2H). Elemental analysis: calcd. for C 16 H 13 FN 4 O 2 S, C, 55.80; H, 3.81; N, 16.27; measured: C, 55.43; H, 3.54; N, 16.22.

›Examples33

›Example 6

To a 5 mL microwave vial were added a stirbar, 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (54 mg, 0.17 mmol), 2-bromo-N-cyclohexylbenzenesulfonamide (58 mg, 0.18 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (10 mg, 0.013 mmol), and K 2 CO 3 (80 mg, 0.58 mmol). The vial was capped and flushed with nitrogen before adding 1 mL N 2 sparged DMSO and heating at 80° Celsius for 20 hours. The vial was cooled to rt and the reaction mixture subjected to FCC purification to give the title compound (45 mg, 62%). MS (ESI): mass calcd. for C 22 H 23 FN 4 O 2 S, 426.15; m/z found, 427.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.43-8.35 (m, 1H), 8.05-8.03 (d, J=1.4, 1H), 8.03-7.99 (dd, J=7.9, 1.4, 1H), 7.92-7.84 (m, 1H), 7.70-7.64 (m, 1H), 7.64-7.58 (m, 1H), 7.44-7.37 (m, 2H), 7.32-7.24 (m, 2H), 6.72 (s, 2H), 2.85-2.72 (m, 1H), 1.69-1.52 (m, 5H), 1.48-1.39 (m, 1H), 1.19-0.93 (m, 5H).

›Example 7

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-(2-methylpropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.42-8.37 (m, 1H), 8.05-8.01 (d, J=1.5, 1H), 7.95-7.91 (dd, J=7.9, 1.3, 1H), 7.91-7.86 (m, 1H), 7.70-7.65 (m, 1H), 7.64-7.59 (m, 1H), 7.55-7.49 (m, 1H), 7.44-7.40 (dd, J=7.5, 1.4, 1H), 7.33-7.26 (m, 2H), 6.73 (s, 2H), 2.55-2.51 (m, 2H), 1.65-1.54 (m, 1H), 0.81-0.75 (d, J=6.7, 6H).

›Example 8

The title compound was prepared using analogous conditions to those described in Example 6 utilizing racemic 2-bromo-N-(2,2,2-trifluoro-1-methylethyl)-benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 2 S, 440.09; m/z found, 441.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.54-8.47 (d, J=8.9, 1H), 8.43-8.36 (m, 1H), 8.09-8.00 (m, 2H), 7.93-7.86 (m, 1H), 7.73-7.68 (m, 1H), 7.68-7.61 (m, 1H), 7.44-7.39 (dd, J=7.5, 1.4, 1H), 7.30-7.21 (m, 2H), 6.73 (s, 2H), 3.96-3.83 (m, 1H), 1.19-1.10 (d, J=6.9, 3H).

›Example 9

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-(cyclobutylmethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 2 S, 412.14; m/z found, 413.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.41-8.36 (dd, J=2.2, 1.4, 1H), 8.06-8.01 (d, J=1.5, 1H), 7.97-7.91 (dd, J=7.9, 1.4, 1H), 7.91-7.85 (m, 1H), 7.71-7.65 (m, 1H), 7.65-7.59 (m, 1H), 7.52-7.47 (m, 1H), 7.44-7.39 (dd. J=7.5, 1.4, 1H), 7.33-7.24 (m, 2H), 6.73 (s, 2H), 2.79-2.69 (dd, J=7.2, 5.8, 2H), 2.35-2.24 (m, 1H), 1.93-1.82 (m, 2H), 1.81-1.67 (m, 2H), 1.59-1.50 (m, 2H).

›Example 10

The title compound was prepared using analogous conditions to those described in Example 6 utilizing racemic (endo)-N-Bicyclo[2.2.1]hept-2-yl-2-bromobenzenesulfonamide. MS (ESI): mass calcd. for C 23 H 23 FN 4 O 2 S, 438.15; m/z found, 439.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.42-8.36 (m, 1H), 8.06-8.01 (d, J=1.5, 1H), 7.99-7.94 (dd, J=7.9, 1.3, 1H), 7.91-7.85 (m, 1H), 7.71-7.65 (m, 1H), 7.65-7.60 (m, 1H), 7.43-7.39 (dd, J=7.5, 1.4, 1H), 7.39-7.34 (d, J=6.9, 1H), 7.30-7.22 (m, 2H), 6.73 (s, 2H), 2.83-2.74 (m, 1H), 2.12-2.06 (m, 1H), 1.97-1.92 (m, 1H), 1.47-1.37 (m, 2H), 1.34-1.21 (m, 3H), 1.01-0.77 (m, 4H).

›Example 11

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-(1-methylcyclobutyl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 2 S, 412.14; m/z found, 413.1 [M+H] + . 1 H NMR (600 MHz, CDCl 3 ) δ 8.52 (s, 1H), 8.26 (s, 1H), 8.16-8.11 (dd, J=7.9, 1.3, 1H), 8.11-8.05 (m, 1H), 7.62-7.58 (m, 1H), 7.56-7.51 (m, 1H), 7.40-7.37 (dd, J=8.1, 1.7, 1H), 7.34-7.28 (m, 2H), 4.37 (s, 1H), 2.13-2.00 (m, 2H), 1.82-1.73 (m, 2H), 1.69-1.59 (m, 2H), 1.24 (s, 3H).

›Example 12

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-(1,1-dimethylpropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 2 S, 414.15; m/z found, 415.1 [M+H] + . 1 H NMR (600 MHz, CDCl 3 ) δ 8.56 (s, 1H), 8.28 (s, 1H), 8.18-8.13 (dd, J=7.9, 1.3, 1H), 8.12-8.06 (m, 1H), 7.62-7.56 (m, 1H), 7.55-7.49 (m, 1H), 7.44-7.39 (dd, J=8.1, 1.7, 1H), 7.35-7.28 (m, 2H), 3.90 (s, 1H), 1.50-1.39 (q, J=7.4, 2H), 1.01 (s, 6H), 0.78-0.68 (t, J=7.4, 3H).

›Example 13

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-(2,2,2-trifluoro-1,1-dimethylethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 18 F 4 N 4 O 2 S, 454.11; m/z found, 455.1 [M+H] + . 1 H NMR (600 MHz, CDCl 3 ) δ 8.54 (s, 1H), 8.27 (s, 1H), 8.15-8.10 (dd, J=8.0, 1.3, 1H), 8.10-8.04 (m, 1H), 7.66-7.59 (m, 1H), 7.57-7.52 (m, 1H), 7.40-7.27 (m, 3H), 4.49 (s, 1H), 1.33 (s, 6H).

›Example 14

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-cyclopentylbenzenesulfonamide. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 2 S, 412.14; m/z found, 413.1 [M+H] + . 1 H NMR (600 MHz, CDCl 3 ) δ 8.46 (s, 1H), 8.21 (s, 1H), 8.14-8.10 (dd, J=8.0, 1.4, 1H), 8.10-8.04 (m, 1H), 7.64-7.59 (m, 1H), 7.57-7.51 (m, 1H), 7.38-7.25 (m, 3H), 4.42-4.25 (d, J=6.6, 1H), 3.49-3.35 (m, 1H), 1.80-1.66 (m, 2H), 1.63-1.48 (m, 2H), 1.48-1.38 (m, 2H), 1.35-1.19 (m, 2H).

›Example 15

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-methylbenzenesulfonamide. MS (ESI): mass calcd. for C 17 H 15 FN 4 O 2 S, 358.09; m/z found, 359.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.32 (s, 2H), 8.07-8.01 (dd, J=7.9, 1.4, 1H), 7.99-7.94 (m, 1H), 7.71-7.64 (m, 1H), 7.63-7.57 (m, 1H), 7.43-7.37 (dd, J=7.5, 1.4, 1H), 7.35-7.26 (m, 2H), 2.45 (s, 3H).

›Example 16

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-ethylbenzenesulfonamide. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.11; m/z found, 373.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.30 (s, 1H), 8.10-8.01 (dd, J=8.0, 1.5, 1H), 8.01-7.93 (m, 1H), 7.70-7.62 (m, 1H), 7.62-7.54 (m, 1H), 7.42-7.36 (dd, J=7.6, 1.5, 1H), 7.35-7.25 (m, 2H), 2.91-2.74 (q, J=7.2, 2H), 1.08-0.93 (t, J=7.2, 3H).

›Example 17

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-(2-phenylethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 21 FN 4 O 2 S, 448.14; m/z found, 449.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.35 (s, 1H), 8.14 (s, 1H), 8.10-8.05 (dd, J=7.9, 1.3, 1H), 7.99-7.91 (m, 1H), 7.63-7.57 (m, 1H), 7.57-7.49 (m, 1H), 7.31-7.26 (dd, J=7.5, 1.4, 1H), 7.23-7.17 (m, 2H), 7.17-7.09 (m, 3H), 7.05-6.98 (m, 2H), 4.82-4.67 (m, 1H), 3.15-3.00 (m, 2H), 2.75-2.65 (t, J=7.1, 2H).

›Example 18

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 18 F 4 N 4 O 2 S, 502.08; m/z found, 503.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.37-8.31 (s, 1H), 8.23-8.18 (dd, J=8.0, 1.4, 1H), 7.99-7.93 (d, J=1.6, 1H), 7.87-7.80 (m, 1H), 7.63-7.57 (m, 1H), 7.55-7.49 (m, 1H), 7.36-7.31 (d, J=7.4, 1H), 7.30-7.25 (m, 2H), 7.23-7.18 (d, J=7.6, 1H), 7.20-7.10 (m, 2H), 7.11-7.02 (m, 2H), 5.04-4.93 (s, 2H), 4.84-4.72 (m, 1H).

›Example 19

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(1S)-2,2,2-trifluoro-1-phenylethyl]-benzenesulfonamide.

›Example 20

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 2 S, 440.09; m/z found, 441.0 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.21-8.12 (m, 2H), 7.92-7.85 (s, 1H), 7.85-7.79 (m, 1H), 7.62-7.55 (m, 1H), 7.54-7.47 (m, 1H), 7.43-7.36 (d, J=8.0, 1H), 7.33-7.27 (dd, J=7.5, 1.4, 1H), 7.19-7.07 (d, J=12.6, 1H), 5.45-5.13 (s, 2H), 4.04-3.90 (m, 1H), 1.31-1.22 (d, J=7.0, 3H).

›Example 21

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-(2,3-dihydro-1H-inden-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 21 FN 4 O 2 S, 460.14; m/z found, 461.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.44-8.39 (m, 1H), 8.24-8.18 (dd, J=8.0, 1.4, 1H), 8.05-8.00 (d, J=1.5, 1H), 7.91-7.84 (m, 1H), 7.65-7.58 (m, 1H), 7.58-7.51 (m, 1H), 7.34-7.29 (dd, J=7.5, 1.4, 1H), 7.27-7.21 (m, 1H), 7.15-7.04 (m, 5H), 4.89-4.74 (s, 2H), 4.74-4.61 (d, J=6.6, 1H), 4.00-3.89 (m, 1H), 3.06-2.92 (dd, J=15.9, 6.9, 2H), 2.70-2.58 (dd, J=15.9, 5.6, 2H).

›Example 22

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(1S)-2,3-dihydro-1H-inden-1-yl]benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 21 FN 4 O 2 S, 460.14; m/z found, 461.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.30-8.24 (dd, J=7.9, 1.4, 1H), 8.24-8.19 (m, 1H), 8.00-7.95 (d, J=1.5, 1H), 7.85-7.78 (m, 1H), 7.65-7.58 (m, 1H), 7.58-7.52 (m, 1H), 7.34-7.27 (dd, J=7.5, 1.4, 1H), 7.23-7.18 (d, J=7.7, 1H), 7.18-7.12 (dd, J=4.9, 1.1, 2H), 7.07-6.98 (m, 2H), 6.96-6.88 (d, J=7.6, 1H), 5.05-4.90 (d, J=8.7, 1H), 4.87-4.79 (s, 2H), 4.79-4.71 (m, 1H), 2.86-2.74 (m, 1H), 2.74-2.60 (m, 1H), 2.28-2.16 (m, 1H), 1.79-1.64 (m, 1H).

›Example 23

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzenesulfonamide.

›Example 24

The title compound was prepared using analogous conditions to those described in Example 6 using 2-bromo-N-[(1R)-1-phenylethyl]benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 21 FN 4 O 2 S, 448.14; m/z found, 449.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.44-8.37 (d, J=1.4, 1H), 8.19-8.12 (m, 1H), 8.10-8.03 (dd, J=8.0, 1.3, 1H), 7.97-7.89 (m, 1H), 7.61-7.53 (m, 1H), 7.52-7.45 (m, 1H), 7.22-7.15 (m, 4H), 7.12-7.00 (s, 1H), 6.97-6.91 (m, 2H), 6.89-6.78 (s, 1H), 4.68-4.51 (d, J=7.0, 1H), 4.39-4.25 (m, 1H), 1.45-1.33 (d, J=6.9, 3H).

›Example 25

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(1R)-2-hydroxy-1-methylethyl]benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.12; m/z found, 403.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.28 (m, 2H), 8.16-8.11 (dd, J=8.0, 1.3, 1H), 8.01-7.93 (m, 1H), 7.71-7.63 (m, 1H), 7.62-7.55 (m, 1H), 7.43-7.37 (dd, J=7.6, 1.4, 1H), 7.37-7.30 (m, 2H), 3.42-3.37 (m, 1H), 3.30-3.25 (dd, J=10.9, 6.3, 1H), 3.24-3.16 (m, 1H), 1.04-0.98 (d, J=6.6, 3H).

›Example 26

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-phenylbenzenesulfonamide. MS (ESI): mass calcd. for C 22 H 17 FN 4 O 2 S, 420.11; m/z found, 421.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 10.12 (s, 1H), 8.45-8.37 (m, 1H), 8.13-8.06 (d, J=1.5, 1H), 8.06-8.00 (dd, J=8.0, 1.4, 1H), 7.92-7.84 (t, J=8.3, 1H), 7.70-7.63 (m, 1H), 7.63-7.57 (m, 1H), 7.39-7.32 (dd, J=7.6, 1.4, 1H), 7.24-7.16 (dd, J=8.5, 7.3, 2H), 7.12 (s, 1H), 7.11-7.08 (dd, J=4.1, 1.6, 1H), 7.01-6.96 (m, 1H), 6.95-6.89 (m, 2H).

›Example 27

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(3S)-1-ethyl-2-oxoazepan-3-yl]benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 26 FN 5 O 3 S, 483.17; m/z found, 484.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.39-8.33 (d, J=1.4, 1H), 8.25-8.20 (d, J=1.4, 1H), 8.10-8.05 (m, 1H), 8.05-8.00 (dd, J=8.0, 1.3, 1H), 7.61-7.55 (m, 1H), 7.53-7.47 (m, 1H), 7.43-7.38 (dd, J=8.1, 1.7, 1H), 7.34-7.30 (dd, J=7.5, 1.4, 1H), 7.30-7.25 (dd, J=12.3, 1.7, 1H), 6.02-5.93 (d, J=5.5, 1H), 3.91-3.83 (m, 1H), 3.45-3.20 (m, 3H), 3.18-3.10 (m, 1H), 2.04-1.94 (m, 1H), 1.92-1.81 (m, 1H), 1.81-1.70 (m, 1H), 1.66-1.53 (m, 1H), 1.52-1.42 (m, 1H), 1.34-1.21 (m, 1H), 1.09-0.99 (t, J=7.2, 3H).

›Example 28

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(3S)-2-oxoazepan-3-yl]benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 22 FN 5 O 3 S, 455.14; m/z found, 456.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.46-8.33 (s, 1H), 8.24-8.14 (s, 1H), 8.10-8.00 (m, 2H), 7.63-7.56 (m, 1H), 7.56-7.48 (m, 1H), 7.41-7.35 (dd, J=8.0, 1.7, 1H), 7.35-7.29 (dd, J=7.4, 1.4, 1H), 7.29-7.25 (d, J=1.8, 1H), 7.00-6.82 (s, 1H), 5.88-5.71 (d, J=6.0, 1H), 3.89-3.73 (d, J=9.4, 1H), 3.24-3.11 (m, 1H), 3.11-2.97 (m, 1H), 2.09-1.98 (d, J=12.5, 1H), 1.98-1.85 (d, J=13.2, 1H), 1.81-1.67 (m, 1H), 1.64-1.44 (m, 2H), 1.37-1.21 (m, 1H).

›Example 29

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(3S)-1-methyl-2-oxoazepan-3-yl]benzenesulfonamide. MS (ESI): mass calcd. for C 23 H 24 FN 5 O 3 S, 469.16; m/z found, 470.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.44-8.38 (d, J=1.3, 1H), 8.22 (s, 1H), 8.10-8.05 (m, 1H), 8.05-8.00 (dd, J=7.9, 1.3, 1H), 7.63-7.56 (m, 1H), 7.54-7.47 (m, 1H), 7.43-7.37 (dd, J=8.1, 1.5, 1H), 7.34-7.29 (dd, J=7.6, 1.4, 1H), 7.28-7.24 (m, 1H), 6.00-5.85 (d, J=5.6, 1H), 3.98-3.86 (d, J=11.4, 1H), 3.39-3.28 (dd, J=15.2, 11.4, 1H), 3.16-3.05 (dd, J=15.3, 5.1, 1H), 2.95 (s, 3H), 2.04-1.93 (dd, J=17.1, 4.1, 1H), 1.91-1.81 (m, 1H), 1.77-1.66 (m, 1H), 1.65-1.53 (m, 1H), 1.53-1.42 (m, 1H), 1.38-1.26 (m, 1H).

›Example 30

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 26 H 32 FN 5 O 2 S, 497.23; m/z found, 498.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39-8.35 (d, J=1.4, 1H), 8.35-8.30 (m, 1H), 8.18-8.13 (dd, J=8.0, 1.3, 1H), 8.05-7.99 (m, 1H), 7.73-7.67 (m, 1H), 7.65-7.59 (m, 1H), 7.45-7.40 (dd, J=7.6, 1.3, 1H), 7.39-7.36 (m, 1H), 7.36-7.32 (dd, J=2.9, 1.5, 1H), 3.49-3.39 (m, 1H), 2.75 (s, 3H), 1.95-1.87 (m, 2H), 1.75-1.64 (m, 2H), 1.38 (s, 6H), 1.30 (s, 6H).

›Example 31

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-pyridin-3-ylbenzenesulfonamide. MS (ESI): mass calcd. for C 21 H 16 FN 5 O 2 S, 421.10; m/z found, 422.1 [M+H] + . 1 H NMR (600 MHz. CD 3 OD) δ 8.38-8.34 (d, J=1.5, 1H), 8.34-8.30 (m, 2H), 8.29-8.23 (m, 2H), 7.91-7.85 (m, 1H), 7.83-7.79 (m, 1H), 7.75-7.71 (m, 1H), 7.71-7.68 (dd, J=8.6, 5.4, 1H), 7.68-7.64 (m, 1H), 7.41-7.37 (dd, J=7.6, 1.3, 1H), 7.20-7.15 (dd, J=12.1, 1.7, 1H), 7.15-7.12 (dd, J=8.0, 1.7, 1H).

›Example 32

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-bromo-N-[(1S)-2-hydroxy-1-methylethyl]benzenesulfonamide.

›Example 33

To a solution of tert-butanol (13 mg, 0.18 mmol) in DCM (5 mL) was added chlorosulfonylisocyanate (25 mg, 0.18 mmol) at 0° Celsius. The resulting solution containing N-(tert-butoxycarbonyl)sulfamoyl chloride was added to a reaction flask containing 5-(2′-amino-3-fluorobiphenyl-4-yl)pyrazin-2-amine (50 mg, 0.18 mmol) and triethylamine (36 mg, 0.36 mmol) in anhydrous DCM (10 mL) at 0° Celsius. The mixture was warmed to rt, stirred 2 hours, then concentrated to dryness, re-dissolved in TFA/DCM (5 mL/5 mL), stirred at rt for 1 hour, and concentrated to dryness. The residue was diluted with water (10 mL) and saturated NaHCO 3(aq) (10 mL), extracted with DCM (10 mL×3) and the combined organic extracts washed with brine, dried over Na 2 SO 4 , filtered and concentrated to dryness. The residue was purified by HPLC to give the title compound (10 mg, 16%). MS (ESI): mass calcd. for C 16 H 14 FN 5 O 2 S, 359.09; m/z found, 360.0 [M+H] + ; 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.33 (s, 1H), 8.04 (d, J=1.3, 1H), 7.91 (m, 1H), 7.63 (d, J=7.8, 1H), 7.44-7.22 (m, 4H), 7.24 (m, 1H), 7.05 (s, 2H), 6.70 (s, 2H).

›Example 34

To a solution of 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (309 mg, 1.15 mmol) in DMSO (5 mL) was added K 2 CO 3 (317 mg, 2.3 mmol). The mixture was sparged with N 2 several times. Pd(PPh 3 ) 4 (66 mg, 0.058 mmol) and (2-(1-methylethylsulfonamido)-phenyl)boronic acid (280 mg, 1.15 mmol) were added and the resultant mixture sparged with N 2 . The mixture was heated at 80° Celsius for 14 hours before cooling to rt and diluting with water (70 mL). The precipitate was collected, rinsed with water, air dried, and then purified by HPLC to give the title compound (40 mg, 9%). MS (ESI): mass calcd. for C 19 H 19 FN 4 O 2 S, 386.12; m/z found, 387.1 [M+H] + . 1 H NMR (300 MHz, CD 3 OD) δ 8.72 (s, 1H), 8.25 (d, J=1.2, 1H), 8.16 (m, 1H), 7.50 (d, J=7.8, 1H), 7.47-7.34 (m, 5H), 3.15-3.03 (m, 1H), 1.23 (d, J=6.8, 6H).

›Example 35

The title compound was prepared using analogous conditions to those described in Example 34 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and N-(2-bromophenyl)ethanesulfonamide. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.11; m/z found, 372.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.08 (s, 1H), 8.43-8.36 (m, 1H), 8.04 (d, J=1.0, 1H), 7.93 (m, 1H), 7.46-7.28 (m, 6H), 6.72 (s, 2H), 2.91 (q, J=7.4, 2H), 1.07 (t, J=7.3, 3H).

›Example 36

The title compound was prepared using analogous conditions to those described in Example 34 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-bromo-2-(propylsulfonyl)benzene. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 2 S, 386.12; m/z found, 387.3 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.09 (s, 1H), 8.38 (s, 1H), 8.04 (d, J=1.3, 1H), 7.93 (m, 1H), 7.42-7.35 (m, 6H), 6.71 (s, 2H), 2.87-2.74 (m, 2H), 1.59-1.44 (m, 2H), 0.81 (t, J=7.4, 3H).

›Example 37

The title compound was prepared using analogous conditions to those described in Example 34 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and N-(2-bromophenyl)isobutylsulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.38 (s, 1H), 8.14 (s, 1H), 7.96 (m, 1H), 7.49 (d, J=7.0, 1H), 7.45-7.30 (m, 5H), 2.77 (d, J=6.5, 2H), 2.15-2.02 (m, 1H), 0.97 (d, J=6.7, 6H).

Example 38

›Step A: 2-(di-tert-Butyloxycarbonyl)amino-5-(4-bromo-2-fluorophenyl)pyrazine

2-Amino-5-(4-bromo-2-fluorophenyl)pyrazine (3.0 g, 11 mmol) was dissolved in pyridine (40 mL), and then slowly treated with (Boc) 2 O (6.8 g, 34 mmol) at rt. The mixture was stirred at rt for 18 hours, concentrated to dryness and purified by FCC to give 2-(di-tert-butyloxycarbonyl)amino-5-(4-bromo-2-fluorophenyl)pyrazine (3.6 g, 68%) as a white solid. MS (ESI): mass calcd. for C 20 H 23 FBrN 3 O 4 S, 467.09; m/z found, 468.0 [M+H] + .

›Step B: 2-(di-tert-Butyloxycarbonyl)amino-5-(2′-amino-3-fluorobiphenyl-4-yl)pyrazine

To a solution of 2-(di-tert-butyloxycarbonyl)amino-5-(4-bromo-2-fluorophenyl)-pyrazine (232 mg, 0.5 mmol) and 2-aminophenylboronic acid hydrochloride (174 mg, 1.0 mmol) in 1,4-dioxane/H 2 O (10 mL/0.5 mL) was added Na 2 CO 3 (232 mg, 2.0 mmol). The mixture was sparged with N 2 several times. Pd(PPh 3 ) 4 (29 mg, 0.025 mmol) was added and the resulted mixture was stirred at 80° Celsius for 14 hours under N 2 . After cooling to rt, the mixture was diluted with water (50 mL) and extracted with DCM (15 mL×3). The combined organic extracts were washed with brine, dried over Na 2 SO 4 , filtered and concentrated to dryness to give 2-(di-tert-butyloxycarbonyl)amino-5-(2′-amino-3-fluorobiphenyl-4-yl)pyrazine, which was directly used in next step without any further purification. MS (ESI): mass calcd. for C 26 H 29 FN 4 O 4 S, 480.22; m/z found, 481.0 [M+H] + .

›Step C

To a solution of 2-(di-tert-butyloxycarbonyl)amino-5-(2′-amino-3-fluorobiphenyl-4-yl)pyrazine (280 mg crude, 0.5 mmol) in pyridine (5 mL) was slowly added cyclopropane-sulfonyl chloride (105 mg, 0.75 mmol) at rt. The resultant mixture was stirred at 60° Celsius for 16 hours. The mixture was concentrated to dryness, the residue diluted with 40 mL of water and extracted with DCM (10 mL×2). The combined organic extracts were washed with brine, dried over Na 2 SO 4 , filtered and concentrated to dryness. The residue was purified by FCC to give 230 mg of impure product. The solid was dissolved in HCl (4 N) in EtOH (5 mL) and stirred at rt for 1 hour, then concentrated to dryness. The residue was purified by HPLC to give the title compound (55 mg, 37% yield). MS (ESI): mass calcd. for C 19 H 17 FN 4 O 4 S, 384.11; m/z found, 385.1 [M+H] + . 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.14 (s, 1H), 8.39 (s, 1H), 8.05 (d, J=1.3, 1H), 7.92 (m, 1H), 7.51 (d, J=7.8, 1H), 7.48-7.34 (m, 5H), 6.81 (s, 2H), 2.48-2.42 (m, 1H), 0.89-0.75 (m, 4H).

›Examples174

›Example 39

The title compound was prepared using analogous conditions to those described in Example 38 utilizing hexane-1-sulfonyl chloride. MS (ESI): mass calcd. for C 22 H 25 FN 4 O 2 S, 428.17; m/z found, 429.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.13 (s, 1H), 8.40 (s, 1H), 8.04 (d, J=1.1, 1H), 7.96 (m, 1H), 7.48-7.34 (m, 6H), 6.73 (s, 2H), 2.77-2.63 (m, 2H), 1.41-1.33 (m, 2H), 1.16-0.95 (m, 6H), 0.72 (t, J=6.9, 3H).

›Example 40

The title compound was prepared using analogous conditions to those described in Example 38 utilizing cyclobutanesulfonyl chloride. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 2 S, 398.12; m/z found, 399.0 [M+H] + . 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.07 (s, 1H), 8.38 (s, 1H), 8.04 (s, 1H), 7.92 (m, 1H), 7.47-7.31 (m, 6H), 6.71 (s, 2H), 3.66 (p, J=7.7, 1H), 2.21-2.08 (m, 2H), 2.03-1.92 (m, 2H), 1.86-1.70 (m, 2H).

›Example 41

Trifluoromethanesulfonic anhydride (263 mg, 0.95 mmol) was added drop-wise to a solution consisting of 2-(di-tert-butyloxycarbonyl)amino-5-(2′-amino-3-fluorobiphenyl-4-yl)pyrazine (300 mg, 0.62 mmol) and Et 3 N (190 mg, 1.86 mmol) and DCM (10 mL), at rt. The resulting mixture was stirred at rt for 16 hours, then quenched with sat. NaHCO 3 (20 mL), diluted with water (40 mL), and extracted with DCM (15 mL×3). The combined organic fractions were washed with brine, dried over Na 2 SO 4 and concentrated to dryness. The solid was dissolved in 4 N HCl in EtOH (10 mL) and stirred at rt for 1 hour, concentrated to dryness and purified by HPLC to give the title compound. MS (ESI): mass calcd. for C 1 H 12 F 4 N 4 O 2 S, 412.06; m/z found, 413.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.41 (s, 1H), 8.06 (s, 1H), 7.96 (m, 1H), 7.56-7.45 (m, 3H), 7.44-7.32 (m, 3H), 6.77 (s, 2H).

›Example 42

To a 20 mL vial were 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (50 mg, 0.19 mmol), (2-(N,N-dimethylsulfamoyl)phenyl)boronic acid, K 2 CO 3 (43 mg, 0.19 mmol), and Pd(dppf)Cl 2 .CH 2 Cl 2 (8 mg, 0.009 mmol), and a stir-bar. The vial was sealed with a teflon lined cap and sparged with N 2 . The vial was then charged with freshly sparged DMSO (2 mL) and then stirred 16 hours at 80° Celsius. The reaction mixture was then cooled to rt, filtered, and purified by HPLC to give the title compound (36 mg, 40%). MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.11; m/z found, 373.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.33 (s, 2H), 8.06-7.96 (m, 2H), 7.72-7.67 (m, 1H), 7.64-7.59 (m, 1H), 7.43-7.39 (m, 1H), 7.32-7.26 (m, 2H), 2.49 (s, 6H).

›Example 43

The title compound was prepared in a manner similar to that described in Example 42 using 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine and (2-(piperidin-1-ylsulfonyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 2 S, 412.14; m/z found, 413.3 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.40-8.30 (m, 2H), 8.10-8.06 (m, 1H), 7.98 (m, 1H), 7.79-7.73 (m, 1H), 7.71-7.64 (m, 1H), 7.62-7.56 (m, 1H), 7.43-7.39 (m, 1H), 7.34-7.28 (m, 1H), 2.86 (d, J=5.3, 4H), 1.50-1.38 (m, 6H).

›Example 44

The title compound was prepared in a manner similar to that described in Example 42 using 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine and (2-(morpholinosulfonyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 3 S, 414.12; m/z found, 415.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.38 (s, 1H), 8.31 (s, 1H), 8.13-8.09 (m, 1H), 7.99 (m, 1H), 7.75-7.69 (m, 1H), 7.65-7.60 (m, 1H), 7.46-7.43 (m, 1H), 7.37-7.31 (m, 2H), 3.54-3.46 (m, 4H), 2.91-2.84 (m, 4H).

›Example 45

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 4-((2-bromophenyl)sulfonyl)thiomorpholine 1,1-dioxide. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 4 S 2 , 462.08: m/z found, 463.0 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.62-8.60 (m, 1H), 8.16-8.14 (m, 1H), 8.13-8.12 (m, 1H), 8.05 (t, J=8.1 Hz, 1H), 7.69-7.65 (m, 1H), 7.59-7.54 (m, 1H), 7.39-7.36 (m, 1H), 7.25-7.21 (m, 2H), 4.81 (s, 2H), 3.36-3.30 (m, 4H), 3.02-2.98 (m, 4H).

›Example 46

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)piperazine. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.39 (m, 1H), 8.21-8.13 (m, 2H), 8.01-7.95 (m, 1H), 7.79-7.74 (m, 1H), 7.69-7.63 (m, 1H), 7.50-7.46 (m, 1H), 7.37-7.30 (m, 2H), 3.14-3.08 (m, 4H), 3.06-2.99 (m, 4H).

›Example 47

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N,N-diethylbenzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.29 (d, J=1.4, 1H), 8.08-8.04 (m, 1H), 8.0-7.94 (m, 1H), 7.70-7.64 (m, 1H), 7.61-7.55 (m, 1H), 7.41-7.36 (m, 1H), 7.32-7.25 (m, 2H), 2.96 (q, J=7.1, 4H), 1.00 (t, J=7.1, 6H).

›Example 48

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)pyrrolidine. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 2 S, 398.12; m/z found, 399.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.38 (s, 1H), 8.28 (d, J=1.4, 1H), 8.12-8.08 (m, 1H), 8.0-7.94 (m, 1H), 7.71-7.65 (m, 2H), 7.62-7.56 (m, 1H), 7.42-7.39 (m, 1H), 7.34-7.27 (m, 2H), 2.94 (t, J=6.7, 4H), 1.81-1.69 (m, 4H).

›Example 49

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-4,4-difluoropiperidine. MS (ESI): mass calcd. for C 21 H 19 F 3 N 4 O 2 S, 448.12: m/z found, 449.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.35 (s, 1H), 8.27 (d, J=1.4, 1H), 8.12 (d, J=8.0, 1H), 7.98 (m, 1H), 7.75-7.67 (m, 1H), 7.63 (m, 1H), 7.43 (d, J=7.6, 1H), 7.32 (d, J=10.6, 2H), 3.02-2.93 (m, 4H), 1.90-1.73 (m, 4H).

›Example 50

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-3,3-difluoropiperidine. MS (ESI): mass calcd. for C 21 H 19 F 3 N 4 O 2 S, 448.12; m/z found, 449.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.35-8.27 (m, 2H), 8.12-8.05 (m, 1H), 8.01-7.94 (m, 1H), 7.74-7.67 (m, 1H), 7.65-7.58 (m, 1H), 7.44-7.38 (m, 1H), 7.32-7.24 (m, 2H), 3.04-2.96 (m, 2H), 2.95-2.88 (m, 2H), 1.96-1.82 (m, 2H), 1.69-1.61 (m, 2H).

›Example 51

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-3,3-difluoropyrrolidine. MS (ESI): mass calcd. for C 20 H 17 F 3 N 4 O 2 S, 434.10; m/z found, 435.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.35 (d, J=1.3, 1H), 8.27 (d, J=1.4, 1H), 8.11 (d, J=7.9, 1H), 7.99 (m, 1H), 7.77-7.69 (m, 1H), 7.67-7.59 (m, 1H), 7.47-7.40 (m, 1H), 7.34-7.25 (m, 2H), 3.23 (t, J=12.9, 2H), 3.14 (t, J=7.3, 2H), 2.28-2.14 (m, 2H).

›Example 52

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-3,3-difluoroazetidine. MS (ESI): mass calcd. for C 19 H 15 F 3 N 4 O 2 S, 420.09; m/z found, 421.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37-8.26 (m, 2H), 8.14-8.07 (m, 1H), 8.02-7.95 (m, 1H), 7.77-7.69 (m, 1H), 7.66-7.57 (m, 1H), 7.48-7.40 (m, 1H), 7.35-7.24 (m, 2H), 4.02-3.92 (m, 4H).

›Example 53

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)azepane. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 2 S, 426.15; m/z found, 427.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.21 (s, 1H), 8.02 (d, J=7.9, 1H), 7.96 (t, J=8.2, 1H), 7.66 (m, 1H), 7.60-7.55 (m, 1H), 7.38 (d, J=6.5, 1H), 7.31-7.24 (m, 2H), 1.63-1.52 (m, 12H).

›Example 54

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-4-methylpiperazine. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.2 [M+H] + . 1 H NMR (400 MHz. CD 3 OD) δ 8.37 (m, 1H), 8.23 (d, J=1.4, 1H), 8.16-8.12 (m, 1H), 8.02-7.96 (m, 1H), 7.78-7.73 (m, 1H), 7.68-7.62 (m, 1H), 7.48-7.45 (m, 1H), 7.34 (s, 1H), 7.32-7.30 (m, 1H), 3.61-3.33 (m, 4H), 3.01-2.70 (m, 7H).

›Example 55

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-4-(trifluoromethyl)piperidin-4-d. MS (ESI): mass calcd. for C 22 H 20 F 4 N 4 O 3 S, 496.12; m/z found, 497.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.38 (s, 1H), 8.23 (d, J=1.1, 1H), 8.15-8.11 (m, 1H), 7.94 (m, 1H), 7.75-7.67 (m, 1H), 7.64-7.58 (m, 1H), 7.45-7.41 (m, 1H), 7.35-7.27 (m, 2H), 3.29-3.22 (m, 2H), 2.79-2.64 (m, 2H), 1.65-1.48 (m, 4H).

›Example 56

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-4-(methylsulfonyl)piperazine. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 4 S 2 , 491.11; m/z found, 492.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.23 (s, 1H), 8.13 (d, J=7.0, 1H), 7.97 (m, 1H), 7.77-7.71 (m, 1H), 7.67-7.61 (m, 1H), 7.46 (d, J=6.4, 1H), 7.39-7.32 (m, 2H), 3.03-2.94 (m, 8H), 2.78 (s, 3H).

›Example 57

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluor-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-(4-((2-bromophenyl)sulfonyl)piperazin-1-yl)ethanone. MS (ESI): mass calcd. for C 22 H 22 FN 5 O 3 S, 455.14; m/z found, 456.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.34 (d, J=6.0, 2H), 8.11-8.08 (m, 1H), 8.00 (m, 1H), 7.75-7.70 (m, 1H), 7.65-7.60 (m, 1H), 7.45-7.41 (m, 1H), 7.37-7.29 (m, 2H), 3.43-3.34 (m, 4H), 2.96-2.81 (m, 4H), 2.02 (s, 3H).

›Example 58

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and (4-((2-bromophenyl)sulfonyl)piperazin-1-yl)(cyclopropyl)-methanone. MS (ESI): mass calcd. for C 24 H 24 FN 5 O 3 S, 481.16: m/z found, 482.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.63-8.59 (m, 1H), 8.16-8.10 (m, 2H), 8.00 (m, 1H), 7.67-7.62 (m, 1H), 7.58-7.53 (m, 1H), 7.39-7.36 (m, 1H), 7.32-7.30 (m, 1H), 7.28 (s, 1H), 4.76 (s, 2H), 3.48 (s, 4H), 2.94-2.82 (m, 4H), 1.63-1.54 (m, 1H), 0.97-0.89 (m, 2H), 0.79-0.70 (m, 2H).

›Example 59

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-(4-((2-bromophenyl)sulfonyl)piperazin-1-yl)ethanol. MS (ESI): mass calcd. for C 22 H 24 FN 5 O 3 S, 457.16; m/z found, 458.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.38 (m, 1H), 8.21 (d, J=1.5, 1H), 8.16-8.13 (m, 1H), 7.98 (m, 1H), 7.79-7.73 (m, 1H), 7.68-7.63 (m, 1H), 7.49-7.45 (m, 1H), 7.36-7.30 (m, 2H), 3.86-3.78 (m, 2H), 3.66-3.32 (m, 4H), 3.24-3.20 (m, 2H), 3.15-2.72 (m, 4H).

›Example 60

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-4-cyclopropylpiperazine. MS (ESI): mass calcd. for C 23 H 24 FN 5 O 2 S, 453.16; m/z found, 454.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.40 (s, 1H), 8.18-8.12 (m, 2H), 7.97 (m, 1H), 7.79-7.74 (m, 1H), 7.68-7.63 (m, 1H), 7.49-7.46 (m, 1H), 7.34-7.30 (m, 2H), 3.28-2.98 (d, J=1.6, 8H), 2.82-2.75 (m, 1H), 0.96-0.85 (m, 4H).

›Example 61

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic 2-((2-bromophenyl)sulfonyl)octahydropyrrolo[1,2-a]pyrazine. MS (ESI): mass calcd. for C 23 H 24 FN 5 O 2 S, 453.16; m/z found, 454.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (d, J=1.4, 1H), 8.24 (d, J=1.4, 1H), 8.17-8.13 (m, 1H), 7.99 (m, 1H), 7.78-7.73 (m, 1H), 7.68-7.63 (m, 1H), 7.48-7.45 (m, 1H), 7.36-7.30 (m, 2H), 3.89-3.35 (m, 4H), 3.26-2.53 (m, 6H), 2.18-1.97 (m, 3H).

›Example 62

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and Racemic-1-((2-bromophenyl)sulfonyl)-3,5-dimethylpiperazine. MS (ESI): mass calcd. for C 22 H 24 FN 5 O 2 S, 441.16; m/z found, 442.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.24 (d, J=1.4, 1H), 8.17-8.14 (m, 1H), 7.99 (m, 1H), 7.79-7.73 (m, 1H), 7.68-7.63 (m, 1H), 7.49-7.46 (m, 1H), 7.37-7.32 (m, 2H), 3.49-3.42 (m, 2H), 3.14-3.01 (m, 2H), 2.47-2.39 (m, 2H), 1.17 (d, J=6.6, 6H).

›Example 63

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic 1-((2-bromophenyl)sulfonyl)piperidine-3-carbonitrile. MS (ESI): mass calcd. for C 22 H 20 FN 5 O 2 S, 437.13; m/z found, 438.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.35 (s, 1H), 8.29 (d, J=1.1, 1H), 8.11-8.07 (m, 1H), 7.98 (m, 1H), 7.74-7.68 (m, 1H), 7.65-7.60 (m, 1H), 7.44-7.40 (m, 1H), 7.36-7.30 (m, 2H), 3.06-3.02 (m, 2H), 2.90-2.86 (m, 2H), 2.80-2.74 (m, 1H), 1.89-1.80 (m, 1H), 1.77-1.61 (m, 2H), 1.53-1.42 (m, 1H).

›Example 64

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)piperidine-4-carbonitrile. MS (ESI): mass calcd. for C 22 H 20 FN 5 O 2 S, 437.13; m/z found, 438.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.35 (s, 1H), 8.29 (d, J=1.1, 1H), 8.12-8.09 (m, 1H), 7.99 (m, 1H), 7.74-7.69 (m, 1H), 7.65-7.60 (m, 1H), 7.45-7.42 (m, 1H), 7.34 (s, 1H), 7.32-7.30 (m, 1H), 3.10-3.02 (m, 2H), 2.86-2.73 (m, 3H), 1.82-1.73 (m, 2H), 1.64-1.53 (m, 2H).

›Example 65

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)piperidin-4-amine. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.36 (s, 1H), 8.25-8.23 (d. J=1.4, 1H), 8.11-8.08 (m, 1H), 7.96 (m, 1H), 7.74-7.69 (m, 1H), 7.65-7.60 (m, 1H), 7.45-7.41 (m, 1H), 7.32-7.29 (m, 1H), 7.28 (s, 1H), 3.47-3.40 (m, 2H), 3.18-3.08 (m, 1H), 2.57-2.43 (m, 2H), 1.91-1.84 (m, 2H), 1.51-1.39 (m, 2H).

›Example 66

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 4-((2-bromophenyl)sulfonyl)piperazin-2-one. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 3 S, 427.11; m/z found, 428.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.27 (d, J=1.4, 1H), 8.17-8.13 (m, 1H), 7.98 (m, 1H), 7.77-7.72 (m, 1H), 7.67-7.62 (m, 1H), 7.47-7.43 (m, 1H), 7.34-7.26 (m, 2H), 3.39 (s, 2H), 3.14 (s, 4H).

›Example 67

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)piperidin-4-ol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.36-8.31 (m, 2H), 8.10-8.06 (m, 1H), 7.99 (m, 1H), 7.73-7.67 (m, 1H), 7.64-7.58 (m, 1H), 7.44-7.40 (m, 1H), 7.34-7.28 (m, 2H), 3.66-3.55 (m, 1H), 3.20-3.08 (m, 2H), 2.71-2.61 (m, 2H), 1.72-1.63 (m, 2H), 1.39-1.26 (m, 2H).

›Example 68

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and (1-((2-bromophenyl)sulfonyl)piperidin-4-yl)methanol. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.36-8.29 (m, 2H), 8.11-8.07 (m, 1H), 7.98 (m, 1H), 7.74-7.67 (m, 1H), 7.64-7.59 (m, 1H), 7.44-7.41 (m, 1H), 7.36-7.29 (m, 2H), 3.40-3.32 (m, 4H), 2.46-2.36 (m, 2H), 1.59 (d, J=10.5, 2H), 1.48-1.36 (m, 1H), 1.01-0.89 (m, 2H).

›Example 69

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-(1-((2-bromophenyl)sulfonyl)piperidin-4-yl)ethanol. MS (ESI): mass calcd. for C 23 H 25 FN 4 O 3 S, 456.16; m/z found, 457.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.34 (s, 1H), 8.31 (d, J=1.2, 1H), 8.10-8.07 (m, 1H), 7.98 (m, 1H), 7.73-7.67 (m, 1H), 7.64-7.58 (m, 1H), 7.44-7.41 (m, 1H), 7.34 (s, 1H), 7.32-7.30 (m, 1H), 3.56-3.48 (m, 2H), 3.32 (d, J=4.5, 2H), 2.45-2.36 (m, 2H), 1.61-1.54 (m, 2H), 1.46-1.34 (m, 3H), 1.01-0.87 (m, 2H).

›Example 70

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic-1-((2-bromophenyl)sulfonyl)piperidin-3-ol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.34 (s, 1H), 8.31 (d, J=1.4, 1H), 8.11-8.06 (m, 1H), 8.01-7.96 (m, 1H), 7.73-7.68 (m, 1H), 7.64-7.59 (m, 1H), 7.44-7.40 (m, 1H), 7.34-7.32 (m, 1H), 7.31-7.29 (m, 1H), 3.44-3.35 (m, 1H), 3.27-3.21 (m, 1H), 3.15-3.06 (m, 1H), 2.48-2.38 (m, 1H), 2.27-2.21 (m, 1H), 1.88-1.79 (m, 1H), 1.68-1.59 (m, 1H), 1.41-1.28 (m, 1H), 1.26-1.15 (m, 1H).

›Example 71

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic-2-(1-((2-bromophenyl)sulfonyl)piperidin-3-yl)ethanol. MS (ESI): mass calcd. for C 23 H 25 FN 4 O 3 S, 456.16; m/z found, 457.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.36-8.31 (m, 2H), 8.10-8.05 (m, 1H), 8.01-7.95 (m, 1H), 7.73-7.67 (m, 1H), 7.64-7.58 (m, 1H), 7.44-7.40 (m, 1H), 7.36-7.29 (m, 2H), 3.52-3.40 (m, 2H), 3.26-3.16 (m, 2H), 2.48-2.36 (m, 1H), 2.14-2.08 (m, 1H), 1.77-1.67 (m, 1H), 1.62-1.53 (m, 1H), 1.49-1.37 (m, 1H), 1.36-1.25 (m, 3H), 1.02-0.89 (m, 1H).

›Example 72

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-N-methylpiperidin-4-amine. MS (ESI): mass calcd. for C 22 H 24 FN 5 O 2 S, 441.16; m/z found, 442.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.21 (d, J=1.4, 1H), 8.12-8.09 (m, 1H), 7.96 (m, 1H), 7.75-7.70 (m, 1H), 7.65-7.60 (m, 1H), 7.45-7.41 (m, 1H), 7.32-7.30 (m, 1H), 7.28 (s, 1H), 3.49-3.42 (m, 2H), 3.10-3.01 (m, 1H), 2.63 (s, 3H), 2.54-2.42 (m, 2H), 2.00-1.92 (m, 2H), 1.47-1.35 (m, 2H).

›Example 73

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)-N,N-dimethylpiperidin-4-amine. MS (ESI): mass calcd. for C 23 H 26 FN 5 O 2 S, 455.18; m/z found, 456.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.38 (m, 1H), 8.20 (d, J=1.5, 1H), 8.14-8.10 (m, 1H), 7.99-7.94 (m, 1H), 7.76-7.71 (m, 1H), 7.66-7.61 (m, 1H), 7.47-7.43 (m, 1H), 7.36-7.30 (m, 2H), 3.52-3.45 (m, 2H), 3.26-3.16 (m, 1H), 2.78 (s, 6H), 2.55-2.44 (m, 2H), 1.93 (d, J=11.6, 2H), 1.48-1.36 (m, 2H).

›Example 74

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic-1-((2-bromophenyl)sulfonyl)piperidin-3-amine. MS (ESI): mass calcd. for C 26 H 30 FN 5 O 4 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.45 (s, 1H), 8.33 (s, 1H), 8.11-8.07 (m, 1H), 8.03 (m, 1H), 7.76-7.70 (m, 1H), 7.67-7.62 (m, 1H), 7.46-7.42 (m, 1H), 7.36-7.29 (m, 2H), 3.40-3.41 (m, 1H), 3.13-3.02 (m, 2H), 2.66-2.60 (m, 2H), 2.01-1.92 (m, 1H), 1.78-1.67 (m, 1H), 1.55-1.42 (m, 2H).

›Example 75

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and N-(1-((2-bromophenyl)sulfonyl)piperidin-4-yl)acetamide. MS (ESI): mass calcd. for C 23 H 24 FN 5 O 3 S, 469.16; m/z found, 470.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.41-8.38 (m, 1H), 8.08 (d, J=1.4, 1H), 8.01-7.97 (m, 1H), 7.90 (m, 1H), 7.80 (d, J=7.6, 1H), 7.77-7.72 (m, 1H), 7.68-7.63 (m, 1H), 7.46-7.42 (m, 1H), 7.33-7.24 (m, 2H), 3.61-3.50 (m, 1H), 3.26-3.18 (m, 2H), 2.59-2.52 (m, 2H), 1.76 (s, 3H), 1.67-1.59 (m, 2H), 1.27-1.15 (m, 2H).

›Example 76

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic (1-((2-bromophenyl)sulfonyl)piperidin-3-yl)methanol. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.33 (d, J=8.7, 2H), 8.10-8.06 (m, 1H), 7.96 (m, 1H), 7.73-7.67 (m, 1H), 7.64-7.58 (m, 1H), 7.44-7.40 (m, 1H), 7.36-7.29 (m, 2H), 3.43-3.32 (m, 2H), 3.27-3.16 (m, 2H), 2.43-2.34 (m, 1H), 2.22-2.14 (m, 1H), 1.68-1.54 (m, 2H), 1.53-1.42 (m, 1H), 1.35-1.21 (m, 1H), 1.03-0.91 (m, 1H).

›Example 77

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic tert-butyl (1-((2-bromophenyl)sulfonyl)piperidin-3-yl)carbamate. MS (ESI): mass calcd. for C 26 H 30 FN 5 O 4 S, 527.20: m/z found, 528.3 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.34 (d, J=9.1, 2H), 8.10-8.07 (m, 1H), 8.00 (m, 1H), 7.73-7.68 (m, 1H), 7.64-7.59 (m, 1H), 7.44-7.40 (m, 1H), 7.35-7.29 (m, 2H), 3.30-3.20 (m, 2H), 3.15-3.06 (m, 1H), 2.51-2.40 (m, 1H), 2.30-2.21 (m, 1H), 1.79-1.70 (m, 1H), 1.65-1.56 (m, 1H), 1.39-1.28 (m, 10H), 1.26-1.14 (m, 1H).

›Example 78

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N-((1S,2S)-1,3-dihydroxy-1-phenylpropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 23 FN 4 O 4 S, 494.14; m/z found, 495.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.45 (d. J=1.4, 1H), 8.10 (s, 1H), 7.87-7.80 (m, 2H), 7.55 (t, J=7.5, 1H), 7.43-7.36 (m, 2H), 7.30-7.14 (m, 8H), 4.89 (d, J=4.0, 1H), 3.65-3.57 (m, 1H), 3.36 (d, J=1.4, 2H).

›Example 79

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and (S)-2-bromo-N-(1-hydroxy-4-methylpentan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 25 FN 4 O 3 S, 444.16; m/z found, 445.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.33 (s, 1H), 8.29 (d, J=1.4, 1H), 8.16-8.12 (m, 1H), 7.98-7.92 (m, 1H), 7.68-7.63 (m, 1H), 7.60-7.55 (m, 1H), 7.40-7.28 (m, 3H), 3.41-3.34 (m, 1H), 3.29-3.22 (m, 2H), 1.59-1.47 (m, 1H), 1.35-1.17 (m, 2H), 0.81 (d, J=6.7, 3H), 0.73 (d, J=6.5, 3H).

›Example 80

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N-(3-hydroxypropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.12; m/z found, 403.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (d, J=1.2, 1H), 8.30 (s, 1H), 8.08-8.03 (m, 1H), 8.01-7.96 (m, 1H), 7.70-7.63 (m, 1H), 7.62-7.56 (m, 1H), 7.42-7.32 (m, 1H), 7.36-7.28 (m, 2H), 3.51 (t, J=6.2, 2H), 2.88 (t, J=7.0, 2H), 1.65-1.54 (m, 2H).

›Example 81

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and (S)-2-bromo-N-(2-hydroxy-1-phenylethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 21 FN 4 O 3 S, 464.13; m/z found, 465.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.30 (m, 2H), 8.05-8.01 (m, 1H), 7.85 (t, J=8.2, 1H), 7.61-7.56 (m, 1H), 7.50-7.44 (m, 1H), 7.26-7.19 (m, 4H), 7.10-6.97 (m, 4H), 4.20 (t, J=6.6, 1H), 3.69-3.58 (m, 2H).

›Example 82

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and (R)-2-bromo-N-(2-hydroxy-1-phenylethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 21 FN 4 O 3 S, 464.13; m/z found, 465.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.36-8.32 (m, 1H), 8.07-8.01 (m, 2H), 7.75 (t, J=8.2, 1H), 7.60-7.54 (m, 1H), 7.49-7.44 (m, 1H), 7.25-7.18 (m, 4H), 7.07-7.00 (m, 3H), 6.98-6.92 (m, 1H), 4.19 (t, J=6.6, 1H), 3.69-3.58 (m, 2H).

›Example 83

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N-((1S,2S)-1-hydroxy-1-phenylpropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 23 FN 4 O 3 S, 478.15; m/z found, 479.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.36 (s, 1H), 8.12-8.05 (m, 2H), 7.89-7.83 (m, 1H), 7.67-7.62 (m, 1H), 7.59-7.54 (m, 1H), 7.37-7.34 (m, 1H), 7.27-7.12 (m, 7H), 4.60 (t, J=4.4, 1H), 3.42-3.34 (m, 1H), 0.91-0.84 (m, 3H).

›Example 84

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N-((2S,3S)-1-hydroxy-3-methylpentan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 25 FN 4 O 3 S, 444.16; m/z found, 445.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.16-8.13 (m, 1H), 8.06 (d, J=1.4, 1H), 7.86 (m, 1H), 7.67-7.62 (m, 1H), 7.58-7.53 (m, 1H), 7.39-7.28 (m, 3H), 3.46-3.35 (m, 2H), 3.13 (q, J=5.4, 1H), 1.60-1.49 (m, 1H), 1.48-1.36 (m, 1H), 1.07-0.93 (m, 1H), 0.84-0.74 (m, 6H).

›Example 85

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N-((1R,2R)-2-hydroxycyclohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37-8.30 (m, 2H), 8.21-8.16 (m, 1H), 7.97 (m, 1H), 7.68-7.62 (m, 1H), 7.60-7.54 (m, 1H), 7.40-7.32 (m, 3H), 3.26-3.18 (m, 1H), 2.87-2.79 (m, 1H), 1.94-1.77 (m, 2H), 1.67-1.50 (m, 2H), 1.26-1.09 (m, 4H).

›Example 86

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and (R)-2-bromo-N-(1-hydroxybutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.32 (m, 2H), 8.16-8.12 (m, 1H), 7.96 (m, 1H), 7.68-7.63 (m, 1H), 7.60-7.55 (m, 1H), 7.40-7.30 (m, 3H), 3.43-3.35 (m, 1H), 3.33 (d, J=5.9, 1H), 3.12-3.05 (m, 1H), 1.60-1.48 (m, 1H), 1.42-1.28 (m, 1H), 0.79 (t, J=7.4, 3H).

›Example 87

The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N-((1R,2S)-2-hydroxycyclohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.33 (s, 2H), 8.15-8.11 (m, 1H), 7.98 (m, 1H), 7.69-7.64 (m, 1H), 7.61-7.56 (m, 1H), 7.42-7.32 (m, 3H), 3.70-3.63 (m, 1H), 3.09-3.03 (m, 1H), 1.70-1.61 (m, 1H), 1.60-1.44 (m, 3H), 1.42-1.24 (m, 3H), 1.22-1.10 (m, 1H).

›Example 88

5-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (40 mg, 0.13 mmol) and 2-bromo-N-(2-hydroxyethyl)benzenesulfonamide (53 mg, 0.19 mmol) were added to a 5 mL sealable vial equipped with a stir bar. 1,4-Dioxane (0.7 mL) and Na 2 CO 3 (0.3 mL, 2 M) were added. Argon was bubbled through the solvent while it was rapidly stirred for 10 min before adding Pd(dppf)Cl 2 .CH 2 Cl 2 (5 mg, 0.006 mmol) and heating the mixture heated 15 hours at 80° Celsius. The reaction was cooled to rt, diluted with 2 mL of ethylacetate, 2 mL of water and extracted with of ethyl acetate (3×10 mL). The combined organic extracts were then dried with Na 2 SO 4 and concentrated to dryness. The crude product was purified by HPLC to give the title compound. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 3 S, 388.10; m/z found, 389.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.37 (dd, J=2.2, 1.5, 1H), 8.11-8.06 (m, 2H), 7.93-7.86 (m, 1H), 7.70-7.64 (m, 1H), 7.62-7.56 (m, 1H), 7.44-7.38 (dd, J=7.6, 1.3, 1H), 7.35-7.27 (m, 2H), 3.49-3.44 (t, J=5.9, 2H), 2.90-2.84 (t, J=5.9, 2H).

›Example 89

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-cyclopropylbenzenesulfonamide. MS (ESI): mass calcd. for C 19 H 17 FN 4 O 2 S, 384.11; m/z found, 385.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39-8.31 (d, J=1.6, 1H), 8.26-8.18 (d, J=1.5, 1H), 8.14-8.08 (dd, J=8.0, 1.3, 1H), 7.97-7.89 (m, 1H), 7.73-7.66 (m, 1H), 7.65-7.57 (m, 1H), 7.46-7.37 (dd, J=7.6, 1.4, 1H), 7.33-7.23 (m, 3H), 2.22-2.13 (m, 1H), 0.50-0.43 (m, 2H), 0.41-0.34 (m, 2H).

›Example 90

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(cyclopropylmethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 2 S, 398.12; m/z found, 399.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.33 (m, 1H), 8.15-8.10 (dd, J=8.0, 1.3, 1H), 8.09-8.06 (d, J=1.5, 1H), 7.91-7.82 (m, 1H), 7.70-7.63 (m, 1H), 7.61-7.53 (m, 1H), 7.40-7.35 (dd, J=7.6, 1.4, 1H), 7.25 (s, 1H), 7.24-7.21 (m, 1H), 1.21 (m, 3H), 0.50-0.46 (m, 2H), 0.39-0.28 (m, 2H).

›Example 91

The title compound was prepared in a manner similar to that described in Example 88 using (R)-(1-((2-bromophenyl)sulfonyl)pyrrolidin-2-yl)methanol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39-8.34 (m, 1H), 8.24-8.19 (d, J=1.5, 1H), 8.14-8.08 (dd, J=8.0, 1.3, 1H), 7.98-7.91 (m, 1H), 7.73-7.66 (m, 1H), 7.65-7.57 (m, 1H), 7.46-7.39 (dd, J=7.6, 1.3, 1H), 7.33-7.32 (m, 1H), 7.32-7.27 (dd, J=6.0, 1.6, 1H), 3.52-3.45 (m, 1H), 3.41-3.34 (dd, J=11.0, 3.9, 1H), 3.24-3.13 (m, 1H), 3.02-2.89 (m, 2H), 1.88-1.73 (m, 3H), 1.71-1.62 (dd, J=6.9, 4.6, 1H).

›Example 92

The title compound was prepared in a manner similar to that described in Example 88 using (R)-1-((2-bromophenyl)sulfonyl)pyrrolidin-3-amine, followed by removal of the Boc group with trifluoroacetic acid in dichloromethane at rt. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.44-8.29 (m, 1H), 8.17-8.13 (d, J=1.5, 1H), 8.13-8.09 (dd, J=8.0, 1.3, 1H), 7.99-7.88 (m, 1H), 7.79-7.69 (m, 1H), 7.69-7.59 (m, 1H), 7.50-7.42 (dd, J=7.6, 1.4, 1H), 7.32 (s, 1H), 7.31-7.29 (dd, J=2.9, 1.5, 1H), 3.77-3.60 (m, 1H), 3.29-3.25 (m, 1H), 3.21-3.12 (dd. J=10.9, 6.7, 1H), 3.12-3.01 (dd, J=10.9, 5.0, 1H), 2.98-2.86 (m, 1H), 2.23-2.12 (m, 1H), 1.94-1.78 (m, 1H).

›Example 93

The title compound was prepared in a manner similar to that described in Example 88 using (S)-1-((2-bromophenyl)sulfonyl)pyrrolidin-3-amine, followed by removal of the Boc group with trifluoroacetic acid in dichloromethane at rt. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.35 (m, 1H), 8.16-8.13 (d, J=1.4, 1H), 8.13-8.09 (dd, J=8.0, 1.3, 1H), 7.98-7.90 (m, 1H), 7.77-7.71 (m, 1H), 7.68-7.60 (m, 1H), 7.47-7.43 (dd, J=7.5, 1.3, 1H), 7.34-7.31 (m, 1H), 7.31-7.29 (q, J=1.5, 1H), 3.73-3.63 (p, J=6.1, 1H), 3.29-3.23 (m, 1H), 3.19-3.13 (dd, J=10.8, 6.7, 1H), 3.10-3.03 (dd, J=10.9, 5.0, 1H), 2.98-2.85 (m, 1H), 2.25-2.11 (m, 1H), 1.93-1.80 (m, 1H).

›Example 94

The title compound was prepared in a manner similar to that described in Example 88 using (R)-(1-((2-bromophenyl)sulfonyl)pyrrolidin-2-yl)-methan-amine. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.38 (m, 1H), 8.16-8.13 (dd, J=8.1, 1.3, 1H), 8.13-8.12 (d, J=1.5, 1H), 7.94-7.89 (m, 1H), 7.78-7.73 (m, 1H), 7.69-7.63 (m, 1H), 7.48-7.45 (dd, J=7.6, 1.3, 1H), 7.36-7.30 (m, 2H), 3.71-3.62 (m, 1H), 3.15-3.08 (m, 1H), 3.05-2.98 (m, 1H), 2.86-2.74 (m, 2H), 1.92-1.76 (m, 2H), 1.73-1.62 (m, 2H).

›Example 95

The title compound was prepared in a manner similar to that described in Example 88 using (S)-(1-((2-bromophenyl)sulfonyl)pyrrolidin-2-yl)methanol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.37-8.34 (m, 1H), 8.24-8.22 (d, J=1.4, 1H), 8.13-8.09 (dd, J=8.0, 1.3, 1H), 7.98-7.93 (m, 1H), 7.73-7.67 (m, 1H), 7.63-7.59 (m, 1H), 7.44-7.40 (dd, J=7.6, 1.3, 1H), 7.34-7.32 (m, 1H), 7.32-7.30 (dd, J=5.9, 1.6, 1H), 3.52-3.45 (dd, J=7.6, 4.0, 1H), 3.40-3.34 (m, 1H), 3.22-3.11 (dd, J=10.8, 7.9, 1H), 3.02-2.87 (m, 2H), 1.90-1.72 (m, 3H), 1.71-1.62 (dd, J=6.7, 4.5, 1H).

›Example 96

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(methylsulfonyl)benzenesulfonamide. MS (ESI): mass calcd. for C 17 H 15 FN 4 O 4 S 2 , 422.05; m/z found, 423.0 [M+H] + . 1 H NMR (500 MHz, acetone-d 6 ) δ 8.56 (s, 1H), 8.25-8.18 (dd, J=7.9, 1.4, 1H), 8.16 (s, 1H), 7.90-7.84 (m, 1H), 7.64-7.57 (m, 1H), 7.57-7.50 (m, 1H), 7.46-7.40 (dd, J=8.2, 1.6, 1H), 7.38-7.31 (d, J=13.3, 1H), 7.31-7.26 (dd, J=7.4, 1.4, 1H), 2.96 (s, 3H).

›Example 97

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(2-hydroxypropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.12; m/z found, 403.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.27-8.19 (m, 1H), 8.11-8.03 (dd, J=8.0, 1.3, 1H), 7.99-7.91 (m, 1H), 7.72-7.64 (m, 1H), 7.64-7.55 (m, 1H), 7.45-7.38 (d, J=7.5, 1H), 7.37-7.27 (m, 2H), 3.74-3.61 (m, 1H), 2.80-2.72 (m, 1H), 2.72-2.64 (m, 1H), 1.10-0.99 (d, J=6.2, 3H).

›Example 98

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(2-hydroxypropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.12; m/z found, 403.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.35 (m, 1H), 8.21-8.17 (d, J=1.5, 1H), 8.10-8.04 (dd, J=8.0, 1.3, 1H), 7.96-7.91 (m, 1H), 7.71-7.65 (m, 1H), 7.62-7.57 (m, 1H), 7.44-7.39 (dd, J=7.5, 1.3, 1H), 7.36-7.29 (m, 2H), 3.73-3.60 (m, 1H), 2.77-2.72 (m, 1H), 2.71-2.65 (m, 1H), 1.08-1.03 (d, J=6.3, 3H).

›Example 99

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-((1-hydroxycyclohexyl)methyl)-benzenesulfonamide. MS (ESI): mass calcd. for C 23 H 25 FN 4 O 3 S, 456.16; m/z found, 457.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.44-8.37 (dd, J=2.2, 1.5, 1H), 8.10-8.04 (m, 2H), 7.96-7.87 (m, 1H), 7.71-7.64 (m, 1H), 7.63-7.56 (m, 1H), 7.46-7.39 (dd, J=7.6, 1.4, 1H), 7.37-7.28 (m, 2H), 2.67 (s, 2H), 1.61-1.22 (m, 10H).

›Example 100

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(1-hydroxy-2-methylpropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.35 (m, 1H), 8.18-8.13 (m, 2H), 7.97-7.90 (m, 1H), 7.69-7.63 (m, 1H), 7.60-7.54 (m, 1H), 7.41-7.38 (dd, J=7.7, 1.4, 1H), 7.38-7.33 (m, 2H), 3.27 (s, 2H), 1.01 (s, 6H).

›Example 101

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.38 (dd, J=2.2, 1.4, 1H), 8.10-8.07 (d, J=1.5, 1H), 8.07-8.03 (dd, J=7.9, 1.0, 1H), 7.93-7.88 (m, 1H), 7.70-7.64 (m, 1H), 7.62-7.57 (m, 1H), 7.44-7.40 (dd, J=7.5, 1.2, 1H), 7.36-7.28 (m, 2H), 2.67 (s, 2H), 1.09 (s, 6H).

›Example 102

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(4-hydroxy-2-methylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.36 (m, 1H), 8.18-8.16 (d, J=1.5, 1H), 8.16-8.12 (dd, J=8.0, 1.3, 1H), 7.96-7.89 (m, 1H), 7.68-7.62 (m, 1H), 7.60-7.54 (m, 1H), 7.42-7.37 (dd, J=7.6, 1.4, 1H), 7.37-7.35 (m, 1H), 7.35-7.32 (dd. J=3.9, 1.6, 1H), 3.61-3.53 (t, J=6.7, 2H), 1.67-1.62 (t, J=6.7, 2H), 1.08 (s, 6H).

›Example 103

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(3-hydroxy-2,2-dimethylpropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.35 (m, 1H), 8.10-8.06 (d, J=1.5, 1H), 8.05-8.02 (dd, J=8.0, 1.3, 1H), 7.95-7.85 (m, 1H), 7.71-7.63 (m, 1H), 7.63-7.54 (m, 1H), 7.45-7.39 (dd, J=7.6, 1.3, 1H), 7.38-7.28 (m, 2H), 3.19 (s, 2H), 2.62 (s, 2H), 0.77 (s, 6H).

›Example 104

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(2,3-dihydroxypropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 4 S, 418.11; m/z found, 419.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.33 (m, 1H), 8.27-8.23 (d, J=1.4, 1H), 8.11-8.05 (dd, J=8.0, 1.3, 1H), 7.99-7.93 (m, 1H), 7.72-7.64 (m, 1H), 7.63-7.57 (m, 1H), 7.44-7.39 (dd, J=7.6, 1.4, 1H), 7.38-7.29 (m, 2H), 3.62-3.53 (m, 1H), 3.43-3.39 (m, 2H), 2.97-2.90 (dd, J=13.2, 4.8, 1H), 2.79-2.71 (dd, J=13.2, 7.0, 1H).

›Example 105

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(2,3-dihydroxypropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 4 S, 418.11; m/z found, 419.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.32 (m, 1H), 8.29-8.22 (d, J=1.4, 1H), 8.11-8.05 (dd, J=8.0, 1.3, 1H), 8.00-7.91 (m, 1H), 7.72-7.64 (m, 1H), 7.64-7.58 (m, 1H), 7.44-7.40 (dd, J=7.6, 1.3, 1H), 7.37-7.29 (m, 2H), 3.61-3.52 (m, 1H), 3.43-3.39 (m, 2H), 2.97-2.90 (dd, J=13.1, 4.8, 1H), 2.80-2.72 (dd, J=13.1, 7.0, 1H).

›Example 106

The title compound was prepared in a manner similar to that described in Example 88 using (trans)-1-((2-bromophenyl)sulfonyl)pyrrolidine-3,4-diol. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 4 S, 430.11; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39-8.34 (m, 1H), 8.24-8.20 (d, J=1.5 Hz, 1H), 8.15-8.08 (dd. J=8.0, 1.3 Hz, 1H), 7.97-7.88 (m, 1H), 7.70-7.64 (td, J=7.5, 1.4 Hz, 1H), 7.62-7.54 (td, J=7.7, 1.4 Hz, 1H), 7.47-7.38 (dd, J=7.6, 1.3 Hz, 1H), 7.34-7.31 (dd, J=8.0, 1.7 Hz, 1H), 7.31-7.27 (dd, J=12.3, 1.7 Hz, 1H), 4.00-3.97 (m, 2H), 3.29-3.27 (m, 2H), 3.07-3.03 (m, 2H).

›Example 107

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(2-oxopyrrolidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 3 S, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.38 (dd, J=2.2, 1.4, 1H), 8.26-8.22 (dd, J=8.2, 1.3, 1H), 8.08-8.06 (d, J=1.5, 1H), 7.91-7.84 (m, 1H), 7.70-7.64 (m, 1H), 7.61-7.55 (m, 1H), 7.41-7.38 (dd, J=7.6, 1.3, 1H), 7.38-7.32 (m, 2H), 3.88-3.81 (dd, J=10.3, 8.3, 1H), 3.28-3.22 (m, 1H), 3.22-3.15 (m, 1H), 2.38-2.30 (m, 1H), 1.96-1.86 (m, 1H).

›Example 108

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(2-oxopiperidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 3 S, 441.13; m/z found, 442.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.25-8.15 (m, 2H), 7.97-7.88 (m, 1H), 7.71-7.62 (m, 1H), 7.62-7.54 (m, 1H), 7.42-7.30 (m, 3H), 3.67-3.57 (dd, J=10.4, 5.8, 1H), 3.22-3.17 (m, 2H), 2.19-2.07 (d, J=10.6, 1H), 1.90-1.79 (m, 1H), 1.78-1.64 (m, 2H).

›Example 109

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(1-hydroxy-3-methylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.37 (dd, J=2.2, 1.4, 1H), 8.16-8.11 (dd, J=8.0, 1.3, 1H), 8.10-8.06 (d, J=1.5, 1H), 7.91-7.84 (m, 1H), 7.68-7.61 (m, 1H), 7.60-7.53 (m, 1H), 7.39-7.35 (dd, J=7.7, 1.4, 1H), 7.36-7.28 (m, 2H), 3.45-3.39 (m, 1H), 3.38-3.33 (m, 1H), 3.10-3.03 (m, 1H), 1.89-1.75 (m, 1H), 0.86-0.75 (dd, J=6.9, 4.4, 6H).

›Example 110

The title compound was prepared in a manner similar to that described in Example 88 using trans-2-bromo-N-(4-hydroxycyclohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.34 (m, 1H), 8.22-8.17 (d, J=1.5, 1H), 8.14-8.08 (dd, J=7.9, 1.3, 1H), 7.96-7.90 (m, 1H), 7.69-7.64 (m, 1H), 7.62-7.56 (m, 1H), 7.43-7.38 (dd, J=7.7, 1.3, 1H), 7.35-7.28 (m, 2H), 3.43-3.36 (m, 1H), 2.89-2.77 (m, 1H), 1.87-1.77 (m, 2H), 1.77-1.68 (dd, J=8.3, 4.0, 2H), 1.27-1.05 (m, 4H).

›Example 111

The title compound was prepared in a manner similar to that described in Example 88 using (R)-(1-((2-bromophenyl)sulfonyl)pyrrolidin-3-yl)methanol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.22-8.19 (d, J=1.5, 1H), 8.14-8.08 (dd, J=8.1, 1.3, 1H), 7.97-7.93 (m, 1H), 7.75-7.66 (m, 1H), 7.65-7.57 (m, 1H), 7.45-7.39 (dd, J=7.6, 1.3, 1H), 7.37-7.25 (m, 2H), 3.42-3.36 (m, 1H), 3.09-3.03 (dd, J=9.5, 7.5, 1H), 3.03-2.97 (m, 1H), 2.95-2.85 (m, 1H), 2.75-2.64 (dd, J=9.6, 7.2, 1H), 2.29-2.17 (m, 1H), 1.86-1.76 (m, 1H), 1.54-1.41 (m, 1H).

›Example 112

The title compound was prepared in a manner similar to that described in Example 88 using (S)-(1-((2-bromophenyl)sulfonyl)pyrrolidin-3-yl)methanol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.32 (m, 1H), 8.24-8.17 (d, J=1.5, 1H), 8.12-8.07 (dd, J=8.0, 1.3, 1H), 7.99-7.93 (m, 1H), 7.72-7.66 (m, 1H), 7.64-7.58 (m, 1H), 7.44-7.40 (dd, J=7.5, 1.3, 1H), 7.35-7.26 (m, 2H), 3.43-3.36 (m, 1H), 3.33-3.28 (m, 1H), 3.08-3.03 (dd, J=9.6, 7.6, 1H), 3.03-2.98 (m, 1H), 2.94-2.86 (m, 1H), 2.74-2.65 (dd, J=9.6, 7.1, 1H), 2.30-2.13 (m, 1H), 1.87-1.74 (m, 1H), 1.56-1.41 (m, 1H).

›Example 113

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(2-oxopiperidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 3 S, 441.13; m/z found, 442.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.37-8.34 (m, 1H), 8.26-8.19 (m, 2H), 7.97-7.91 (m, 1H), 7.69-7.64 (m, 1H), 7.62-7.54 (m, 1H), 7.42-7.34 (m, 3H), 3.67-3.58 (dd, J=10.4, 5.9, 1H), 3.22-3.16 (m, 2H), 2.19-2.10 (m, 1H), 1.88-1.80 (m, 1H), 1.78-1.64 (m, 2H).

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-methyl-N-(piperidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 2 H 24 FN 5 O 2 S, 441.16; m/z found, 442.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.37 (m, 1H), 8.20-8.16 (dd, J=8.1, 1.3, 1H), 8.16-8.14 (d, J=1.5, 1H), 8.00-7.92 (m, 1H), 7.78-7.71 (m, 1H), 7.68-7.61 (m, 1H), 7.48-7.43 (dd, J=7.6, 1.3, 1H), 7.37-7.35 (m, 1H), 7.35-7.32 (dd, J=7.0, 1.7, 1H), 3.64-3.53 (m, 1H), 3.23-3.17 (d, J=12.8, 1H), 3.06-3.00 (t, J=5.9, 1H), 3.00-2.93 (m, 1H), 2.78-2.70 (m, 1H), 2.42 (s, 3H), 1.92-1.81 (dd, J=16.5, 3.2, 1H), 1.68-1.57 (m, 1H), 1.57-1.44 (m, 1H), 1.44-1.33 (d, J=12.3, 1H).

›Example 115

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-methyl-N-(piperidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 24 FN 5 O 2 S, 441.16; m/z found, 442.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.36 (m, 1H), 8.21-8.15 (dd, J=8.1, 1.3, 1H), 8.14-8.09 (d, J=1.5, 1H), 7.99-7.90 (m, 1H), 7.78-7.72 (m, 1H), 7.67-7.61 (m, 1H), 7.49-7.43 (dd, J=7.6, 1.3, 1H), 7.36-7.35 (m, 1H), 7.35-7.32 (dd, J=7.1, 1.7, 1H), 3.64-3.52 (m, 1H), 3.22-3.17 (d, J=13.2, 1H), 3.05-3.00 (m, 1H), 3.00-2.93 (m, 1H), 2.79-2.69 (m, 1H), 2.42 (s, 3H), 1.93-1.82 (m, 1H), 1.67-1.56 (m, 1H), 1.56-1.45 (m, 1H), 1.43-1.34 (m, 1H).

›Example 116

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(1-hydroxy-3-phenylpropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 23 FN 4 O 3 S, 478.15; m/z found, 479.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.35 (m, 1H), 8.10-8.05 (d, J=1.5, 1H), 7.99-7.95 (dd, J=8.0, 1.3, 1H), 7.86-7.79 (t, J=8.1, 1H), 7.63-7.57 (m, 1H), 7.51-7.45 (m, 1H), 7.31-7.26 (dd, J=7.6, 1.3, 1H), 7.19-7.07 (m, 5H), 7.08-7.02 (dd, J=8.0, 1.5, 2H), 3.49-3.41 (m, 2H), 3.41-3.34 (m, 1H), 2.92-2.82 (dd, J=13.9, 6.3, 1H), 2.68-2.59 (dd, J=13.9, 6.8, 1H).

›Example 117

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(2-hydroxy-2-phenylethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 21 FN 4 O 3 S, 464.13; m/z found, 465.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.33 (m, 1H), 8.11-8.03 (m, 2H), 7.90-7.82 (t, J=8.2, 1H), 7.70-7.63 (m, 1H), 7.61-7.54 (m, 1H), 7.42-7.36 (dd, J=7.6, 1.3, 1H), 7.30-7.16 (m, 7H), 4.60-4.53 (dd, J=7.9, 4.8, 1H), 2.98-2.92 (m, 1H), 2.92-2.86 (m, 1H).

›Example 118

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-((1S,2S)-1-hydroxy-1-phenylpropan-2-yl)-N-methylbenzenesulfonamide. MS (ESI): mass calcd. for C 26 H 25 FN 4 O 3 S, 492.16; m/z found, 493.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.35 (m, 1H), 8.16-8.11 (dd, J=8.0, 1.3, 1H), 8.10-8.07 (d, J=1.5, 1H), 7.92-7.84 (t, J=8.0, 1H), 7.68-7.61 (m, 1H), 7.60-7.54 (m, 1H), 7.40-7.35 (dd, J=7.6, 1.4, 1H), 7.33-7.20 (m, 7H), 4.57-4.43 (d, J=8.4, 1H), 3.91-3.79 (m, 1H), 2.49 (s, 3H), 0.75-0.62 (d, J=6.8, 3H).

›Example 119

The title compound was prepared in a manner similar to that described in Example 88 using 1-((2-bromophenyl)sulfonyl)azetidin-3-ol. MS (ESI): mass calcd. for C 19 H 17 FN 4 O 3 S, 400.10; m/z found, 401.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.29 (m, 1H), 8.22-8.17 (d, J=1.4, 1H), 8.10-8.05 (dd, J=8.0, 1.3, 1H), 7.97-7.91 (m, 1H), 7.75-7.67 (m, 1H), 7.64-7.56 (m, 1H), 7.46-7.40 (dd, J=7.5, 1.3, 1H), 7.36-7.27 (m, 2H), 4.37-4.25 (m, 1H), 3.70-3.60 (m, 2H), 3.60-3.53 (m, 2H).

›Example 120

The title compound was prepared in a manner similar to that described in Example 88 using racemic-(trans)-2-bromo-N-(2-hydroxycyclohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.37 (s, 1H), 8.21-8.16 (m, 2H), 7.95-7.90 (m, 1H), 7.68-7.62 (m, 1H), 7.60-7.55 (m, 1H), 7.40-7.36 (dd, J=7.6, 1.3, 1H), 7.36-7.35 (m, 1H), 7.35-7.32 (dd, J=6.2, 1.6, 1H), 3.25-3.19 (m, 1H), 2.86-2.79 (m, 1H), 1.94-1.86 (m, 1H), 1.85-1.77 (m, 1H), 1.66-1.58 (m, 1H), 1.58-1.51 (m, 1H), 1.26-1.09 (m, 4H).

›Example 121

The title compound was prepared in a manner similar to that described in Example 88 using racemic (trans)-2-bromo-N-(2-(hydroxymethyl)cyclohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 23 H 25 FN 4 O 3 S, 456.16; m/z found, 457.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.34 (m, 1H), 8.20-8.14 (d, J=1.5, 1H), 8.14-8.08 (dd, J=8.1, 1.3, 1H), 7.97-7.88 (m, 1H), 7.70-7.63 (m, 1H), 7.63-7.55 (m, 1H), 7.43-7.36 (dd, J=7.7, 1.4, 1H), 7.35-7.25 (m, 2H), 3.61-3.52 (dd, J=11.1, 3.7, 1H), 3.43-3.36 (dd, J=11.0, 6.4, 1H), 2.92-2.79 (m, 1H), 1.86-1.80 (m, 1H), 1.66-1.53 (m, 3H), 1.34-1.26 (m, 1H), 1.18-1.03 (m, 4H).

›Example 122

The title compound was prepared in a manner similar to that described in Example 88 using racemic cis-2-bromo-N-(2-(hydroxymethyl)cyclohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 23 H 25 FN 4 O 3 S, 456.16; m/z found, 457.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.37 (m, 1H), 8.16-8.10 (dd, J=8.0, 1.3, 1H), 8.09-8.07 (d, J=1.5, 1H), 7.92-7.85 (m, 1H), 7.70-7.63 (m, 1H), 7.62-7.55 (m, 1H), 7.43-7.37 (dd, J=7.5, 1.4, 1H), 7.34-7.26 (m, 2H), 3.58-3.51 (dd, J=11.1, 7.1, 1H), 3.47-3.39 (m, 1H), 3.38-3.33 (m, 1H), 1.69-1.59 (m, 1H), 1.58-1.50 (m, 1H), 1.47-1.16 (m, 7H).

›Example 123

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(piperidin-4-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.37 (m, 1H), 8.16-8.10 (m, 2H), 7.95-7.89 (m, 1H), 7.74-7.66 (m, 1H), 7.64-7.56 (m, 1H), 7.46-7.40 (dd, J=7.7, 1.3, 1H), 7.38-7.29 (m, 2H), 3.30-3.22 (m, 2H), 3.21-3.14 (m, 1H), 2.98-2.89 (m, 2H), 1.98-1.85 (dd, J=14.6, 3.9, 2H), 1.65-1.48 (m, 2H).

›Example 124

The title compound was prepared in a manner similar to that described in Example 88 using (1-((2-bromophenyl)sulfonyl)azetidin-3-yl)methanamine. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.37 (m, 1H), 8.14-8.11 (d, J=1.5, 1H), 8.11-8.07 (dd, J=8.0, 1.3, 1H), 7.97-7.90 (m, 1H), 7.76-7.70 (m, 1H), 7.65-7.57 (m, 1H), 7.52-7.42 (dd, J=7.7, 1.3, 1H), 7.39-7.25 (m, 2H), 3.81-3.67 (t, J=8.1, 2H), 3.42-3.36 (dd, J=8.1, 5.5, 2H), 3.07-3.00 (d, J=7.5, 2H), 2.72-2.59 (m, 1H).

›Example 125

The title compound was prepared in a manner similar to that described in Example 88 using N-(azetidin-3-ylmethyl)-2-bromobenzenesulfonamide. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.37 (m, 1H), 8.17-8.12 (d, J=1.5, 1H), 8.09-8.05 (dd, J=8.0, 1.3, 1H), 7.97-7.88 (m, 1H), 7.73-7.66 (m, 1H), 7.65-7.58 (m, 1H), 7.47-7.41 (dd, J=7.6, 1.4, 1H), 7.36-7.28 (m, 2H), 4.02-3.95 (dd, J=11.2, 7.7, 2H), 3.91-3.78 (dd, J=11.3, 6.1, 2H), 3.04-2.91 (m, 3H).

›Example 126

The title compound was prepared in a manner similar to that described in Example 88 using (R)-1-((2-bromophenyl)sulfonyl)-N-methylpyrrolidin-3-amine. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.44-8.35 (m, 1H), 8.15-8.08 (m, 2H), 7.98-7.91 (m, 1H), 7.78-7.71 (m, 1H), 7.68-7.61 (m, 1H), 7.48-7.43 (dd, J=7.7, 1.3, 1H), 7.34-7.27 (m, 2H), 3.69-3.57 (m, 1H), 3.29-3.23 (m, 1H), 3.22-3.16 (m, 1H), 3.16-3.11 (m, 1H), 2.99-2.85 (m, 1H), 2.65 (s, 3H), 2.28-2.14 (m, 1H), 1.99-1.87 (m, 1H).

›Example 127

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(1,1,1-trifluoropropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 2 S, 440.09; m/z found, 441.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.38 (dd, J=2.1, 1.5, 1H), 8.13-8.09 (dd, J=8.1, 1.3, 1H), 8.09-8.07 (d, J=1.5, 1H), 7.90-7.85 (m, 1H), 7.70-7.64 (m, 1H), 7.61-7.55 (m, 1H), 7.41-7.36 (dd, J=7.7, 1.4, 1H), 7.30-7.27 (dd, J=8.0, 1.7, 1H), 7.27-7.22 (dd, J=12.3, 1.7, 1H), 3.91-3.79 (m, 1H), 1.24-1.16 (d, J=7.0, 3H).

›Example 128

The title compound was prepared in a manner similar to that described in Example 88 using 5-((2-bromophenyl)sulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]-pyridine. MS (ESI): mass calcd. for C 22 H 19 FN 6 O 2 S, 450.13; m/z found, 451.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.35 (m, 1H), 8.21-8.14 (dd, J=8.1, 1.3, 1H), 8.11-8.07 (d, J=1.5, 1H), 7.85-7.79 (m, 1H), 7.76-7.68 (m, 1H), 7.65-7.59 (m, 1H), 7.45-7.37 (dd, J=7.5, 1.4, 1H), 7.31-7.14 (m, 3H), 4.02-3.88 (m, 2H), 3.28-3.22 (t, J=5.9, 2H), 2.59-2.48 (t, J=5.9, 2H).

›Example 129

The title compound was prepared in a manner similar to that described in Example 88 using 4-(1-((2-bromophenyl)sulfonyl)piperidin-4-yl)-1H-1,2,4-triazol-5(4H)-one. MS (ESI): mass calcd. for C 23 H 22 FN 7 O 3 S, 495.15; m/z found, 496.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.35 (m, 1H), 8.24-8.22 (d, J=1.5, 1H), 8.15-8.11 (dd, J=8.1, 1.3, 1H), 8.01-7.96 (m, 1H), 7.78 (s, 1H), 7.76-7.70 (m, 1H), 7.66-7.60 (m, 1H), 7.48-7.43 (dd, J=7.6, 1.3, 1H), 7.41-7.33 (m, 2H), 3.88-3.76 (m, 1H), 3.51-3.42 (m, 2H), 2.64-2.53 (m, 2H), 1.88-1.79 (d, J=12.3, 2H), 1.68-1.50 (m, 2H).

›Example 130

The title compound was prepared in a manner similar to that described in Example 88 using (1R,4R)-2-((2-bromophenyl)sulfonyl)-2,5-diazabicyclo[2.2.1]heptane. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 2 S, 425.13; m/z found, 426.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.38 (m, 1H), 8.19-8.14 (dd, J=8.1, 1.3, 1H), 8.14-8.10 (d, J=1.5, 1H), 7.99-7.91 (m, 1H), 7.79-7.72 (m, 1H), 7.68-7.60 (m, 1H), 7.51-7.43 (dd, J=7.6, 1.3, 1H), 7.38-7.35 (m, 1H), 7.33 (s, 1H), 4.32 (s, 1H), 4.05 (s, 1H), 3.38-3.33 (m, 1H), 3.30-3.25 (m, 1H), 3.21-3.14 (dd, J=11.6, 2.2, 1H), 3.04-2.98 (dd, J=11.0, 2.6, 1H), 1.85-1.72 (m, 2H).

›Example 131

The title compound was prepared in a manner similar to that described in Example 88 using (1S,4S)-2-((2-bromophenyl)sulfonyl)-2,5-diazabicyclo[2.2.1]heptane. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 2 S, 425.13; m/z found, 426.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.36 (m, 1H), 8.17-8.14 (m, 2H), 8.00-7.92 (m, 1H), 7.79-7.72 (m, 1H), 7.68-7.61 (m, 1H), 7.49-7.45 (dd, J=7.6, 1.3, 1H), 7.39-7.35 (m, 1H), 7.34 (s, 1H), 4.38-4.28 (m1H), 4.05 (s, 1H), 3.38-3.32 (dd, J=11.6, 1.7, 1H), 3.30-3.26 (m, 1H), 3.23-3.12 (dd, J=11.6, 2.2, 1H), 3.08-2.95 (dd, J=11.0, 2.6, 1H), 1.85-1.74 (m, 2H).

›Example 132

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(5-hydroxypentyl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.44-8.38 (m, 1H), 8.10-8.07 (d, J=1.5, 1H), 8.07-8.04 (dd, J=8.0, 1.3, 1H), 7.92-7.87 (m, 1H), 7.68-7.64 (m, 1H), 7.62-7.55 (m, 1H), 7.43-7.38 (dd, J=7.6, 1.4, 1H), 7.33-7.27 (m, 2H), 3.49-3.45 (t, J=6.6, 2H), 2.78-2.73 (t, J=7.1, 2H), 1.48-1.41 (m, 2H), 1.41-1.34 (m, 2H), 1.31-1.21 (m, 2H).

›Example 133

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(6-hydroxyhexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 25 FN 4 O 3 S, 444.16; m/z found, 445.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.38 (m, 1H), 8.09-8.08 (d, J=1.5, 1H), 8.08-8.04 (dd, J=7.9, 1.3, 1H), 7.94-7.85 (m, 1H), 7.70-7.63 (m, 1H), 7.62-7.56 (m, 1H), 7.43-7.37 (dd, J=7.7, 1.4, 1H), 7.33-7.26 (m, 2H), 3.51-3.46 (t, J=6.6, 2H), 2.78-2.72 (t, J=7.1, 2H), 1.51-1.41 (m, 2H), 1.42-1.33 (p, J=7.2, 2H), 1.33-1.16 (m, 4H).

›Example 134

The title compound was prepared in a manner similar to that described in Example 88 using (cis)-N-(4-aminocyclohexyl)-2-bromobenzenesulfonamide. MS (ESI): mass calcd. for C 22 H 24 FN 5 O 2 S, 441.16; m/z found, 442.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.36 (m, 1H), 8.19-8.14 (m, 1H), 8.13-8.07 (dd, J=8.0, 1.3, 1H), 7.97-7.91 (m, 1H), 7.73-7.67 (m, 1H), 7.65-7.58 (m, 1H), 7.46-7.41 (dd, J=7.5, 1.3, 1H), 7.35-7.33 (m, 1H), 7.33-7.31 (dd, J=6.2, 1.6, 1H), 3.15-3.00 (m, 2H), 1.80-1.69 (m, 4H), 1.68-1.57 (m, 2H), 1.58-1.48 (m, 2H).

›Example 135

The title compound was prepared in a manner similar to that described in Example 88 using (S)-(1-((2-bromophenyl)sulfonyl)indolin-2-yl)methanol. MS (ESI): mass calcd. for C 25 H 21 FN 4 O 3 S, 476.13; m/z found, 477.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.36-8.33 (m, 1H), 8.22-8.20 (d, J=1.5, 1H), 8.19-8.14 (dd, J=8.0, 1.3, 1H), 7.85-7.79 (m, 1H), 7.69-7.63 (m, 1H), 7.61-7.56 (m, 1H), 7.32-7.28 (dd, J=7.5, 1.4, 1H), 7.11-7.06 (m, 2H), 7.01-6.95 (dd, J=12.2, 1.7, 1H), 6.91-6.80 (m, 3H), 3.85-3.74 (m, 1H), 3.67-3.58 (dd, J=10.9, 4.2, 1H), 3.40-3.33 (dd, J=11.0, 7.8, 1H), 2.89-2.72 (m, 2H).

›Example 136

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-cyclohexyl-N-(2-hydroxyethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 27 FN 4 O 3 S, 470.18; m/z found, 471.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.40-8.34 (m, 1H), 8.21-8.18 (d, J=1.5, 1H), 8.16-8.12 (dd, J=8.0, 1.4, 1H), 7.99-7.92 (m, 1H), 7.72-7.65 (m, 1H), 7.63-7.56 (m, 1H), 7.42-7.38 (dd, J=7.6, 1.4, 1H), 7.35-7.32 (m, 1H), 7.32-7.28 (dd, J=5.5, 1.6, 1H), 3.43-3.34 (dd, J=8.0, 6.9, 2H), 3.19-3.09 (m, 1H), 2.95-2.87 (dd, J=8.0, 6.9, 2H), 1.73-1.58 (d, J=12.6, 2H), 1.58-1.40 (m, 3H), 1.38-1.23 (m, 2H), 1.17-0.93 (m, 3H).

›Example 137

The title compound was prepared in a manner similar to that described in Example 88 using (S)-1-((2-bromophenyl)sulfonyl)piperidin-3-amine. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.41-8.37 (m, 1H), 8.18-8.14 (d, J=1.5, 1H), 8.14-8.08 (dd, J=8.0, 1.3, 1H), 7.97-7.90 (m, 1H), 7.79-7.71 (m, 1H), 7.68-7.61 (m, 1H), 7.49-7.42 (dd, J=7.6, 1.4, 1H), 7.33-7.31 (m, 1H), 7.31-7.28 (dd, J=5.2, 1.6, 1H), 3.37-3.32 (m, 1H), 3.10-2.98 (m, 2H), 2.73-2.62 (m, 1H), 2.62-2.50 (dd, J=12.7, 8.9, 1H), 2.00-1.88 (m, 1H), 1.81-1.66 (m, 1H), 1.59-1.33 (m, 2H).

›Example 138

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N,N-bis(2-hydroxyethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 4 S, 432.13; m/z found, 433.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.37-8.33 (m, 1H), 8.30-8.25 (d, J=1.4, 1H), 8.10-8.05 (dd, J=7.9, 1.3, 1H), 8.01-7.94 (m, 1H), 7.72-7.65 (m, 1H), 7.65-7.56 (m, 1H), 7.43-7.38 (dd, J=7.6, 1.4, 1H), 7.34-7.33 (m, 1H), 7.32-7.29 (dd, J=5.2, 1.6, 1H), 3.57-3.49 (t, J=6.0, 4H), 3.09-3.01 (t, J=6.0, 4H).

›Example 139

The title compound was prepared in a manner similar to that described in Example 88 using racemic 1-((2-bromophenyl)sulfonyl)azetidine-2-carboxamide. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 3 S, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.38 (m, 1H), 8.19-8.13 (m, 1H), 8.09-8.07 (d, J=1.5, 1H), 7.93-7.87 (m, 1H), 7.79-7.73 (m, 1H), 7.68-7.61 (m, 1H), 7.49-7.43 (dd, J=7.6, 1.3, 1H), 7.38-7.31 (m, 2H), 4.57-4.49 (dd, J=9.5, 7.8, 1H), 3.80-3.68 (m, 1H), 2.39-2.28 (m, 1H), 2.26-2.15 (m, 1H). (one proton obscured under methanol signal)

›Example 140

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-cyclopropyl-N-(tetrahydro-2H-pyran-4-yl)-benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 25 FN 4 O 3 S, 468.16; m/z found, 469.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.33 (m, 1H), 8.20-8.17 (dd, J=8.0, 1.3, 1H), 8.16-8.15 (d, J=1.5, 1H), 7.95-7.90 (m, 1H), 7.74-7.68 (m, 1H), 7.66-7.59 (m, 1H), 7.44-7.39 (dd, J=7.6, 1.3, 1H), 7.35-7.27 (m, 2H), 3.83-3.75 (dd, J=11.4, 4.3, 2H), 3.52-3.43 (m, 1H), 3.20-3.11 (m, 2H), 2.25-2.17 (m, 1H), 1.93-1.81 (m, 2H), 1.26-1.19 (d, J=12.0, 2H), 0.54-0.47 (m, 2H), 0.31-0.26 (dd, J=4.0, 2.3, 2H).

›Example 141

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(2-hydroxyethyl)-N-isopropylbenzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.36 (m, 1H), 8.21-8.17 (d, J=1.5, 1H), 8.14-8.10 (dd, J=8.0, 1.3, 1H), 8.00-7.91 (m, 1H), 7.72-7.66 (m, 1H), 7.63-7.56 (m, 1H), 7.44-7.38 (dd, J=7.5, 1.3, 1H), 7.36-7.27 (m, 2H), 3.69-3.55 (m, 1H), 3.43-3.37 (dd, J=7.8, 6.9, 2H), 2.92-2.84 (t, J=7.3, 2H), 1.01-0.97 (d, J=6.7, 6H).

›Example 142

The title compound was prepared in a manner similar to that described in Example 88 using racemic (4-((2-bromophenyl)sulfonyl)morpholin-2-yl)methanol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 4 S, 444.13; m/z found, 445.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.34 (m, 1H), 8.24-8.18 (d, J=1.4, 1H), 8.14-8.07 (dd, J=8.0, 1.3, 1H), 7.98-7.92 (m, 1H), 7.76-7.69 (m, 1H), 7.69-7.60 (m, 1H), 7.49-7.43 (dd, J=7.6, 1.3, 1H), 7.35 (s, 1H), 7.34-7.31 (dd, J=3.6, 1.5, 1H), 3.78-3.70 (dd, J=11.3, 3.0, 1H), 3.45-3.39 (m, 1H), 3.38-3.33 (m, 1H), 3.29-3.25 (m, 1H), 3.22-3.16 (m, 2H), 3.12-3.04 (d, J=12.3, 1H), 2.62-2.49 (m, 1H), 2.45-2.31 (m, 1H).

›Example 143

The title compound was prepared in a manner similar to that described in Example 88 using endo-3-((2-bromophenyl)sulfonyl)-3-azabicyclo[3.1.0]hexan-6-amine. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 2 S, 425.13: m/z found, 426.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.38 (m, 1H), 8.16-8.14 (d, J=1.5, 1H), 8.11-8.06 (dd, J=8.1, 1.3, 1H), 7.98-7.91 (m, 1H), 7.75-7.69 (m, 1H), 7.65-7.59 (m, 1H), 7.46-7.42 (dd, J=7.7, 1.3, 1H), 7.35-7.28 (m, 2H), 3.28 (s, 1H), 2.99-2.90 (m, 2H), 2.25-2.16 (t, J=2.3, 1H), 1.90-1.80 (m, 2H).

›Example 144

The title compound was prepared in a manner similar to that described in Example 88 using (S)-1-((2-bromophenyl)sulfonyl)-2-methylpiperazine. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz. CD 3 OD) δ 8.43-8.37 (m, 1H), 8.23-8.17 (dd, J=8.0, 1.3, 1H), 8.15-8.10 (d, J=1.5, 1H), 8.01-7.91 (m, 1H), 7.80-7.73 (m, 1H), 7.69-7.60 (m, 1H), 7.53-7.46 (dd, J=7.7, 1.3, 1H), 7.44-7.35 (d, J=9.9, 2H), 3.93-3.80 (m 1H), 3.23-3.15 (m, 1H), 3.15-3.03 (m, 3H), 2.79-2.63 (m, 2H), 1.21-1.14 (d, J=7.1, 3H).

›Example 145

The title compound was prepared in a manner similar to that described in Example 88 using (R)-1-((2-bromophenyl)sulfonyl)-2-methylpiperazine. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.38 (m, 1H), 8.23-8.16 (dd, J=8.1, 1.3, 1H), 8.16-8.12 (d, J=1.5, 1H), 8.01-7.95 (m, 1H), 7.80-7.73 (m, 1H), 7.68-7.62 (m, 1H), 7.52-7.45 (dd, J=7.6, 1.3, 1H), 7.44-7.36 (m, 2H), 3.95-3.79 (dd, J=7.1, 4.4, 1H), 3.23-3.15 (m, 1H), 3.15-3.03 (m, 3H), 2.79-2.64 (m, 2H), 1.19-1.15 (d, J=7.1, 3H).

›Example 146

The title compound was prepared in a manner similar to that described in Example 88 using (R)-(1-((2-bromophenyl)sulfonyl)piperazin-2-yl)methanol. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 3 S, 443.14; m/z found, 444.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.37 (m, 1H), 8.24-8.17 (dd, J=8.0, 1.3, 1H), 8.16-8.11 (d, J=1.5, 1H), 8.01-7.94 (m, 1H), 7.82-7.74 (m, 1H), 7.69-7.61 (m, 1H), 7.53-7.46 (dd, J=7.7, 1.3, 1H), 7.41 (s, 1H), 7.40-7.36 (dd, J=4.3, 1.6, 1H), 3.79-3.64 (m, 3H), 3.49-3.43 (m, 1H), 3.43-3.35 (m, 1H), 3.29-3.25 (d, J=3.7, 1H), 3.21-3.11 (m, 1H), 2.81-2.70 (m, 1H), 2.70-2.62 (dd, J=13.1, 4.7, 1H).

›Example 147

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(1,3-dihydroxy-2-methylpropan-2-yl)-benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 4 S, 432.13; m/z found, 433.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.37 (dd, J=2.2, 1.5, 1H), 8.20-8.14 (dd, J=8.0, 1.3, 1H), 8.10-8.06 (d, J=1.5, 1H), 7.93-7.84 (m, 1H), 7.69-7.63 (m, 1H), 7.60-7.54 (m, 1H), 7.42-7.38 (dd, J=7.5, 1.3, 1H), 7.38-7.32 (m, 2H), 3.45-3.39 (m, 2H), 3.39-3.33 (m, 2H), 0.97 (s, 3H).

›Example 148

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(1-hydroxy-3-methylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.38 (d, J=1.7, 1H), 8.15-8.12 (dd, J=8.0, 1.3, 1H), 8.09-8.06 (d, J=1.5, 1H), 7.90-7.84 (m, 1H), 7.67-7.61 (m, 1H), 7.60-7.54 (m, 1H), 7.39-7.35 (dd, J=7.6, 1.4, 1H), 7.35-7.29 (m, 2H), 3.46-3.39 (m, 1H), 3.39-3.33 (m, 1H), 3.09-3.02 (q, J=5.5, 1H), 1.90-1.75 (m, 1H), 0.83-0.76 (dd, J=6.9, 4.4, 6H).

›Example 149

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(1-hydroxy-3,3-dimethylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 25 FN 4 O 3 S, 444.16; m/z found, 445.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.35 (dd, J=2.2, 1.5, 1H), 8.16-8.11 (dd, J=8.1, 1.3, 1H), 8.10-8.06 (d, J=1.5, 1H), 7.93-7.83 (m, 1H), 7.65-7.59 (m, 1H), 7.58-7.52 (m, 1H), 7.37-7.35 (dd, J=3.3, 1.6, 1H), 7.35-7.31 (m, 2H), 3.55-3.49 (m, 1H), 3.49-3.43 (m, 1H), 3.11-3.04 (dd, J=5.9, 4.2, 1H), 0.82 (s, 9H).

›Example 150

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(1-hydroxy-3,3-dimethylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 25 FN 4 O 3 S, 444.16; m/z found, 445.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.37 (m, 1H), 8.15-8.11 (dd, J=8.0, 1.3, 1H), 8.09-8.05 (d, J=1.5, 1H), 7.92-7.86 (m, 1H), 7.65-7.59 (m, 1H), 7.58-7.52 (m, 1H), 7.38-7.35 (dd, J=3.3, 1.5, 1H), 7.35-7.31 (m, 2H), 3.55-3.49 (m, 1H), 3.49-3.42 (m, 1H), 3.10-3.04 (dd, J=5.9, 4.2, 1H), 0.82 (s, 9H).

›Example 151

The title compound was prepared in a manner similar to that described in Example 88 using tert-butyl-(2-(2-bromophenylsulfonamido)ethyl)carbamate. MS (ESI): mass calcd. for C 23 H 26 FN 5 O 4 S, 487.17; m/z found, 488.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.57-8.54 (m, 1H), 8.18-8.13 (dd, J=8.0, 1.4, 1H), 8.11-8.08 (d, J=1.5, 1H), 8.05-7.98 (m, 1H), 7.65-7.59 (m, 1H), 7.58-7.52 (m, 1H), 7.37-7.33 (m, 2H), 7.32-7.29 (dd, J=11.8, 1.7, 1H), 4.78 (s, 3H), 4.46 (s, 1H), 3.17-3.04 (d, J=5.9, 2H), 2.97-2.77 (m, 2H), 1.38 (s, 9H).

›Example 152

The title compound was prepared in a manner similar to that described in Example 88 using N-(2-aminoethyl)-2-bromobenzenesulfonamide. MS (ESI): mass calcd. for C 18 H 18 FN 5 O 2 S, 387.12; m/z found, 388.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.38 (d, J=1.7, 1H), 8.15-8.11 (d, J=1.5, 1H), 8.10-8.06 (dd, J=8.0, 1.3, 1H), 7.98-7.91 (m, 1H), 7.74-7.69 (m, 1H), 7.65-7.59 (m, 1H), 7.47-7.43 (dd, J=7.6, 1.3, 1H), 7.33-7.32 (dd, J=4.1, 1.8, 1H), 7.31-7.29 (dd, J=8.2, 1.6, 1H), 3.05-2.98 (t, J=5.9, 2H), 2.97-2.92 (m, 2H).

›Example 153

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(1-hydroxybutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.35 (d, J=1.6, 1H), 8.23-8.17 (d, J=1.5, 1H), 8.17-8.10 (dd, J=8.0, 1.3, 1H), 7.97-7.88 (m, 1H), 7.69-7.61 (m, 1H), 7.61-7.55 (m, 1H), 7.41-7.36 (dd, J=7.5, 1.4, 1H), 7.36-7.28 (m, 2H), 3.43-3.36 (m, 1H), 3.34-3.31 (m, 1H), 3.12-3.05 (m, 1H), 1.60-1.46 (m, 1H), 1.42-1.28 (m, 1H), 0.85-0.72 (t, J=7.4, 3H).

›Example 154

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(pyrrolidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.37 (m, 1H), 8.15-8.10 (m, 2H), 7.96-7.90 (m, 1H), 7.75-7.69 (m, 1H), 7.66-7.60 (m, 1H), 7.45 (dd, J=7.6, 1.3 Hz, 1H), 7.33 (s, 1H), 7.31 (dd, J=3.7, 1.6 Hz, 1H), 3.74-3.60 (m, 1H), 3.33-3.32 (m, 1H), 3.28-3.26 (m, 1H), 3.25-3.18 (m, 1H), 3.11 (dd, J=12.3, 5.4 Hz, 1H), 2.17-2.04 (m, 1H), 1.85-1.73 (m, 1H).

›Example 155

The title compound was prepared in a manner similar to that described in Example 88 using N-(2-(2-bromophenylsulfonamido)ethyl)acetamide. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 3 S, 429.13; m/z found, 430.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39-8.33 (m, 1H), 8.28-8.25 (d, J=1.4, 1H), 8.09-8.03 (dd, J=8.0, 1.3, 1H), 8.00-7.93 (m, 1H), 7.70-7.65 (dd, J=7.5, 1.4, 1H), 7.63-7.56 (m, 1H), 7.43-7.39 (dd, J=7.5, 1.4, 1H), 7.36-7.28 (m, 2H), 3.19-3.12 (t, J=6.3, 2H), 2.89-2.83 (t, J=6.3, 2H), 1.86 (s, 3H).

›Example 156

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-(2-bromophenylsulfonamido)propanoic acid. MS (ESI): mass calcd. for C 19 H 17 FN 4 O 4 S, 416.10; m/z found, 417.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39-8.34 (m, 1H), 8.23-8.20 (d, J=1.4, 1H), 8.13-8.08 (dd, J=8.0, 1.3, 1H), 7.96-7.89 (m, 1H), 7.69-7.62 (m, 1H), 7.60-7.54 (m, 1H), 7.39-7.36 (dd, J=7.6, 1.3, 1H), 7.36-7.34 (dd, J=8.0, 1.7, 1H), 7.34-7.30 (dd, J=12.3, 1.7, 1H), 3.77-3.66 (q, J=7.2, 1H), 1.33-1.25 (d, J=7.2, 3H).

›Example 157

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(2-ureidoethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 6 O 3 S, 430.12; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.32 (m, 1H), 8.29 (s, 1H), 8.09-8.03 (dd, J=8.0, 1.3, 1H), 8.01-7.93 (m, 1H), 7.73-7.64 (m, 1H), 7.64-7.55 (m, 1H), 7.45-7.38 (dd, J=7.6, 1.4, 1H), 7.37-7.28 (m, 2H), 3.15-3.04 (t, J=6.2, 2H), 2.87-2.78 (t, J=6.2, 2H).

›Example 158

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-((1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 21 FN 4 O 3 S, 476.13; m/z found, 477.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.34 (m, 1H), 8.29-8.24 (dd, J=8.0, 1.3, 1H), 8.07-8.05 (d, J=1.5, 1H), 7.84-7.79 (m, 1H), 7.71-7.66 (m, 1H), 7.63-7.58 (m, 1H), 7.42-7.37 (dd, J=7.6, 1.3, 1H), 7.31-7.23 (m, 2H), 7.21-7.13 (m, 2H), 7.12-7.07 (m, 1H), 7.03-6.97 (m, 1H), 4.49-4.45 (d, J=5.3, 1H), 4.28-4.22 (m, 1H), 3.19-3.11 (dd, J=15.8, 6.7, 1H), 2.70-2.64 (dd, J=15.8, 5.9, 1H).

›Example 159

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-((1R,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 21 FN 4 O 3 S, 476.13; m/z found, 477.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.34 (m, 1H), 8.29-8.25 (dd, J=8.1, 1.3, 1H), 8.07-8.04 (d, J=1.5, 1H), 7.86-7.78 (m, 1H), 7.73-7.65 (m, 1H), 7.65-7.57 (m, 1H), 7.44-7.36 (dd, J=7.6, 1.3, 1H), 7.32-7.23 (m, 2H), 7.22-7.12 (m, 2H), 7.12-7.06 (m, 1H), 7.02-6.95 (d, J=7.6, 1H), 4.51-4.43 (d, J=5.4, 1H), 4.30-4.21 (m, 1H), 3.20-3.10 (dd, J=15.9, 6.7, 1H), 2.72-2.58 (dd, J=15.8, 6.0, 1H).

›Example 160

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 21 FN 4 O 3 S, 476.13; m/z found, 477.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39-8.33 (m, 1H), 8.27-8.22 (dd. J=8.0, 1.3, 1H), 8.08-8.04 (d, J=1.5, 1H), 7.88-7.80 (m, 1H), 7.72-7.67 (m, 1H), 7.65-7.58 (m, 1H), 7.42-7.37 (dd. J=7.7, 1.4, 1H), 7.31-7.26 (dd, J=8.0, 1.7, 1H), 7.26-7.21 (dd, J=12.2, 1.7, 1H), 7.20-7.16 (dd, J=4.7, 1.2, 2H), 7.12-7.05 (m, 1H), 7.06-7.01 (m, 1H), 4.64-4.56 (dd, J=5.1, 1.0, 1H), 4.30-4.24 (m, 1H), 3.01-2.93 (dd, J=16.2, 5.2, 1H), 2.80-2.72 (dd, J=16.2, 2.6, 1H).

›Example 161

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-((1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 25 H 21 FN 4 O 3 S, 476.13; m/z found, 477.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.32 (m, 1H), 8.28-8.21 (dd, J=8.0, 1.3, 1H), 8.09-8.02 (d, J=1.5, 1H), 7.88-7.79 (m, 1H), 7.73-7.66 (m, 1H), 7.65-7.57 (m, 1H), 7.42-7.38 (dd, J=7.6, 1.4, 1H), 7.30-7.26 (dd, J=8.0, 1.7, 1H), 7.26-7.21 (dd, J=12.2, 1.7, 1H), 7.20-7.16 (dd, J=4.7, 1.2, 2H), 7.11-7.05 (m, 1H), 7.06-7.01 (m, 1H), 4.62-4.55 (d, J=5.3, 1H), 4.30-4.21 (m, 1H), 3.04-2.92 (dd, J=16.2, 5.2, 1H), 2.81-2.72 (dd, J=16.1, 2.6, 1H).

›Example 162

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-((1S,2S)-2-hydroxycyclohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] 4 . 1 H NMR (500 MHz, CD 3 OD) δ 8.36 (s, 1H), 8.26-8.22 (d, J=1.5, 2H), 8.22-8.15 (dd, J=8.0, 1.3, 2H), 7.97-7.90 (m, 2H), 7.69-7.62 (m, 2H), 7.61-7.54 (m, 2H), 7.41-7.32 (m, 5H), 3.25-3.18 (m, 1H), 2.88-2.77 (m, 2H), 1.96-1.84 (m, 2H), 1.85-1.77 (m, 2H), 1.68-1.59 (m, 2H), 1.59-1.49 (m, 2H), 1.25-1.18 (m, 4H), 1.18-1.11 (m, 3H).

›Example 163

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(6-(trifluoromethyl)pyridin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 15 F 4 N 5 O 2 S, 489.09; m/z found, 490.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.38 (m, 1H), 8.29-8.24 (dd, J=8.0, 1.4, 1H), 8.11-8.08 (d, J=1.5, 1H), 8.08-8.06 (d, J=2.6, 1H), 7.87-7.80 (m, 1H), 7.72-7.67 (m, 1H), 7.67-7.61 (m, 1H), 7.58-7.52 (d, J=8.7, 1H), 7.46-7.42 (dd, J=8.7, 2.5, 1H), 7.38-7.33 (dd, J=7.5, 1.4, 1H), 7.16-7.10 (dd, J=12.1, 1.7, 1H), 7.10-7.05 (dd, J=8.0, 1.7, 1H).

›Example 164

The title compound was prepared in a manner similar to that described in Example 88 using 1-((2-bromophenyl)sulfonyl)-4-(1H-imidazol-4-yl)piperidine. MS (ESI): mass calcd. for C 24 H 23 FN 6 O 2 S, 478.16; m/z found, 479.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.83-8.76 (d, J=1.4, 1H), 8.39-8.33 (m, 1H), 8.16-8.08 (m, 2H), 7.98-7.85 (m, 1H), 7.75-7.68 (m, 1H), 7.65-7.60 (m, 1H), 7.48-7.41 (dd, J=7.5, 1.3, 1H), 7.34 (s, 1H), 7.32-7.31 (m, 1H), 7.30-7.26 (d, J=1.2, 1H), 3.48-3.39 (d, J=13.3, 2H), 2.84-2.69 (m, 1H), 2.64-2.48 (m, 2H), 1.93-1.80 (d, J=12.9, 2H), 1.52-1.33 (m, 2H).

›Example 165

The title compound was prepared in a manner similar to that described in Example 88 using N-((4-amino-2-methylpyrimidin-5-yl)methyl)-2-bromobenzenesulfonamide. MS (ESI): mass calcd. for C 22 H 20 FN 7 O 2 S, 465.14; m/z found, 466.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.36 (s, 1H), 8.26-8.18 (d, J=1.4, 1H), 8.12-8.06 (d, J=7.9, 1H), 7.98-7.92 (m, 1H), 7.90 (s, 1H), 7.76-7.69 (m, 1H), 7.68-7.59 (m, 1H), 7.48-7.41 (dd, J=7.6, 1.4, 1H), 7.39-7.29 (m, 2H), 3.88 (s, 2H), 2.50 (s, 3H).

›Example 166

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(2,6-dimethoxypyrimidin-4-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 19 FN 6 O 4 S, 482.12; m/z found, 483.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.36 (m, 1H), 8.28-8.20 (d, J=8.0, 1H), 8.10-8.06 (d, J=1.5, 1H), 7.84-7.77 (m, 1H), 7.66-7.52 (m, 3H), 7.34-7.29 (d, J=7.3, 1H), 7.14-7.05 (m, 2H), 3.75 (s, 3H), 3.60 (s, 3H).

›Example 167

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(5-methylpyrazin-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 17 FN 6 O 2 S, 436.11; m/z found, 437.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.37 (m, 1H), 8.25-8.21 (dd, J=8.1, 1.0, 1H), 8.10-8.07 (d, J=1.5, 1H), 7.94-7.85 (m, 2H), 7.82-7.76 (m, 1H), 7.67-7.60 (m, 1H), 7.61-7.54 (m, 1H), 7.34-7.27 (m, 1H), 7.15-7.05 (m, 2H), 2.23 (s, 3H).

›Example 168

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-(2-bromophenylsulfonamido)-4-methylpentanamide. MS (ESI): mass calcd. for C 22 H 24 FN 5 O 3 S, 457.16; m/z found, 458.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.37 (m, 1H), 8.13-8.09 (dd, J=8.0, 1.3, 1H), 8.09-8.06 (d, J=1.5, 1H), 7.90-7.85 (m, 1H), 7.69-7.62 (m, 1H), 7.59-7.53 (m, 1H), 7.40-7.36 (dd, J=7.6, 1.3, 1H), 7.36-7.29 (m, 2H), 3.79-3.73 (dd, J=9.1, 5.7, 1H), 1.72-1.54 (m, 1H), 1.51-1.34 (m, 2H), 0.88-0.84 (d, J=6.6, 3H), 0.81-0.78 (d, J=6.6, 3H).

›Example 169

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(2-cyanoethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 FN 5 O 2 S, 397.10; m/z found, 398.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39-8.34 (m, 1H), 8.21-8.17 (d, J=1.5, 1H), 8.09-8.06 (dd, J=8.0, 1.3, 1H), 7.96-7.90 (m, 1H), 7.72-7.66 (m, 1H), 7.64-7.57 (m, 1H), 7.43-7.39 (dd, J=7.7, 1.4, 1H), 7.37-7.27 (m, 2H), 3.09-3.02 (t, J=6.6, 2H), 2.56-2.50 (t, J=6.6, 2H).

›Example 170

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(1-cyanopropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 2 S, 411.12; m/z found, 412.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.36 (m, 1H), 8.17-8.14 (d, J=1.4, 1H), 8.14-8.10 (dd, J=8.0, 1.3, 1H), 7.96-7.87 (m, 1H), 7.72-7.65 (m, 1H), 7.63-7.56 (m, 1H), 7.44-7.38 (dd, J=7.7, 1.4, 1H), 7.37-7.29 (m, 2H), 3.47-3.39 (dd, J=12.3, 6.1, 1H), 2.61-2.46 (m, 2H), 1.18-1.11 (d, J=6.7, 3H).

›Example 171

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(1-cyanopropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 2 S, 411.12; m/z found, 412.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.38 (dd, J=2.2, 1.5, 1H), 8.16-8.09 (dd, J=8.0, 1.3, 1H), 8.09-8.07 (d, J=1.5, 1H), 7.93-7.86 (m, 1H), 7.71-7.65 (m, 1H), 7.64-7.56 (m, 1H), 7.45-7.38 (dd, J=7.5, 1.3, 1H), 7.37-7.28 (m, 2H), 3.51-3.37 (m, 1H), 2.64-2.45 (m, 2H), 1.18-1.11 (d, J=6.7, 3H).

›Example 172

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(2-cyanoethyl)-N-cyclopropylbenzenesulfonamide. MS (ESI): mass calcd. for C 22 H 20 FN 5 O 2 S, 437.13; m/z found, 438.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.34 (d, J=1.6, 1H), 8.23-8.18 (d, J=1.4, 1H), 8.18-8.13 (dd, J=8.0, 1.3, 1H), 8.00-7.92 (m, 1H), 7.76-7.71 (m, 1H), 7.68-7.60 (m, 1H), 7.43-7.38 (dd, J=7.6, 1.3, 1H), 7.22 (s, 1H), 7.21-7.19 (dd, J=4.4, 1.5, 1H), 3.02-2.95 (t, J=6.7, 2H), 2.62-2.55 (t, J=6.7, 2H), 2.52-2.35 (m, 1H), 0.63-0.52 (m, 2H), 0.42-0.34 (m, 2H).

›Example 173

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(3-methyloxetan-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 3 S, 414.12; m/z found, 415.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38 (s, 1H), 8.17 (s, 1H), 8.14-8.08 (d, J=8.0, 1H), 7.97-7.88 (m, 1H), 7.73-7.65 (m, 1H), 7.65-7.55 (m, 1H), 7.47-7.38 (d, J=7.6, 1H), 7.37-7.25 (m, 2H), 4.57-4.49 (d, J=6.3, 2H), 4.20-4.13 (d, J=6.2, 2H), 1.46 (s, 3H).

›Example 174

The title compound was prepared in a manner similar to that described in Example 88 using 3-(4-((2-bromophenyl)sulfonyl)piperazin-1-yl)propanenitrile. MS (ESI): mass calcd. for C 23 H 23 FN 6 O 2 S, 466.16; m/z found, 467.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40-8.38 (m, 1H), 8.15-8.11 (m, 2H), 8.00-7.92 (m, 1H), 7.78-7.70 (m, 1H), 7.67-7.60 (m, 1H), 7.49-7.43 (dd, J=7.6, 1.3, 1H), 7.34-7.32 (d, J=0.9, 1H), 7.32-7.30 (dd. J=3.7, 1.6, 1H), 3.13-3.07 (t, J=7.1, 2H), 3.07-3.02 (t. J=4.7, 4H), 2.87-2.81 (d, J=4.8, 4H), 2.81-2.76 (t, J=7.0, 2H).

›Example 175

The title compound was prepared in a manner similar to that described in Example 88 using (S)-2-bromo-N-(1-methoxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.37 (m, 1H), 8.16-8.11 (dd, J=8.0, 1.3, 1H), 8.10-8.06 (d, J=1.5, 1H), 7.91-7.86 (m, 1H), 7.70-7.62 (m, 1H), 7.61-7.53 (m, 1H), 7.42-7.36 (dd, J=7.5, 1.4, 1H), 7.35-7.26 (m, 2H), 3.37-3.31 (m, 1H), 3.22-3.18 (m, 1H), 3.17 (s, 3H), 3.15-3.10 (m, 1H), 1.06-1.00 (d, J=6.7, 3H).

›Example 176

The title compound was prepared in a manner similar to that described in Example 88 using 2-(4-((2-bromophenyl)sulfonyl)piperazin-1-yl)pyrazine. MS (ESI): mass calcd. for C 24 H 22 FN 7 O 2 S, 491.15; m/z found, 492.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.32 (m, 1H), 8.23-8.17 (d, J=1.4, 1H), 8.16-8.10 (m, 2H), 8.09-8.05 (m, 1H), 7.97-7.90 (m, 1H), 7.80-7.76 (d, J=2.7, 1H), 7.75-7.70 (m, 1H), 7.67-7.60 (m, 1H), 7.47-7.42 (dd. J=7.6, 1.3, 1H), 7.36-7.33 (dd, J=5.1, 1.6, 1H), 7.33 (s, 1H), 3.53-3.39 (t, J=5.1, 4H), 3.02-2.95 (t, J=5.1, 4H).

›Example 177

The title compound was prepared in a manner similar to that described in Example 88 using 2-(4-((2-bromophenyl)sulfonyl)piperazin-1-yl)pyrimidine. MS (ESI): mass calcd. for C 24 H 22 FN 7 O 2 S, 491.15; m/z found, 492.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.39 (s, 1H), 8.29-8.23 (d, J=4.7, 2H), 8.16-8.10 (d, J=8.0, 1H), 8.08 (s, 1H), 7.95-7.87 (m, 1H), 7.76-7.68 (m, 1H), 7.66-7.57 (m, 1H), 7.50-7.42 (d, J=7.5, 1H), 7.34-7.32 (d, J=3.6, 1H), 7.31 (s, 1H), 6.68-6.51 (t, J=4.8, 1H), 3.73-3.56 (t, J=5.0, 4H), 2.97-2.85 (t, J=4.9, 4H).

›Example 178

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromoaniline. MS (ESI): mass calcd. for C 16 H 13 FN 4 , 280.11; m/z found, 281.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.36 (s, 1H), 8.02 (s, 1H), 7.91 (m, 1H), 7.31 (d, J=12.7, 2H), 7.04 (d, J=7.3, 2H), 6.82-6.58 (m, 4H), 4.94 (s, 2H).

›Example 179

The title compound was prepared in a manner similar to that described in Example 584 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-bromo-N-(1-(hydroxymethyl)-cyclopentyl)benzenesulfonamide in Step B. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.42 (s, 1H), 8.39 (s, 1H), 8.18 (d, J=7.3, 1H), 8.08 (m, 1H), 7.66-7.60 (m, 1H), 7.58-7.52 (m, 1H), 7.43 (dd, J=8.1, 1.8, 1H), 7.38-7.32 (m, 2H), 4.12 (s, 1H), 3.49 (s, 2H), 1.64-1.39 (m, 8H).

›Example 180

The title compound was prepared in a manner similar to that described in Example 584 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic 1-((2-bromophenyl)sulfonyl)-3-phenylpyrrolidin-3-ol in Step B. MS (ESI): mass calcd. for C 26 H 23 FN 4 O 3 S, 490.15; m/z found, 491.2 [M+H] 4 . 1 H NMR (500 MHz, CDCl 3 ) δ 8.57 (s, 1H), 8.20 (d, J=9.2, 1H), 8.11 (d, J=1.5, 1H), 8.00 (t, J=8.1, 1H), 7.61 (dd, J=7.5, 6.2, 1H), 7.53 (m, 1H), 7.40-7.34 (m, 3H), 7.34-7.28 (m, 5H), 4.68 (s, 2H), 3.41-3.23 (m, 4H), 3.18 (d, J=10.8, 1H), 2.21-2.11 (m, 1H), 2.10-2.01 (m, 1H).

›Example 181

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and N-(2-bromophenyl)pyrrolidine-1-sulfonamide in Step B. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.40 (dd, J=5.4, 1.4, 2H), 8.14 (m, 1H), 7.61 (dd, J=8.3, 1.1, 1H), 7.42-7.35 (m, 1H), 7.32 (dd, J=8.0, 1.7, 1H), 7.23 (dd, J=3.6, 1.6, 1H), 7.22-7.15 (m, 1H), 6.44 (s, 1H), 3.33-3.25 (m, 4H), 1.87 (dd, J=7.0, 0.9, 4H).

›Example 182

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and N-(2-bromophenyl) N,N-dimethylsulfonamide in Step B. MS (ESI): mass calcd. for C 18 H 18 FN 5 O 2 S, 387.12; m/z found, 388.3 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.60 (dd, J=2.3, 1.4, 1H), 8.12 (d, J=1.5, 1H), 8.07 (m, 1H), 7.61 (dd, J=8.3, 1.1, 1H), 7.40-7.34 (m, 1H), 7.29-7.26 (m, 1H), 7.25-7.24 (m, 1H), 7.21-7.16 (m, 2H), 6.42 (s, 1H), 4.72 (s, 2H), 2.79 (s, 6H).

›Example 183

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and N-(2-bromophenyl)morpholine-4-sulfonamide. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 3 S, 429.13; m/z found, 430.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.45 (s, 1H), 8.34 (d, J=1.4, 1H), 8.14 (m, 1H), 7.63 (d, J=8.0, 1H), 7.43-7.35 (m, 1H), 7.31 (dd, J=8.0, 1.7, 1H), 7.24-7.19 (m, 2H), 6.39 (s, 1H), 3.67 (dd, J=5.8, 3.7, 4H), 3.23-3.14 (m, 4H).

›Example 184

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and (S)-1-((2-bromophenyl)sulfonyl)pyrrolidin-3-ol in Step B. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 3 S, 414.12; m/z found, 415.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.44 (d, J=1.3, 1H), 8.33 (d, J=1.5, 1H), 8.13 (dd, J=7.9, 1.3, 1H), 8.07 (m, 1H), 7.62 (m, 1H), 7.58-7.52 (m, 1H), 7.41-7.29 (m, 3H), 4.44-4.36 (m, 1H), 3.23-3.15 (m, 3H), 3.07-2.99 (m, 1H), 1.98-1.88 (m, 1H), 1.88-1.78 (m, 1H).

›Example 185

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and (R)-1-((2-bromophenyl)sulfonyl)pyrrolidin-3-ol in Step B. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 3 S, 414.12; m/z found, 415.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.43 (d, J=1.4, 1H), 8.33 (d, J=1.5, 1H), 8.13 (dd, J=7.7, 1.3, 1H), 8.07 (m, 1H), 7.62 (m, 1H), 7.55 (m, 1H), 1.98-1.88 (m, 1H), 7.42-7.29 (m, 3H), 3.24-3.15 (m, 3H), 3.04 (t, J=1.5, 1H), 1.86 (s, 1H), 4.44-4.35 (m, 1H).

›Example 186

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and Racemic-1′-((2-bromophenyl)sulfonyl)-[1,3′-bipyrrolidin]-4′-ol in Step B. MS (ESI): mass calcd. for C 24 H 26 FN 5 O 3 S, 483.17; m/z found, 484.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.60-8.57 (m, 1H), 8.15 (d, J=6.8, 1H), 8.11 (d, J=1.5, 1H), 7.97 (m, 1H), 7.61 (dd, J=7.5, 6.1, 1H), 7.55-7.49 (m, 1H), 7.38-7.28 (m, 3H), 4.68 (s, 2H), 4.18-4.12 (m, 1H), 3.30 (dd, J=10.5, 6.2, 1H), 3.23 (dd, J=10.1, 6.8, 1H), 2.95 (dd, J=10.0, 6.4, 1H), 2.88 (dd, J=10.4, 4.4, 1H), 2.63-2.57 (m, 1H), 2.52-2.38 (m, 5H), 1.74-1.67 (m, 4H).

›Example 187

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and Racemic-1-((2-bromophenyl)sulfonyl)-4-morpholinopyrrolidin-3-ol in Step B. MS (ESI): mass calcd. for C 24 H 26 FN 5 O 4 S, 499.17; m/z found, 500.3 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.41 (s, 1H), 8.32 (s, 1H), 8.13-8.09 (m, 1H), 7.99 (m, 1H), 7.70-7.64 (m, 1H), 7.61-7.56 (m, 1H), 7.38 (dd, J=7.5, 1.3, 1H), 7.35-7.30 (m, 2H), 4.72-4.63 (m, 2H), 3.94-3.85 (m, 3H), 3.40-3.25 (m, 3H), 3.22-3.10 (m, 3H), 3.05-2.94 (m, 2H), 2.92-2.84 (m, 2H), 2.08-2.02 (m, 2H).

›Example 188

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and Racemic-1-((2-bromophenyl)sulfonyl)-4-(4-methylpiperazin-1-yl)pyrrolidin-3-ol in Step B. MS (ESI): mass calcd. for C 25 H 29 FN 6 O 3 S, 512.20; m/z found, 513.3 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 6.90-6.87 (m, 1H), 6.63-6.57 (m, 2H), 6.45-6.40 (m, 1H), 6.23-6.17 (m, 1H), 6.12-6.07 (m, 1H), 5.95-5.89 (m, 1H), 5.83-5.76 (m, 2H), 2.58-2.50 (m, 1H), 2.46 (s, 2H), 1.84-1.81 (m, 2H), 1.77-1.72 (m, 2H), 1.63-1.58 (m, 1H), 1.32 (s, 3H), 1.31-1.26 (m, 1H), 1.23-1.13 (m, 3H),

›Example 189

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-trifluorothiomethylbromobenzene. MS (ESI): mass calcd. for C 17 H 11 F 4 N 3 S, 365.06; m/z found, 366.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.46-8.37 (m, 1H), 8.09 (d, J=1.3, 1H), 7.93 (m, 1H), 7.87 (d, J=7.7, 1H), 7.69-7.60 (m, 1H), 7.55-7.50 (m, 2H), 7.28-7.17 (m, 2H).

›Example 190

The title compound was prepared using analogous conditions to those described in The title compound was prepared using analogous conditions to those described in Example 6 utilizing (2-bromophenyl)(tert-butyl)sulfane. MS (ESI): mass calcd. for C 20 H 20 FN 3 S, 353.14; m/z found, 354.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.44-8.36 (m, 1H), 8.10-8.03 (d, J=1.5, 1H), 7.93-7.86 (m, 1H), 7.73-7.65 (dd, J=7.8, 1.4, 1H), 7.56-7.49 (m, 1H), 7.49-7.41 (m, 2H), 7.34-7.25 (m, 2H), 1.99 (s, 1H), 1.02 (s, 9H).

›Example 191

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and N-(2-bromophenyl)ethane-1-sulfonamide. MS (ESI): mass calcd. for C 18 H 16 FN 3 O 2 S, 357.09; m/z found, 358.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.48-8.36 (m, 1H), 8.16 (dd, J=7.9, 1.3, 1H), 8.09 (d, J=1.4, 1H), 7.94 (m, 1H), 7.78 (m, 1H), 7.68 (m, 1H), 7.48 (dd, J=7.5, 1.3, 1H), 7.34 (s, 1H), 7.31 (d, J=2.4, 1H), 2.84 (q, J=7.4, 2H), 1.06 (t, J=7.4, 3H).

›Example 192

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-bromo-2-(propylsulfonyl)benzene. MS (ESI): mass calcd. for C 19 H 18 FN 3 O 2 S, 371.11; m/z found, 372.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.40 (s, 1H), 8.14 (d, J=1.2, 1H), 8.08 (dd, J=7.8, 1.1, 1H), 7.95 (m, 1H), 7.81 (m, 1H), 7.72 (m, 1H), 7.48 (dd, J=7.4, 1.1, 1H), 7.38 (dd, J=12.4, 1.4, 1H), 7.32 (dd, J=8.0, 1.6, 1H), 2.94-2.81 (m, 2H), 1.49-1.32 (m, 2H), 0.79 (t, J=7.4, 3H).

›Example 193

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-bromo-2-(isobutylsulfonyl)benzene. MS (ESI): mass calcd. for C 20 H 20 FN 3 O 2 S, 385.13; m/z found, 386.2 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.42 (s, 1H), 8.12 (dd, J=7.9, 1.1, 1H), 8.05 (d, J=1.4, 1H), 7.96 (m, 1H), 7.81 (m, 1H), 7.73 (m, 1H), 7.49 (dd, J=7.5, 1.0, 1H), 7.37 (dd, J=12.4, 1.5, 1H), 7.32 (dd. J=8.0, 1.6, 1H), 6.76 (s, 2H), 2.81 (d, J=6.4, 2H), 1.85-1.75 (m, 1H), 0.82 (d, J=6.7, 6H).

›Example 194

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 1-bromo-2-(tert-butylsulfonyl)benzene. MS (ESI): mass calcd. for C 20 H 20 FN 3 O 2 S, 385.13; m/z found, 386.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.51-8.44 (d, J=1.4, 1H), 8.27-8.20 (d, J=1.4, 1H), 8.10-8.04 (dd, J=8.0, 1.4, 1H), 8.04-7.98 (m, 1H), 7.70-7.63 (m, 1H), 7.62-7.55 (m, 1H), 7.36-7.30 (dd, J=7.6, 1.4, 1H), 7.29-7.25 (dd, J=8.1, 1.7, 1H), 7.22-7.17 (dd, J=12.3, 1.7, 1H), 1.23-1.11 (s, 9H).

›Example 195

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-bromo-2-(cyclopentylsulfonyl)benzene MS (ESI): mass calcd. for C 21 H 2 FN 3 O 2 S, 397.13; m/z found, 398.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.65 (d, J=1.3, 1H), 8.30 (d, J=1.3, 1H), 8.19 (dd, J=7.9, 1.2, 1H), 8.14 (m, 1H), 7.79 (m, 1H), 7.71 (m, 1H), 7.48 (dd, J=7.5, 1.2, 1H), 7.42 (s, 1H), 7.41-7.38 (m, 1H), 3.23-3.15 (m, 1H), 1.92-1.81 (m, 2H), 1.77-1.63 (m, 4H), 1.60-1.51 (m, 2H).

›Example 196

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-bromo-2-(cyclobutylsulfonyl)benzene. MS (ESI): mass calcd. for C 20 H 18 FN 3 O 2 S, 383.11; m/z found, 384.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.44 (s, 1H), 8.17 (dd, J=7.9, 1.1, 1H), 8.13 (d, J=1.4, 1H), 7.96 (m, 1H), 7.77 (m, 1H), 7.68 (m, 1H), 7.46 (dd, J=7.6, 1.1, 1H), 7.34 (s, 1H), 7.31 (dd, J=6.4, 1.5, 1H), 3.65-3.53 (m, 1H), 2.39-2.26 (m, 2H), 2.08-1.98 (m, 2H), 1.98-1.87 (m, 2H).

›Example 197

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-bromo-2-(cyclopropylsulfonyl)benzene. MS (ESI): mass calcd. for C 19 H 16 FN 3 O 2 S, 369.09; m/z found, 370.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.55-8.49 (m, 1H), 8.33 (s, 1H), 8.13 (dd, J=8.0, 1.2, 1H), 8.11-8.05 (m, 1H), 7.77 (m, 1H), 7.68 (m, 1H), 7.48 (dd, J=7.6, 1.1, 1H), 7.43-7.36 (m, 2H), 2.35-2.26 (m, 1H), 1.04-0.91 (m, 4H).

›Example 198

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-bromo-2-(hexylsulfonyl)benzene MS (ESI): mass calcd. for C 22 H 24 FN 3 O 2 S, 413.16; m/z found, 414.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.66 (s, 1H), 8.31 (s, 1H), 8.21-8.13 (m, 2H), 7.81 (m, 1H), 7.72 (m, 1H), 7.49 (dd, J=7.6, 1.2, 1H), 7.43 (dd, J=3.6, 1.4, 1H), 7.40 (s, 1H), 2.89-2.80 (m, 2H), 1.50 (m, 2H), 1.31-1.11 (m, 6H), 0.85 (t, J=7.1, 3H).

›Example 199

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-bromo-2-(isopropylsulfonyl)benzene. MS (ESI): mass calcd. for C 19 H 18 FN 3 O 2 S, 371.11; m/z found, 372.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.42 (s, 1H), 8.15 (dd, J=8.0, 1.1, 1H), 8.09 (d, J=1.4, 1H), 7.93 (m, 1H), 7.78 (m, 1H), 7.68 (m, 1H), 7.51-7.44 (m, 1H), 7.37-7.28 (m, 2H), 2.90-2.77 (m, 1H), 1.09 (d, J=6.8, 6H).

›Example 200

The title compound was prepared in a manner similar to that described in Example 88 using 2-((2-bromophenyl)thio)acetamide. MS (ESI): mass calcd. for C 18 H 15 FN 4 OS, 354.10; m/z found, 355.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.36 (dd, J=2.2, 1.4, 1H), 8.10-8.06 (d, J=1.5, 1H), 7.93-7.87 (m, 1H), 7.53-7.48 (m, 1H), 7.39-7.34 (m, 1H), 7.33-7.25 (m, 4H), 3.52 (s, 2H).

›Example 201

The title compound was prepared in a manner similar to that described in Example 88 using 2-((2-bromophenyl)thio)-N,N-diethylacetamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 OS, 410.16; m/z found, 411.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.42-8.35 (d, J=1.9, 1H), 8.12-8.06 (d, J=1.5, 1H), 7.94-7.86 (m, 1H), 7.63-7.55 (dd, J=7.1, 2.1, 1H), 7.41-7.23 (m, 5H), 3.62 (s, 2H), 3.31-3.26 (m, 4H), 1.13-1.08 (t, J=7.1, 3H), 1.07-1.03 (t, J=7.1, 3H).

›Example 202

The title compound was prepared in a manner similar to that described in Example 88 using 2-((2-bromophenyl)thio)-1-morpholinoethanone. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.39 (m, 1H), 8.10-8.08 (d, J=1.5, 1H), 7.95-7.89 (m, 1H), 7.68-7.61 (m, 1H), 7.41-7.34 (m, 2H), 7.34-7.29 (m, 2H), 7.29-7.25 (dd, J=12.2, 1.7, 1H), 3.66 (s, 2H), 3.58-3.53 (t, J=4.9, 2H), 3.54-3.49 (t, J=4.8, 2H), 3.49-3.44 (m, 2H), 3.40-3.35 (t, J=4.8, 2H).

›Example 203

The title compound was prepared in a manner similar to that described in Example 88 using racemic 5-(((2-bromophenyl)thio)methyl)oxazolidin-2-one. MS (ESI): mass calcd. for C 20 H 17 FN 4 O 2 S, 396.11; m/z found, 397.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.37 (m, 1H), 8.09-8.07 (d, J=1.5, 1H), 7.94-7.88 (m, 1H), 7.65-7.59 (m, 1H), 7.43-7.37 (m, 1H), 7.37-7.29 (m, 3H), 7.28-7.23 (dd, J=12.2, 1.7, 1H), 4.68-4.54 (m, 1H), 3.56-3.48 (t, J=8.8, 1H), 3.29-3.22 (dd, J=9.2, 6.4, 1H), 3.20-3.13 (m, 1H), 3.07-3.01 (m, 1H).

›Example 204

The title compound was prepared in a manner similar to that described in Example 88 using N-(2-((2-bromophenyl)thio)ethyl)benzamide. MS (ESI): mass calcd. for C 25 H 21 FN 4 OS, 444.14; m/z found, 445.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.32 (m, 1H), 8.09-8.03 (d, J=1.4, 1H), 7.89-7.83 (t, J=8.1, 1H), 7.73-7.67 (m, 2H), 7.67-7.63 (d, J=7.9, 1H), 7.52-7.45 (m, 1H), 7.44-7.34 (m, 3H), 7.30-7.26 (m, 3H), 7.26-7.21 (dd, J=12.4, 1.7, 1H), 3.53-3.46 (t. J=7.0, 2H), 3.11-3.03 (t, J=7.0, 2H).

›Example 205

The title compound was prepared in a manner similar to that described in Example 88 using (2-bromophenyl)(4-(methylsulfonyl)benzyl)sulfane. MS (ESI): mass calcd. for C 24 H 20 FN 3 O 2 S 2 , 465.10; m/z found, 466.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.35 (m, 1H), 8.12-8.04 (d, J=1.5, 1H), 7.87-7.81 (m, 1H), 7.79-7.73 (m, 2H), 7.59-7.48 (m, 1H), 7.39-7.30 (m, 4H), 7.29-7.24 (m, 1H), 7.18-7.12 (dd, J=8.0, 1.7, 1H), 7.11-7.03 (dd, J=12.3, 1.7, 1H), 4.04 (s, 2H), 3.08 (s, 3H).

›Example 206

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-5-(trifluoromethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 17 H 12 F 4 N 4 O 2 S, 412.06; m/z found, 413.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41 (s, 1H), 8.38 (s, 1H), 8.22-8.16 (m, 1H), 8.01-7.92 (m, 2H), 7.63-7.58 (d, J=8.0, 1H), 7.40-7.30 (m, 2H).

›Example 207

The title compound was prepared in a manner similar to that described in Example 88 using 1-bromo-2-(methylsulfonyl)-4-(trifluoromethyl)benzene and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 18 H 13 F 4 N 3 O 2 S, 411.07; m/z found, 412.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.45-8.44 (d, J=2.0, 1H), 8.43 (s, 1H), 8.10-8.09 (d, J=1.5, 1H), 8.09-8.06 (dd, J=7.8, 1.7, 1H), 8.02-7.97 (m, 1H), 7.71-7.68 (d, J=7.9, 1H), 7.41-7.39 (m, 1H), 7.39-7.37 (m, 1H), 2.88 (s, 3H).

›Example 208

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-methyl-5-(trifluoromethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 18 H 14 F 4 N 4 O 2 S, 426.08; m/z found, 427.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.36 (m, 1H), 8.34-8.27 (d, J=1.9, 1H), 8.21-8.14 (d, J=1.4, 1H), 8.02-7.92 (m, 2H), 7.66-7.61 (d, J=7.9, 1H), 7.35 (s, 1H), 7.34-7.32 (dd, J=4.3, 1.6, 1H), 2.46 (s, 3H).

›Example 209

The title compound was prepared in a manner similar to that described in Example 88 using 4-((2-bromo-5-(trifluoromethyl)phenyl)sulfonyl)piperazin-2-one. MS (ESI): mass calcd. for C 21 H 17 F 4 N 5 O 3 S, 495.10; m/z found, 496.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43-8.37 (m, 2H), 8.24-8.21 (d, J=1.4, 1H), 8.08-8.04 (dd, J=8.0, 1.8, 1H), 8.04-7.99 (m, 1H), 7.69-7.65 (d, J=7.9, 1H), 7.38-7.35 (m, 1H), 7.35-7.32 (dd, J=5.8, 1.6, 1H), 3.38 (s, 2H), 3.15 (s, 4H).

›Example 210

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(2-hydroxyethyl)-5-(trifluoromethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 3 S, 456.09; m/z found, 457.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.39 (m, 1H), 8.36 (s, 1H), 8.16-8.13 (d, J=1.5, 1H), 7.99-7.93 (m, 2H), 7.64-7.61 (d, J=8.0, 1H), 7.38-7.36 (m, 1H), 7.36-7.33 (dd, J=5.0, 1.6, 1H), 3.49-3.45 (t, J=5.9, 2H), 2.93-2.86 (t, J=5.8, 2H).

›Example 211

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-ethyl-5-(trifluoromethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 2 S, 440.09; m/z found, 441.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.41-8.37 (m, 1H), 8.34-8.31 (m, 1H), 8.20-8.16 (d, J=1.5, 1H), 8.01-7.94 (m, 2H), 7.65-7.59 (d, J=7.9, 1H), 7.37-7.34 (m, 1H), 7.34-7.31 (dd, J=2.9, 1.5, 1H), 2.88-2.76 (q, J=7.2, 2H), 1.07-0.94 (t, J=7.2, 3H).

›Example 212

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-ethyl-5-(trifluoromethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 21 F 4 N 5 O 2 S, 495.14; m/z found, 496.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.44-8.41 (m, 1H), 8.41-8.38 (d, J=2.0, 1H), 8.13-8.10 (d, J=1.5, 1H), 8.10-8.06 (m, 1H), 8.05-7.97 (m, 1H), 7.73-7.60 (d, J=8.0, 1H), 7.39-7.37 (dd, J=6.6, 1.6, 1H), 7.37-7.35 (dd, J=2.8, 1.7, 1H), 2.85 (s, 3H), 3.93-2.45 (br m, 8H).

Example 213

›Step A: Ethyl 3-(2-bromophenylthio)propanoate

A mixture of 2-bromobenzenethiol (6 g, 30 mmol), ethyl 3-chloropropanoate (13 g, 96 mmol), K 2 CO 3 (8.8 g, 64 mmol) and acetone (150 mL) was refluxed for 15 h. The reaction mixture was filtered and the filter cake washed with acetone (50 mL). The filtrate was concentrated to dryness and subjected to FCC to give ethyl 3-(2-bromophenylthio)propanoate (7 g, 78%). MS (ESI): mass calcd. for C 11 H 13 O 2 S, 287.98; m/z found, 288.8 [M+H] + .

›Step B: Ethyl 3-(4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-ylthio) propanoate

A mixture of ethyl 3-(2-bromophenylthio)propanoate (7 g, 24 mmol), 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (7.6 g, 24 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (378 mg, 0.52 mmol) and Na 2 CO 3 (5 g, 48 mmol) in dioxane/water (20 mL/5 mL) was stirred at 80° Celsius for 5 hours under N 2 , then poured into water (60 mL) and extracted with EtOAc (50 mL×3). The combined organic extracts were dried over Na 2 SO 4 , filtered, concentrated to dryness and purified by FCC to give ethyl 3-(4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-ylthio) propanoate (7.7 g, 80%) as a white solid. MS (ESI): mass calcd. for C 21 H 20 FN 3 O 2 S, 397.13; m/z found, 397.9 [M+H] + .

›Step C: 4′-(5-Aminopyrazin-2-yl)-5′-fluorobiphenyl-2-thiol

To a solution consisting of ethyl 3-(4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-ylthio) propanoate (7.7 g, 19.4 mmol) and THF (60 mL) was added t-BuOK (4.3 g, 38.8 mmol) and the mixture stirred for 1 hour at rt. The reaction mixture was poured into water (100 mL) and the system brought to a pH=5-6 with 1 M HCl. The mixture was, extracted with EtOAc (80 mL×3) and the combined extracts dried over Na 2 SO 4 , filtered and concentrated to dryness to give 4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-thiol (4.6 g, 80%). MS (ESI): mass calcd. for C 16 H 12 FN 3 S, 297.07; m/z found, 298.0 [M+H] + .

›Step D

To a solution of 4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-thiol (400 mg, 1.34 mmol) and 2-chloropyrimidine (167 mg, 1.47 mmol) in DMF (8 mL) were added DIPEA (345 mg, 2.68 mmol) and Ph 3 P (351 mg, 1.34 mmol) and the resultant mixture heated at 80° Celsius for 1 hour under a N 2 atmosphere for 15 h. The mixture was cooled to rt, concentrated to dryness and the residue subjected to FCC to give the title compound (350 mg, 68%). MS (ESI): mass calcd. for C 20 H 14 FN 5 S.HCl, 375.10; m/z found, 376.0 [M+H] + . 1 H NMR (300 MHz, CD 3 OD) δ 8.42 (d, J=4.9, 2H), 8.33-8.28 (m, 1H), 8.03 (d, J=1.4, 1H), 7.79-7.69 (m, 2H), 7.60-7.53 (m, 1H), 7.51-7.43 (m, 2H), 7.21 (dd, J=8.0, 1.7, 1H), 7.15 (dd, J=12.3, 1.6, 1H), 7.06 (m, 1H).

›Examples16

›Example 214

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(5-aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 4-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 14 FN 5 S, 375.10; m/z found, 375.9 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.84 (d, J=1.1, 1H), 8.46 (d, J=1.4, 2H), 8.44 (d, J=5.6, 1H), 7.81-7.75 (m, 1H), 7.73-7.65 (m, 1H), 7.62-7.51 (m, 3H), 7.30 (dd, J 20=11.8, 1.6, 1H), 7.24 (dd, J=7.9, 1.7, 1H), 6.96 (dd, J=5.6, 1.3, 1H), 6.90 (s, 2H).

›Example 215

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(5-aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 4-amino-6-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 391.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.29-8.25 (m, 3H), 7.94 (m 1H), 7.82 (d, J=7.4, 1H), 7.74 (m, 1H), 7.67-7.58 (m, 2H), 7.34-7.23 (m, 2H), 5.94 (s, 1H).

›Example 216

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(5-aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 4-amino-2-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 390.9 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.31 (m, 1H), 8.16 (s, 1H), 7.88 (m, 1H), 7.83-7.75 (m, 2H), 7.71-7.63 (m, 1H), 7.58-7.52 (m, 2H), 7.32-7.21 (m, 2H), 6.37 (d, J=7.2, 1H).

›Example 217

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(5-aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 5-amino-4-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11: m/z found, 391.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d) δ 8.35-8.30 (m, 1H), 8.22 (s, 1H), 8.02 (d, J=1.4, 1H), 7.90 (s, 1H), 7.80 (m, 1H), 7.59-7.54 (m, 2H), 7.52-7.44 (m, 2H), 7.24 (dd, J=6.5, 1.6, 1H), 7.21 (m, 1H).

›Example 218

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(5-aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 2-chloropyrazine. MS (ESI): mass calcd. for C 20 H 14 FN 5 S, 375.10; m/z found, 375.9 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.26-8.24 (m, 3H), 8.18 (d, J=2.6, 1H), 8.08 (d, J=1.4, 1H), 7.84 (m, 1H), 7.77-7.69 (m, 1H), 7.64-7.55 (m, 1H), 7.55-7.46 (m, 2H), 7.27-7.14 (m, 2H).

›Example 219

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(5-aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 5-amino-2-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 391.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.36 (s, 1H), 8.24 (s, 1H), 7.95 (s, 2H), 7.88 (m, 1H), 7.65-7.59 (m, 1H), 7.53-7.38 (m, 3H), 7.27-7.16 (m, 2H).

›Example 220

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-(2-bromophenyl)-N-methylmethanesulfonamide. MS (ESI): mass calcd. for C 16 H 17 FN 4 O 2 S, 372.11; m/z found, 373.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.34 (s, 1H), 8.25 (s, 1H), 7.99 (m, 1H), 7.68-7.60 (m, 1H), 7.50-7.40 (m, 2H), 7.39-7.31 (m, 3H), 4.36 (s, 2H), 2.49 (s, 3H).

›Example 221

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-(2-bromophenyl)-N-(2-hydroxyethyl)methanesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.12; m/z found, 403.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.38 (d, J=1.2, 1H), 8.31 (s, 1H), 8.02 (m, 1H), 7.70-7.63 (m, 1H), 7.49-7.40 (m, 2H), 7.40-7.30 (m, 3H), 4.40 (s, 2H), 3.51 (t, J=5.9, 2H), 2.95 (t, J=5.9, 2H), 2.66 (s, 1H).

›Example 222

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-((2-bromobenzyl)sulfonyl)azetidin-3-ol. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 3 S, 414.12; m/z found, 414.9 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.43-8.38 (m, 1H), 8.08 (d, J=1.5, 1H), 7.95 (m, 1H), 7.68-7.60 (m, 1H), 7.49-7.41 (m, 2H), 7.39-7.28 (m, 3H), 4.45-4.36 (m, 3H), 3.79-3.70 (m, 2H), 3.67-3.59 (m, 2H).

›Example 223

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 4-((2-bromobenzyl)sulfonyl)piperazin-2-one. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 3 S, 441.13; m/z found, 441.9 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.41 (s, 1H), 8.08 (d, J=1.3, 1H), 7.96 (m, 1H), 7.70-7.62 (m, 1H), 7.52-7.28 (m, 5H), 4.48 (s, 2H), 3.63 (s, 2H), 3.25 (s, 4H).

›Example 224

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and(S)-1-(2-bromophenyl)-N-(1-hydroxypropan-2-yl)methanesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 416.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d) 8.43-8.36 (m, 1H), 8.03 (d, J=1.5, 1H), 7.92 (m, 1H), 7.70-7.59 (m, 1H), 7.47-7.28 (m, 5H), 7.12 (d, J=6.6, 1H), 6.71 (s, 2H), 4.75 (t, J=5.4, 1H), 4.35 (q, J=14.1, 2H), 3.31-3.11 (m, 3H), 1.01 (d, J=6.2, 3H).

›Example 225

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and (R)-1-(2-bromophenyl)-N-(1-hydroxypropan-2-yl)methanesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.48; m/z found, 417.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.32 (d, J=3.7, 2H), 7.99 (m, 1H), 7.77-7.66 (m, 1H), 7.50-7.39 (m, 2H), 7.39-7.28 (m, 3H), 4.41 (q, J=13.9, 2H), 3.49-3.33 (m, 3H), 1.11 (d, J=6.3, 3H).

›Example 226

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and trans-1-(2-bromophenyl)-N-((trans)-4-hydroxycyclohexyl)-methane-sulfonamide. MS (ESI): mass calcd. for C 23 H 25 FN 4 O 3 S.HCO 2 H, 456.16; m/z found, 457.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.40 (s, 1H), 8.08 (d, J=1.3, 1H), 7.94 (m, 1H), 7.72-7.63 (m, 1H), 7.47-7.38 (m, 1H), 7.38-7.27 (m, 3H), 4.36 (s, 2H), 3.42 (s, 1H), 2.97 (s, 1H), 1.84 (d, J=9.0, 4H), 1.38-1.10 (m, 4H).

›Example 227

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and (S)-1-(2-bromophenyl)-N-(2-hydroxypropyl)-methane-sulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.67 (s, 1H), 8.28-8.23 (m, 1H), 8.13 (m, 1H), 7.70-7.62 (m, 1H), 7.49-7.30 (m, 5H), 4.40 (s, 2H), 3.77-3.65 (m, 1H), 2.80 (d. J=5.9, 2H), 1.09 (d, J=6.3, 3H).

›Example 228

›Example 229

Step A: tert-Butyl 1-((4′-(5-aminopyrazin-2-yl-5′-fluorobiphenyl-2-yl)methylsulfonyl)-piperidin-4-ylcarbamate

A mixture of tert-butyl (1-((2-bromobenzyl)sulfonyl)piperidin-4-yl)carbamate (200 mg, 0.46 mmol), 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (175 mg, 0.55 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (34 mg, 0.046 mmol) and Na 2 CO 3 (150 mg, 1.36 mmol) in dry DMF (15 mL) was stirred at 130° Celsius under N 2 . After 5 hours, the solvent was removed under vacuum and the residue was subjected to FCC purification to give tert-butyl 1-((4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methylsulfonyl)piperidin-4-ylcarbamate (190 mg, 76%). MS (ESI): mass calcd. for C 27 H 32 FN 5 O 2 S, 541.22; m/z found, 542.1 [M+H] + . 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.03 (s, 1H), 7.95 (s, 1H), 7.78-7.29 (m, 7H), 6.87 (d, J=5.2, 1H), 6.73 (s, 2H), 4.34 (s, 2H), 3.45-3.33 (m, 3H), 2.85-2.75 (m, 2H), 1.72 (d, J=12.4, 2H), 1.45-1.30 (m, 11H).

›Step B

A mixture of tert-butyl 1-((4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methylsulfonyl)piperidin-4-ylcarbamate (190 mg, 0.35 mmol) in HCl (20 mL, 6 N in methanol) was stirred at rt for 24 hours. The solvent was removed under reduced pressure and the residue purified by HPLC to give the title compound (80 mg HCl salt, 61%). MS (ESI): mass calcd. for C 22 H 24 FN 5 O 2 S, 441.16; m/z found, 442.1 [M+H] + . 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.38 (s, 1H), 8.10 (br, 4H), 7.95 (m, 1H), 7.64-7.55 (m, 1H), 7.52-7.32 (m, 4H), 4.80 (br, 4H), 4.37 (s, 2H), 3.50 (d, J=13.0, 2H), 3.10 (s, 1H), 2.76 (t. J=12.6, 2H), 1.91 (d. J=11.0, 3H), 1.58-1.41 (m, 2H).

›Examples5

›Example 230

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and (2-bromophenyl)methanesulfonamide. MS (ESI): mass calcd. for C 17 H 15 FN 4 O 2 S, 358.09; m/z found, 359.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.36 (s, 1H), 8.12 (s, 1H), 7.92 (m, 1H), 7.66-7.56 (m, 1H), 7.38 (m, 5H), 6.98 (s, 2H), 4.31 (s, 2H).

›Example 231

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-(2-bromophenyl)-N-ethylmethanesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 2 S, 386.12; m/z found, 387.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.39 (s, 1H), 8.08 (d, J=1.4, 1H), 7.93 (m, 1H), 7.71-7.61 (m, 1H), 7.49-7.27 (m, 5H), 4.36 (s, 2H), 2.85 (q, J=7.2, 2H), 1.06 (t, J=7.2, 3H).

›Example 232

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-(1-((2-bromobenzyl)sulfonyl)piperidin-4-yl)urea. MS (ESI): mass calcd. for C 23 H 25 FN 6 O 3 S, 484.17; m/z found, 485.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.37 (s, 1H), 8.16 (s, 1H), 7.96 (t, J=8.2, 1H), 7.66-7.28 (m, 6H), 4.35 (s, 2H), 3.41-3.32 (m, 2H), 2.85-2.70 (m, 2H), 1.83-1.70 (m, 2H), 1.33-1.19 (m, 2H).

›Example 233

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and N-(1-((2-bromobenzyl)sulfonyl)piperidin-4-yl)acetamide. MS (ESI): mass calcd. for C 24 H 26 FN 5 O 3 S, 483.17; m/z found, 484.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.03 (d, J=1.3, 1H), 7.95 (m, 1H), 7.81 (d, J=7.3, 1H), 7.64-7.55 (m, 1H), 7.50-7.31 (m, 5H), 6.73 (s, 2H), 4.35 (s, 2H), 3.71-3.56 (m, 1H), 3.39 (d, J=11.6, 2H), 2.79 (t, J=10.8, 2H), 1.82-1.67 (m, 5H), 1.41-1.24 (m, 3H).

Example 234

›Step A: (4′-(5-Aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methanol

A mixture of 2-(hydroxymethyl)phenylboronic acid (1 g, 7 mmol), 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (1.76 g, 6.6 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (483 mg, 0.66 mmol) and Na 2 CO 3 (2.1 g, 20 mmol) in DMF (50 mL) was stirred at 110° Celsius overnight under N 2 . The solution was concentrated to dryness and the residue purified by FCC to give (4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methanol (1.2 g, 62%). 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.38 (s, 1H), 8.02 (d, J=1.4, 1H), 7.90 (m, 1H), 7.57 (d, J=7.4, 1H), 7.49-7.26 (m, 5H), 6.69 (s, 2H), 5.20 (t, J=5.3, 1H), 4.44 (d, J=5.3, 2H).

›Step B: 5-(6′-(Chloromethyl)-3-fluorobiphenyl-4-yl)pyrazin-2-amine

A mixture of (4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methanol (1.8 g, 6.1 mmol) and SOCl 2 (6 mL) in DCM (20 mL) was stirred at 70° Celsius for 4 hours. The reaction mixture was cooled to rt and concentrated to dryness to give 5-(6′-(chloromethyl)-3-fluorobiphenyl-4-yl)pyrazin-2-amine (1.86 g, 98%). 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.40 (s, 1H), 8.04 (s, 1H), 7.96 (m, 1H), 7.66-7.57 (m, 1H), 7.51-7.42 (m, 2H), 7.40-7.30 (m, 3H), 6.89-6.62 (br s, 2H), 4.73 (s, 2H).

›Step C: S-(4′-(5-Aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methyl ethanethioate

A mixture of 5-(6′-(chloromethyl)-3-fluorobiphenyl-4-yl)pyrazin-2-amine (1.86 g, 5.94 mmol) and KSAc (0.81 g, 7.1 mmol) in 1,4-dioxane/H 2 O (30 mL/6 mL) was stirred at rt for 2 hours. Then the solvent was removed under vacuum and the residue purified by FCC to give S-(4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methyl ethanethioate (1.42 g, 68%). MS (ESI): mass calcd. for C 19 H 18 FN 3 OS, 353.10; m/z found, 353.9 [M+H] + .

›Step D

To a solution of S-(4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methyl ethanethioate (100 mg, 0.28 mmol) in CH 3 OH (30 mL) were added Ph 3 P (147 mg, 0.56 mmol) and K 2 CO 3 (78 mg, 0.56 mmol) followed by drop-wise addition of bromoethane (60 mg, 0.56 mmol). After 16 hours, the mixture was concentrated to dryness and the residue was purified by prep-TLC and followed by HPLC to give the title compound (70 mg HCOOH salt, 73%). MS (ESI): mass calcd. for C 19 H 18 FN 3 S, 339.12; m/z found, 340.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.38 (m, 1H), 8.07 (d, J=1.5, 1H), 7.89 (m, 1H), 7.48-7.40 (m, 1H), 7.37-7.21 (m, 5H), 3.71 (s, 2H), 2.42 (q, J=7.4, 2H), 1.13 (t, J=7.4, 3H).

›Examples13

›Example 235

The title compound was prepared using analogous conditions to those described in Example 234 utilizing iodomethane. MS (ESI): mass calcd. for C 18 H 16 FN 3 S, 325.10; m/z found, 326.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.45 (s, 1H), 8.30 (d, J=1.0, 1H), 8.04 (m, 1H), 7.49-7.24 (m, 6H), 3.68 (s, 2H).

The title

›Example 236

The title compound was prepared using analogous conditions to those described in Example 234 utilizing 2-iodopropane. MS (ESI): mass calcd. for C 20 H 20 FN 3 S, 353.14; m/z found, 354.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.66 (s, 1H), 8.23 (d, J=1.2, 1H), 8.12 (m, 1H), 7.48-7.23 (m, 6H), 3.73 (s, 2H), 2.84-2.71 (m, 1H), 1.16 (d, J=6.7, 6H).

›Example 237

The title compound was prepared using analogous conditions to those described in Example 234 utilizing 4-amino-2-chloropyrimidine. MS (ESI): mass calcd. for C 18 H 16 FN 3 S, 404.12; m/z found, 404.9 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.77-8.68 (m, 1H), 8.21 (d, J=1.3, 1H), 8.10 (m, 1H), 7.79 (d, J=6.9, 1H), 7.63-7.55 (m, 1H), 7.45-7.22 (m, 5H), 6.73 (d, J=6.8, 1H), 4.57 (s, 2H).

›Example 238

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 4-amino-6-chloropyrimidine. MS (ESI): mass calcd. for C 21 H 17 FN 6 S, 404.12; m/z found, 405.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.78-8.68 (m, 1H), 8.38 (d, J=0.6, 1H), 8.26 (d, J=1.3, 1H), 8.16 (m, 1H), 7.66-7.57 (m, 1H), 7.50-7.44 (m, 2H), 7.42-7.31 (m, 3H), 6.58 (d, J=3.4, 1H), 4.51 (s, 2H).

›Example 239

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 3-chloropyrazine. MS (ESI): mass calcd. for C 21 H 16 FN 5 S, 389.11; m/z found, 390.1 [M+H] 4 . 1 H NMR (400 MHz. CD 3 OD) δ 9.33-9.24 (m, 1H), 8.74 (s, 1H), 8.31-8.20 (m, 2H), 8.14 (m, 2H), 7.72-7.64 (m, 1H), 7.50-7.33 (m, 5H), 4.63 (s, 2H).

›Example 240

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 3-chloropyrazine. MS (ESI): mass calcd. for C 21 H 17 FN 6 S, 404.12; m/z found, 405.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.70-8.63 (m, 1H), 8.28 (d, J=1.1, 1H), 8.12 (m, 1H), 7.65-7.57 (m, 2H), 7.46-7.41 (m, 2H), 7.39 (dd, J=8.1, 1.6, 1H), 7.36-7.30 (m, 3H), 4.43 (s, 2H).

›Example 241

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 4-((2-bromophenyl)sulfonyl)tetrahydro-2H-thiopyran 1,1-dioxide. MS (ESI): mass calcd. for C 21 H 20 FN 3 O 4 S 2 , 461.09; m/z found, 462.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.42 (s, 1H), 8.07-8.04 (m, 2H), 7.92 (m, 1H), 7.84 (m, 1H), 7.75 (m, 1H), 7.49 (dd, J=7.5, 1.0, 1H), 7.38-7.31 (m, 1H), 7.29 (dd, J=8.0, 1.6, 1H), 6.74 (s, 2H), 3.25-3.06 (m, 5H), 2.16-2.04 (m, 2H), 2.02-1.86 (m, 2H).

›Example 242

The title compound was prepared using analogous conditions to those described in Example 234 utilizing 2-amino-4-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 391.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39-8.32 (m, 1H), 8.01 (d, J=1.5, 1H), 7.94 (d, J=6.1, 1H), 7.85 (m, 1H), 7.76 (d, J=7.8, 1H), 7.71-7.65 (m, 1H), 7.62-7.53 (m, 2H), 7.35-7.24 (m, 2H), 6.88 (s, 2H), 6.18 (d, J=6.4, 1H).

›Example 243

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 4-chloropyrimidine. MS (ESI): mass calcd. for C 18 H 16 FN 3 S, 389.11; m/z found, 390.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.70 (d, J=1.4, 1H), 8.53 (d, J=4.9, 2H), 8.20 (d, J=1.3, 1H), 8.10 (m, 1H), 7.65-7.55 (m, 1H), 7.39-7.25 (m, 5H), 7.13 (m, 1H), 4.46 (s, 2H).

›Example 244

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)-pyrazin-2-amine and (2-(((2-bromophenyl)thio)methoxy)ethyl)trimethylsilane. MS (ESI): mass calcd. for C 22 H 26 FN 3 OSSi, 427.16; m/z found, 428.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.43-8.36 (m, 1H), 8.07 (d, J=1.5, 1H), 7.89 (m, 1H), 7.73 (dd, J=6.7, 1.4, 1H), 7.40-7.17 (m, 5H), 4.90 (s, 2H), 3.64-3.50 (m, 2H), 0.91-0.78 (m, 2H). 0.04 (s, 9H).

›Example 245

The title compound was prepared using analogous conditions to those described in Example Example 244 utilizing 5-[3-fluoro-2′-({[2-(trimethylsilyl)ethoxy]methyl}sulfanyl-biphenyl-4-yl]-pyrazin-2-amine. MS (ESI): mass calcd. for C 22 H 26 FN 3 O 3 SSi, 459.14; m/z found, 459.9 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.44-8.39 (m, 1H), 8.18 (dd, J=8.0, 1.3, 1H), 8.08 (d, J=1.4, 1H), 7.94 (m, 1H), 7.80-7.75 (m, 1H), 7.72-7.65 (m, 1H), 7.47 (dd, J=7.5, 1.4, 1H), 7.31 (dd, J=3.6, 1.7, 1H), 7.28 (dd, J=7.7, 1.5, 1H), 4.34 (s, 2H), 3.77-3.68 (m, 2H), 0.85-0.75 (m, 2H), 0.08 (s, 9H).

›Example 246

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 1-bromo-2-((3-(methylsulfonyl)propyl)sulfonyl)benzene. MS (ESI): mass calcd. for C 20 H 20 FN 3 O 4 S 2 , 449.53; m/z found, 450.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.69 (d, J=1.3, 1H), 8.25 (d, J=1.3, 1H), 8.18 (dd, J=7.9, 1.3, 1H), 8.12 (m, 1H), 7.81 (m, 1H), 7.71 (m, 1H), 7.48 (dd, J=7.4, 1.3, 1H), 7.44-7.34 (m, 2H), 3.20-3.09 (m, 4H), 2.89 (s, 3H), 2.12-1.96 (m, 2H).

›Example 247

Step A: (R)-tert-Butyl 4-((4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-yl)sulfonyl-3-methylpiperazine-1-carboxylate

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (R)-tert-butyl 4-((2-bromophenyl)sulfonyl)-3-methypiperazine-1-carboxylate. MS (ESI): mass calcd. for C 26 H 30 FN 5 O 4 S, 527.20; m/z found, 528.2 [M+H] + .

›Step B

The title compound was prepared by dissolving (R)-tert-butyl 4-((4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-yl)sulfonyl)-3-methylpiperazine-1-carboxylate (42 mg, 0.08 mmol) in a 50/50 mixture of DCM/TFA (1 mL) and allowing it to stir at rt for 2 h. The reaction mixture was concentrated to dryness and the residue subjected to HPLC purification to give the title compound (29 mg, 85%). MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (d, J=1.4, 2H), 8.16 (dd, J=8.0, 1.4, 1H), 7.65-7.58 (m, 1H), 7.56-7.49 (m, 1H), 7.48-7.39 (m, 1H), 7.38-7.31 (m, 3H), 5.18 (s, 2H), 3.64-3.52 (m, 1H), 2.99-2.87 (m, 2H), 2.81-2.69 (m, 1H), 2.61-2.41 (m, 4H), 1.18 (d, J=6.8, 3H).

›Examples6

›Example 248

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-phenyl)pyrimidin-2-amine and (S)-2-bromo-N-(1-hydroxybutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.47 (d, J=1.3, 2H), 8.18 (dd, J=7.9, 1.4, 1H), 7.67-7.57 (m, 1H), 7.59-7.49 (m, 1H), 7.42-7.30 (m, 4H), 5.39 (s, 2H), 5.07 (d, J=8.0, 1H), 3.55-3.38 (m, 2H), 3.25-3.11 (m, 1H), 1.93 (s, 1H), 1.54-1.29 (m, 2H), 0.80 (t, J=7.4, 3H).

›Example 249

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phenyl)pyrimidin-2-amine and 2-bromo-N-(2-cyanoethyl)-N-cyclopropylbenzenesulfonamide. MS (ESI): mass calcd. for C 22 H 20 FN 5 O 2 S, 437.13; m/z found, 438.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.57 (d, J=1.4, 2H), 8.17 (dd, J=7.9, 1.3, 1H), 7.71-7.62 (m, 1H), 7.62-7.52 (m, 1H), 7.49-7.40 (m, 1H), 7.33 (dd, J=7.5, 1.4, 1H), 7.20 (dd, J=8.0, 1.7, 1H), 7.14 (dd, J=11.1, 1.7, 1H), 5.20 (s, 2H), 3.02 (t, J=7.0, 2H), 2.59-2.41 (m, 3H), 0.65-0.55 (m, 2H), 0.39-0.28 (m, 2H).

›Example 250

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phenyl)pyrimidin-2-amine and 2-bromo-N-(2-cyanoethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 FN 5 O 2 S, 397.10; m/z found, 398.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) 8.50 (d, J=1.4, 2H), 8.18 (dd, J=7.9, 1.4, 1H), 7.70-7.64 (m, 1H), 7.62-7.55 (m, 1H), 7.49-7.42 (m, 1H), 7.40-7.32 (m, 3H), 5.36 (s, 2H), 5.24 (t, J=6.5, 1H), 3.07 (m, 2H), 2.50 (t, J=6.5, 2H).

›Example 251

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phenyl)pyrimidin-2-amine and 2-bromo-N-(3-hydroxy-2,2-dimethylpropyl)-benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.53 (d, J=1.4, 2H), 8.12 (dd, J=7.8, 1.5, 1H), 7.62-7.55 (m, 1H), 7.55-7.48 (m, 1H), 7.48-7.38 (m, 1H), 7.38-7.27 (m, 3H), 5.08 (s, 2H), 4.23 (t, J=6.6, 1H), 3.33-3.21 (m, 2H), 2.61 (d, J=6.8, 2H), 1.40 (s, 6H).

›Example 252

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phenyl)pyrimidin-2-amine and racemic (4-((2-bromophenyl)sulfonyl)morpholin-2-yl)methanol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 4 S, 444.13; m/z found, 445.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (d, J=1.4, 2H), 8.10 (dd, J=7.9, 1.4, 1H), 7.70-7.60 (m, 1H), 7.60-7.52 (m, 1H), 7.47-7.35 (m, 2H), 7.33-7.26 (m, 2H), 5.22 (s, 2H), 3.86-3.76 (m, 1H), 3.63-3.51 (m, 1H), 3.51-3.29 (m, 3H), 3.24-3.09 (m, 2H), 2.64-2.52 (m, 1H), 2.45 (dd, J=12.4, 10.5, 1H), 1.95 (s, 1H).

›Example 253

Step A: (S-tert-Butyl 4-((4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-yl)sulfonyl-3-methylpiperazine-1-carboxylate

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (S)-tert-butyl 4-((2-bromophenyl)sulfonyl)-3-methypiperazine-1-carboxylate. MS (ESI): mass calcd. for C 26 H 30 FN 5 O 4 S, 527.20: m/z found, 528.2 [M+H] + .

›Step B

The title compound was prepared as described in the preparation of Example 252 using (S)-tert-butyl 4-((4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-yl)sulfonyl)-3-methylpiperazine-1-carboxylate. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 2 S, 427.15; m/z found, 428.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) b 8.56 (d, J=1.4, 2H), 8.16 (dd, J=7.9, 1.3, 1H), 7.65-7.58 (m, 1H), 7.56-7.49 (m, 1H), 7.48-7.39 (m, 1H), 7.38-7.31 (m, 3H), 5.16 (s, 2H), 3.64-3.51 (m, 1H), 3.02-2.86 (m, 2H), 2.81-2.70 (m, 1H), 2.63-2.41 (m, 4H), 1.18 (d, J=6.8, 3H).

›Examples3

›Example 254

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and 1-bromo-2-(cyclopropylsulfonyl)benzene. MS (ESI): mass calcd. for C 19 H 16 FN 3 O 2 S, 369.10; m/z found, 370.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.59 (d, J=1.5, 2H), 8.14 (dd, J=7.9, 1.5, 1H), 7.70-7.63 (m, 1H), 7.62-7.54 (m, 1H), 7.45 (m, 1H), 7.41-7.28 (m, 3H), 5.23 (s, 2H), 2.19-2.06 (m, 1H), 1.16-1.07 (m, 2H), 0.93-0.81 (m, 2H).

›Example 255

›Example 256

Step A: (S)-tert-Butyl 3-(4′-2-aminopyrimidin-5-yl)-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-ylsulfonamido)piperidine-1-carboxylate

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (S)-tert-butyl 3-(2-bromo-N-methylphenylsulfonamido)-piperidine-1-carboxylate yielding 41 mg (48%) of the title compound after HPLC purification. MS (ESI): mass calcd. for C 27 H 32 FN 5 O 4 S, 541.21; m/z found, 542.1 [M+H] + .

›Step B

The title compound was prepared as described in the preparation of Example 247 using (S)-tert-butyl 3-(4′-2-aminopyrimidin-5-yl)-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-ylsulfonamido)piperidine-1-carboxylate. The crude product was purified by HPLC to give the title compound (35 mg, 91%). MS (ESI): mass calcd. for C 22 H 24 FN 5 O 2 S, 441.16; m/z found, 442.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (d, J=1.4, 2H), 8.14 (dd, J=7.9, 1.4, 1H), 7.65-7.57 (m, 1H), 7.56-7.49 (m, 1H), 7.48-7.38 (m, 1H), 7.37-7.24 (m, 3H), 5.19 (s, 2H), 3.43-3.24 (m, 1H), 2.96-2.74 (m, 2H), 2.51 (t, J=11.3, 1H), 2.42 (s, 4H), 2.38-2.27 (m, 1H), 1.78-1.21 (m, 4H).

›Example 257

Step A: R)-tert-Butyl 3-(4′-2-aminopyrimidin-5-yl)-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-ylsulfonamido)piperidine-1-carboxylate

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (R)-tert-butyl 3-(2-bromo-N-methylphenylsulfonamido)piperidine-1-carboxylate. MS (ESI): mass calcd. for C 27 H 32 FN 5 O 4 S, 541.21; m/z found, 542.2 [M+H] + .

›Step B

The title compound was prepared as described in the preparation of Example 247 using (R)-tert-butyl 3-(4′-2-aminopyrimidin-5-yl)-3′-fluoro-N-methyl-[1,1′-biphenyl]-2-ylsulfonamido)piperidine-1-carboxylate. MS (ESI): mass calcd. for C 22 H 24 FN 5 O 2 S, 441.16; m/z found, 442.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (d, J=1.4, 2H), 8.14 (dd, J=8.0, 1.4, 1H), 7.65-7.57 (m, 1H), 7.56-7.49 (m, 1H), 7.47-7.36 (m, 1H), 7.37-7.25 (m, 3H), 5.18 (s, 2H), 3.42-3.26 (m, 1H), 2.93-2.73 (m, 2H), 2.57-2.46 (m, 1H), 2.42 (s, 3H), 2.38-2.27 (m, 2H), 1.73-1.23 (m, 4H).

›Example 258

Step A: (R)-tert-Butyl 4-((4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-yl)sulfonyl)-3-(hydroxymethyl)piperazine-1-carboxylate

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (R)-tert-butyl 4-((2-bromophenyl)sulfonyl)-3-hydroxymethy)piperazine-1-carboxylate. MS (ESI): mass calcd. for C 26 H 30 FN 5 O 5 S, 543.20; m/z found, 544.2 [M+H] + .

›Step B

The title compound was prepared as described in the preparation of Example 247 using (R)-tert-butyl 4-((4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-yl)sulfonyl)-3-(hydroxymethyl)piperazine-1-carboxylate. MS (ESI): mass calcd. for C 21 H 22 FN 5 O 3 S, 443.14; m/z found, 444.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (d, J=1.4, 2H), 8.18 (dd, J=8.0, 1.3, 1H), 7.66-7.59 (m, 1H), 7.57-7.49 (m, 1H), 7.47-7.40 (m, 1H), 7.39-7.31 (m, 3H), 5.19 (s, 2H), 3.94-3.77 (m, 2H), 3.52-3.39 (m, 1H), 3.34-3.18 (m, 1H), 3.17-2.99 (m, 2H), 2.88-2.77 (m, 1H), 2.65-2.46 (m, 2H), 1.65 (br s, 2H).

›Examples83

›Example 259

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and racemic 2-bromo-N-((cis)-2-hydroxycyclohexyl)-benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.51 (d, J=1.3, 2H), 8.17 (dd, J=8.0, 1.4, 1H), 7.64-7.59 (m, 1H), 7.57-7.51 (m, 1H), 7.44-7.31 (m, 4H), 5.30 (s, 2H), 4.83 (d, J 20=7.7, 1H), 3.78 (s, 1H), 3.20-3.11 (m, 1H), 1.72-1.65 (m, 1H), 1.57-1.10 (m, 8H).

›Example 260

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and 2-bromo-N-((trans)-2-hydroxycylohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.51 (d, J=1.3, 2H), 8.17 (dd, J=8.0, 1.4, 1H), 7.64-7.59 (m, 1H), 7.57-7.51 (m, 1H), 7.44-7.31 (m, 4H), 5.30 (s, 2H), 4.83 (d, J=7.7, 1H), 3.78 (s, 1H), 3.20-3.11 (m, 1H), 1.72-1.65 (m, 1H), 1.57-1.10 (m, 8H).

›Example 261

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and 2-bromo-N-(2-hydroxyethyl)-N-isopropylbenzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (d. J=1.4, 2H), 8.10 (dd. J=8.0, 1.4, 1H), 7.65-7.57 (m, 1H), 7.58-7.49 (m, 1H), 7.49-7.38 (m, 1H), 7.37-7.28 (m, 3H), 5.22 (s, 2H), 3.72 (p, J=6.7, 1H), 3.65-3.50 (m, 2H), 2.99 (t, J=6.0, 2H), 2.19 (d, J=7.0, 1H), 1.04 (d, J=6.7, 6H).

›Example 262

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and trans-2-bromo-N-4-hydroxycyclohexyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 23 FN 4 O 3 S, 442.15; m/z found, 443.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.53 (s, 1H), 8.22-8.15 (m, 1H), 7.67-7.60 (m, 1H), 7.59-7.51 (m, 1H), 7.48-7.39 (m, 1H), 7.39-7.31 (m, 3H), 5.26 (s, 2H), 4.11 (d, J=7.1, 1H), 3.60-3.43 (m, 1H), 3.10-2.94 (m, 1H), 1.93-1.73 (m, 4H), 1.38 (d, J=4.4, 1H), 1.34-1.00 (m, 5H).

›Example 263

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (S)-2-bromo-N-(2-oxopyrrolidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 3 S, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.51 (dd, J=2.2, 1.3, 2H), 8.18 (dd, J=7.9, 1.3, 1H), 7.67-7.60 (m, 1H), 7.58-7.51 (m, 1H), 7.45-7.31 (m, 4H), 6.05 (d, J=9.3, 1H), 5.51 (dd, J=9.8, 3.3, 1H), 5.35 (d, J=3.1, 2H), 3.67-3.55 (m, 1H), 3.39-3.19 (m, 2H), 2.65-2.50 (m, 1H), 2.16-1.99 (m, 1H).

›Example 264

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 4-((2-bromophenyl)sulfonyl)thiomorpholine 1,1-dioxide. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 4 S 2 . 462.08; m/z found, 463.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.78 (d, J=0.9, 2H), 8.15 (dd, J=8.0, 1.1, 1H), 7.75 (m, 1H), 7.71-7.62 (m, 2H), 7.44 (dd, J=7.6, 1.1, 1H), 7.40-7.31 (m, 2H), 3.34 (dd, J=7.8, 3.2, 4H), 3.04-2.99 (m, 4H).

›Example 265

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 1-((2-bromophenyl)sulfonyl)azetidin-3-ol. MS (ESI): mass calcd. for C 19 H 17 FN 4 O 3 S, 400.10; m/z found, 401.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.79 (d, J=0.7, 2H), 8.08 (dd, J=8.0, 1.1, 1H), 7.72 (m, 1H), 7.68-7.55 (m, 2H), 7.47-7.38 (m, 1H), 7.36 (dd, J=8.3, 1.5, 2H), 4.36 (m, 1H), 3.76-3.64 (m, 2H), 3.60-3.53 (m, 2H).

›Example 266

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (R)-2-bromo-N-(2-oxopiperidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 3 S, 441.13; m/z found, 442.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.71 (d, J=0.7, 2H), 8.24 (dd, J=8.0, 1.2, 1H), 7.67 (m, 1H), 7.58 (m, 2H), 7.42 (s, 1H), 7.41-7.39 (m, 1H), 7.38 (dd, J=7.6, 1.2, 1H), 3.63 (dd, J=10.5, 5.8, 1H), 3.20 (dd, J=8.9, 5.1, 2H), 2.17 (m, 1H), 1.89-1.80 (m, 1H), 1.78-1.64 (m, 2H).

›Example 267

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (S)-2-bromo-N-(2-oxopiperidin-3-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 3 S, 441.13; m/z found, 442.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.74 (d, J=0.8, 2H), 8.24 (dd, J=8.0, 1.1, 1H), 7.67 (m, 1H), 7.62-7.54 (m, 2H), 7.42 (s, 1H), 7.42-7.40 (m, 1H), 7.38 (dd, J=7.6, 1.2, 1H), 3.64 (dd, J=10.5, 5.8, 1H), 3.20 (dd, J=8.7, 5.0, 2H), 2.17 (m, 1H), 1.89-1.80 (m, 1H), 1.80-1.65 (m, 2H).

›Example 268

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (R)-2-bromo-N-(1,1,1-trifluoropropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 2 S, 440.09; m/z found, 441.0 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.64 (d, J=0.9, 2H), 8.10 (dd, J=8.0, 1.1, 1H), 7.67 (m, 1H), 7.59 (m, 1H), 7.55 (m, 1H), 7.37 (dd, J=7.6, 1.2, 1H), 7.33-7.24 (m, 2H), 3.86 (m, 1H), 1.22 (m, 3H).

›Example 269

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (R)-2-bromo-N-(1-hydroxy-3,3-dimethylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 25 FN 4 O 3 S, 444.16; m/z found, 445.2 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.68 (d, J=1.0, 2H), 8.15 (dd, J=8.0, 1.1, 1H), 7.62 (m, 1H), 7.58-7.49 (m, 2H), 7.42-7.35 (m, 2H), 7.35-7.29 (m, 1H), 3.50 (m, 2H), 3.06 (dd, J=5.8, 4.3, 1H), 0.84 (s, 9H).

›Example 270

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (S)-2-bromo-N-(1-hydroxy-3,3-dimethylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 25 FN 4 O 3 S, 444.16; m/z found, 445.2 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.69 (d, J=1.0, 2H), 8.15 (dd, J=8.0, 1.1, 1H), 7.63 (m, 1H), 7.59-7.47 (m, 2H), 7.41-7.36 (m, 2H), 7.33 (m, 1H), 3.50 (m, 2H), 3.06 (dd, J=5.9, 4.2, 1H), 0.84 (s, 9H).

›Example 271

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (S)-2-bromo-N-(1-hydroxy-3-methylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.71 (d, J=0.9, 2H), 8.15 (dd, J=8.0, 1.1, 1H), 7.66-7.61 (m, 1H), 7.60-7.54 (m, 2H), 7.36 (m, 3H), 3.47-3.38 (m, 1H), 3.38-3.32 (m, 1H), 3.06 (q, J=5.5, 1H), 1.84 (m, 1H), 0.83-0.78 (m, 6H).

›Example 272

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.1 [M+H] 4 . 1 H NMR (600 MHz. CD 3 OD) δ 8.75 (d, J=1.0 Hz, 2H), 8.04 (dd, J=8.0, 1.3 Hz, 1H), 7.70-7.65 (m, 1H), 7.64-7.58 (m, 2H), 7.41 (dd, J=7.6, 1.3 Hz, 1H), 7.39-7.35 (m, 2H), 2.71 (s, 2H), 1.11 (s, 6H).

›Example 273

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (R)-2-bromo-N-(1-hydroxy-3-methylbutan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.71 (d, J=0.9, 2H), 8.15 (dd, J=8.0, 1.1, 1H), 7.66-7.61 (m, 1H), 7.60-7.54 (m, 2H), 7.36 (m, 3H), 3.47-3.38 (m, 1H), 3.38-3.32 (m, 1H), 3.06 (q, J=5.5, 1H), 1.84 (m, 1H), 0.83-0.78 (m, 6H).

›Example 274

›Example 275

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-(2-hydroxyethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 3 S, 388.10; m/z found, 389.1 [M+H] 4 . 1 H NMR (600 MHz, CD 3 OD) δ 8.75 (d, J=0.9, 2H), 8.07 (m, 1H), 7.71-7.66 (m, 1H), 7.63-7.59 (m, 2H), 7.40 (dd, J=7.6, 1.1, 1H), 7.37 (m, 2H), 3.49 (t, J=5.9, 2H), 2.90 (t, J=5.9, 2H).

›Example 276

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (R)-(1-((2-bromophenyl)sulfonyl)pyrrolidin-2-yl)methanol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) G 8.70 (d, J=1.0, 2H), 8.10 (dd, J=8.0, 1.2, 1H), 7.70 (m, 1H), 7.64-7.61 (m, 1H), 7.59 (dd, J=10.9, 5.4, 1H), 7.41 (dd, J=7.6, 1.2, 1H), 7.37-7.32 (m, 2H), 3.50 (m, 1H), 3.37 (dd, J=10.8, 3.9, 1H), 3.21-3.15 (m, 1H), 3.03-2.95 (m, 2H), 1.88-1.75 (m, 3H), 1.73-1.66 (m, 1H).

›Example 277

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (S)-(1-((2-bromophenyl)sulfonyl)pyrrolidin-2-yl)methanol. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.70 (d, J=1.0, 2H), 8.10 (dd, J=8.0, 1.2, 1H), 7.70 (m, 1H), 7.64-7.61 (m, 1H), 7.59 (dd, J=10.9, 5.4, 1H), 7.41 (dd, J=7.6, 1.2, 1H), 7.37-7.32 (m, 2H), 3.50 (m, 1H), 3.37 (dd, J=10.8, 3.9, 1H), 3.21-3.15 (m, 1H), 3.03-2.95 (m, 2H), 1.88-1.75 (m, 3H), 1.73-1.66 (m, 1H).

›Example 278

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (R)-2-bromo-N-(2-hydroxypropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.12; m/z found, 403.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.60 (d, J=1.2 Hz, 2H), 8.06 (dd, J=8.0, 1.3 Hz, 1H), 7.71-7.65 (m, 1H), 7.63-7.58 (m, 1H), 7.58-7.51 (m, 1H), 7.41 (dd, J=7.5, 1.4 Hz, 1H), 7.35 (s, 1H), 7.34-7.30 (m, 1H), 3.74-3.63 (m, 1H), 2.76 (dd, J=13.1, 5.0 Hz, 1H), 2.69 (dd, J=13.0, 6.8 Hz, 1H), 1.06 (d, J=6.3 Hz, 3H).

›Example 279

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (S)-2-bromo-N-(2-hydroxypropyl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.12; m/z found, 403.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.60 (d, J=1.2 Hz, 2H), 8.06 (dd, J=8.0, 1.3 Hz, 1H), 7.71-7.65 (m, 1H), 7.63-7.58 (m, 1H), 7.58-7.51 (m, 1H), 7.41 (dd, J=7.5, 1.4 Hz, 1H), 7.35 (s, 1H), 7.34-7.30 (m, 1H), 3.74-3.63 (m, 1H), 2.76 (dd, J=13.1, 5.0 Hz, 1H), 2.69 (dd, J=13.0, 6.8 Hz, 1H), 1.06 (d, J=6.3 Hz, 3H)

›Example 280

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-(1-hydroxy-2-methylpropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 3 S, 416.13; m/z found, 417.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.69 (s, 2H), 8.16 (dd, J=8.0, 1.2, 1H), 7.66 (m, 1H), 7.61-7.55 (m, 2H), 7.38 (dd, J=7.8, 1.3, 3H), 3.27 (s, 2H), 1.03 (s, 6H).

›Example 281

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 1-((2-bromophenyl)sulfonyl)-4-cyclopropylpiperazine. MS (ESI): mass calcd. for C 23 H 24 FN 5 O 2 S, 453.16; m/z found, 454.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.75 (d, J=0.6, 2H), 8.13 (dd, J=8.0, 1.2, 1H), 7.79-7.74 (m, 1H), 7.69-7.59 (m, 2H), 7.45 (dd, J=7.6, 1.2, 1H), 7.37-7.32 (m, 2H), 3.59-3.33 (m, 4H), 3.28-3.00 (m, 4H), 2.82 (m, 1H), 1.00-0.86 (m, 4H).

›Example 282

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-(4-((2-bromophenyl)sulfonyl)piperazin-1-yl)ethanol. MS (ESI): mass calcd. for C 22 H 24 FN 5 O 3 S, 457.16; m/z found, 458.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.72 (s, 2H), 8.13 (dd, J=8.0, 1.2, 1H), 7.77 (m, 1H), 7.71-7.59 (m, 2H), 7.46 (dd, J=7.6, 1.2, 1H), 7.39-7.33 (m, 2H), 3.85-3.80 (m, 2H), 3.68-3.33 (m, 4H), 3.26-3.22 (m, 2H), 3.17-2.81 (m, 4H).

›Example 283

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-(cyclopropylmethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 2 S, 398.12; m/z found, 399.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.67 (s, 2H), 8.10 (dd, J=8.0, 1.4 Hz, 1H), 7.70-7.65 (m, 1H), 7.65-7.53 (m, 2H), 7.39-7.35 (m, 1H), 7.31-7.25 (m, 2H), 1.22 (s, 3H), 0.52-0.48 (m, 2H), 0.38-0.33 (m, 2H).

›Example 284

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-cyclopropylbenzenesulfonamide. MS (ESI): mass calcd. for C 19 H 17 FN 4 O 2 S, 384.10; m/z found, 385.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.68 (d, J=1.0, 2H), 8.11 (dd, J=8.0, 1.2, 1H), 7.69 (m, 1H), 7.62 (m, 1H), 7.56 (m, 1H), 7.40 (dd, J=7.6, 1.2, 1H), 7.35-7.22 (m, 2H), 2.20 (m, 1H), 0.55-0.34 (m, 4H).

›Example 285

›Example 286

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.11; m/z found, 403.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.59 (d, J=1.3, 2H), 8.07 (dd, J=7.9, 1.4, 1H), 7.68 (td, J=7.5, 1.4, 1H), 7.65-7.58 (m, 2H), 7.39 (dd, J=7.5, 1.4, 1H), 7.35 (dd, J=11.8, 1.8, 1H), 7.29 (dd, J=7.9, 1.8, 1H), 7.25 (d, J=7.5, 1H), 3.30 (dd, J=10.3, 4.9, 1H), 3.14-3.09 (m, 1H), 3.09-3.01 (m, 1H), 0.96 (d. J=6.5, 3H).

›Example 287

To a 6 mL microwave vial the following were added 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine (60 mg, 0.19 mmol), N-(tert-butyl)-2-chloro-6-methylbenzenesulfonamide (62 mg, 0.24 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1-1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (3 mg, 0.004 mmol). The vial was flushed with nitrogen and charged with N 2 sparged THF (0.3 mL) and N 2 sparged K 3 PO 4 (0.8 mL, 0.5 M). The resulting biphasic mixture was stirred at rt for 1 h and at 45° C. for 1 h. The resulting mixture was concentrated to dryness and the resulting residue was purified by HPLC to provide the title compound. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 2 S, 414.15: m/z found, 415.1 [M+H] + .

›Example 288

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-methylbenzenesulfonamide. MS (ESI): mass calcd. for C 17 H 15 FN 4 O 2 S, 358.09; m/z found, 359.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.59 (s, 2H), 7.93 (dd, J=7.8, 1.4, 1H), 7.70 (td, J=7.5, 1.4, 1H), 7.67-7.58 (m, 2H), 7.42 (dd, J=7.5, 1.5, 1H), 7.34 (dd, J=11.8, 1.8, 1H), 7.31-7.26 (m, 4H), 2.41 (d, J=4.8, 3H).

›Example 289

Method 1

Method 2

A mixture of 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine (30.0 g, 95.2 mmol), K 3 PO 4 (70.7 g, 333 mmol), (R)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide (28.0 g, 95.2 mmol), PdCl 2 (dppf).CH 2 Cl 2 (0.70 g, 0.95 mmol), acetonitrile (476 mL), and water (190 mL) was sparged with N 2 and stirred at 75° Celsius for 26 hours. After filtration, water was added and the reaction mixture was cooled to rt. Solid precipitate was collected by vacuum filtration and dried in a vacuum oven at 70° Celsius (24.0 g, 63%). The solid was recrystallized from EtOH and treated successively with activated charcoal and silica-supported thiol to remove residual Pd and afford the title compound (21.6 g, 57%). MS (ESI): mass calcd. for C 19 H 19 FN 4 O 3 S, 402.12; m/z found, 403.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.52 (d, J=1.4, 2H), 8.12-7.99 (m, 1H), 7.73-7.65 (m, 1H), 7.65-7.53 (m, 2H), 7.39 (dd, J=7.5, 1.4, 1H), 7.36-7.31 (m, 1H), 7.28 (dd, J=7.9, 1.8, 1H), 7.23 (d, J=7.5, 1H), 6.92 (s, 2H), 4.75-4.67 (m, 1H), 3.33-3.27 (m, 1H), 3.16-3.01 (m, 2H), 0.96 (d, J=6.4, 3H). Chiral HPLC: Chiralpak IC 4.6×250 mm column, 30% EtOH+0.2% TEA, 70% CO 2 , 2 mL/min, retention time 22.4 min, ee>99%.

›Example 290

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 1-((2-bromophenyl)sulfonyl)piperazine. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.63 (s, 2H), 8.54 (d, J=1.0, 2H), 8.08-8.04 (m, 1H), 7.81 (m, 1H), 7.74-7.68 (m, 1H), 7.61 (m, 1H), 7.50 (d, J=7.6, 1H), 7.36 (dd, J=11.6, 1.5, 1H), 7.29 (dd, J=7.9, 1.7, 1H), 7.05 (s, 2H), 3.04-2.86 (m, 8H).

›Example 291

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (R)-2-bromo-N-(2,2,2-trifluoro-1-phenylethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 18 F 4 N 4 O 2 S, 502.11; m/z found, 503.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 9.28 (d, J=10.1, 1H), 8.54 (d, J=1.2, 2H), 7.88 (dd, J=8.1, 1.1, 1H), 7.59 (m, 1H), 7.53 (t, J=8.3, 1H), 7.46-7.40 (m, 3H), 7.41-7.30 (m, 3H), 7.27 (dd, J=7.6, 1.2, 1H), 7.12-6.97 (m, 4H), 5.14-4.96 (m, 1H).

›Example 292

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (S)-2-bromo-N-(2,2,2-trifluoro-1-phenylethyl)benzenesulfonamide. MS (ESI): mass calcd. for C 24 H 18 F 4 N 4 O 2 S, 502.11; m/z found, 503.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d) δ 9.29 (d, J=10.1, 1H), 8.59 (s, 2H), 7.88 (dd, J=8.0, 1.0, 1H), 7.60 (m, 1H), 7.54 (t, J=8.2, 1H), 7.47-7.42 (m, 3H), 7.38-7.31 (m, 3H), 7.27 (dd, J=7.6, 1.0, 1H), 7.11-7.04 (m, 2H), 5.11-5.03 (m, 1H).

›Example 293

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 1-bromo-2-(tert-butylsulfonyl)benzene. MS (ESI): mass calcd. for C 20 H 20 FN 3 O 2 S, 385.12; m/z found, 386.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.57 (d, J=0.8, 2H), 8.03 (dd, J=8.0, 1.2, 1H), 7.81 (m, 1H), 7.72 (m, 1H), 7.56 (m, 1H), 7.41 (dd, J=7.6, 1.2, 1H), 7.32 (dd, J=11.9, 1.6, 1H), 7.25 (dd, J=7.9, 1.7, 1H), 7.14 (s, 2H), 1.08 (s, 9H).

›Example 294

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-isobutylbenzenesulfonamide. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.53 (s, 2H), 7.94 (dd, J=7.9, 1.0, 1H), 7.68 (m, 1H), 7.65-7.57 (m, 2H), 7.52 (m, 1H), 7.41 (dd, J=7.5, 1.1, 1H), 7.33 (dd, J=11.8, 1.4, 1H), 7.29 (dd, J=7.9, 1.6, 1H), 7.03 (s, 2H), 2.53 (t, J=6.4, 2H), 1.60 (m, 1H), 0.79 (d, J=6.7, 6H).

›Example 295

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-ethylbenzenesulfonamide. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.11; m/z found, 373.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.57 (d, J=1.3, 2H), 7.96 (dd, J=7.9, 1.4, 1H), 7.69 (td, J=7.5, 1.4, 1H), 7.66-7.58 (m, 2H), 7.44-7.40 (m, 2H), 7.34 (dd, J=11.8, 1.8, 1H), 7.29 (dd, J=7.9, 1.7, 1H), 7.18 (s, 2H), 2.77 (qd, J=7.2, 5.6, 2H), 0.97 (t. J=7.2, 3H).

›Example 296

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-bromo-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 20 H 18 F 4 N 4 O 2 S, 454.11; m/z found, 455.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.65 (s, 2H), 8.12 (dd, J=8.0, 1.1, 1H), 7.67 (m, 1H), 7.60 (m, 1H), 7.55 (m, 1H), 7.39 (dd, J=7.5, 1.2, 1H), 7.32 (dd, J=6.0, 4.7, 2H), 1.29 (s, 6H).

›Example 297

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and (S)-2-bromo-N-(1,1,1-trifluoropropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 2 S, 440.09; m/z found, 441.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.71 (s, 2H), 8.10 (d, J=7.9, 1H), 7.68 (m, 1H), 7.63-7.53 (m, 2H), 7.40-7.34 (m, 1H), 7.33-7.26 (m, 2H), 3.87 (m, 1H), 1.23 (d, J=7.0, 3H).

›Example 298

The title compound was prepared using analogous conditions to those described in Example 287 using 5-(4-chloro-2-fluorophenyl)pyrimidin-2-amine and (2-(pyrrolidin-1-ylsulfonyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 2 S, 398.12; m/z found, 399.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.54 (d. J=1.2, 2H), 7.98 (dd. J=7.9, 1.1, 1H), 7.73 (m, 1H), 7.67-7.59 (m, 2H), 7.43 (dd, J=7.5, 1.1, 1H), 7.34 (dd, J=11.8, 1.6, 1H), 7.28 (dd. J=7.9, 1.7, 1H), 7.05 (s, 2H), 2.88 (t, J=6.7, 4H), 1.76-1.60 (m, 4H).

›Example 299

The title compound was prepared using analogous conditions to those described in Example 287 using 5-(4-chloro-2-fluorophenyl)pyrimidin-2-amine and (2-(N,N-dimethyl-sulfamoyl)phenyl)boronic acid MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.10; m/z found, 373.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.56 (d, J=1.1, 2H), 7.95 (dd, J=7.9, 1.2, 1H), 7.73 (m, 1H), 7.66 (m, 1H), 7.61 (m, 1H), 7.43 (dd, J=7.5, 1.2, 1H), 7.32 (dd, J=11.8, 1.6, 1H), 7.26 (dd, J=7.9, 1.7, 1H), 2.50 (s, 6H).

›Example 300

The title compound was prepared using analogous conditions to those described in Example 287 using 5-(4-chloro-2-fluorophenyl)pyrimidin-2-amine and (2-(N,N-diethyl-sulfamoyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.54 (d, J=1.3, 2H), 7.96 (dd, J=8.0, 1.2, 1H), 7.71 (m, 1H), 7.63 (m, 2H), 7.41 (dd, J=7.5, 1.2, 1H), 7.30 (m, 1H), 7.26 (m, 1H), 7.04 (s, 2H), 2.93 (q, J=7.1, 4H), 0.94 (t, J=7.1, 6H).

›Example 301

The title compound was prepared using analogous conditions to those described in Example 287 using 5-(4-chloro-2-fluorophenyl)pyrimidin-2-amine and (2-(piperidin-1-ylsulfonyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 21 H 21 FN 4 O 2 S, 412.14; m/z found, 413.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.54 (d, J=1.2, 2H), 7.99 (dd, J=8.0, 1.2, 1H), 7.73 (m, 1H), 7.69-7.57 (m, 2H), 7.44 (dd, J=7.6, 1.2, 1H), 7.33 (m, 1H), 7.27 (dd, J=7.9, 1.7, 1H), 7.05 (s, 2H), 2.84-2.74 (m, 4H), 1.43-1.25 (m, 6H).

›Example 302

Trifluoroacetic acid (1 mL) was added to neat 4′-(2-aminopyrimidin-5-yl)-N-(tert-butyl)-3′-fluoro-[1,1′-biphenyl]-2-sulfonamide (52 mg, 0.13 mmol). After 4 hours, the resulting solution was concentrated to dryness and purified by HPLC to provide the title compound (33 mg, 59%) as a clear glassy solid. MS (ESI): mass calcd. for C 16 H 13 FN 4 O 2 S, 344.07; m/z found, 345.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.54 (d, J=1.3, 2H), 8.05 (dd, J=7.8, 1.4, 1H), 7.70-7.56 (m, 3H), 7.40-7.28 (m, 5H), 7.03 (s, 2H).

›Example 303

The title compound was prepared using analogous conditions to those described in Example 287 using 5-(4-chloro-2-fluorophenyl)pyrimidin-2-amine and (2-(morpholino-sulfonyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 3 S, 414.12; m/z found, 415.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.56 (d, J=1.3, 2H), 8.02 (dd, J=8.0, 1.2, 1H), 7.77 (m, 1H), 7.68 (m, 1H), 7.62 (m, 1H), 7.46 (dd, J=7.6, 1.2, 1H), 7.38 (dd, J=11.8, 1.6, 1H), 7.31 (dd, J=7.9, 1.7, 1H), 3.46-3.37 (m, 4H), 2.83-2.73 (m, 4H).

›Example 304

The title compound was prepared using analogous conditions to those described in Example 287 using 5-(4-chloro-2-fluorophenyl)pyrimidin-2-amine and (2-(methyl-sulfonyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 17 H 14 FN 3 O 2 S, 343.08; m/z found, 344.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.57 (d, J=1.3, 2H), 8.12 (dd, J=8.0, 1.2, 1H), 7.80 (m, 1H), 7.72 (m, 1H), 7.65 (m, 1H), 7.46 (dd, J=7.5, 1.2, 1H), 7.40 (dd, J=11.7, 1.7, 1H), 7.33 (dd, J=7.9, 1.7, 1H), 2.96 (s, 3H).

›Example 305

The title compound was prepared using analogous conditions to those described in Example 287 using 5-(4-chloro-2-fluorophenyl)pyrimidin-2-amine and (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.55 (s, 2H), 8.06 (dd, J=7.9, 1.3, 1H), 7.66 (m, 1H), 7.63-7.57 (m, 2H), 7.38 (dd, J=7.5, 1.2, 1H), 7.33 (dd, J=11.9, 1.5, 1H), 7.28 (dd, J=7.9, 1.6, 1H), 6.99-6.88 (m, 1H), 1.03 (s, 9H).

›Example 306

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 4-((2-bromophenyl)sulfonyl)piperazin-2-one. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 3 S, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 7.22 (d, J=0.7, 2H), 6.61 (m, 1H), 6.22 (m, 1H), 6.12 (m, 1H), 6.07 (dd, J=11.3, 4.9, 1H), 5.92 (dd, J=7.6, 1.2, 1H), 5.82 (t, J=1.8, 1H), 5.80 (dd, J=5.4, 1.4, 1H), 1.81 (s, 2H), 1.63 (m, 4H).

›Example 307

The title compound was prepared using analogous conditions to those described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (S)-tert-butyl 2-(2-bromophenylsulfonamido)propanoate. MS (ESI): mass calcd. for C 23 H 25 FN 4 O 4 S, 472.16; m/z found, 473.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.65 (d, J=1.1, 2H), 8.08 (dd, J=8.0, 1.2, 1H), 7.66 (m, 1H), 7.61-7.49 (m, 2H), 7.37 (m, 3H), 3.66 (q, J=7.2, 1H), 1.34 (s, 9H), 1.26 (d, J=7.2, 3H).

›Example 308

Trifluoroacetic acid (0.5 mL) was added to a solution of tert-butyl N-{[4′-(2-aminopyrimidin-5-yl)-3′-fluorobiphenyl-2-yl]sulfonyl}-L-alaninate (80 mg, 0.17 mmol) in DCM (1 mL) at rt. After 2 hours, the solution was concentrated to dryness and purified by HPLC to afford the title compound (70 mg, 89%). MS (ESI): mass calcd. for C 19 H 17 FN 4 O 4 S, 416.10; m/z found, 417.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.72 (s, 2H), 8.10 (dd, J=8.0, 1.2, 1H), 7.66 (m, 1H), 7.61-7.53 (m, 2H), 7.37 (m, 3H), 3.73 (q, J=7.2, 1H), 1.31 (d, J=7.2, 3H).

›Example 309

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and N-(2-bromophenyl)pyrrolidine-1-sulfonamide MS (ESI): mass calcd. for C 20 H 20 FN 5 O 2 S, 413.13; m/z found, 414.4 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) 8.63 (s, 2H), 7.59 (d, J=8.4, 1H), 7.50 (m, 1H), 7.39 (m, 1H), 7.32-7.29 (m, 2H), 7.24-7.22 (m, 1H), 7.22-7.15 (m, 1H), 6.87-6.79 (m, 2H), 6.36 (s, 1H), 3.37-3.26 (m, 4H), 1.94-1.83 (m, 4H).

›Example 310

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and N-(2-bromophenyl)morpholine-4-sulfonamide. MS (ESI): mass calcd. for C 20 H 20 FN 5 O 3 S, 429.13; m/z found, 430.4 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.63 (d, J=1.2, 2H), 7.70-7.54 (m, 2H), 7.48-7.25 (m, 5H), 3.70-3.55 (m, 4H), 3.05 (dd, J=5.7, 3.8, 4H).

›Example 311

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and N-(2-bromophenyl)-N,N-dimethylsulfonamide. MS (ESI): mass calcd. for C 18 H 18 FN 5 O 2 S, 387.12; m/z found, 388.3 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.57 (d, J=1.4, 2H), 7.61-7.55 (m, 1H), 7.50 (m, 1H), 7.42-7.35 (m, 1H), 7.24-7.21 (m, 1H), 7.21-7.17 (m, 2H), 6.36 (s, 1H), 5.17 (s, 2H), 2.82 (s, 6H).

›Example 312

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 6-((2-bromophenyl)sulfonyl)-2-oxa-6-azaspiro[3.3]heptanes and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 19 FN 4 O 3 S, 426.12; m/z found, 426.9 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.53 (s, 2H), 8.05-7.96 (d, J=7.9, 1H), 7.78-7.71 (m, 1H), 7.68-7.58 (m, 2H), 7.47-7.41 (d, J=7.5, 1H), 7.35-7.28 (m, 1H), 7.28-7.23 (m, 1H), 6.90 (s, 2H), 4.51 (d, J=1.3, 4H), 3.71 (d, J=1.4, 4H).

›Example 313

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 6-((2-bromophenyl)sulfonyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 19 FN 4 O 4 S 2 , 474.08; m/z found, 474.8 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.56-8.50 (d, J=1.4, 2H), 8.05-7.99 (dd, J=8.0, 1.3, 1H), 7.80-7.73 (m, 1H), 7.69-7.60 (m, 2H), 7.48-7.43 (dd, J=7.6, 1.3, 1H), 7.38-7.32 (dd, J=11.8, 1.8, 1H), 7.31-7.26 (dd, J=7.9, 1.7, 1H), 6.90 (s, 2H), 4.32 (s, 4H), 3.76 (s, 4H).

›Example 314

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 1-((2-bromophenyl)sulfonyl)azetidine-3-carbonitrile and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 20 H 16 FN 5 O 2 S, 409.10; m/z found, 409.9 [M+H] + . 1 H NMR (500 MHz, DMSO-d) δ 8.52 (s, 2H), 8.08-8.00 (d, J=8.0, 1H), 7.83-7.75 (m, 1H), 7.71-7.65 (m, 1H), 7.65-7.58 (m, 1H), 7.51-7.43 (d, J=7.5, 1H), 7.38-7.31 (d, J=11.7, 1H), 7.31-7.26 (m, 1H), 6.89 (s, 2H), 3.96-3.87 (m, 2H), 3.68-3.59 (m, 3H).

›Example 315

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 1-((2-bromophenyl)sulfonyl)-3-(trifluoromethyl)azetidin-3-ol and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 20 H 16 F 4 N 4 O 3 S, 468.09; m/z found, 469.0 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.53-8.47 (d, J=1.4, 2H), 8.06-8.01 (dd, J=8.0, 1.3, 1H), 7.81-7.76 (m, 1H), 7.70-7.65 (m, 1H), 7.64-7.58 (m, 1H), 7.51-7.45 (m, 2H), 7.35-7.29 (dd, J=11.7, 1.8, 1H), 7.28-7.24 (dd, J=7.8, 1.7, 1H), 6.94 (s, 2H), 3.81-3.76 (d, J=9.3, 2H), 3.71-3.66 (m, 2H)

›Example 316

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 4-((2-bromophenyl)sulfonyl)tetrahydro-2H-thiopyran 1,1-dioxide. MS (ESI): mass calcd. for C 21 H 20 FN 3 O 4 S 2 , 461.09; m/z found, 461.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.55 (s, 2H), 8.06 (d, J=7.9, 1H), 7.85 (m, 1H), 7.76 (m, 1H), 7.61 (m, 1H), 7.49 (d, J=7.5, 1H), 7.37 (d, J=11.6, 1H), 7.30 (d, J=8.0, 1H), 6.94 (s, 2H), 3.26-3.07 (m, 5H), 2.12-2.09 (m, 2H), 2.01-1.86 (m, 2H).

›Example 317

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 2-(((2-bromophenyl)sulfonyl)methyl)quinazolin-4(3H)-one. MS (ESI): mass calcd. for C 25 H 18 FN 5 O 3 S, 487.11; m/z found, 487.9 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 12.36 (s, 1H), 8.60-8.43 (d, J=1.4, 2H), 8.12-8.02 (dd, J=8.0, 1.5, 1H), 7.96-7.89 (dd, J=8.0, 1.3, 1H), 7.84-7.71 (m, 2H), 7.66-7.42 (m, 4H), 7.42-7.22 (m, 3H), 6.91 (s, 2H), 4.37 (s, 2H).

›Example 318

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine and 1-(3-((2-bromophenyl)sulfonyl)propyl)-1H-benzo[d]imidazol-2(3H)-one. MS (ESI): mass calcd. for C 26 H 22 FN 5 O 3 S, 503.14; m/z found, 503.9 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 10.85 (s, 1H), 8.45 (s, 2H), 8.12-8.03 (d, J=7.8, 1H), 7.83-7.75 (m, 1H), 7.75-7.66 (m, 1H), 7.45-7.30 (m, 2H), 7.27-7.19 (d, J=11.5, 1H), 7.09-6.88 (m, 6H), 3.79-3.72 (t, J=6.5, 2H), 2.97-2.88 (dd, J=9.7, 6.3, 2H), 1.79-1.68 (m, 2H).

›Example 319

The title compound was prepared in a manner similar to that described in Example 88 using 1-bromo-2-((3-(cyclohexylsulfonyl)propyl)sulfonyl)benzene and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 25 H 28 FN 3 O 4 S 2 , 517.15; m/z found, 518.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.59-8.51 (d, J=1.4, 2H), 8.20-8.14 (dd, J=8.0, 1.3, 1H), 7.82-7.76 (m, 1H), 7.72-7.67 (m, 1H), 7.59-7.52 (m, 1H), 7.51-7.46 (dd, J=7.7, 1.3, 1H), 7.38-7.31 (m, 2H), 3.16-3.08 (t, J=7.5, 2H), 3.08-3.01 (t, J=7.3, 2H), 2.94-2.82 (m, 1H), 2.07-1.97 (m, 4H), 1.91-1.80 (m, 2H), 1.79-1.62 (d, J=13.0, 1H), 1.48-1.35 (m, 2H), 1.35-1.25 (m, 2H), 1.24-1.12 (m, 1H).

›Example 320

The title compound was prepared in a manner similar to that described in Example 88 using 2-((2-bromophenyl)sulfonyl)-1-methyl-1H-benzo[d]imidazole and 5-(2-fluor-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 24 H 18 FN 5 O 2 S, 459.12; m/z found, 460.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 7.03-6.96 (dd, J=7.8, 1.5, 1H), 6.88-6.86 (d, J=1.4, 2H), 6.43-6.28 (m, 1.5, 2H), 6.15-6.09 (d, J=8.2, 1H), 6.08-5.99 (m, 2H), 5.97-5.86 (m, 2H), 5.64-5.53 (m, 1H), 5.34-5.30 (dd, J=7.8, 1.7, 1H), 5.30-5.23 (dd, J=11.3, 1.7, 1H), 2.22 (s, 3H).

›Example 321

The title compound was prepared in a manner similar to that described in Example 88 using 5-(((2-bromophenyl)sulfonyl)methyl)-3-cyclopropyl-1,2,4-oxadiazole and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine. MS (ESI): mass calcd. for C 22 H 18 FN 5 O 3 S, 451.11: m/z found, 452.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.56 (s, 1H), 7.98-7.94 (m, 1H), 7.85-7.77 (dd, J=8.2, 6.9, 1H), 7.67-7.61 (m, 1H), 7.61-7.57 (m, 1H), 7.52-7.46 (d, J=7.6, 1H), 7.39-7.35 (dd, J=7.9, 1.6, 1H), 7.35-7.31 (m, 1H), 2.05-1.94 (m, 1H), 1.04-0.94 (m, 1H), 0.79-0.72 (m, 1H).

›Example 322

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-5-(trifluoromethyl)benzenesulfonamide and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 17 H 12 F 4 N 4 O 2 S, 412.06; m/z found, 413.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.56-8.53 (d, J=1.4, 2H), 8.43-8.40 (m, 1H), 7.98-7.92 (d, J=7.7, 1H), 7.63-7.58 (d, J=8.0, 1H), 7.58-7.52 (m, 1H), 7.37-7.35 (m, 1H), 7.35-7.32 (m, 1H).

›Example 323

The title compound was prepared in a manner similar to that described in Example 88 using 1-bromo-2-(methylsulfonyl)-4-(trifluoromethyl)benzene and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 18 H 13 F 4 N 3 O 2 S, 411.07; m/z found, 412.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.61-8.51 (d, J=1.4, 2H), 8.44 (s, 1H), 8.11-8.05 (d, J=7.5, 1H), 7.72-7.66 (d, J=8.0, 1H), 7.66-7.59 (m, 1H), 7.45-7.35 (m, 2H), 2.89 (s, 3H).

›Example 324

The title compound was prepared in a manner similar to that described in Example 88 using 4-((2-bromo-5-(trifluoromethyl)phenyl)-sulfonyl)-piperazin-2-one and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 17 F 4 N 5 O 3 S, 495.10; m/z found, 496.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.70-8.61 (d, J=1.2, 2H), 8.40 (s, 1H), 8.10-8.03 (d, J=7.7, 1H), 7.71-7.64 (d, J=7.9, 1H), 7.64-7.58 (m, 1H), 7.39-7.37 (m, 1H), 7.36 (s, 1H), 3.34 (s, 2H), 3.22-3.17 (m, 2H), 3.17-3.12 (m, 2H).

›Example 325

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-methyl-5-(trifluoromethyl)benzenesulfonamide and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 18 H 14 F 4 N 4 O 2 S, 426.08; m/z found, 427.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.57-8.52 (d, J=1.4, 2H), 8.33-8.27 (m, 1H), 8.02-7.94 (m, 1H), 7.66-7.60 (d, J=7.9, 1H), 7.60-7.52 (m, 1H), 7.38-7.31 (m, 2H), 2.46 (s, 3H).

›Example 326

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-(2-hydroxyethyl)-5-(trifluoromethyl)benzenesulfonamide and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrimidin-2-amine. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 3 S, 456.09; m/z found, 457.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.57-8.53 (d, J=1.4, 2H), 8.38-8.35 (m, 1H), 8.00-7.96 (dd, J=8.1, 1.5, 1H), 7.63-7.60 (d, J=8.0, 1H), 7.59-7.54 (m, 1H), 7.38-7.36 (dd, J=6.1, 1.6, 1H), 7.36-7.34 (m, 1H), 3.51-3.45 (t, J=5.9, 2H), 2.95-2.86 (t, J=5.9, 2H).

›Example 327

The title compound was prepared in a manner similar to that described in Example 88 using 2-bromo-N-ethyl-5-(trifluoromethyl)benzenesulfonamide and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 19 H 16 F 4 N 4 O 2 S, 440.09; m/z found, 441.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.56-8.53 (d, J=1.4, 2H), 8.34-8.31 (m, 1H), 7.99-7.95 (m, 1H), 7.63-7.59 (d, J=8.0, 1H), 7.59-7.53 (m, 1H), 7.36-7.34 (dd, J=7.1, 1.6, 1H), 7.34-7.32 (m, 1H), 2.97-2.71 (q, J=7.2, 2H), 1.15-0.84 (t, J=7.2, 3H).

›Example 328

The title compound was prepared in a manner similar to that described in Example 88 using 1-((2-bromo-5-(trifluoromethyl)phenyl)sulfonyl)-4-methylpiperazine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 22 H 21 F 4 N 5 O 2 S, 495.14; m/z found, 496.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.63-8.61 (d, J=1.4, 2H), 8.40-8.37 (d, J=1.4, 1H), 8.10-8.05 (m, 1H), 7.70-7.67 (d, J=8.0, 1H), 7.67-7.63 (m, 1H), 7.46-7.30 (m, 2H), 2.86 (s, 3H), 3.83-2.53 (br m, 8H).

›Example 329

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 5-amino-2-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 391.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.47 (d, J=1.4, 2H), 7.95 (s, 2H), 7.66-7.59 (m, 1H), 7.55-7.48 (m, 2H), 7.46-7.41 (m, 2H), 7.27-7.20 (m, 2H), 6.89 (s, 2H), 5.45 (s, 2H).

›Example 330

The title compound was prepared using analogous conditions to those described in Example 213 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 4-amino-2-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 390.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.47 (d, J=1.4, 2H), 7.80 (d, J=5.8, 1H), 7.73-7.66 (m, 1H), 7.57-7.50 (m, 2H), 7.48-7.44 (m, 2H), 7.32-7.23 (m, 2H), 6.90-6.88 (m, 4H), 6.11 (d, J=5.8, 1H).

›Example 331

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 5-amino-4-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 5 FN 6 S, 390.11; m/z found, 391.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.46 (d, J=1.4, 2H), 8.16 (s, 1H), 7.92 (s, 1H), 7.59-7.49 (m, 3H), 7.49-7.44 (m, 2H), 7.30-7.20 (m, 2H), 6.89 (s, 2H), 5.44 (s, 2H).

›Example 332

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and and 2-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 14 FN 5 S, 375.10; m/z found, 375.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.66 (s, 2H), 8.56 (d, J=4.9, 2H), 7.79-7.73 (m, 1H), 7.63-7.56 (m, 2H), 7.55-7.48 (m, 2H), 7.33-7.24 (m, 2H), 7.21 (m, 1H), 6.23 (s, 2H).

›Example 333

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 2-chloropyrazine. MS (ESI): mass calcd. for C 2 H 14 FN 5 S, 375.10; m/z found, 375.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.70-8.57 (m, 2H), 8.41 (dd, J=2.5, 1.6, 1H), 8.35 (d, J=2.6, 1H), 8.27 (d. J=1.5, 1H), 7.72 (dd. J=8.0, 1.2, 1H), 7.64-7.57 (m, 2H), 7.56-7.50 (m, 2H), 7.34 (d, J=11.8, 1H), 7.27 (d, J=8.0, 1H), 6.01 (s, 2H).

›Example 334

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 4-amino-6-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 390.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d) δ 8.48 (d, J=1.4, 2H), 8.06 (s, 1H), 7.77-7.71 (m, 1H), 7.68-7.61 (m, 1H), 7.60-7.52 (m, 3H), 7.29 (dd, J=11.9, 1.5, 1H), 7.25 (dd, J=7.9, 1.7, 1H), 6.88 (s, 2H), 6.78 (s, 2H), 5.78 (d, J=0.9, 1H).

›Example 335

The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 2-amino-4-chloropyrimidine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 390.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.47 (d, J=1.3, 2H), 7.90 (d, J=5.3, 1H), 7.78-7.71 (m, 1H), 7.68-7.61 (m, 1H), 7.59-7.51 (m, 3H), 7.30 (dd. J=11.8, 1.6, 1H), 7.25 (dd, J=7.9, 1.7, 1H), 6.89 (s, 2H), 6.64 (s, 2H), 5.86 (d, J=5.3, 1H).

›Example 336

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 2-amino-6-chloropyrazine. MS (ESI): mass calcd. for C 20 H 15 FN 6 S, 390.11; m/z found, 391.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.47 (d, J=1.3, 2H), 7.67-7.60 (m, 1H), 7.59-7.51 (m, 3H), 7.49-7.46 (m, 2H), 7.31 (dd, J=11.9, 1.5, 1H), 7.26 (dd, J=7.9, 1.7, 1H), 7.18 (s, 1H), 6.90 (s, 2H), 6.57 (s, 2H).

›Example 337

To a solution of 5-{2′-[(5-aminopyrimidin-4-yl)sulfanyl]-3-fluorobiphenyl-4-yl}-pyrimidin-2-amine (200 mg, 0.51 mmol) in MeCN/DCM/H 2 O (5 mL/5 mL/5 mL) were added NaIO 4 (326 mg, 1.50 mmol) and RuCl 3 (16 mg, 0.075 mmol). The reaction mixture was stirred at rt for 10 hours then poured into water (50 mL) and extracted with EtOAc (30 mL×3). The combined organic extracts were concentrated and purified by HPLC to give the title compound as a white solid. MS (ESI): mass calcd. for C 20 H 15 FN 6 O 2 S, 422.10; m/z found, 423.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.57 (s, 2H), 8.30-8.25 (m, 2H), 8.22 (s, 1H), 7.83 (m, 1H), 7.77 (m, 1H), 7.44-7.33 (m, 2H), 6.88 (d, J=9.5, 2H), 6.29 (s, 2H).

›Example 338

The title compound was prepared using analogous conditions to those described in Example 337 utilizing 5-[3-fluoro-2′-({[2-(trimethylsilyl)-ethoxy]methyl}-sulfanyl)-biphenyl-4-yl]pyrimidin-2-amine. MS (ESI): mass calcd. for C 22 H 26 FN 3 O 3 SSi, 459.14; m/z found, 460.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.63 (s, 2H), 8.19 (dd, J=7.9, 1.4, 1H), 7.79 (m, 1H), 7.70 (m, 1H), 7.59 (m, 1H), 7.46 (dd, J=7.5, 1.3, 1H), 7.34-7.31 (m, 2H), 4.36 (s, 2H), 3.80-3.68 (m, 2H), 0.87-0.76 (m, 2H), 0.08 (s, 9H).

›Example 339

The title compound was prepared using analogous conditions to those described in Example 337 utilizing 5-{2′-[(5-Aminopyrimidin-2-yl)sulfanyl]-3-fluorobiphenyl-4-yl}pyrimidin-2-amine formate salt MS (ESI): mass calcd. for C 20 H 15 FN 6 O 2 S, 422.10; m/z found, 423.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.83 (s, 2H), 8.34 (dd, J=7.7, 1.5, 1H), 7.94 (s, 2H), 7.79-7.69 (m, 2H), 7.44 (m, 1H), 7.34 (dd, J=7.3, 1.4, 1H), 6.93 (dd, J=7.9, 1.6, 1H), 6.88 (dd, J=11.5, 1.5, 1H).

›Example 340

The title compound was prepared using analogous conditions to those described in Example 6 utilizing utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (2-(((2-bromophenyl)thio)methoxy)ethyl)trimethylsilane. MS (ESI): mass calcd. for C 22 H 26 FN 3 OSSi, 427.16; m/z found, 428.0 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.47 (d, J=1.4, 2H), 7.69 (dd, J=7.7, 1.1, 1H), 7.44 (m, 1H), 7.34-7.15 (m, 5H), 4.86 (s, 2H), 3.60-3.47 (m, 2H), 0.88-0.76 (m, 2H), 0.06 (s, 9H)

Example 341

›Step A: 5-(4-Chloro-2-fluorophenyl)pyridin-2-amine

Solid 4-chloro-2-fluorobenzeneboronic acid (10.0 g, 57.4 mmol), 2-amino-5-bromopyridine (9.92 g, 57.4 mmol), palladium (II) trifluoroacetate (0.381 g, 1.15 mmol), and triphenylphosphine (0.602 g, 2.29 mmol) were combined in a 1 L flask under nitrogen, then toluene (150 mL), EtOH (150 mL), and 2 M Na 2 CO 3 (100 mL) were added. The mixture was sparged with nitrogen for 30 min using a gas dispersion tube, then heated at 80° Celsius for 20 hours with vigorous stirring. The mixture was cooled to rt, diluted with EtOAc (200 mL), and transferred to a separatory funnel. The aqueous phase was removed, and the organic phase washed with brine. The combined aqueous phases were extracted with an equal volume of EtOAc, and the combined organic phases were dried and concentrated to dryness. The residue was subjected to FCC to provide 5-(4-chloro-2-fluorophenyl)pyridin-2-amine (9.10 g, 71%). MS (Cl): mass calcd. for C 11 H 8 CFN 2 , 222.04; m/z found, 223.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.54-8.22 (s, 2H), 8.22-8.18 (d, J=2.1, 1H), 8.15-8.10 (m, 1H), 7.68-7.58 (m, 2H), 7.48-7.38 (m, 1H), 7.16-7.06 (d, J=9.3, 1H).

›Step B: 5-(3-Fluoro-2′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)pyridin-2-amine

5-(4-Chloro-2-fluorophenyl)pyridin-2-amine (100 mg, 0.449 mmol), 2-(methylsulfonyl)phenylboronic acid (112 mg, 0.561 mmol), and chloro(2-dicyclohexyl-phosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]palladium(II) (33 mg, 0.045 mmol) were placed in a sealable reaction tube under nitrogen. THF (2 mL, sparged with nitrogen) and K 3 PO 4 (2 mL, 0.5 M sparged with nitrogen) were added, and the reaction vessel was sealed and heated at 60° Celsius for 16 hours with vigorous stirring. The mixture was cooled to rt, diluted with EtOAc, and washed with 2 M K 2 CO 3 , then dried and concentrated to dryness. The residue was subjected to FCC to provide the title compound (45 mg, 29%). MS (Cl): mass calcd. for C 18 H 15 FN 2 O 2 S, 342.08; m/z found, 343.0 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.38-8.31 (s, 1H), 8.29-8.22 (m, 1H), 7.77-7.71 (m, 1H), 7.71-7.65 (m, 1H), 7.64-7.57 (m, 1H), 7.52-7.45 (m, 1H). 7.42-7.37 (m, 1H), 7.36-7.27 (m, 2H), 6.64-6.59 (m, 1H), 4.66-4.51 (s, 2H), 2.81-2.69 (s, 2H).

›Examples5

›Example 342

The title compound was prepared in a manner similar to that described in Example 341, using (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid in Step B. MS (Cl): mass calcd. for C 21 H 22 FN 3 O 2 S, 399.14; m/z found, 400.2 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.22-8.13 (s, 1H), 8.10-8.03 (d, J=7.8, 1H), 7.67-7.57 (m, 3H), 7.53-7.48 (m, 1H), 7.40-7.36 (d, J=7.4, 1H), 7.31-7.22 (m, 2H), 6.94-6.89 (s, 1H), 6.60-6.52 (d, J=8.6, 1H), 6.24-6.11 (s, 2H), 1.07-0.99 (s, 9H).

›Example 343

The title compound was prepared in a manner similar to that described in Example 341, using (2-(N,N-diethylsulfamoyl)phenyl)boronic acid in Step B. MS (Cl): mass calcd. for C 21 H 22 FN 3 O 2 S, 399.14; m/z found, 400.2 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.28-8.22 (d, J=1.9, 1H), 8.18-8.12 (d, J=9.3, 1H), 8.12-7.88 (m, 1H), 7.76-7.69 (m, 1H), 7.68-7.59 (m, 2H), 7.43-7.38 (dd, J=7.5, 1.1, 1H), 7.37-7.32 (m, 1H), 7.32-7.27 (m, 1H), 7.09-7.04 (d, J=9.2, 1H), 2.99-2.90 (m, 3H), 1.00-0.90 (m, 4H).

The title compound was prepared in a manner similar to that described in

›Example 344

The title compound was prepared in a manner similar to that described in Example 341, using (2-(pyrrolidin-1-ylsulfonyl)phenyl)boronic acid in Step B. MS (Cl): mass calcd. for C 21 H 20 FN 3 O 2 S, 397.13; m/z found, 398.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.37-8.11 (m, 4H), 8.01-7.95 (m, 1H), 7.77-7.71 (m, 1H), 7.69-7.61 (m, 2H), 7.44-7.36 (m, 2H), 7.35-7.30 (m, 1H), 7.15-7.10 (d, J=9.3, 1H), 2.99-2.80 (m, 4H), 1.77-1.62 (m, 4H).

›Example 345

The title compound was prepared in a manner similar to that described in Example 341, using (2-(piperidin-1-ylsulfonyl)phenyl)boronic acid in Step B. MS (Cl): mass calcd. for C 22 H 22 FN 3 O 2 S, 411.14; m/z found, 412.2 [M+H] + . 1 H NMR (500 MHz, DMSO-d) δ 8.47-8.16 (m, 4H), 8.02-7.96 (m, 1H), 7.79-7.72 (m, 1H), 7.71-7.60 (m, 2H), 7.46-7.36 (m, 2H), 7.35-7.29 (m, 1H), 7.16-7.11 (d, J=9.3, 1H), 2.86-2.74 (m, 4H), 1.45-1.27 (m, 6H).

Example 346

›Step A: (4-(6-Aminopyridin-3-yl)-3-fluorophenyl)boronic acid

5-(4-Chloro-2-fluorophenyl)pyridin-2-amine (2.0 g, 9.0 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.9 g, 11.0 mmol), chloro(2-dicyclohexyl-phosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (0.14 g, 0.18 mmol), and KOAc (2.7 g, 27 mmol) were combined in a sealable reaction vessel under nitrogen, and then treated with anhydrous 1,4-dioxane (100 mL, sparged with nitrogen). The vessel was sealed and then heated at 80° Celsius for 16 hours. The mixture was cooled to rt, HCl (1 m, 50 mL) was added and the mixture stirred for 20 min. The mixture was then diluted with EtOAc (200 mL) and the aqueous phase was collected. The organic phase was extracted with 1 M HCl (2×75 mL). The combined aqueous phases were cooled in an icebath and the pH was adjusted to ca. 7 using solid sodium bicarbonate. The resulting precipitate was collected by filtration, washed well with water, and dried to provide the title compound (2.1 g, 98%). MS (Cl): mass calcd. for C 11 H 10 BFN 2 O 2 , 232.08; m/z found, 233.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.29-8.20 (s, 2H), 8.18-8.13 (s, 1H), 7.80-7.72 (m, 1H), 7.69-7.63 (m, 1H), 7.63-7.57 (m, 1H), 7.51-7.44 (m, 1H), 6.84-6.57 (m, 3H).

›Step B: 4′-(6-Aminopyridin-3-yl)-N-cyclohexyl-3′-fluoro-[1,1′-biphenyl]-2-sulfonamide

A mixture of (4-(6-aminopyridin-3-yl)-3-fluorophenyl)boronic acid (75 mg, 0.32 mmol), 2-bromo-N-cyclohexylbenzenesulfonamide (0.11 g, 0.36 mmol), 1,1′-bis[di-tert-butylphosphino)ferrocene]palladium(II) chloride (11 mg, 0.016 mmol), K 2 CO 3 (2 M, 1.6 mL, sparged with nitrogen) and THF (2 mL, sparged with nitrogen) were combined in a sealed vessel under nitrogen. The mixture was vigorously stirred at rt for 16 hours, then diluted with EtOAc. The aqueous phase was removed and the organic layer was dried and concentrated. The residue was subjected to FCC to provide the title compound (15 mg, 11%). MS (Cl): mass calcd. for C 23 H 24 FN 3 O 2 S, 425.16; m/z found, 426.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.20-8.14 (s, 1H), 8.05-7.96 (m, 1H), 7.70-7.57 (m, 3H), 7.55-7.47 (m, 1H), 7.44-7.35 (m, 2H), 7.30-7.20 (m, 2H), 6.59-6.52 (d, J=8.6, 1H), 6.23-6.11 (s, 2H), 2.83-2.69 (d, J=7.4, 1H), 1.68-1.52 (m, 4H), 1.49-1.38 (s, 1H), 1.19-0.92 (m, 6H).

›Examples23

›Example 347

A mixture of (4-(6-aminopyridin-3-yl)-3-fluorophenyl)boronic acid (100 mg, 0.43 mmol), (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide (160 mg, 0.54 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (18 mg, 0.022 mmol), K 2 CO 3 (340 mg, 2.4 mmol), and DMSO (3 mL) was sparged with nitrogen, then the reaction vessel was sealed and heated at 80° Celsius for 16 hours. The mixture was cooled to rt, then filtered, and subjected to HPLC purification to provide the title compound. MS (Cl): mass calcd. for C 20 H 20 FN 3 O 3 S, 401.12; m/z found, 402.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.31-7.93 (m, 5H), 7.72-7.57 (m, 3H), 7.42-7.25 (m, 4H), 7.11-7.04 (d, J=9.2, 1H), 3.34-3.25 (s, 1H), 3.18-3.00 (m, 2H), 1.00-0.91 (d, J=6.5, 3H).

›Example 348

The title compound was prepared in a manner similar to that described in Example 347 using 2-bromo-N-iso-butylbenzenesulfonamide. MS (Cl): mass calcd. for C 21 H 22 FN 3 O 2 S, 399.14; m/z found, 400.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 5 ) δ 8.26-8.19 (d, J=2.1, 1H), 8.18-8.11 (d, J=9.2, 1H), 8.08-7.79 (m, 3H), 7.72-7.53 (m, 4H), 7.43-7.30 (m, 3H), 7.08-7.00 (d, J=9.2, 1H), 2.57-2.52 (m, 2H), 1.66-1.56 (m, 1H), 0.82-0.75 (d, J=6.7, 6H).

›Example 349

The title compound was prepared in a manner similar to that described in Example 347 using 2-bromo-N-(tert-pentyl)benzenesulfonamide. MS (Cl): mass calcd. for C 22 H 24 FN 3 O 2 S, 413.16; m/z found, 414.2 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.23-8.19 (d, J=2.0, 1H), 8.19-8.11 (d, J=9.0, 1H), 8.10-8.05 (m, 1H), 8.05-7.79 (s, 2H), 7.69-7.57 (m, 3H), 7.40-7.29 (m, 3H), 7.09-7.02 (d, J=9.2, 1H), 6.98-6.91 (s, 1H), 1.48-1.36 (m, 2H), 1.04-0.91 (s, 6H), 0.79-0.67 (m, 3H).

›Example 350

The title compound was prepared in a manner similar to that described in Example 347 using 2-bromo-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzenesulfonamide. MS (Cl): mass calcd. for C 21 H 19 F 4 N 3 O 2 S, 453.11; m/z found, 454.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.28-8.19 (m, 2H), 8.17-8.11 (d, J=9.1, 1H), 8.07-8.02 (m, 1H), 8.03-7.80 (s, 2H), 7.74-7.65 (m, 2H), 7.64-7.58 (m, 1H), 7.43-7.39 (m, 1H), 7.38-7.32 (m, 1H), 7.32-7.28 (dd, J=7.9, 1.7, 1H), 7.07-7.00 (d, J=9.2, 1H), 1.29-1.17 (s, 6H).

›Example 351

The title compound was prepared in a manner similar to that described in Example 347 using (S)-2-bromo-N-(2,2,2-trifluoro-1-phenylethyl)benzenesulfonamide. MS (Cl): mass calcd. for C 25 H 19 F 4 N 3 O 2 S, 501.11; m/z found, 502.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 9.32-9.24 (d, J=10.1, 1H), 8.24-8.20 (d, J=2.1, 1H), 8.20-8.11 (d, J=9.2, 1H), 8.11-7.90 (s, 2H), 7.90-7.85 (m, 1H), 7.64-7.58 (m, 1H), 7.57-7.51 (m, 1H), 7.49-7.40 (m, 3H), 7.40-7.31 (m, 3H), 7.29-7.24 (dd, J=7.6, 1.2, 1H), 7.15-7.03 (m, 3H), 5.22-4.90 (m, 1H).

›Example 352

The title compound was prepared in a manner similar to that described in Example 347 using (R)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (Cl): mass calcd. for C 20 H 20 FN 3 O 3 S, 401.12; m/z found, 402.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.26-8.20 (d, J=2.1, 1H), 8.19-8.11 (d, J=9.2, 1H), 8.09-8.05 (m, 1H), 8.05-7.84 (s, 2H), 7.72-7.58 (m, 3H), 7.41-7.35 (m, 2H), 7.35-7.27 (m, 2H), 7.08-7.02 (d, J=9.2, 1H), 5.05-4.29 (m, 1H), 3.34-3.27 (dd, J=10.3, 5.0, 1H), 3.14-3.02 (m, 2H), 1.00-0.93 (d, J=6.5, 3H).

›Example 353

The title compound was prepared in a manner similar to that described in Example 347 using 2-bromo-N-(1-methylcyclobutyl)benzenesulfonamide. MS (Cl): mass calcd. for C 22 H 22 FN 3 O 2 S, 411.14; m/z found, 412.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.24-8.20 (s, 1H), 8.20-8.15 (d, J=9.5, 1H), 8.15-7.90 (m, 3H), 7.70-7.58 (m, 3H), 7.55-7.51 (s, 1H), 7.41-7.28 (m, 3H), 7.10-7.05 (d. J=9.2, 1H), 2.15-2.05 (m, 2H), 1.71-1.51 (m, 4H), 1.26-1.18 (s, 3H).

›Example 354

The title compound was prepared in a manner similar to that described in Example 347 using 4-((2-bromophenyl)sulfonyl)thiomorpholine 1,1-dioxide. MS (Cl): mass calcd. for C 21 H 20 FN 3 O 4 S 2 , 461.09; m/z found, 462.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.27-8.21 (d, J=2.0, 1H), 8.20-8.14 (d, J=9.1, 1H), 8.13-7.88 (m, 3H), 7.82-7.76 (m, 1H), 7.72-7.62 (m, 2H), 7.48-7.39 (m, 2H), 7.37-7.31 (m, 1H), 7.10-7.02 (d, J=9.2, 1H), 3.12-3.04 (m, 4H), 3.34-3.26 (m, 4H).

›Example 355

The title compound was prepared in a manner similar to that described in Example 347 using (S)-2-bromo-N-(1,1,1-trifluoropropan-2-yl)benzenesulfonamide. MS (Cl): mass calcd. for C 20 H 17 F 4 N 3 O 2 S, 439.10; m/z found, 440.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.56-8.49 (d, J=8.9, 1H), 8.26-8.20 (s, 1H), 8.20-8.12 (d, J=9.5, 1H), 8.09-7.82 (m, 3H), 7.74-7.59 (m, 3H), 7.42-7.37 (m, 1H), 7.36-7.27 (m, 2H), 7.09-7.01 (d, J=9.1, 1H), 3.98-3.86 (m, 1H), 1.22-1.11 (d, J=7.0, 3H).

›Example 356

The title compound was prepared in a manner similar to that described in Example 347 using (1S,4S)-5-((2-bromophenyl)sulfonyl)-2-oxa-5-azabicyclo[2.2.1]heptane. MS (Cl): mass calcd. for C 22 H 20 FN 3 O 3 S, 425.12; m/z found, 426.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.27-8.23 (d, J=2.0, 1H), 8.20-8.15 (d, J=9.2, 1H), 8.15-7.89 (m, 3H), 7.79-7.74 (m, 1H), 7.70-7.62 (m, 2H), 7.47-7.38 (m, 2H), 7.37-7.32 (m, 1H), 7.10-7.03 (d, J=9.2, 1H), 4.53-4.47 (s, 1H), 4.01-3.96 (s, 1H), 3.63-3.30 (m, 2H), 2.99-2.87 (m, 2H), 1.72-1.61 (d, J=10.0, 1H), 1.47-1.36 (m, 1H).

›Example 357

The title compound was prepared in a manner similar to that described in Example 347 using tert-butyl 3-((2-bromophenylsulfonamido)methyl)-3-hydroxyazetidine-1-carboxylate. MS (Cl): mass calcd. for C 26 H 29 FN 4 O 5 S, 528.18; m/z found, 529.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.26-8.21 (d, J=2.0, 1H), 8.20-8.13 (d, J=9.4, 1H), 8.11-7.86 (m, 3H), 7.86-7.80 (m, 1H), 7.74-7.67 (m, 1H), 7.67-7.58 (m, 2H), 7.44-7.31 (m, 3H), 7.09-7.02 (d, J=9.1, 1H), 3.79-3.73 (m, 2H), 3.55-3.52 (m, 2H), 2.93-2.86 (d, J=6.5, 2H), 1.40-1.28 (s, 9H).

›Example 358

A mixture of tert-butyl 3-((2-bromophenylsulfonamido)methyl)-3-hydroxyazetidine-1-carboxylate (15 mg, 0.028 mmol), TFA (1 mL), and MeOH (1 mL) was maintained at rt for 2 hours, then concentrated to dryness. The residue was purified by HPLC to provide the title compound (8.0 mg, 52%) MS (Cl): mass calcd. for C 21 H 21 FN 4 O 3 S, 428.13; m/z found, 429.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.84-8.70 (s, 1H), 8.68-8.52 (s, 1H), 8.26-8.19 (d, J=2.1, 1H), 8.13-8.03 (d, J=7.4, 1H), 8.01-7.94 (m, 1H), 7.94-7.88 (m, 1H), 7.74-7.71 (m, 1H), 7.69-7.65 (m, 1H), 7.63-7.59 (m, 1H), 7.48-7.42 (m, 1H), 7.42-7.31 (m, 2H), 7.05-6.91 (d, J=8.8, 1H), 6.33-6.17 (s, 1H), 3.94-3.87 (m, 2H), 3.76-3.69 (m, 2H), 3.05-3.00 (d, J=6.5, 2H).

›Example 359

The title compound was prepared in a manner similar to that described in Example 347 using 2-(1-((2-bromophenyl)sulfonyl)piperidin-4-yl)ethanol. MS (Cl): mass calcd. for C 24 H 26 FN 3 O 3 S, 455.17; m/z found, 456.3 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.24-8.20 (d, J=2.2, 1H), 8.17-8.09 (d, J=9.1, 1H), 8.02-7.98 (m, 1H), 3.37-3.36 (m, 5H), 7.97-7.78 (s, 2H), 7.77-7.73 (m, 1H), 7.69-7.64 (m, 1H), 7.64-7.59 (m, 1H), 7.44-7.41 (m, 1H), 7.41-7.35 (m, 1H), 7.34-7.30 (dd, J=7.9, 1.7, 1H), 7.07-6.99 (d, J=9.2, 1H), 3.40-3.34 (m, 3H), 3.25-3.21 (d, J=12.3, 2H), 2.43-2.34 (m, 2H), 1.59-1.50 (d, J=10.7, 2H), 1.45-1.31 (s, 1H), 1.31-1.20 (m, 2H), 0.89-0.78 (m, 2H).

›Example 360

The title compound was prepared in a manner similar to that described in Example 347 using 1-((2-bromophenyl)sulfonyl)piperidin-4-ol. MS (Cl): mass calcd. for C 22 H 22 FN 3 O 3 S, 427.14; m/z found, 428.2 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.26-8.22 (d, J=2.0, 1H), 8.19-8.15 (d, J=9.4, 1H), 8.14-7.92 (m, 3H), 7.78-7.73 (m, 1H), 7.69-7.65 (m, 1H), 7.65-7.60 (m, 1H), 7.45-7.40 (dd, J=7.6, 1.2, 1H), 7.40-7.35 (m, 1H), 7.33-7.28 (m, 1H), 7.09-7.04 (d, J=9.2, 1H), 3.54-3.52 (m, 2H), 3.09-3.01 (m, 2H), 2.69-2.61 (m, 2H), 1.64-1.53 (m, 2H), 1.28-1.17 (m, 2H).

›Example 361

The title compound was prepared in a manner similar to that described in Example 347 using (1-((2-bromophenyl)sulfonyl)piperidin-4-yl)methanol. MS (Cl): mass calcd. for C 23 H 24 FN 3 O 3 S, 441.15; m/z found, 442.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.26-7.94 (m, 5H), 7.78-7.72 (m, 1H), 7.70-7.60 (m, 2H), 7.45-7.36 (m, 2H), 7.34-7.30 (dd, J=8.0, 1.6, 1H), 7.10-7.04 (d, J=9.2, 1H), 3.29-3.24 (d, J=12.4, 2H), 3.19-3.14 (d, J=6.3, 2H), 2.45-2.36 (m, 2H), 1.60-1.52 (d, J=10.7, 2H), 1.41-1.29 (s, 1H), 0.94-0.78 (m, 2H).

›Example 362

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine and (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 20 FN 3 O 3 S, 425.12; m/z found, 426.0 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 9.57 (s, 1H), 8.29-8.22 (m, 2H), 7.95-7.85 (m, 1H), 7.69-7.61 (m, 1H), 7.61-7.53 (m, 1H), 7.42-7.33 (m, 4H), 7.29 (d, J=7.8, 1H), 6.54-6.49 (m, 1H), 5.92 (d, J=6.7, 1H), 3.64-3.51 (m, 1H), 3.47-3.34 (m, 2H), 2.34 (s, 1H), 1.03 (d, J=6.5, 3H).

›Example 363

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine and (R)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 20 FN 3 O 3 S, 425.12; m/z found, 426.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.65 (s, 1H), 8.30-8.19 (m, 2H), 7.93-7.84 (m, 1H), 7.69-7.61 (m, 1H), 7.61-7.53 (m, 1H), 7.44-7.31 (m, 4H), 7.27 (d, J=7.8, 1H), 6.56-7.47 (m, 1H), 6.07 (d, J=6.5, 1H), 3.57 (t, J=7.0, 1H), 3.49-3.32 (m, 2H), 2.41 (s, 1H), 1.04 (d, J=6.4, 3H).

›Example 364

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine and (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 23 H 19 FN 4 O 3 S, 450.12; m/z found, 451.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ Complex due to the presence of multiple conformations on the NMR time-scale, peaks listed for identification purposes only: δ 9.35 (s), 9.23 (s), 8.51-8.42 (m), 8.41-8.31 (m), 8.24-8.17 (m), 8.13-8.00 (m), 7.68-7.61 (m), 7.59-7.49 (m), 7.46-7.38 (m), 7.38-7.29 (m), 6.57-6.51 (m), 6.38 (s), 6.13 (s), 6.05 (s), 5.68 (s), 3.69-3.57 (m), 3.40-3.18 (m), 2.61-2.48 (m), 2.25-1.96 (m).

›Example 365

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine and 1-bromo-2-(cyclopropylsulfonyl)benzene. MS (ESI): mass calcd. for C 22 H 17 FN 2 O 2 S, 392.10; m/z found, 393.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.26 (s, 1H), 8.62-8.52 (m, 1H), 8.24-8.12 (m, 2H), 7.71-7.63 (m, 1H), 7.62-7.53 (m, 2H), 7.45-7.31 (m, 4H), 6.64-6.55 (m, 1H), 2.19-2.08 (m, 1H), 1.18-1.08 (m, 2H), 0.93-0.82 (m, 2H).

›Example 366

The title compound was prepared in a manner similar to that described in Example 88 using 5-bromo-1H-pyrrolo[2,3-b]pyridine and 3′-fluoro-N-(2-hydroxyethyl)-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide. MS (ESI): mass calcd. for C 21 H 18 FN 3 O 3 S, 411.11; m/z found, 412.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.44-8.41 (m, 1H), 8.24-8.21 (m, 1H), 8.14-8.05 (dd, J=8.0, 1.3, 1H), 7.71-7.64 (m, 1H), 7.63-7.55 (m, 2H), 7.46-7.44 (d, J=3.5, 1H), 7.44-7.41 (dd, J=7.6, 1.2, 1H), 7.36-7.34 (dd, J=3.8, 1.7, 1H), 7.34-7.31 (dd, J=7.3, 1.4, 1H), 6.59-6.55 (d, J=3.5, 1H), 3.52-3.47 (t, J=5.9, 2H), 2.92-2.87 (t. J=5.9, 2H).

›Example 367

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-1H-pyrrolo[2,3-b]pyridine. MS (ESI): mass calcd. for C 23 H 22 FN 3 O 2 S, 423.14; m/z found, 424.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.56-8.45 (m, 2H), 8.18-8.11 (dd, J=8.0, 1.3, 1H), 7.70-7.61 (m, 2H), 7.61-7.55 (m, 3H), 7.44-7.35 (m, 3H), 6.76-6.69 (d, J=3.5, 1H), 1.09 (s, 9H).

›Example 368

The title compound was prepared by forming N-tert-butyl-3′-fluoro-4′-(1H-pyrrolo[2,3-b]pyridin-5-yl)biphenyl-2-sulfonamide then removing the tert-butyl group by dissolving the crude N-tert-butyl-3′-fluoro-4′-(1H-pyrrolo[2,3-b]pyridin-5-yl)biphenyl-2-sulfonamide in 1 mL of trifluoroacetic acid and heating it at 60° Celsius for 2 hours, after which time the reaction was cooled, concentrated to dryness and purified using FCC. MS (ESI): mass calcd. for C 19 H 14 FN 3 O 2 S, 367.08; m/z found, 368.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.43 (s, 1H), 8.26-8.22 (m, 1H), 8.17-8.12 (dd, J=8.0, 1.3, 1H), 7.69-7.62 (m, 1H), 7.62-7.55 (m, 2H), 7.47-7.44 (d, J=3.5, 1H), 7.44-7.40 (dd, J=7.6, 1.4, 1H), 7.38-7.30 (m, 2H), 6.60-6.56 (d, J=3.5, 1H).

Example 369

›Step A: 2-(4-Bromo-2-fluorphenyl)-5H-pyrrolo[2,3-b]pyrazine

To a 150 mL screw-cap vessel under nitrogen was added 5-bromo-4,7-diazaindole (1.0 g, 5.05 mmol), 4-bromo-2-fluorophenyl boronic acid (1.33 g, 6.06 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (0.2 g, 0.24 mmol), K 2 CO 3 (2.09 g, 15.2 mmol), 1,4-dioxane (35 mL) and water (13 mL). The mixture was sparged with nitrogen for 10 minutes, the vessel capped and the reaction heated at 95° Celsius for 24 hours. The reaction was then cooled to rt, diluted with ethyl acetate (200 mL) and washed with water (1×100 mL) and brine (1×100 mL). The organic layer was dried with Na 2 SO 4 and evaporated to dryness. The crude product was purified by HPLC giving the title compound (515 mg, 35%). MS (ESI): mass calcd. for C 12 H 7 BrFN 2 , 290.98; m/z found, 292.0 [M+H] + .

›Step B

To a mixture of 2-(4-bromo-2-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine (50 mg, 0.17 mmol), N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-methane-sulfonamide (61 mg, 0.21 mmol) and Pd(dppf)Cl 2 .CH 2 Cl 2 (6.7 mg, 0.009 mmol) in a microwave vial were added acetonitrile (2.0 mL) and sat. NaHCO 3 (2.0 mL). The vial was sparged with nitrogen for 5 min then heated at 110° Celsius for 90 min via microwave irradiation. After cooling to rt, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water (25 mL) and brine (25 mL), dried (Na 2 SO 4 ) and concentrated to dryness. The crude product was purified by HPLC giving the title compound (45 mg, 69%). MS (ESI): mass calcd. for C 19 H 15 FN 4 O 2 S, 382.09; m/z found, 383.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 10.38 (s, 1H), 8.78 (d, J=2.7, 1H), 8.20-8.12 (m, 1H), 7.71-7.64 (m, 2H), 7.48-7.39 (m, 1H), 7.37-7.31 (m, 2H), 7.28-7.21 (m, 2H), 6.91 (s, 1H), 6.81-6.75 (m, 1H), 2.93 (s, 3H).

›Examples8

›Example 370

The title compound was prepared using methods analogous to those described in Example 369 using N,N-dimethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide in Step B. MS (ESI): mass calcd. for C 20 H 17 FN 4 O 2 S, 396.11; m/z found, 397.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 10.57 (s, 1H), 8.79 (d, J=2.6, 1H), 8.15-8.04 (m, 2H), 7.69-7.59 (m, 2H), 7.58-7.51 (m, 1H), 7.41-7.31 (m, 3H), 6.81-6.74 (m, 1H), 2.48 (s, 6H).

›Example 371

The title compound was prepared using methods analogous to those described in Example 369 using (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid in Step B. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.69 (d, J=2.6, 1H), 8.13-8.04 (m, 1H), 8.03-7.93 (m, 2H), 7.74-7.55 (m, 2H), 7.47-7.32 (m, 3H), 7.02 (s, 1H), 6.73 (d, J=3.6, 1H), 1.04 (s, 9H).

›Example 372

The title compound was prepared using methods analogous to those described in Example 369 using (2-(pyrrolidin-1-ylsulfonyl)phenyl)boronic acid in Step B. MS (ESI): mass calcd. for C 22 H 19 FN 4 O 2 S, 422.12; m/z found, 423.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.22 (br s, 1H), 8.83 (d, J=2.5, 1H), 8.24 (d, J=2.5, 1H), 8.19-8.13 (m, 1H), 8.14-8.07 (m, 1H), 7.96-7.90 (m, 1H), 7.72-7.65 (m, 1H), 7.65-7.58 (m, 1H), 7.57-7.49 (m, 1H), 7.49-7.30 (m, 1H), 6.88-6.79 (m, 1H), 3.02-2.90 (m, 3H), 1.77-1.66 (m, 3H), 1.59 (s, 2H).

›Example 373

The title compound was prepared using methods analogous to those described in Example 369 using (2-(N,N-diethylsulfamoyl)phenyl)boronic acid in Step B. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.23 (s, 1H), 8.83 (d, J=2.5, 1H), 8.15-8.05 (m, 2H), 7.71-7.66 (m, 1H), 7.63-7.56 (m, 1H), 7.55-7.48 (m, 1H), 7.39-7.30 (m, 3H), 6.86-6.82 (m, 1H), 3.03-2.88 (m, 4H), 1.00 (t, J=7.15, 6H).

›Example 374

The title compound was prepared using methods analogous to those described in Example 369 using (2-(piperidin-1-ylsulfonyl)phenyl)boronic acid in Step B. MS (ESI): mass calcd. for C 23 H 21 FN 4 O 2 S, 436.14; m/z found, 437.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.20 (s, 1H), 8.83 (d, J=2.5, 1H), 8.18-8.03 (m, 2H), 7.71-7.65 (m, 1H), 7.65-7.58 (m, 1H), 7.57-7.51 (m, 1H), 7.41-7.32 (m, 3H), 6.87-6.82 (m, 1H), 2.93-2.81 (m, 4H), 1.46-1.36 (m, 6H).

›Example 375

The title compound was prepared using methods analogous to those described in Example 369 using (2-(morphilinosulfonyl)phenyl)boronic acid in Step B. MS (ESI): mass calcd. for C 22 H 19 FN 4 O 3 S, 438.12; m/z found, 439.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 10.69 (s, 1H), 8.79 (d, J=2.6, 1H), 8.17-8.06 (m, 2H), 7.71-7.61 (m, 2H), 7.61-7.53 (m, 1H), 7.44-7.33 (m, 3H), 6.80-6.74 (m, 1H), 3.54-3.45 (m, 4H), 2.94-2.83 (m, 4H).

›Example 376

To a mixture of 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5H-pyrrolo[2,3-b]pyrazine (32 mg, 0.09 mmol), racemic 2-bromo-N-(1,1,1-trifluoropropan-2-yl)benzenesulfonamide (38 mg, 0.11 mmol) and Pd(dppf)Cl 2 .CH 2 Cl 2 (6 mg, 0.007 mmol) in a microwave vial were added acetonitrile (2.0 mL) and sat. NaHCO 3 (2.0 mL). The mixture was sparged with nitrogen for 5 min and then the vial capped and heated at 110° Celsius for 90 min. After cooling, the reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried (Na 2 SO 4 ) and concentrated to dryness. The crude product was purified by HPLC to give the title compound (28 mg, 64%). MS (ESI): mass calcd. C 21 H 16 F 4 N 4 O 2 S, 464.09; m/z found, 465.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.81 (s, 1H), 8.47 (s, 1H), 8.27-8.17 (m, 1H), 7.75-7.41 (m, 5H), 7.40-7.32 (m, 2H), 7.20 (d, J=12.6, 1H), 6.74-6.67 (m, 1H), 4.12-3.94 (m, 1H), 1.39-1.19 (m, 3H).

Example 377

›Step A: 2-[3-Fluoro-2′-(methylsulfanyl)biphenyl-4-yl]-5H-pyrrolo[2,3-b]pyrazine

The title compound was prepared using methods analogous to those described in Example 369 using (2-(methylthio)phenyl)boronic acid in Step B. MS (ESI): mass calcd. for C 19 H 14 FN 3 S., 335.09; m/z found, 336.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.97 (s, 1H), 8.81 (d, J=2.5, 1H), 8.11-8.01 (m, 1H), 7.69-7.63 (m, 1H), 7.44-7.19 (m, 6H), 6.87-6.82 (m, 1H), 2.41 (s, 3H).

›Step B

To a 10 mL round bottomed flask under nitrogen at rt were added 2-[3-fluoro-2′-(methylsulfanyl)biphenyl-4-yl]-5H-pyrrolo[2,3-b]pyrazine (32 mg, 0.07 mmol), m-CPBA (0.33 mg, 0.19 mmol) and DCM (1 mL). The mixture was stirred at rt for 2 hours. An additional 0.5 equivalents of mCPBA was added at this time and the reaction stirred an additional 1 hour. The reaction was then poured into sat. NaHCO 3 and extracted with DCM (×2). The solvent was then removed and the crude product purified by HPLC to give the title compound (12 mg, 35%). MS (ESI): mass calcd. for C 19 H 14 FN 3 O 2 S, 481.08; m/z found, 368.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.48 (s, 1H), 8.82 (s, 1H), 8.27 (d, J=8.0, 1H), 8.18-8.09 (m, 1H), 7.77-7.67 (m, 2H), 7.66-7.57 (m, 1H), 7.48-7.36 (m, 3H), 6.89-6.83 (m, 1H), 2.76 (s, 3H).

›Examples4

›Example 378

The title compound was prepared using methods analogous to those described in Example 376 using (R)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. C 21 H 19 FN 4 O 3 S, 426.12; m/z found, 427.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.40 (s, 1H), 8.74 (d, J=2.7, 1H), 8.60 (s, 1H), 8.29-8.20 (m, 1H), 7.83-7.74 (m, 1H), 7.71-7.62 (m, 2H), 7.61-7.50 (m, 1H), 7.47-7.36 (m, 2H), 7.35-7.16 (m, 1H), 5.50 (s, 1H), 3.65-3.49 (m, 1H), 3.48-3.28 (m, 2H), 2.16-1.94 (m, 1H), 1.04 (d, J=6.6, 3H).

›Example 379

The title compound was prepared using methods analogous to those described in Example 376 using 2-bromo-N-methylbenzenesulfonamide. MS (ESI): mass calcd. C 19 H 15 FN 4 O 2 S, 382.09; m/z found, 383.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.35 (s, 1H), 8.67 (d, J=2.2, 1H), 8.29-8.18 (m, 1H), 8.03-7.83 (m, 1H), 7.71-7.55 (m, 3H), 7.47-7.29 (m, 3H), 6.83-6.73 (m, 1H), 4.85 (s, 1H), 2.56 (d, J=5.2, 3H).

›Example 380

The title compound was prepared using methods analogous to those described in Example 376 using (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. C 21 H 19 FN 4 O 3 S, 426.12; m/z found, 427.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.40 (s, 1H), 8.74 (d, J=2.7, 1H), 8.60 (s, 1H), 8.29-8.20 (m, 1H), 7.83-7.74 (m, 1H), 7.71-7.62 (m, 2H), 7.61-7.50 (m, 1H), 7.47-7.36 (m, 2H), 7.35-7.16 (m, 1H), 5.50 (s, 1H), 3.65-3.49 (m, 1H), 3.48-3.28 (m, 2H), 2.16-1.94 (m, 1H), 1.04 (d, J=6.6, 3H).

›Example 381

Step A: tert-Butyl (1-((3′-fluoro-4′-(1H-pyrrolo[2,3-b]pyridin-5-yl)-[1,1′-biphenyl]-2-yl)-sulfonyl)piperidin-4-yl)carbamate

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine and tert-butyl (1-((2-bromophenyl)sulfonyl)piperidin-4-yl)carbamate. MS (ESI): mass calcd. for C 28 H 30 FN5O4S, 551.20; m/z found, 552.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.04 (s, 1H), 8.81 (d. J=2.4, 1H), 8.18-8.04 (m, 2H), 7.69-7.59 (m, 2H), 7.60-7.48 (m, 1H), 7.48-7.30 (m, 4H), 6.85 (dd, J=3.7, 1.9, 1H), 4.44 (d, J=8.2, 1H), 3.79 (d, J=13.2, 1H), 3.49-3.27 (m, 3H), 2.91 (t, J=11.7, 1H), 2.47 (t, J=12.2, 2H), 1.98 (d, J=13.4, 1H), 1.79 (d, J=11.8, 2H), 1.42 (d, J=9.5, 12H), 1.31-1.10 (m, 3H).

›Step B

The title compound was prepared as described in the preparation of Example 247 using tert-butyl (1-((3′-fluoro-4′-(1H-pyrrolo[2,3-b]pyridin-5-yl)-[1,1′-biphenyl]-2-yl)sulfonyl)piperidin-4-yl)carbamate. MS (ESI): mass calcd. for C 23 H 22 FN 5 O 2 S, 451.15; m/z found, 452.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.66 (s, 1H), 8.82 (d, J=2.5, 1H), 8.20-8.04 (m, 2H), 7.69 (d, J=3.7, 1H), 7.66-7.59 (m, 1H), 7.58-7.51 (m, 1H), 7.42-7.32 (m, 3H), 6.83 (d, J=3.7, 1H), 3.43-3.30 (m, 2H), 2.70-2.59 (m, 1H), 2.55-2.40 (m, 2H), 1.75-1.65 (m, 2H), 1.56 (br s, 2H), 1.24-1.07 (m, 2H).

›Examples11

›Example 382

The title compound was prepared using methods analogous to those described in Example 376 using 4-((2-bromophenyl)sulfonyl)thiomorpholine 1,1-dioxide. MS (ESI): mass calcd. for C 22 H 19 FN 4 O 4 S 2 , 486.08; m/z found, 487.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.19 (s, 1H), 8.83 (d, J=2.5, 1H), 8.22-8.11 (m, 2H), 7.75-7.65 (m, 2H), 7.64-7.55 (m, 1H), 7.43-7.37 (m, 1H), 7.34-7.21 (m, 2H), 6.88-6.80 (m, 1H), 3.45-3.26 (m, 4H), 3.09-2.94 (m, 4H).

›Example 383

The title compound was prepared using methods analogous to those described in Example 369 using (5-fluoro-2-(methylthio)phenyl)boronic acid in Step B. MS (ESI): mass calcd. for C 19 H 13 F 2 N 3 S, 353.08; m/z found, 354.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.98 (s, 1H), 8.82 (d, J=2.6, 1H), 8.14-8.05 (m, 1H), 7.70-7.63 (m, 1H), 7.41-7.28 (m, 3H), 7.13-7.01 (m, 2H), 6.87-6.80 (m, 1H), 2.36 (s, 3H).

›Example 384

The title compound was prepared using methods analogous to those described in Example 369 using (2-(ethylthio)phenyl)boronic acid in Step B. MS (ESI): mass calcd. for C 20 H 16 FN 3 S, 349.10: m/z found, 350.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.12 (s, 1H), 8.83 (d, J=2.6, 1H), 8.11-8.02 (m, 1H), 7.69-7.63 (m, 1H), 7.44-7.21 (m, 6H), 6.86-6.81 (m, 1H), 2.85 (q, J=7.4, 2H), 1.26 (t, J=7.4, 3H).

›Example 385

The title compound was prepared in a manner similar to that described in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine and 1-bromo-2-(methylsulfonyl)benzene. MS (ESI): mass calcd. for C 20 H 17 FN 2 O 3 S, 384.09; m/z found, 385.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.27-8.24 (m, 1H), 7.99-7.93 (m, 1H), 7.71-7.65 (m, 1H), 7.63-7.57 (m, 1H), 7.47 (m, 1H), 7.41-7.38 (m, 1H), 7.33-7.27 (m, 3H), 4.32-4.24 (m, 2H), 3.67-3.59 (m, 2H), 2.76 (s, 3H).

›Example 386

The title compound was prepared in a manner similar to that described in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine and 1-((2-bromophenyl)sulfonyl)piperidine. MS (ESI): mass calcd. for C 24 H 24 FN 3 O 3 S, 453.15; m/z found, 454.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.07-8.03 (m, 1H), 7.82 (d, J=1.0, 1H), 7.73-7.67 (m, 2H), 7.65-7.55 (m, 2H), 7.42-7.39 (m, 1H), 7.36-7.30 (m, 2H), 4.41-4.32 (m, 2H), 3.74-3.71 (m, 2H), 2.91-2.79 (m, 4H), 1.49-1.37 (m, 6H).

›Example 387

The title compound was prepared in a manner similar to that described in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine and 2-bromobenzenesulfonamide. MS (ESI): mass calcd. for C 19 H 16 FN 3 O 3 S, 385.09; m/z found, 386.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.14-8.11 (m, 1H), 7.80 (d, J=1.0, 1H), 7.73-7.71 (m, 1H), 7.68-7.62 (m, 1H), 7.61-7.52 (m, 2H), 7.39-7.31 (m, 3H), 4.40-4.34 (m, 2H), 3.75-3.69 (m, 2H).

›Example 388

The title compound was prepared in a manner similar to that described in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine and (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 22 FN 3 O 4 S, 443.13; m/z found, 444.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.15-8.12 (m, 1H), 7.80 (m, 1H), 7.72 (d, J=1.3, 1H), 7.69-7.64 (m, 1H), 7.62-7.52 (m, 2H), 7.40-7.33 (m, 3H), 4.37 (t, J=4.6, 2H), 3.76-3.69 (m, 2H), 3.43-3.36 (m, 1H), 3.30-3.26 (m, 1H), 3.24-3.16 (m, 1H), 1.04-1.01 (m, 3H).

›Example 389

The title compound was prepared in a manner similar to that described in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine and 1-((2-bromophenyl)sulfonyl)piperidin-4-amine. MS (ESI): mass calcd. for C 24 H 25 FN 4 O 3 S, 468.16; m/z found, 469.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.09-8.05 (m, 1H), 7.83 (d, J=1.1, 1H), 7.75-7.68 (m, 2H), 7.66-7.55 (m, 2H), 7.43-7.39 (m, 1H), 7.34-7.26 (m, 2H), 4.39-4.35 (m, 2H), 3.76-3.68 (m, 2H), 3.47 (d, J=13.4, 2H), 3.21-3.11 (m, 1H), 2.60-2.50 (m, 2H), 1.96-1.87 (m, 2H), 1.56-1.43 (m, 2H).

›Example 390

The title compound was prepared in a manner similar to that described in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine and (R)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 22 FN 3 O 4 S, 443.13; m/z found, 444.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.16-8.10 (m, 1H), 7.82-7.79 (m, 1H), 7.74-7.71 (m, 1H), 7.70-7.64 (m, 1H), 7.61-7.57 (m, 1H), 7.54-7.46 (m, 1H), 7.40-7.33 (m, 3H), 4.40-4.36 (m, 2H), 3.75-3.69 (m, 2H), 3.48-3.33 (m, 2H), 3.24-3.16 (m, 1H), 1.05-1.01 (m, 3H).

›Example 391

The title compound was prepared in a manner similar to that described in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine and 2-bromo-N,N-diethylbenzenesulfonamide. MS (ESI): mass calcd. for C 23 H 24 FN 3 O 3 S, 441.15; m/z found, 442.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.03-8.00 (m, 1H), 7.82 (d, J=1.0, 1H), 7.73-7.65 (m, 2H), 7.62-7.55 (m, 2H), 7.40-7.36 (m, 1H), 7.31 (s, 1H), 7.30-7.28 (m, 1H), 4.39-4.35 (m, 2H), 3.74-3.70 (m, 2H), 2.99 (q, J=7.1, 4H), 1.01 (t. J=7.1, 6H).

Example 392

›Step A: 7-(4-Chloro-2-fluorophenyl-3,4-dihydro-2H-pyrido[3,2-b][1.4]oxazine

Prepared in a manner similar to that found in Example 1 using of 7-bromo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine with (4-chloro-2-fluorophenyl)boronic acid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.84 (m, 1H), 7.35-7.28 (m, 1H), 7.20-7.14 (m, 3H), 4.29-4.25 (m, 2H), 3.64-3.58 (m, 2H).

Step B: 7-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine

Into a 100 mL flask were added 7-(4-chloro-2-fluorophenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine (1.25 g, 4.72 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (1.5 g, 5.9 mmol), KOAc (1.39 g, 14.2 mmol). Chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II), 186 g, 0.236 mmol), and a stir bar. The flask was sealed with a rubber septum and sparged with N 2 . The flask was charged with freshly sparged 1,4-dioxane (25 mL) and heated at 80° Celsius for 16 hours. The reaction was cooled to rt and concentrated to dryness. The crude product was purified by FCC to give 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine (1.208 g, 71%). 1 H NMR (500 MHz, CDCl 3 ) δ 7.86-7.84 (m, 1H), 7.61-7.59 (m, 1H), 7.56-7.53 (m, 1H), 7.38 (m, 1H), 7.27-7.24 (m, 1H), 4.27-4.22 (m, 2H), 3.61-3.58 (m, 2H), 2.09 (s, 1H), 1.35 (s, 12H).

›Step C

7-{2′-[(1,1-Dioxidothiomorpholin-4-yl)sulfonyl]-3-fluorobiphenyl-4-yl}-3,4-dihydro-2H-pyrido[3,2-b]-b][1,4]oxazine. Prepared in a manner similar to that found in Example 444 using 7-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b]-b][1,4]oxazine with 4-((2-bromophenyl)sulfonyl)thiomorpholine 1,1-dioxide. MS (ESI): mass calcd. for C 23 H 22 FN 3 O 5 S 2 , 503.10; m/z found, 504.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.16-8.13 (m, 1H), 7.85-7.83 (m, 1H), 7.78-7.72 (m, 2H), 7.69-7.60 (m, 2H), 7.45-7.41 (m, 1H), 7.37-7.30 (m, 2H), 4.41-4.35 (m, 2H), 3.76-3.68 (m, 2H), 3.38-3.33 (m, 4H), 3.06-2.98 (m, 4H).

›Examples3

›Example 393

The title compound was prepared in a manner similar to that described in Example 444 using N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 7-bromo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine. MS (ESI): mass calcd. for C 23 H 24 FN 3 O 3 S, 441.15; m/z found, 442.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.15-8.12 (m, 1H), 7.80 (d, J=0.9, 1H), 7.72-7.69 (m, 1H), 7.68-7.62 (m, 1H), 7.60-7.54 (m, 2H), 7.39-7.33 (m, 3H), 4.42-4.33 (m, 2H), 3.75-3.69 (m, 2H), 1.09 (s, 9H).

›Example 394

The title compound was prepared using methods analogous to those described in Example 369 using (2-(isopropylthio)-5-(trifluoromethyl)pyridine-3-yl)boronic acid in Step B. MS (ESI): mass calcd. for C 21 H 16 F 4 N 4 S, 432.10; m/z found, 433.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.12 (s, 1H), 8.83 (d, J=2.6, 1H), 8.74-8.68 (m, 1H), 8.19-8.10 (m, 1H), 7.71-7.66 (m, 1H), 7.62 (d, J=1.9, 1H), 7.42-7.37 (m, 1H), 7.33 (dd, J=1.7, 11.52, 1H), 6.87-6.82 (m, 1H), 4.19-4.03 (m, 1H), 1.40 (d, J=6.8, 6H).

Example 395

›Step A: 3-Bromo-2-(isopropylthio)pyridine

3-Bromopyridine-2-thiol (500 mg, 2.63 mmol) was added drop-wise to a suspension of sodium hydride in mineral oil (60%, 126 mg, 3.16 mmol) in DMF (5.0 mL) at 0° Celsius. The mixture was then stirred at 0° Celsius for 30 min followed by removal of the ice bath and stirring at rt for an additional 30 min. 2-Iodopropane (537 mg, 3.16 mmol) was then added and the reaction stirred at 60° Celsius for 18 hours. The reaction was cooled to rt, carefully diluted with water (100 mL), and extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried with Na 2 SO 4 , filtered and concentrated to dryness. The crude product was purified by FCC giving 453 mg (74%) of the target thioether. MS (ESI): mass calcd. for C 8 H 10 BrNS, 230.97; m/z found, 232.1 [M+H] + .

›Step B: 3-Bromo-2-(isopropylsulfonyl)pyridine

3-Bromo-2-(isopropylthio)pyridine (100 mg, 0.43 mmol) was dissolved in DCM (6.0 mL) and m-CPBA (198 mg, 1.15 mmol) added. The reaction was stirred for 1.5 hours, and then treated with additional m-CPBA (100 mg, 0.058 mmol). Once complete conversion was achieved, the mixture was poured into sat. NaHCO 3 (50 mL) and extracted with DCM (2×50 mL). The combined extracts were concentrated to dryness and the crude product (112 mg, 98%) was used in next step without further purification.

›Step C

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 3-bromo-2-(isopropylsulfonyl)pyridine yielding 52 mg (88%) of the title compound. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.11; m/z found, 373.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.69 (dd, J=4.6, 1.7, 1H), 8.60 (dd, J=2.1, 1.5, 1H), 8.10 (d, J=1.5, 1H), 8.08-7.98 (m, 1H), 7.81 (dd, J=7.8, 1.6, 1H), 7.58 (dd, J=7.8, 4.6, 1H), 7.38 (dd, J=8.0, 1.8, 1H), 7.32 (dd, J=11.7, 1.7, 1H), 4.71 (s, 2H), 4.19 (hept, J=6.8, 1H), 1.31 (d, J=6.9, 6H).

›Examples12

›Example 396

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 3-bromo-2-(isopropylthio)pyridine. MS (ESI): mass calcd. for C 18 H 17 FN 4 S, 340.12; m/z found, 341.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.62-8.57 (m, 1H), 8.49-8.43 (m, 1H), 8.12 (d, J=1.5, 1H), 8.04-7.93 (m, 1H), 7.45-7.39 (m, 1H), 7.34-7.30 (m, 1H), 7.29-7.22 (m, 1H), 7.11-7.03 (m, 1H), 4.69 (s, 2H), 4.17-4.00 (m, 1H), 1.37 (d, J=6.8, 6H).

›Example 397

The title compound was prepared using methods analogous to those described in Example 369 using (2-((2,2,2-trifluoroethoxy)pyridine-3-yl)boronic acid in Step B. MS (ESI): mass calcd. for C 19 H 12 F 4 N 4 O, 388.09; m/z found, 389.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.10 (s, 1H), 8.83 (d, J=2.5, 1H), 8.21-8.16 (m, 1H), 8.16-8.07 (m, 1H), 7.82-7.76 (m, 1H), 7.71-7.64 (m, 1H), 7.57-7.52 (m, 1H), 7.51-7.44 (m, 1H), 7.16-7.09 (m, 1H), 6.87-6.82 (m, 1H), 4.95-4.79 (m, 2H).

›Example 398

The title compound was prepared using methods analogous to those described in Example 369 using (2-isobutoxypyridin-3-yl)boronic acid in Step B. MS (ESI): mass calcd. for C 21 H 19 FN 4 O, 362.15; m/z found, 363.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.26 (s, 1H), 8.84 (d, J=2.5, 1H), 8.23-8.15 (m, 1H), 8.14-8.04 (m, 1H), 7.74-7.65 (m, 2H), 7.59-7.48 (m, 2H), 7.03-6.96 (m, 1H), 6.88-6.81 (m, 1H), 4.17 (d, J=6.6, 2H), 2.33-1.99 (m, 1H), 1.02 (d, J=6.7, 6H).

›Example 399

The title compound was prepared using methods analogous to those described in Example 369 using (2-isopropoxypyridin-3-yl)boronic acid in Step B. MS (ESI): mass calcd. for C 20 H 17 FN 4 O, 348.14; m/z found, 349.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.22 (s, 1H), 8.83 (d, J=2.5, 1H), 8.17 (dd, J=1.9, 4.9, 1H), 8.11-8.01 (m, 1H), 7.72-7.64 (m, 2H), 7.57-7.46 (m, 2H), 6.96 (dd, J=5.0, 7.3, 1H), 6.87-6.80 (m, 1H), 5.52-5.37 (m, 1H), 1.38 (d, J=6.2, 6H).

›Example 400

The title compound was prepared using methods analogous to those described in Example 369 using (2-(cyclopropylmethoxy)pyridin-3-yl)boronic acid in Step B. MS (ESI): mass calcd. for C 21 H 17 FN 4 O, 360.14; m/z found, 361.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) G 9.28 (s, 1H), 8.83 (d, J=2.5, 1H), 8.19-8.14 (m, 1H), 8.13-8.04 (m, 1H), 7.74-7.64 (m, 2H), 7.61-7.53 (m, 2H), 6.99 (dd, J=5.0, 7.4, 1H), 6.84 (dd, J=1.9, 3.7, 1H), 4.25 (d, J=7.0, 2H), 1.39-1.23 (m, 1H), 0.67-0.57 (m, 2H), 0.41-0.31 (m, 2H).

›Example 401

The title compound was prepared using methods analogous to those described in Example 369 using (2-isopropoxypyridin-3-yl)boronic acid and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 18 H 17 FN 4 O, 324.14; m/z found, 325.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.63-8.57 (m, 1H), 8.18-8.13 (m, 1H), 8.12 (d, J=1.4, 1H), 7.99-7.90 (m, 1H), 7.69-7.62 (m, 1H), 7.58-7.41 (m, 2H), 6.98-6.91 (m, 1H), 5.49-5.35 (m, 1H), 4.68 (s, 2H), 1.37 (d, J=6.2, 6H).

›Example 402

The title compound was prepared using methods analogous to those described in Example 369 using (2-(cyclopentyloxy)pyridin-3-yl)boronic acid and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 20 H 19 FN 4 O, 350.15; m/z found, 351.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.62-8.58 (m, 1H), 8.19-8.15 (m, 1H), 8.12 (d, J=1.5, 1H), 8.00-7.90 (m, 1H), 7.69-7.63 (m, 1H), 7.48-7.40 (m, 2H), 6.98-6.92 (m, 1H), 5.59-5.50 (m, 1H), 4.68 (s, 2H), 2.03-1.89 (m, 2H), 1.89-1.70 (m, 4H), 1.71-1.55 (m, 2H).

›Example 403

The title compound was prepared using methods analogous to those described in Example 369 using (2-(cyclohexyloxy)pyridin-3-yl)boronic acid and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 21 H 21 FN 4 O, 364.17; m/z found, 365.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.64-8.57 (m, 1H), 8.18-8.10 (m, 2H), 8.00-7.92 (m, 1H), 7.70-7.63 (m, 1H), 7.52-7.43 (m, 2H), 6.94 (dd, J=5.0, 7.4, 1H), 5.26-5.16 (m, 1H), 4.66 (s, 2H), 2.05-1.91 (m, 2H), 1.82-1.68 (m, 2H), 1.66-1.24 (m, 6H).

›Example 404

The title compound was prepared using methods analogous to those described in Example 369 using (2-(methoxy)pyridin-3-yl)boronic acid and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 16 H 13 FN 4 O, 296.11; m/z found, 297.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.62-8.56 (m, 1H), 8.19 (dd, J=1.9, 5.0, 1H), 8.12 (d, J=1.5, 1H), 8.01-7.94 (m, 1H), 7.70-7.65 (m, 1H), 7.48-7.41 (m, 2H), 7.00 (dd, J=5.0, 7.31, 1H), 4.66 (s, 2H), 4.00 (s, 3H).

›Example 405

The title compound was prepared using methods analogous to those described in Example 369 using (2-(cyclobutoxy)pyridin-3-yl)boronic acid and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 19 H 17 FN 4 O, 336.14; m/z found, 337.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.63-8.57 (m, 1H), 8.17-8.10 (m, 2H), 8.01-7.92 (m, 1H), 7.66 (dd, J=1.9, 7.4, 1H), 7.52-7.43 (m, 2H), 7.00-6.93 (m, 1H), 5.38-5.22 (m, 1H), 4.67 (s, 2H), 2.57-2.37 (m, 2H), 2.26-2.05 (m, 2H), 1.90-1.61 (m, 2H).

›Example 406

The title compound was prepared using methods analogous to those described in Example 369 using tert-butyl 3-(((3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-yl)oxy)methyl)pyrrolidine-1-carboxylate and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 25 H 28 FN 5 O 3 , 465.22; m/z found, 466.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.63-8.58 (m, 1H), 8.18-8.09 (m, 2H), 8.03-7.94 (m, 1H), 7.73-7.64 (m, 1H), 7.48-7.36 (m, 2H), 7.05-6.96 (m, 1H), 4.70 (s, 2H), 4.47-4.22 (m, 2H), 3.68-3.26 (m, 3H), 3.25-3.09 (m, 1H), 2.77-2.60 (m, 1H), 2.14-1.98 (m, 1H), 1.84-1.68 (m, 1H), 1.44 (s, 9H).

›Example 407

Step A: Tert-butyl 3-(((3-(4-(5-aminopyrazin-2-yl)-3-fluorophenyl)pyridine-2-yl)oxy)methyl)pyrrolidine-1-carboxylate

The title compound was prepared using methods analogous to those described in Example 369 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and tert-butyl 3-(((3-bromopyridin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate yielding the title compound (47 mg, 54%). MS (ESI): mass calcd. for C 25 H 28 FN 5 O 3 , 465.22; m/z found, 466.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.63-8.58 (m, 1H), 8.18-8.09 (m, 2H), 8.03-7.94 (m, 1H), 7.73-7.64 (m, 1H), 7.48-7.36 (m, 2H), 7.05-6.96 (m, 1H), 4.70 (s, 2H), 4.47-4.22 (m, 2H), 3.68-3.26 (m, 3H), 3.25-3.09 (m, 1H), 2.77-2.60 (m, 1H), 2.14-1.98 (m, 1H), 1.84-1.68 (m, 1H), 1.44 (s, 9H).

›Step B

The title compound was prepared as described in the preparation of Example 249 using tert-butyl 3-(((3-(4-(5-aminopyrazin-2-yl)-3-fluorophenyl)pyridine-2-yl)oxy)methyl)pyrrolidine-1-carboxylate to give the title compound (15 mg, 41%). MS (ESI): mass calcd. for C 20 H 20 FN 5 O, 365.17; m/z found, 366.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.63-8.57 (m, 1H), 8.20-8.13 (m, 1H), 8.12 (d, J=1.5, 1H), 8.02-7.93 (m, 1H), 7.72-7.65 (m, 1H), 7.49-7.38 (m, 2H), 7.03-6.96 (m, 1H), 4.69 (s, 2H), 4.40-4.20 (m, 2H), 3.09 (dd, J=11.2, 7.7, 1H), 3.04-2.83 (m, 2H), 2.76 (dd, J=11.2, 6.1, 1H), 2.66-2.49 (m, 1H), 2.06-1.89 (m, 1H), 1.61-1.49 (m, 2H).

›Examples13

›Example 408

To a microwave vial the following were added 5-(4-chloro-2-fluorophenyl)-pyrimidin-2-amine (50 mg, 0.22 mmol), (2-isopropoxypyridin-3-yl)boronic acid (51 mg, 0.28 mmol) and X-Phos precatalyst (4 mg, 0.005 mmol). The vial was flushed with nitrogen and then THF (0.5 mL) and 0.5 M K 3 PO 4 (0.9 mL) were added. Both THF and the K 3 PO 4 solution were sparged separately for 30 min prior to use. The resulting biphasic mixture was stirred at rt overnight. The reaction mixture was then poured into sat. NaHCO 3 (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (1×50 mL) and brine (1×50 mL), dried (Na 2 SO 4 ) and concentrated to dryness. The crude product was purified by HPLC to give the title compound (35 mg, 48%). MS (ESI): mass calcd. for C 18 H 17 FN 4 O, 324.14; m/z found, 325.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.57 (d, J=1.4, 2H), 8.21-8.13 (m, 1H), 7.68-7.60 (m, 1H), 7.50-7.36 (m, 3H), 6.99-6.91 (m, 1H), 5.51-5.37 (m, 1H), 5.15 (s, 2H), 1.38 (d, J=6.2, 6H).

›Example 409

The title compound was prepared in a manner similar to that described in Example 88 using 3-bromopyridin-2-amine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 15 H 12 FN 5 , 281.11; m/z found, 282.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.64-8.54 (m, 1H), 8.00-7.89 (m, 1H), 7.74-7.64 (m, 1H), 7.46-7.36 (m, 1H), 7.09-7.03 (m, 1H).

›Example 410

The title compound was prepared in manner similar to that described in Example 88 using (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide and 3-amino-6-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 3 S, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (400 MHz. CD 3 OD) δ8.73 (d, J=2.1, 1H), 8.16 (dd. J=7.9, 1.4, 1H), 7.93 (m, 1H), 7.69 (m, 1H), 7.60 (m, 1H), 7.45-7.28 (m, 3H), 3.47-3.36 (m, 1H), 3.34-3.18 (m, 2H), 1.03 (d. J=6.6, 3H).

›Example 411

The title compound was prepared in manner similar to that described in Example 88 using 1-bromo-2-(cyclopropylsulfonyl)benzene and 3-amino-6-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 20 H 15 FN 4 O 2 S, 394.09; m/z found, 395.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.84 (d, J=1.8, 1H), 8.14 (dd, J=8.0, 1.4, 1H), 8.01 (m, 1H), 7.66 (m, 1H), 7.58 (m, 1H), 7.39-7.35 (m, 3H), 5.34 (s, 2H), 2.13-2.05 (m, 1H), 1.13-1.06 (m, 2H), 0.88-0.82 (m, 2H).

›Example 412

The title compound was prepared in manner similar to that described in Example 88 using (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide and 3-amino-6-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 3 S, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.78 (d, J=1.6, 1H), 8.18 (dd, J=7.9, 1.4, 1H), 8.01 (m, 1H), 7.63 (m, 1H), 7.56 (m, 1H), 7.40-7.32 (m, 3H), 5.43 (s, 2H), 4.46-4.36 (m, 1H), 3.55-3.46 (m, 1H), 3.43-3.28 (m, 2H), 1.76 (t, J=5.7, 1H), 0.99 (d, J=6.6, 3H).

›Example 413

The title compound was prepared in manner similar to that described in Example 88 using 2-bromo-N-(2-hydroxyethyl)benzenesulfonamide and 3-amino-6-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 19 H 16 FN 5 O 3 S, 413.10; m/z found, 414.0 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.81 (d, J=1.8, 1H), 8.17 (dd, J=8.0, 1.4, 1H), 8.02 (m, 1H), 7.64 (m, 1H), 7.56 (m, 1H), 7.40-7.31 (m, 3H), 5.38 (s, 2H), 4.35 (s, 1H), 3.64-3.58 (m, 2H), 2.95-2.87 (m, 2H), 1.64 (t, J=5.2, 1H).

›Example 414

The title compound was prepared in a manner similar to that described in Example 88 using 4-((2-bromophenyl)sulfonyl)piperazin-2-one and 3-amino-6-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 21 H 17 FN 6 O 3 S, 452.11; m/z found, 453.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.65 (d. J=2.1, 1H), 8.05 (dd. J=8.1, 1.3, 1H), 7.85 (m, 1H), 7.65 (m, 1H), 7.55 (m, 1H), 7.36 (dd, J=7.6, 1.3, 1H), 7.26-7.17 (m, 2H), 3.29 (s, 2H), 3.04 (s, 4H).

›Example 415

The title compound was prepared in a manner similar to that described in Example 88 using (R)-2-bromo-N-(2-hydroxypropyl)benzenesulfonamide and 3-amino-6-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 20 H 18 FN 5 O 3 S, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.75 (d, J=2.1, 1H), 8.09 (dd, J=8.0, 1.3, 1H), 7.95 (m, 1H), 7.70 (m, 1H), 7.62 (m, 1H), 7.43 (dd, J=7.6, 1.4, 1H), 7.39-7.31 (m, 2H), 3.74-3.62 (m, 1H), 2.80-2.67 (m, 2H), 1.07 (d, J=6.3, 3H).

›Example 416

The title compound was prepared in a manner similar to that described in Example 88 using (2-bromophenyl)(morpholino)methanone and 3-amino-6-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 22 H 18 FN 5 O 2 , 403.14; m/z found, 404.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 7.45 (d, J=2.1, 1H), 6.71 (m, 1H), 6.32-6.21 (m, 3H), 6.17-6.10 (m, 2H), 6.07 (dd, J=12.4, 1.8, 1H), 2.40-2.22 (m, 3H), 2.13-2.03 (m, 2H), 1.86-1.77 (m, 1H), 1.62-1.49 (m, 2H).

›Example 417

The title compound was prepared in a manner similar to that described in Example 444 using N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 6-chloropyridazin-3-amine. MS (ESI): mass calcd. for C 20 H 21 FN 4 O 2 S, 400.14; m/z found, 401.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.26-8.22 (m, 1H), 8.16-8.13 (m, 1H), 7.91-7.85 (m, 1H), 7.69-7.64 (m, 1H), 7.63-7.56 (m, 2H), 7.44-7.37 (m, 3H), 1.09 (s, 9H).

›Example 418

The title compound was prepared in a manner similar to that described in Example 444 using N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 2-bromo-7H-pyrrolo[2,3-d]pyrimidine. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.2 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 9.31 (s, 1H), 8.82 (s, 1H), 8.15 (m, 1H), 7.90 (d, J=3.6, 1H), 7.68 (d, J=7.5, 1H), 7.63 (d, J=6.3, 1H), 7.50 (s, 1H), 7.42 (d, J=7.1, 1H), 7.02 (d, J=3.6, 1H), 6.66 (d, J=3.6, 1H), 1.12 (s, 9H).

›Example 419

The title compound was prepared in a manner similar to that described in Example 444 using N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 3-bromo-1,8-naphthyridine. MS (ESI): mass calcd. for C 24 H 22 FN 3 O 2 S, 435.14; m/z found, 436.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 9.46 (s, 1H), 9.23 (s, 1H), 8.89 (s, 1H), 8.85 (d, J=7.2, 1H), 8.18-8.14 (m, 1H), 7.94-7.90 (m, 1H), 7.80 (m, 1H), 7.70-7.65 (m, 1H), 7.62-7.57 (m, 1H), 7.49-7.40 (m, 3H), 1.11 (s, 9H).

Example 420

›Step A: 4′-Bromo-N-(tert-butyl)-3′-fluoro-[1,1′-biphenyl]-2-sulfonamide

1-Bromo-2-fluoro-4-iodobenzene (117 mg, 0.389 mmol) and (2-(N-(tert-butyl)sulfamoyl)phenyl) boronic acid (100 mg, 0.389 mmol) were added to a 5 mL sealable vial equipped with a stir bar. 1,4-Dioxane (1 mL) and 2 M Na 2 CO 3 (1 mL) solution were added. Argon was bubbled through the solvent while it was rapidly stirred for 10 min then Pd(dppf)Cl 2 .CH 2 Cl 2 (14 mg, 0.019 mmol) was added. The mixture was then stirred for 15 hours at 80° Celsius under an argon atmosphere. The reaction was diluted with 2 mL of ethyl acetate and 2 mL of water and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic extracts were then dried with Na 2 SO 4 and concentrated to dryness. The crude product was purified by FCC to give the title compound. 1 H NMR (500 MHz, CDCl 3 ) δ 8.20-8.15 (dd, J=7.9, 1.4, 1H), 7.64-7.59 (dd, J=8.2, 7.1, 1H), 7.60-7.55 (m, 1H), 7.54-7.49 (m, 1H), 7.31-7.27 (m, 2H), 7.21-7.16 (dd, J=8.5, 2.2, 1H), 3.65 (s, 1H), 1.07 (s, 9H).

›Step B: N-tert-Butyl-3′-fluoro-4′-quinoxalin-6-ylbiphenyl-2-sulfonamide

4′-Bromo-N-(tert-butyl)-3′-fluoro-[1,1′-biphenyl]-2-sulfonamide (30 mg, 0.078 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxaline (12 mg, 0.085 mmol) were added to a 5 mL sealable vial equipped with a stir bar. Dioxane (0.2 mL) and 2 M Na 2 CO 3 (0.2 mL) were added. Argon was bubbled through the solvent while it was rapidly stirred for 10 min then Pd(dppf)Cl 2 .CH 2 Cl 2 (3 mg, 0.004 mmol) was added, and the mixture heated for 15 hours at 80° Celsius under an argon atmosphere. The reaction was diluted with 2 mL of ethyl acetate and 2 mL of water and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic extracts were then dried with Na 2 SO 4 and concentrated to dryness. The crude product was purified by HPLC to give the title compound. MS (ESI): mass calcd. for C 24 H 22 FN 3 O 2 S, 435.14; m/z found, 436.4 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.93-8.91 (d, J=1.8, 1H), 8.91-8.89 (d, J=1.8, 1H), 8.37-8.34 (m, 1H), 8.24-8.22 (m, 1H), 8.22-8.20 (m, 1H), 8.09-8.04 (m, 1H), 7.71-7.66 (m, 1H), 7.65-7.59 (m, 1H), 7.58-7.52 (m, 1H), 7.51-7.44 (dd, J=7.9, 1.8, 1H), 7.44-7.40 (dd, J=11.3, 1.7, 1H), 7.40-7.36 (dd, J=7.5, 1.4, 1H), 3.74 (s, 1H), 1.10 (s, 9H).

›Examples34

›Example 421

The title compound was prepared in a manner similar to that described in Example 420 using tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate in Step B. After work up, the Boc group was then removed by treatment with trifluoroacetic acid (0.3 mL) in dichloromethane (1 mL) at rt followed by concentration and purification by HPLC to give the title compound. MS (ESI): mass calcd. for C 24 H 23 FN 2 O 2 S, 422.15; m/z found, 423.3 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.27 (s, 1H), 8.23-8.17 (dd, J=8.0, 1.3, 1H), 7.91-7.85 (m, 1H), 7.63-7.56 (m, 2H), 7.55-7.49 (m, 2H), 7.48-7.43 (m, 1H), 7.42-7.36 (m, 2H), 7.36-7.31 (dd, J=11.3, 1.8, 1H), 7.31-7.27 (dd, J=3.2, 2.4, 1H), 6.67-6.61 (m, 1H), 3.72 (s, 1H), 1.06 (s, 9H).

›Example 422

The title compound was prepared in a manner similar to that described in Example 420 using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazole in Step B. MS (ESI): mass calcd. for C 23 H 22 FN 3 O 2 S, 423.14; m/z found, 424.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 9.32-9.21 (d, J=6.0, 1H), 8.18-8.12 (dd, J=8.0, 1.3, 1H), 8.04 (s, 1H), 7.96-7.89 (m, 1H), 7.89-7.82 (m, 1H), 7.69-7.55 (m, 3H), 7.45-7.33 (m, 3H), 1.11 (s, 9H).

›Example 423

The title compound was prepared in a manner similar to that described in Example 420 using (2-(N-methylsulfamoyl)phenyl)boronic acid in Step A and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazole in Step B. MS (ESI): mass calcd. for C 20 H 16 FN 3 O 2 S, 381.09; m/z found, 382.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 9.35 (s, 1H), 8.06 (s, 1H), 8.05-8.03 (dd, J=8.0, 1.3, 1H), 7.96-7.92 (m, 1H), 7.91-7.86 (m, 1H), 7.72-7.67 (m, 1H), 7.65-7.60 (m, 2H), 7.46-7.43 (dd, J=7.5, 1.4, 1H), 7.38-7.32 (m, 2H), 2.50 (s, 3H).

›Example 424

The title compound was prepared in a manner similar to that described in Example 420 using 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-benzo[d]thiazole in Step B. MS (ESI): mass calcd. for C 23 H 21 FN 2 O 2 S 2 , 440.10; m/z found, 441.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 9.07 (s, 1H), 8.39-8.35 (m, 1H), 8.24-8.19 (dd, J=8.0, 1.3, 1H), 8.10-8.05 (dd, J=8.4, 0.6, 1H), 7.75-7.69 (m, 1H), 7.65-7.62 (m, 1H), 7.62-7.58 (m, 1H), 7.57-7.51 (m, 1H), 7.45-7.42 (dd, J=7.8, 1.8, 1H), 7.41-7.38 (dd, J=4.1, 1.5, 1H), 7.38-7.36 (d, J=1.6, 1H), 3.73 (s, 1H), 1.08 (s, 9H).

›Example 425

The title compound was prepared in a manner similar to that described in Example 420 using 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine in Step B. MS (ESI): mass calcd. for C 23 H 22 FN 3 O 2 S, 423.14; m/z found, 424.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.87-8.81 (m, 1H), 8.77-8.70 (d, J=1.5, 1H), 8.20-8.17 (d, J=3.3, 1H), 8.17-8.12 (dd, J=8.0, 1.3, 1H), 7.78-7.71 (m, 1H), 7.71-7.65 (m, 1H), 7.65-7.58 (m, 1H), 7.47-7.44 (dd, J=4.9, 1.5, 1H), 7.44 (s, 1H), 7.43-7.40 (dd, J=7.5, 1.4, 1H), 6.95-6.89 (dd, J=3.2, 0.9, 1H), 1.12 (s, 9H).

›Example 426

The title compound was prepared in a manner similar to that described in Example 420 using (2-(N-methylsulfamoyl)phenyl)boronic acid in Step A and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine in Step B. MS (ESI): mass calcd. for C 20 H 16 FN 3 O 2 S, 381.09; m/z found, 382.1 [M+H] 4 . 1 H NMR (500 MHz, CD 3 OD) δ 8.49 (s, 1H), 8.46-8.37 (m, 1H), 8.13-7.97 (dd, J=7.9, 1.3, 1H), 7.74-7.66 (m, 1H), 7.66-7.57 (m, 2H), 7.57-7.52 (d, J=3.5, 1H), 7.46-7.40 (dd, J=7.7, 1.4, 1H), 7.38-7.30 (m, 2H), 6.72-6.63 (d, J=3.5, 1H), 2.48 (s, 3H).

›Example 427

N-(tert-Butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide (37 mg, 0.085 mmol) and 6-bromopyridin-3-amine (22 mg, 0.13 mmol) were added to a 5 mL sealable vial equipped with a stir bar. 1,4-Dioxane (0.2 mL) and 2 M Na 2 CO 3 (0.2 mL) were added. Argon was bubbled through the solvent while it was rapidly stirred for 10 min then Pd(dppf)Cl 2 .CH 2 Cl 2 (3 mg, 0.004 mmol) was added, and the mixture stirred for 15 hours at 80° Celsius under an argon atmosphere. The reaction was diluted with 2 mL of ethyl acetate and 2 mL of water and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic extracts were then dried with Na 2 SO 4 and concentrated to dryness. The crude product was purified by HPLC to give the title compound. MS (ESI): mass calcd. for C 21 H 22 FN 3 O 2 S, 399.14; m/z found, 400.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.66 (s, 1H), 8.25-8.16 (dd, J=8.0, 1.4, 1H), 7.83-7.76 (dd, J=8.8, 1.7, 1H), 7.77-7.68 (m, 1H), 7.66-7.58 (m, 1H), 7.58-7.48 (m, 2H), 7.46-7.39 (m, 2H), 7.37-7.30 (dd, J=7.4, 1.5, 1H), 4.31 (s, 1H), 1.09 (s, 9H).

›Example 428

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromopyrazine-2,3-diamine. MS (ESI): mass calcd. for C 20 H 22 FN 5 O 2 S, 415.15; m/z found, 416.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.16-8.11 (dd, J=8.0, 1.3, 1H), 8.11-8.06 (m, 1H), 7.66 (s, 1H), 7.66-7.62 (m, 1H), 7.60-7.54 (m, 1H), 7.40-7.35 (dd, J=7.5, 1.4, 1H), 7.35-7.34 (m, 1H), 7.34-7.31 (dd, J=7.7, 1.6, 1H), 1.07 (s, 9H).

›Example 429

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-1H-imidazo[4,5-b]pyrazin-2(3H)-one. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 3 S, 441.13; m/z found, 442.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.45-8.39 (d, J=1.7, 1H), 8.17-8.10 (m, 1H), 8.06-7.98 (m, 1H), 7.70-7.60 (m, 1H), 7.60-7.52 (m, 1H), 7.42-7.38 (dd, J=7.4, 1.3, 1H), 7.38-7.33 (m, 2H), 1.07 (s, 9H).

›Example 430

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-3-fluoropyridin-2-amine. MS (ESI): mass calcd. for C 21 H 21 F 2 N 3 O 2 S, 417.13; m/z found, 418.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.16-8.11 (dd, J=8.0, 1.3, 1H), 8.04-7.97 (m, 2H), 7.69-7.62 (m, 1H), 7.61-7.53 (m, 2H), 7.39-7.32 (m, 3H), 1.24-0.86 (s, 9H).

›Example 431

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine. MS (ESI): mass calcd. for C 23 H 24 FN 3 O 2 S, 425.16; m/z found, 426.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.18-8.06 (dd, J=7.9, 1.3, 1H), 7.95-7.85 (m, 1H), 7.76 (s, 1H), 7.68-7.62 (m, 1H), 7.61-7.49 (m, 2H), 7.43-7.30 (m, 3H), 4.03-3.92 (dd, J=8.8, 7.8, 2H), 3.37-3.32 (m, 2H), 1.10 (s, 9H).

›Example 432

The title compound was prepared in a manner similar to that described in Example 427 using 6-bromo-3H-imidazo[4,5-b]pyridine. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.92 (s, 1H), 8.84-8.74 (m, 1H), 8.40 (s, 1H), 8.21-8.08 (dd, J=8.1, 1.3, 1H), 7.70-7.63 (m, 2H), 7.62-7.55 (m, 1H), 7.46-7.36 (m, 3H), 1.10 (s, 9H).

›Example 433

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-3-methoxypyrazin-2-amine. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 3 S, 430.15; m/z found, 431.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.18-8.10 (m, 2H), 7.95 (s, 1H), 7.68-7.62 (m, 1H), 7.60-7.54 (m, 1H), 7.40-7.35 (m, 2H), 7.35-7.32 (dd, J=12.9, 1.6, 1H), 4.19 (s, 3H), 1.07 (s, 9H).

›Example 434

The title compound was prepared in a manner similar to that described in Example 427 using 3-amino-6-bromopyrazine-2-carbonitrile. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 2 S, 425.13; m/z found, 426.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.76-8.69 (d, J=2.1, 1H), 8.18-8.10 (dd, J=8.0, 1.3, 1H), 7.96-7.89 (m, 1H), 7.68-7.62 (m, 1H), 7.61-7.53 (m, 1H), 7.40-7.37 (dd, J=7.6, 1.4, 1H), 7.37-7.36 (m, 1H), 7.36-7.33 (dd, J=4.4, 1.6, 1H), 1.07 (s, 9H).

›Example 435

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 6-amino-3-(4-bromo-2-fluorophenyl)pyrazine-2-carbonitrile and (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 2 S, 425.13; m/z found, 426.1 [M+H] + . 1 H NMR (600 MHz, CDCl 3 ) δ 8.25 (s, 1H), 8.19 (dd, J=8.0, 1.4, 1H), 7.64-7.56 (m, 2H), 7.54-7.49 (m, 1H), 7.47 (dd, J=7.9, 1.7, 1H), 7.40-7.33 (m, 2H), 1.04 (s, 9H).

›Example 436

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 2-amino-5-(4-bromo-2-fluorophenyl)pyridine-4-carbonitrile and (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.1 [M+H] + . 1 H NMR (600 MHz, CDCl 3 ) δ 8.18 (d, J=7.8, 1H), 8.01 (s, 1H), 7.64-7.58 (m, 1H), 7.57-7.51 (m, 1H), 7.46-7.28 (m, 4H), 3.91 (s, 1H), 1.04 (s, 9H).

›Example 437

The title compound was prepared using analogous conditions to those described in Example 6 utilizing N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 6-amino-3-bromo-2-cyanopyridine. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 424.9 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.11-8.04 (d, J=7.9, 1H), 7.71-7.64 (m, 1H), 7.64-7.58 (m, 2H), 7.54-7.48 (m, 1H), 7.45-7.36 (dd, J=19.2, 9.2, 2H), 7.36-7.30 (dd, J=7.9, 1.6, 1H), 6.89-6.83 (d, J=8.7, 1H), 6.83-6.75 (d, J=10.0, 3H), 1.03 (s, 9H).

›Example 438

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1,3,4-thiadiazol-2-amine and 2-bromo-N-(tert-butyl)benzenesulfonamide. MS (ESI): mass calcd. for C 18 H 19 FN 4 O 2 S 2 , 406.09; m/z found, 407.1 [M+H] + . 1 H NMR (300 MHz, CD 3 OD) δ 8.20-8.10 (m, 2H), 7.69-7.56 (m, 2H), 7.46-7.36 (m, 3H), 1.08 (s, 9H).

›Example 439

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1,3,4-thiadiazol-2-amine and (R)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide. MS (ESI): mass calcd. for C 17 H 17 FN 4 O 3 S 2 , 408.07; m/z found, 409.1 [M+H] + . 1 H NMR (300 MHz, CD 3 OD) δ 8.15-8.12 (m, 2H), 7.68 (m, 1H), 7.61 (m, 1H), 7.44-7.38 (m, 3H), 3.42-3.38 (m, 1H), 3.30-3.25 (m, 1H), 3.22-3.18 (m, 1H), 1.02 (d, J=6.6, 3H).

›Example 440

The title compound was prepared using analogous conditions to those described in Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1,3,4-thiadiazol-2-amine and 4-((2-bromophenyl)sulfonyl)thiomorpholine 1,1-dioxide. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 4 S 2 , 468.04; m/z found, 469.0 [M+H] + . 1 H NMR (300 MHz, CD 3 OD) δ 8.19 (m, 1H), 8.15 (dd, J=8.0, 1.1, 1H), 7.76 (m, 1H), 7.67 (m, 1H), 7.45 (dd, J=7.6, 1.2, 1H), 7.39 (dd, J=11.9, 1.4, 1H), 7.36 (dd, J=8.1, 1.6, 1H), 3.42-3.33 (m, 4H), 3.09-3.02 (m, 4H).

›Example 441

To a 25 mL round-bottomed flask were added a stirbar, 52 mg (0.13 mmol) 4′-(5-aminopyrazin-2-yl)-N-tert-butyl-3′-fluorobiphenyl-2-sulfonamide, 27 mg (0.20 mmol) N-chlorosuccinamide, and dry DMF (2.0 mL). The flask was sparged with nitrogen and heated at 60° Celsius for 18 hours before cooling to rt and subjecting the reaction mixture (after syringe filtration) to HPLC purification to give the title compound (29.6 mg, 52%). MS (ESI): mass calcd. for C 20 H 20 ClFN 4 O 2 S, 434.10; m/z found, 435.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.44 (d, J=2.0, 1H), 8.06 (dd, J=8.1, 1.5, 1H), 7.85 (dd, J=9.4, 6.8, 1H), 7.70-7.64 (m, 1H), 7.64-7.57 (m, 1H), 7.43-7.27 (m, 3H), 7.13 (s, 2H), 6.98 (d, J=3.7, 1H), 1.02 (s, 9H).

›Example 442

To a 25 mL round-bottomed flask were added a stirbar, (55 mg, 14 mmol) 4′-(5-aminopyrazin-2-yl)-N-tert-butyl-3′-fluorobiphenyl-2-sulfonamide (32 mg, 0.18 mmol) NBS, and dry DMF (2.0 mL). The flask was sparged with nitrogen and stirred at rt for 18 hours before subjecting the reaction mixture (after syringe filtration) to HPLC purification to give the title compound (46 mg, 70%). MS (ESI): mass calcd. for C 20 H 20 BrFN 4 O 2 S, 479.05; m/z found, 479.0 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.45 (d, J=1.8, 1H), 8.06 (dd, J=7.9, 1.4, 1H), 7.88-7.81 (m, 1H), 7.69-7.64 (m, 1H), 7.64-7.58 (m, 1H), 7.37 (dd, J=7.6, 1.4, 1H), 7.35-7.29 (m, 2H), 7.05 (s, 2H), 6.98 (s, 1H), 1.02 (s, 9H).

›Example 443

The title compound was prepared using analogous conditions to those described in Example 6 2-(2′-(cyclopropylsulfonyl)-3-fluoro-[1,1′-biphenyl]-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and 6-amino-3-bromo-2-cyanopyridine. MS (ESI): mass calcd. for C 21 H 16 FN 3 O 2 S, 393.09; m/z found, 393.9 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.07 (d, J=7.9, 1H), 7.71-7.64 (m, 1H), 7.64-7.58 (m, 2H), 7.54-7.48 (m, 1H), 7.40 (dd, J=19.2, 9.2, 2H), 7.33 (dd, J=7.9, 1.6, 1H), 6.86 (d, J=8.7, 1H), 6.79 (d, J=10.0, 3H), 1.03 (s, 9H).

›Example 444

To a 20 mL vial were added N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide (45 mg, 0.10 mmol), 7-bromo-[1,2,4]triazolo[4,3-a]pyridine (21 mg, 0.10 mmol) K 2 CO 3 (29 mg, 0.21 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (4 mg, 0.005 mmol), and a stir bar. The vial was sealed with a teflon lined cap and the vial sparged with N 2 . The vial was then charged with freshly sparged DMSO (2 mL) and stirred for 16 hours at 80° Celsius. The reaction mixture was then cooled to rt, filtered, and purified by HPLC to give the title compound (30 mg, 53%). MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 9.40 (s, 1H), 8.79 (s, 1H), 8.20-8.11 (m, 2H), 7.77 (m, 1H), 7.70-7.57 (m, 3H), 7.47-7.38 (m, 3H), 1.10 (s, 9H).

›Example 445

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-3-methylpyrazin-2-amine. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 2 S, 414.15; m/z found, 415.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.31-8.24 (m, 1H), 8.17-8.12 (dd, J=8.2, 1.3, 1H), 7.97-7.91 (m, 1H), 7.68-7.61 (m, 1H), 7.59-7.53 (m, 1H), 7.43-7.36 (dd, J=7.5, 1.3, 1H), 7.36-7.28 (m, 2H), 2.59-2.35 (m, 3H), 1.06 (s, 9H).

›Example 446

The title compound was prepared by forming 4′-(5-Amino-6-methylpyrazin-2-yl)-N-tert-butyl-3′-fluorobiphenyl-2-sulfonamide then removing the tert-butyl group by dissolving the crude 4′-(5-Amino-6-methylpyrazin-2-yl)-N-tert-butyl-3′-fluorobiphenyl-2-sulfonamide in 1 mL of trifluoroacetic acid and heating it to 60° Celsius for 2 hours, after which time the reaction was cooled to rt, concentrated to dryness and purified using FCC. MS (ESI): mass calcd. for C 17 H 15 FN 4 O 2 S, 358.09; m/z found, 359.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.22 (s, 1H), 8.16-8.10 (dd, J=7.7, 1.3, 1H), 8.03-7.97 (m, 1H), 7.68-7.62 (m, 1H), 7.61-7.54 (m, 1H), 7.41-7.37 (dd, J=7.7, 1.4, 1H), 7.36-7.33 (dd, J=8.0, 1.7, 1H), 7.33-7.29 (dd, J=12.3, 1.6, 1H), 2.66-2.43 (m, 3H).

›Example 447

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-1H-imidazo[4,5-b]pyrazine. MS (ESI): mass calcd. for C 21 H 20 FN 5 O 2 S, 425.13; m/z found, 426.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 9.06-8.88 (d, J=2.1, 1H), 8.80 (s, 1H), 8.18-8.11 (dd, J=8.1, 1.3, 1H), 8.13-8.04 (m, 1H), 7.71-7.64 (m, 1H), 7.63-7.54 (m, 1H), 7.48-7.39 (m, 3H), 1.09 (s, 9H).

›Example 448

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromopyridine-2,3-diamine. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 2 S, 414.15; m/z found, 415.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.18-8.06 (m, 1H), 7.69-7.62 (m, 1H), 7.61-7.56 (m, 1H), 7.56-7.50 (m, 2H), 7.47-7.42 (m, 1H), 7.40-7.30 (m, 3H), 1.104 (s, 9H).

›Example 449

The title compound was prepared in a manner similar to that described in Example 427 using 5-bromo-3-methylpyrazin-2-amine and 3′-fluoro-N-methyl-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.11; m/z found, 373.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.27 (s, 1H), 8.09-8.00 (d, J=7.9, 1H), 7.96-7.87 (m, 1H), 7.71-7.63 (m, 1H), 7.63-7.55 (m, 1H), 7.44-7.38 (d, J=7.5, 1H), 7.34-7.21 (m, 2H), 2.46 (s, 3H), 2.44 (s, 3H).

›Example 450

The title compound was prepared using analogous conditions to those described in Example 1 using N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 2-amino-5-bromonicotinonitrile. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.49-8.44 (m, 1H), 8.12 (d, J=1.8, 1H), 8.06 (dd, J=7.9, 1.3, 1H), 7.66 (m, 1H), 7.63-7.56 (m, 2H), 7.38 (dd, J=7.5, 1.3, 1H), 7.33 (dd, J=11.9, 1.6, 1H), 7.27 (dd, J=7.9, 1.7, 1H), 7.18 (s, 2H), 6.90 (s, 1H), 1.03 (s, 9H).

›Example 451

The title compound was prepared using analogous conditions to those described in Example 1 using N-(tert-butyl-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 5-bromo-3-chloropyridin-2-amine. MS (ESI): mass calcd. for C 21 H 21 ClFN 3 O 2 S, 433.10; m/z found, 434.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.20 (s, 1H), 8.06 (dd, J=7.9, 1.2, 1H), 7.85 (s, 1H), 7.66 (m, 1H), 7.62-7.54 (m, 2H), 7.37 (m, 1H), 7.31 (dd, J=11.9, 1.6, 1H), 7.26 (dd, J=7.9, 1.7, 1H), 6.89 (s, 1H), 6.62 (s, 2H), 1.03 (s, 9H).

›Example 452

The title compound was prepared using analogous conditions to those described in Example 1 using N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 5-bromo-3-(trifluoromethyl)pyridin-2-amine. MS (ESI): mass calcd. for C 22 H 21 F 4 N 3 O 2 S, 467.13; m/z found, 468.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.47 (s, 1H), 8.07 (dd, J=7.9, 1.2, 1H), 7.96 (s, 1H), 7.66 (m, 1H), 7.63-7.55 (m, 2H), 7.38 (dd, J=7.5, 1.3, 1H), 7.33 (dd, J=11.9, 1.6, 1H), 7.27 (dd, J=7.9, 1.7, 1H), 6.88 (s, 1H), 6.76 (s, 2H), 1.02 (s, 9H).

›Example 453

The title compound was prepared using analogous conditions to those described in Example 1 using N-(tert-butyl-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 5-bromo-4-(trifluoromethyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 20 F 4 N 4 O 2 S, 468.12; m/z found, 469.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.45 (s, 1H), 8.07 (dd, J=7.8, 1.4, 1H), 7.67 (m, 1H), 7.62 (m, 1H), 7.53 (s, 2H), 7.45-7.38 (m, 2H), 7.37-7.29 (m, 2H), 6.74 (s, 1H), 1.01 (s, 9H).

›Example 454

The title compound was prepared using analogous conditions to those described in Example 1 using N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide and 5-bromo-4-methylpyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 23 FN 4 O 2 S, 414.15; m/z found, 415.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.17 (s, 1H), 8.08 (dd, J=8.0, 1.2, 1H), 7.67 (m, 1H), 7.64-7.58 (m, 1H), 7.43-7.38 (m, 2H), 7.36 (dd, J=10.9, 1.6, 1H), 7.30 (dd, J=7.8, 1.7, 1H), 7.13 (s, 2H), 6.86 (s, 1H), 2.25 (d, J=0.8, 3H), 1.00 (s, 9H).

Intermediate HC

›Step A: 5-Bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde

Hexamethylenetetramine (1.08 g, 7.61 mmol) was added to a solution of 5-bromo-1H-pyrrolo[2,3-b]pyridine (1 g, 5 mol) in HOAc (6.34 mL). The mixture was heated at 100° Celsius for 6 hours. The reaction mixture was then cooled to rt and diluted with water. The mixture was extracted with EtOAc, dried (Na 2 SO 4 ), filtered and concentrated to dryness. The residue was purified by FCC to provide the title compound (379 mg, 33%). 1 H NMR (500 MHz, CDCl 3 ) δ 10.02 (s, 1H), 8.77 (d, J=2.2, 1H), 8.48 (d, J=2.2, 1H), 7.99 (d, J=2.7, 1H).

›Step B

The title compound was prepared using analogous conditions to those described in Example 88 using 5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde and 3′-fluoro-N-methyl-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide. MS (ESI): mass calcd. for C 21 H 16 FN 3 O 3 S, 409.09; m/z found, 410.2 [M+H] + .

Intermediate HD

The title compound was prepared using analogous conditions to those described in Example 88 using 5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde and N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide. MS (ESI): mass calcd. for C 24 H 22 FN 3 O 3 S, 451.14; m/z found, 452.2 [M+H] + .

Intermediate HE

The title compound was prepared using analogous conditions to those described in Example 88 using 5-bromo-7-nitroindole and N-(tert-butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide. 1 H NMR (400 MHz, CDCl 3 ) δ 8.42 (s, 1H), 8.27-8.18 (m, 2H), 7.65-7.58 (m, 2H), 7.58-7.50 (m, 1H), 7.50-7.35 (m, 4H), 6.83-6.77 (m, 1H), 1.17-1.03 (m, 9H).

›Examples9

›Example 455

The title compound was prepared using similar methods to those described in Example 457 using N-(tert-butyl)-3′-fluoro-4′-(3-formyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-[1,1′-biphenyl]-2-sulfonamide. MS (ESI): mass calcd. for C 24 H 24 FN 3 O 3 S, 453.15; m/z found, 454.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.50 (s, 1H), 8.26-8.20 (m, 2H), 7.63-7.58 (m, 1H), 7.56-7.48 (m, 3H), 7.44-7.39 (m, 1H), 7.39-7.34 (m, 3H), 4.92 (s, 2H), 1.11 (d, J=12.1, 9H).

›Example 456

The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-indol-7-amine and 2-bromo-N-(1-(hydroxymethyl)-cyclopentyl)benzenesulfonamide in Step B. MS (ESI): mass calcd. for C 26 H 26 FN 3 O 3 S, 479.17; m/z found, 480.3 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.18 (dd, J=8.1, 1.4, 1H), 8.13 (s, 1H), 7.65-7.50 (m, 3H), 7.42 (s, 1H), 7.41-7.31 (m, 3H), 6.87 (m, 1H), 6.61 (dd, J=3.1, 2.0, 1H), 4.05 (s, 1H), 3.48 (s, 2H), 1.50-1.34 (m, 4H), 1.37-1.22 (m, 2H), 0.93-0.73 (m, 2H).

›Example 457

NaBH 4 (4.45 mg, 0.13 mmol) was added to 3′-fluoro-4′-(3-formyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-methyl-[1,1′-biphenyl]-2-sulfonamide (18 mg, 0.044 mmol) in MeOH (0.52 mL). The mixture was stirred at rt for 1 h and then concentrated to dryness. The residue was subjected to FCC purification to give the title compound. MS (ESI): mass calcd. for C 21 H 18 FN 3 O 3 S, 411.11; m/z found, 412.2 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 9.36 (s, 1H), 8.34 (s, 1H), 8.23 (dd, J=7.9, 1.2, 1H), 8.12 (s, 1H), 7.68-7.61 (m, 1H), 7.61-7.54 (m, 1H), 7.42-7.30 (m, 5H), 5.21 (s, 1H), 4.88 (s, 2H), 2.52 (dd, J=13.9, 5.3, 3H).

›Example 458

Zn dust (123 mg, 1.88 mmol) was added to a solution of N-(tert-butyl)-3′-fluoro-4′-(7-nitro-1H-indol-5-yl)-[1,1′-biphenyl]-2-sulfonamide (23 mg, 0.19 mmol) and NH 4 Cl (101 mg, 1.88 mmol) in water (0.75 mL) and acetone (3.76 mL). The mixture was stirred at rt for 1 hour and then filtered through Celite. The resulting filtrate was concentrated to dryness and then taken up in water and extracted with EtOAc. The organic extract was dried (Na 2 SO 4 ), filtered and concentrated to dryness to give the title compound (23 mg, 28%). MS (ESI): mass calcd. for C 24 H 24 FN 3 O 2 S, 437.16: m/z found, 438.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.20 (dd, J=8.0, 1.3, 1H), 8.17-8.10 (m, 1H), 7.63-7.56 (m, 2H), 7.54-7.48 (m, 1H), 7.42 (s, 1H), 7.38 (dd, J=7.8, 1.7, 2H), 7.32 (dd, J=11.4, 1.8, 1H), 6.86 (m, 1H), 6.62 (dd, J=3.2, 2.0, 1H), 3.78-3.68 (m, 2H), 1.05 (s, 9H).

›Example 459

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and N-(2-bromophenyl)acetamide. MS (ESI): mass calcd. for C 18 H 15 FN 4 O, 322.12; m/z found, 322.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.40 (s, 1H), 8.38 (s, 1H), 8.02 (s, 1H), 7.91 (m, 1H), 7.53-7.21 (m, 6H), 6.73 (s, 2H), 1.92 (s, 3H).

›Example 460

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-(2-bromophenyl)urea. MS (ESI): mass calcd. for C 17 H 14 FN 5 O, 323.12; m/z found, 323.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.38 (s, 1H), 8.02 (s, 1H), 7.95 (m, 1H), 7.86 (d, J=8.9, 1H), 7.56 (s, 1H), 7.36-7.19 (m, 4H), 7.08 (m, 1H), 6.73 (s, 2H), 6.01 (s, 2H).

Intermediate HF

A mixture of (4-bromo-2,3-difluorophenyl)boronic acid (400 mg, 1.69 mmol) and 5-bromopyrazin-2-amine (588 mg, 3.38 mmol was suspended in EtOH (5.6 ml) and toluene (5.7 mL) The resulting mixture was treated with aqueous Na 2 CO 3 (2.0 N, 4.2 mL, 8.45 mmol). The resulting mixture was then sparged with nitrogen through the mixture for 10 min, and then Pd(PPh 3 ) 4 (98 mg, 0.085 mmol) was added. The reaction vessel was sealed and heated at 80° Celsius for 17 hours. The reaction mixture was cooled to rt and then partitioned between saturated aqueous NH 4 Cl and EtOAc. The organic layer was dried over MgSO 4 and concentrated to dryness. The residue was suspended in DCM and the solid isolated by filtration to afford the title compound (160 mg, 33%), which was used without further purification. MS (ESI): mass calcd. for C 10 H 6 BrF 2 N 3 . 284.97; m/z found, 286.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.36 (s, 1H), 8.01 (d, J=1.2, 1H), 7.68-7.56 (m, 2H), 6.87 (s, 2H).

›Example 461

Nitrogen sparged DMSO (0.73 ml) was added to a mixture of 5-(4-bromo-2,3-difluorophenyl)pyrazin-2-amine (50 mg, 0.18 mmol), (2-(methylsulfonyl)phenyl)boronic acid (35 mg, 0.18 mmol), K 2 CO 3 (73 mg, 0.532 mmol) and PdCl 2 (dppf).CH 2 Cl 2 (13 mg, 0.018 mmol) and heated at 80° Celsius for 2.5 hours. The mixture was cooled to rt and partitioned between sat. NaHCO 3 and EtOAc. The organic layer was isolated, dried over MgSO 4 , and concentrated to dryness. Purification by FCC afforded the title compound (26 mg, 41%). MS (ESI): mass calcd. for C 17 H 13 F 2 N 3 O 2 S, 361.07; m/z found, 362.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.44-8.41 (m, 1H), 8.14 (dd, J=7.9, 1.4, 1H), 8.04 (d, J=1.5, 1H), 7.84 (m, 1H), 7.78 (m, 1H), 7.75-7.66 (m, 1H), 7.53 (dd, J=7.5, 1.3, 1H), 7.30 (dd, J=11.6, 4.9, 1H), 6.85 (s, 2H), 3.06 (s, 3H).

›Example 462

The title compound was prepared by methods analogous to Example 461 using (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 20 H 20 F 2 N 4 O 2 S, 418.13; m/z found, 419.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.36 (s, 1H), 8.25 (dd, J=7.9, 1.3, 1H), 7.94 (d, J=1.4, 1H), 7.71-7.66 (m, 1H), 7.60 (m, 1H), 7.55 (m, 1H), 7.34 (dd, J=7.4, 1.1, 1H), 7.33-7.28 (m, 1H), 5.47 (s, 1H), 5.19 (s, 2H), 1.20 (s, 9H).

Example 463

›Step A: 5-(4-chloro-2-fluoro-3-methylphenyl)pyrazin-2-amine

The title compound was prepared by methods analogous to Intermediate HF using (4-chloro-2-fluoro-3-methylphenyl)boronic acid. MS (ESI): mass calcd. for C 11 H 9 ClFN 3 , 237.05; m/z found, 238.0 [M+H] + .

›Step B

To a mixture of 5-(4-chloro-2-fluoro-3-methylphenyl)pyrazin-2-amine (75 mg, 0.32 mmol), (2-(methylsulfonamido)phenyl)boronic acid (85 mg, 0.39 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (5.0 mg, 0.006 mmol) in a sealed tube flushed with N 2 were added N 2 sparged K 3 PO 4 (1.26 ml, 0.5 N) followed by N 2 sparged THF (0.63 ml). The reaction mixture was stirred at rt for 18 hours. The reaction mixture was then partitioned between EtOAc and brine. The organic layer was isolated, dried over MgSO 4 , filtered and concentrated to dryness. Purification by FCC afforded the title compound (100 mg, 85%). MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.10; m/z found, 373.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.81 (s, 1H), 8.39-8.35 (m, 1H), 8.02 (d, J=1.5, 1H), 7.70 (m, 1H), 7.47 (dd, J=8.1, 1.0, 1H), 7.45-7.39 (m, 1H), 7.29 (m, 1H), 7.21 (dd, J=7.6, 1.5, 1H), 7.07 (d, J=8.0, 1H), 6.67 (s, 2H), 2.87 (s, 3H), 2.01 (d, J=2.5, 3H).

›Examples18

›Example 464

A suspension of 4′-(5-aminopyrazin-2-yl)-N-tert-butyl-2′,3′-difluorobiphenyl-2-sulfonamide (168 mg, 0.40 mmol) in TFA (3 mL) was heated at 50° Celsius for 3 hours. The reaction was then cooled to rt and carefully partitioned between NaHCO 3 and EtOAc. The organic layer was isolated, dried over MgSO 4 , and concentrated to dryness. Purification by FCC afforded the title compound (140 mg, 96%). MS (ESI): mass calcd. for C 16 H 12 F 2 N 4 O 2 S, 362.06; m/z found, 363.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.40 (s, 1H), 8.12-8.01 (m, 2H), 7.72-7.61 (m, 3H), 7.45-7.36 (m, 3H), 7.19 (m, 1H), 6.81 (s, 2H).

Intermediate HG

The title compound was prepared using analogous conditions to those described in 5-(4-chloro-2-fluorophenyl)pyrazin-2-amine using (4-bromo-2,3-difluorophenyl)boronic acid and 5-bromopyrimidin-2-amine. MS (ESI): mass calcd. for C 10 H 6 BrF 2 N 3 , 284.97; m/z found, 286.0 [M+H] + .

›Example 465

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(4-bromo-2,3-difluorophenyl)pyrimidin-2-amine and (2-(N-methylsulfamoyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 17 H 14 F 2 N 4 O 2 S, 376.08; m/z found, 377.1 [M+H] + . 1 H NMR (600 MHz, DMSO-d 6 ) δ 8.56 (s, 2H), 7.98 (dd, J=7.7, 1.6, 1H), 7.72 (m, 2H), 7.45 (dd, J=7.3, 1.6, 1H), 7.41 (m, 1H), 7.35 (m, 1H), 7.19 (m, 1H), 7.12 (s, 2H), 2.40 (d, J=4.9, 3H).

›Example 466

The title compound was prepared using analogous conditions to those described in Example 1 using 5-(4-bromo-2,3-difluorophenyl)pyrimidin-2-amine and (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid. MS (ESI): mass calcd. for C 20 H 20 F 2 N 4 O 2 S, 418.13; m/z found, 419.1 [M+H] + . 1 H NMR (600 MHz, CD 3 OD) δ 8.63 (d, J=0.9, 2H), 8.15 (dd, J=7.9, 1.2, 1H), 7.67 (m, 1H), 7.63-7.58 (m, 1H), 7.38 (dd, J=7.5, 1.3, 1H), 7.35-7.29 (m, 1H), 7.27-7.18 (m, 1H), 1.13 (s, 9H).

›Example 467

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-fluoro-4-(trifluoromethoxy)bromobenzene. MS (ESI): mass calcd. for C 17 H 10 F 5 N 3 O, 367.07; m/z found, 368.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.40 (s, 1H), 8.03-7.96 (m, 2H), 7.78 (m, 1H), 7.56-7.49 (m, 3H), 7.37 (d, J=8.2, 1H), 6.75 (s, 2H).

›Example 468

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-bromofluorobenzene. MS (ESI): mass calcd. for C 16 H 11 F 2 N 3 , 283.09; m/z found, 284.1 [M+H] + . 1 H NMR (600 MHz, CDCl 3 ) δ 8.63-8.54 (m, 1H), 8.13 (d, J=1.4, 1H), 8.00 (m, 1H), 7.52-7.31 (m, 4H), 7.24-7.12 (m, 2H), 4.72 (s, 2H).

›Example 469

›Example 470

›Example 471

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-fluoro-4-(trifluoromethyl)bromobenzene. MS (ESI): mass calcd. for C 17 H 10 F 5 N 3 , 351.08; m/z found, 351.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.42 (s, 1H), 8.11-7.97 (m, 2H), 7.90-7.83 (m, 2H), 7.71 (d, J=8.1, 1H), 7.61-7.54 (m, 2H), 6.78 (s, 2H).

›Example 472

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-trifluoromethylbromobenzene. MS (ESI): mass calcd. for C 17 H 11 F 4 N 3 , 333.09; m/z found, 334.1 [M+H] + . 1 H NMR (400 MHz, CD 3 OD) δ 8.40 (s, 1H), 8.09 (s, 1H), 7.91 (m, 1H), 7.81 (d, J=7.6, 1H), 7.69 (m, 1H), 7.59 (m, 1H), 7.44 (d, J=7.8, 1H), 7.23 (d, J=8.7, 1H), 7.17 (d, J=11.8, 1H).

›Example 473

›Example 474

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-thiomethylbromobenzene. MS (ESI): mass calcd. for C 17 H 14 FN 3 S, 311.09; m/z found, 312.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d) δ 8.37 (s, 1H), 8.02 (d, J=1.2, 1H), 7.90 (m, 1H), 7.44-7.32 (m, 2H), 7.30 (s, 1H), 7.27-7.18 (m, 3H), 6.71 (s, 2H), 2.40 (s, 3H).

›Example 475

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-(trifluoromethoxy)bromobenzene. MS (ESI): mass calcd. for C 17 H 11 F 4 N 3 O, 349.08; m/z found, 350.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.02 (s, 1H), 7.96 (m, 1H), 7.65-7.47 (m, 4H), 7.42 (d, J=5.1, 1H), 7.39 (s, 1H), 6.73 (s, 2H).

›Example 476

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-bromophenol. MS (ESI): mass calcd. for C 16 H 12 FN 3 O, 281.10; m/z found, 282.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d) δ 9.72 (s, 1H), 8.36 (s, 1H), 8.01 (d, J=1.4, 1H), 7.87 (m, 1H), 7.49 (dd, J=4.4, 1.3, 1H), 7.45 (s, 1H), 7.34 (dd, J=7.4, 1.3, 1H), 7.19 (m, 1H), 6.95 (d, J=7.3, 1H), 6.89 (m, 1H), 6.68 (s, 2H).

›Example 477

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-bromo-2-(phenylsulfonyl)benzene. MS (ESI): mass calcd. for C 22 H 16 FN 3 O 2 S, 405.09; m/z found, 406.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.35 (s, 1H), 8.29 (dd, J=6.7, 2.5, 1H), 8.03 (d, J=1.4, 1H), 7.80-7.66 (m, 3H), 7.58 (m, 1H), 7.41-7.28 (m, 5H), 6.84 (dd, J=8.0, 1.6, 1H), 6.78-6.66 (m, 3H).

›Example 478

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2,6-difluorobromobenzene. MS (ESI): mass calcd. for C 16 H 10 F 3 N 3 , 301.08; m/z found, 302.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.02 (s, 1H), 7.97 (m, 1H), 7.56-7.47 (m, 1H), 7.43 (d, J=12.5, 1H), 7.37 (d, J=7.9, 1H), 7.25 (m, 2H), 6.76 (s, 2H).

›Example 479

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and N-(2-bromophenyl)benzenesulfonamide. MS (ESI): mass calcd. for C 22 H 17 FN 4 O 2 S, 420.11; m/z found, 421.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.73 (s, 1H), 8.38 (s, 1H), 8.04 (s, 1H), 7.85-7.75 (m, 1H), 7.59-7.46 (m, 5H), 7.29-7.10 (m, 6H), 6.71 (s, 2H).

›Example 480

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-ethylbromobenzene. MS (ESI): mass calcd. for C 18 H 16 FN 3 , 293.13; m/z found, 294.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.03 (d, J=1.3, 1H), 7.92 (m, 1H), 7.36 (d, J=3.9, 2H), 7.32-7.19 (m, 4H), 6.71 (s, 2H), 2.60 (q, J=7.5, 2H), 1.06 (t, J=7.5, 3H).

Example 481

›Step A: Methyl 2-((4′-(5-aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-yl)oxy)acetate

To a solution consisting of 4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-ol Example 476 (50 mg, 0.18 mmol) and DMF (1 mL) was added Cs 2 CO 3 (116 mg, 0.36 mmol). The mixture was stirred at rt for 30 min. Methyl 2-bromoacetate (30 mg, 0.19 mmol) was added and the resultant mixture stirred at rt for 1 hour and then poured into 15 mL of water. The precipitate was collected and washed with water and air dried to give methyl 2-((4′-(5-aminopyrazin-2-yl)-3′-fluoro-[1,1′-biphenyl]-2-yl)oxy)acetate (50 mg, 72%). MS (ESI): mass calcd. for C 19 H 16 FN 3 O 3 , 353.12; m/z found, 354.0 [M+H] + . 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.38 (s, 1H), 8.03 (s, 1H), 7.93 (m, 1H), 7.57 (d, J=13.0, 1H), 7.54 (d, J=9.2, 1H), 7.50 (d, J=7.4, 1H), 7.34 (m, 1H), 7.10-7.02 (m, 2H), 6.70 (s, 2H), 4.89 (s, 2H), 3.71 (s, 3H).

›Step B

To a solution of methyl 2-(4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yloxy)acetate (50 mg, 0.14 mmol) in THF (2 mL) were added LiOH.H 2 O (63 mg, 1.5 mmol) and H 2 O (2 mL). The mixture was stirred at rt for 14 hours. The THF was removed under reduced pressure, and the residue diluted with 15 mL of water, washed with DCM (5 mL×2), and then acidified with 1 N HCl to pH=7. The precipitate was collected and washed with water and dried under high vacuum to give the title compound (40 mg, 95% yield). MS (ESI): mass calcd. for C 18 H 14 FN 3 O 3 , 339.10; m/z found, 340.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 13.02 (s, 1H), 8.36 (s, 1H), 8.01 (s, 1H), 7.88 (m, 1H), 7.55 (d, J=13.0, 1H), 7.48 (d, J=9.2, 1H), 7.40 (d, J=7.4, 1H), 7.33 (m, 1H), 7.08-7.00 (m, 2H), 6.69 (s, 2H), 4.76 (s, 2H).

›Examples9

›Example 482

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-isopropylbromobenzene. MS (ESI): mass calcd. for C 19 H 18 FN 3 , 307.15; m/z found, 308.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.03 (s, 1H), 7.91 (m, 1H), 7.49-7.34 (m, 2H), 7.27-7.17 (m, 4H), 6.71 (s, 2H), 3.06-2.97 (m, 1H), 1.14 (d, J=6.8, 6H).

›Example 483

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine and (2-acetylphenyl)boronic acid. MS (ESI): mass calcd. for C 18 H 14 FN 3 O, 307.11; m/z found, 307.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.03 (d. J=1.2, 1H), 7.91 (m, 1H), 7.69 (d, J=7.5, 1H), 7.61 (m, 1H), 7.53 (d, J=7.5, 1H), 7.48 (d, J=8.2, 1H), 7.26 (d, J=12.4, 1H), 7.19 (dd, J=8.0, 1.3, 1H), 6.75 (s, 2H), 2.31 (s, 3H).

›Example 484

The title compound was prepared using analogous conditions to those described in Example 1 utilizing what 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-(2,2,2-trifluoroethoxy)bromobenzene. MS (ESI): mass calcd. for C 18 H 13 F 4 N 3 O, 363.10; m/z found, 363.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39 (s, 1H), 8.03 (s, 1H), 7.91 (m, 1H), 7.56-7.34 (m, 4H), 7.25 (d, J=8.0, 1H), 7.16 (m, 1H), 6.71 (s, 2H), 4.82 (q. J=8.8, 2H).

›Example 485

The title compound was prepared using analogous conditions to those described in Example 1 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 2-bromobenzoic acid. MS (ESI): mass calcd. for C 17 H 12 FN 3 O 2 , 309.09; m/z found, 310.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.88 (s, 1H), 8.36 (s, 1H), 8.02 (s, 1H), 7.87 (m, 1H), 7.76 (d, J=7.5, 1H), 7.60 (m, 1H), 7.50 (d, J=7.2, 1H), 7.44 (d, J=8.2, 1H), 7.25 (d, J=5.1, 1H), 7.22 (s, 1H), 6.70 (s, 2H).

›Example 486

›Example 487

The title compound was prepared using methods analogous to those described in Example 369 3 using (2-isopropoxyphenyl)boronic acid and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 19 H 18 FN 3 O, 323.14; m/z found, 324.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.63-8.57 (m, 1H), 8.12 (d, J=1.4, 1H), 7.97-7.87 (m, 1H), 7.48-7.42 (m, 1.5H), 7.42-7.34 (m, 1.5H), 7.34-7.28 (m, 1H), 7.07-6.97 (m, 2H), 4.65 (s, 2H), 4.59-4.44 (m, 1H), 1.29 (d, J=6.1, 6H).

›Example 488

The title compound was prepared using methods analogous to those described in Example 369 using (2-(cyclopropylmethoxy)pyridin-3-yl)boronic and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 19 H 17 FN 4 O, 336.14; m/z found, 337.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.64-8.59 (m, 1H), 8.17-8.09 (m, 2H), 8.02-7.93 (m, 1H), 7.72-7.66 (m, 1H), 7.54-7.48 (m, 2H), 7.01-6.95 (m, 1H), 4.67 (s, 2H), 4.24 (d, J=7.0, 2H), 1.37-1.22 (m, 1H), 0.66-0.54 (m, 2H), 0.42-0.31 (m, 2H).

›Example 489

The title compound was prepared using methods analogous to those described in Step B of Example 377 using 2-[3,4′-difluoro-2′-(methylthio)-[1,1′-biphenyl-4-yl]-5H-pyrrolo[2,3-b]pyrazine. MS (ESI): mass calcd. for C 19 H 13 F 2 N 3 O 2 S, 385.07; m/z found, 386.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.48 (s, 1H), 8.82 (s, 1H), 8.27 (d, J=8.0, 1H), 8.18-8.09 (m, 1H), 7.77-7.67 (m, 2H), 7.66-7.57 (m, 1H), 7.48-7.36 (m, 2H), 6.89-6.83 (m, 1H), 2.76 (s, 3H).

Example 490

›Step A: N-(2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide

To a solution of 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1 g, 5 mmol) in pyridine (20 mL) was added methanesulfonyl chloride (627 mg, 5.5 mmol) and the mixture stirred at rt for 24 hours. The solvent was then removed under reduced pressure, and the resulting residue redissolved in DCM (200 mL), washed with 1 N HCl (1×100 mL) and 20% NaHCO 3 (1×100 mL). The organic layer was then isolated, dried (Na 2 SO 4 ) and concentrated to dryness. The crude product was purified by crystallization from DCM/hexanes to give the title compound (700 mg, 52%). 1 H NMR (400 MHz, CDCl 3 ) δ 8.43 (s, 1H), 7.82-7.77 (m, 1H), 7.59 (d, J=8.2, 1H), 7.51-7.43 (m, 1H), 7.17-7.10 (m, 1H), 2.95 (s, 3H), 1.37 (s, 12H).

›Step B: —N-Methyl-N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-methane-sulfonamide

To a round bottom flask under nitrogen were added N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide (250 mg, 0.84 mmol), K 2 CO 3 (140 mg, 1.01 mmol) and acetone (5.0 mL). Iodomethane (0.06 mL, 1 mmol) was then added to the mixture dropwise and the reaction stirred for 18 hours at rt. The reaction was then diluted with ethyl acetate (100 mL), washed with water (2×) and brine (1×), dried (Na 2 SO 4 ) and concentrated to dryness. The crude product was purified by FCC providing the title compound (230 mg, 88%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (dd, J=7.3, 1.8, 1H), 7.51-7.43 (m, 1H), 7.40-7.29 (m, 2H), 3.32 (s, 3H), 2.93 (s, 3H), 1.36 (s, 12H).

›Step C

The title compound was prepared using methods analogous to those described in Example 369 using N-methyl-N-(2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. for C 18 H 17 FN 4 O 2 S, 372.11; m/z found, 373.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) 8.61-8.58 (m, 1H), 8.12 (d, J=1.5, 1H), 7.47-7.39 (m, 5H), 7.37-7.31 (m, 1H), 7.30-7.23 (m, 1H), 4.75 (s, 2H), 3.17 (s, 3H), 2.76 (s, 3H).

Example 491

›Step A: N-(2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanesulfonamide

The title compound was prepared using methods analogous to those described in Step A of Example 490 using 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline for 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline and ethanesulfonyl chloride. 1 H NMR (400 MHz, CDCl 3 ) δ 8.52 (s, 1H), 7.82-7.74 (m, 1H), 7.64 (d, J=8.3, 1H), 7.49-7.41 (m, 1H), 7.14-7.06 (m, 1H), 3.12 (q, J=7.4, 2H), 1.37 (s, 12H), 1.32 (t, J=7.4, 3H).

›Step B

The title compound was prepared using methods analogous to those described in Step C of Example 490 using N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanesulfonamide and 2-(4-bromo-2-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine. MS (ESI): mass calcd. for C 20 H 17 FN 4 O 2 S, 396.11; m/z found, 397.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.16 (s, 1H), 8.78 (d, J=2.6, 1H), 8.20-8.11 (m, 2H), 7.75-7.66 (m, 2H), 7.47-7.37 (m, 1H), 7.36-7.28 (m, 2H), 7.27-7.20 (m, 1H), 6.87-6.79 (m, 1H), 6.59 (s, 1H), 3.11 (q, J=7.4, 2H), 1.33-1.18 (m, 3H).

›Examples4

›Example 492

The title compound was prepared using methods analogous to those described in Step C of Example 490 using 2-(4-bromo-2-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine. MS (ESI): mass calcd. C 20 H 17 FN 4 O 2 S, 396.11; m/z found, 397.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d) δ 8.69 (d, J=2.6, 1H), 8.05-7.99 (m, 1H), 7.97 (d, J=3.6, 1H), 7.67-7.61 (m, 1H), 7.57-7.48 (m, 3H), 7.46-7.39 (m, 2H), 6.72 (d, J=3.6, 1H), 4.75 (s, 1H), 3.14 (s, 3H), 2.99 (s, 3H).

›Example 493

The title compound was prepared using methods analogous to those described in Step C of Example 490 using 2-(4-bromo-2-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine. MS (ESI): mass calcd. C 21 H 19 FN 4 O 2 S, 410.12: m/z found, 411.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 11.04 (s, 1H), 8.77 (d, J=2.7, 1H), 8.13-8.05 (m, 1H), 7.70-7.63 (m, 1H), 7.53-7.42 (m, 4H), 7.40-7.30 (m, 2H), 6.78-6.71 (m, 1H), 3.17 (s, 3H), 2.99-2.88 (m, 2H), 1.27 (t, J=7.4, 3H).

›Example 494

The title compound was prepared using methods analogous to those described in Example 369 using N-methyl-N-(2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanesulfonamide and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine in Step B. MS (ESI): mass calcd. C 19 H 19 FN 4 O 2 S, 386.12; m/z found, 387.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.63-8.57 (m, 1H), 8.13-8.09 (d, J=1.5, 1H), 8.04-7.95 (m, 1H), 7.72-7.62 (m, 0.75H), 7.59-7.51 (m, 0.25H), 7.50-7.39 (m, 3.75H), 7.37-7.32 (m, 1H), 7.31-7.28 (m, 0.25H), 4.69 (s, 2H), 3.16 (s, 3H), 2.89 (q, J=7.4, 2H), 1.25 (t, J=7.4, 3H).

Example 495

›Step A: N-(2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-methylpropanesulfonamide

The title compound was prepared using methods analogous to those described in Step B of Example 490 using 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline and isobutylsulfonyl chloride. 1 H NMR (400 MHz, CDCl 3 ) δ 8.48 (s, 1H), 7.81-7.75 (m, 1H), 7.63-7.58 (m, 1H), 7.49-7.41 (m, 1H), 7.14-7.06 (m, 1H), 2.96 (d, J=10.1, 2H), 2.39-2.19 (m, 1H), 1.37 (s, 12H), 1.11-0.99 (m, 6H).

›Step B

The title compound was prepared using methods analogous to those described in Step C of Example 490 using N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)isobutylsulfonamide and 2-(4-bromo-2-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine. MS (ESI): mass calcd. C 22 H 21 FN 4 O 2 S, 424.14; m/z found, 425.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.09 (s, 1H), 8.78 (d, J=2.6, 1H), 8.20-8.11 (m, 1H), 7.73-7.65 (m, 2H), 7.46-7.37 (m, 1H), 7.34-7.29 (m, 2H), 7.26-7.19 (m, 2H), 6.87-6.79 (m, 1H), 6.59 (s, 1H), 2.97 (d, J=6.6, 2H), 2.31-2.13 (m, 1H), 1.05 (d, J=6.7, 6H).

Example 496

›Step A: —N-Ethyl-N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methane-sulfonamide

The title compound was prepared using methods analogous to those described in Step B of Example 490 using iodoethane. 1 H NMR (400 MHz, CDCl 3 ) δ 7.87-7.82 (m, 1H), 7.50-7.44 (m, 1H), 7.40-7.31 (m, 2H), 3.72 (q, J=7.1, 2H), 2.93 (s, 3H), 1.35 (s, 12H), 1.21-1.10 (m, 3H).

›Step B

The title compound was prepared using methods analogous to those described in Step B of Example 369 by using N-ethyl-N-(2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide and 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine. MS (ESI): mass calcd. C 19 H 19 FN 4 O 2 S.C 2 HF 3 O 2 , 386.12; m/z found, 387.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.44 (d, J=1.2, 1H), 8.33 (d, J=1.2, 1H), 8.14-8.04 (m, 1H), 7.51-7.33 (m, 6H), 3.46 (s, 2H), 2.95 (s, 3H), 1.05 (t, J=7.2, 3H).

›Example 497

Step A: —N-Methyl-N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-methylpropanesulfonamide

The title compound was prepared using methods analogous to those described in Step B of Example 490 using N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-methylpropanesulfonamide. 1 H NMR (400 MHz, CDCl 3 ) δ 7.83-7.78 (m, 1H), 7.49-7.43 (m, 1H), 7.38-7.29 (m, 2H), 3.30 (s, 3H), 2.97-2.91 (m, 2H), 2.38-2.23 (m, 1H), 1.36 (s, 12H), 1.12-1.04 (m, 6H).

›Step B

The title compound was prepared using methods analogous to those described in Step B of Example 369 using N-methyl-N-(2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-methylpropanesulfonamide and 5-(4-bromo-2-fluoro-phenyl)pyrazin-2-amine yielding the title compound after purification by HPLC (32 mg, 41%). MS (ESI): mass calcd. C 21 H 23 FN 4 O 2 S, 414.15; m/z found, 415.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.59 (s, 1H), 8.11 (d, J=1.3, 1H), 8.04-7.94 (m, 1H), 7.47-7.37 (m, 4H), 7.36-7.31 (m, 1H), 7.30-7.24 (m, 1H), 4.69 (s, 2H), 3.13 (s, 3H), 2.70 (d, J=6.6, 2H), 2.26-2.11 (m, 1H), 1.00 (d, J=6.7, 6H).

›Examples7

›Example 498

The title compound was prepared using methods analogous to those described in Example 369 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine and (2-bromophenyl)(morpholino)methanone. MS (ESI): mass calcd. for C 24 H 20 FN 3 O 2 , 401.15; m/z found, 402.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.16 (s, 1H), 8.58-8.48 (m, 1H), 8.21-8.13 (m, 1H), 7.61-7.30 (m, 8H), 6.63-6.57 (m, 1H), 3.78-3.56 (m, 3H), 3.48-3.33 (m, 2H), 3.14-3.00 (m, 1H), 2.94-2.75 (m, 2H).

›Example 499

The title compound was prepared using methods analogous to those described in Example 369 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (2-bromophenyl)(morpholino)methanone. MS (ESI): mass calcd. for C 21 H 19 FN 4 O 2 , 378.15; m/z found, 379.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (d, J=1.4, 2H), 7.54-7.41 (m, 5H), 7.36 (dd. J=8.0, 1.8, 1H), 7.32 (dd, J=11.5, 1.8, 1H), 5.20 (s, 2H), 3.74-3.58 (m, 3H), 3.49-3.30 (m, 2H), 3.15-3.01 (m, 1H), 2.94-2.77 (m, 2H).

›Example 500

The title compound was prepared using methods analogous to those described in Example 369 using (2-bromophenyl)(morpholino)methanone. MS (ESI): mass calcd. for C 23 H 19 FN 4 O 2 , 402.15; m/z found, 403.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.12 (s, 1H), 8.82 (d, J=2.5, 1H), 8.19-8.09 (m, 1H), 7.71-7.65 (m, 1H), 7.55-7.34 (m, 6H), 6.87-6.80 (m, 1H), 3.74-3.57 (m, 3H), 3.51-3.30 (m, 2H), 3.15-3.01 (m, 1H), 2.97-2.77 (m, 2H).

›Example 501

The title compound was prepared using methods analogous to those described in Example 369 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N-(tert-butyl)benzamide. MS (ESI): mass calcd. for C 21 H 21 FN 4 O, 364.17; m/z found, 365.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.55-8.50 (m, 1H), 8.13 (d, J=1.4, 1H), 8.04-7.95 (m, 1H), 7.64-7.58 (m, 1H), 7.51-7.44 (m, 1H), 7.43-7.37 (m, 2H), 7.36-7.31 (m, 1H), 7.29-7.22 (m, 1H), 5.69 (s, 1H), 5.45 (s, 2H), 2.65-2.54 (m, 1H), 1.24 (m, 9H).

›Example 502

›Example 503

The title compound was prepared using methods analogous to those described in Example 369 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and 2-bromo-N,N-diethylbenzamide. MS (ESI): mass calcd. for C 21 H 21 FN 4 O, 364.17; m/z found, 365.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.59-8.54 (m, 1H), 8.11 (d, J=1.5, 1H), 8.00-7.90 (m, 1H), 7.50-7.36 (m, 5H), 7.36-7.29 (m, 1H), 4.69 (s, 2H), 3.87-3.69 (m, 1H), 3.17-2.92 (m, 2H), 2.85-2.66 (m, 1H), 0.99 (t, J=7.1, 3H), 0.81 (t, J=7.1, 3H).

Example 504

›Step A: Methyl 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylate

A mixture of methyl 2-bromobenzoate (155 mg, 0.72 mmol), 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (250 mg, 0.79 mmol), Pd(dppf)Cl 2 .CH 2 Cl 2 (31 mg, 0.036 mmol) and K 2 CO 3 (2 mL, 2 N) in 1,4-dioxane (10 mL) was stirred at 60° Celsius under N 2 for 3 hours. The solvent was removed and the crude product was purified by FCC to afford the desired product (218 mg, 93%). MS (ESI): mass calcd. for C 18 H 14 FN 3 O 2 , 323.11; m/z found, 323.9 [M+H] + .

›Step B: 4′-(2-Aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid

A solution of methyl 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylate (218 mg, 0.67 mmol) in NaOH (8 mL, 2 N) and THF (8 mL) was stirred at 80° Celsius for 48 hours, and then concentrated to dryness. The residue was acidified with 2 N HCl. The precipitate was collected by filtration and washed with water several times, and dried in vacuo to afford the desired product (220 mg, 106%). The crude product was used without further purification. MS (ESI): mass calcd. for C 17 H 12 FN 3 O 2 , 309.09; m/z found, 309.9 [M+H] + .

›Step C

To a solution of DIPEA (47 mg, 0.36 mmol) in DMF (2 mL) were added 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid (75 mg, 0.24 mmol), (S)-1,1,1-trifluoropropan-2-amine (30 mg, 0.27 mmol) and HATU (110 mg, 0.290 mmol). The reaction mixture was stirred at rt overnight. The solvent was removed and the residue was purified by FCC to afford the title compound (41 mg, 41%). MS (ESI): mass calcd. for C 20 H 16 F 4 N 4 O, 404.13; m/z found, 404.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.87 (d, J=8.9, 1H), 8.44 (d, J=1.4, 2H), 7.58-7.50 (m, 2H), 7.49-7.40 (m, 3H), 7.26-7.19 (m, 2H), 6.86 (s, 2H), 4.60 (dd, J=15.7, 7.8, 1H), 1.15 (d, J=7.0, 3H).

›Examples46

›Example 505

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid. MS (ESI): mass calcd. for C 20 H 16 F 4 N 4 O, 404.13; m/z found, 405.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.91 (d, J=8.9, 1H), 8.46-8.28 (m, 1H), 8.01 (d, J=1.4, 1H), 7.90-7.80 (m, 1H), 7.57-7.52 (m, 1H), 7.50-7.41 (m, 3H), 7.28-7.20 (m, 2H), 6.69 (s, 2H), 4.66-4.57 (m, 1H), 1.16 (d, J=7.0, 3H).

›Example 506

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and piperazine. MS (ESI): mass calcd. for C 21 H 20 FN 5 O, 377.17; m/z found, 378.2 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.64-8.56 (m, 1H), 8.11 (d, J=1.5, 1H), 8.04-7.93 (m, 1H), 7.53-7.40 (m, 4H), 7.37 (dd, J=8.1, 1.8, 1H), 7.30 (dd, J=12.2, 1.7, 1H), 4.77 (s, 2H), 3.72 (d, J=25.1, 2H), 3.14 (s, 1H), 2.92 (s, 2H), 2.65 (s, 2H), 2.05 (s, 1H).

›Example 507

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid for and 1-(piperazin-1-yl)ethanone. MS (ESI): mass calcd. for C 23 H 22 FN 5 O 2 , 419.18; m/z found, 420.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.65-8.56 (m, 1H), 8.11 (d, J=1.5, 1H), 8.02 (dd, J=10.4, 5.8, 1H), 7.55-7.41 (m, 4H), 7.42-7.32 (m, 1H), 7.34-7.28 (m, 1H), 4.71 (s, 2H), 3.65 (s, 2H), 3.51-2.93 (m, 4H), 2.79 (s, 2H), 1.99 (d, 3H).

›Example 508

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and cyclohexanamine. MS (ESI): mass calcd. for C 23 H 23 FN 4 O, 390.19; m/z found, 391.4 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.60-8.53 (m, 1H), 8.11 (d, J=1.5, 1H), 8.03-7.93 (m, 1H), 7.74-7.62 (m, 1H), 7.54-7.37 (m, 3H), 7.32 (dd, J=8.0, 1.7, 1H), 7.30-7.20 (m, 1H), 5.24 (d, J=8.3, 1H), 4.72 (s, 2H), 3.93-3.73 (m, 1H), 1.78-1.67 (m, 2H), 1.61-1.44 (m, 3H), 1.39-1.27 (m, 2H), 1.14-0.98 (m, 1H), 0.97-0.81 (m, 2H).

›Example 509

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and thiomorpholine 1,1-dioxide. MS (ESI): mass calcd. for C 21 H 19 FN 4 O 3 S, 426.12; m/z found, 427.0 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.60 (s, 1H), 8.11 (s, 1H), 8.11-8.02 (m, 1H), 7.58-7.47 (m, 3H), 7.43 (d, J=7.5, 1H), 7.37 (dd, J=8.1, 1.8, 1H), 7.32 (dd, J=12.1, 1.7, 1H), 4.74 (s, 2H), 4.23 (s, 1H), 4.05 (s, 1H), 3.57-3.48 (m, 1H), 3.38 (s, 1H), 3.01 (s, 1H), 2.85 (s, 1H), 2.62 (s, 1H), 2.05 (s, 1H).

›Example 510

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and methylamine. MS (ESI): mass calcd. for C 18 H 15 FN 4 O, 322.12; m/z found, 323.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.35 (dd, J=2.3, 1.6, 1H), 8.15 (d, J=4.7, 1H), 8.00 (d, J=1.5, 1H), 7.84 (d, J=8.1, 1H), 7.52-7.41 (m, 4H), 7.27 (s, 1H), 7.24 (dd, J=5.5, 1.7, 1H), 6.68 (s, 2H), 2.59 (d, J=4.6, 3H).

›Example 511

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and (R)-1,1,1-trifluoropropan-2-amine. MS (ESI): mass calcd. for C 20 H 16 F 4 N 4 O, 404.13: m/z found, 405.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.91 (d, J=8.8, 1H) 8.34 (s, 1H), 8.01 (d, J=1.2, 1H), 7.90-7.80 (m, 1H), 7.58-7.40 (m, 4H), 7.29-7.18 (m, 2H), 6.69 (s, 2H), 4.68-4.56 (m, 1H), 1.16 (d, J=7.0, 3H).

›Example 512

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and (R)-2-aminopropan-1-ol. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 2 , 366.15; m/z found, 367.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.37 (s, 1H), 8.15-7.97 (m, 2H), 7.94-7.82 (m, 1H), 7.55-7.39 (m, 4H), 7.37-7.26 (m, 2H), 6.71 (s, 2H), 4.64 (s, 1H), 3.92-3.73 (m, 1H), 3.26-3.10 (m, 2H), 0.98 (d, J=6.1, 3H).

›Example 513

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and (S)-2-aminopropan-1-ol for (S)-1,1,1-trifluoropropan-2-amine. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 2 , 366.15; m/z found, 367.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.37 (s, 1H), 8.05 (d, J=5.1, 2H), 7.93-7.83 (m, 1H), 7.54-7.43 (m, 3H), 7.37-7.28 (m, 2H), 6.72 (s, 2H), 4.66 (t, J=5.6, 1H), 3.82 (d, J=7.0, 1H), 3.35 (s, 1H), 3.16 (d, J=10.4, 2H), 0.98 (d, J=6.6, 3H).

›Example 514

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and piperidin-4-ol. MS (ESI): mass calcd. for C 22 H 21 FN 4 O 2 , 392.16; m/z found, 393.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) Complex due to the presence of multiple conformations on the NMR time-scale, peaks listed for identification purposes only: δ 8.54 (d, J=13.9), 8.11-8.05 (m), 7.98-7.83 (m), 7.47-7.27 (m), 6.72 (s), 4.68 (s), 4.24-4.05 (m), 3.76-3.53 (m), 3.27-3.18 (m), 2.91-2.80 (m), 2.62-2.51 (m), 1.82 (m), 1.69 (m), 1.51-1.45 (m), 1.26-1.18 (m), 0.48-0.41 (m).

›Example 515

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-carboxylic acid and piperidin-4-amine. MS (ESI): mass calcd. for C 22 H 22 FN 5 O, 391.18; m/z found, 392.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.34 (s, 1H), 7.99 (s, 1H), 7.88 (s, 1H), 7.48 (d, J=14.8, 3H), 7.35-7.20 (m, 3H), 6.69 (s, 2H), 4.31 (s, 1H), 3.08-2.50 (m, 6H), 1.75 (t, J=80.9, 2H), 1.38-0.86 (m, 2H).

›Example 516

The title compound was prepared using methods analogous to those described in Step C of Example 504 using thiomorpholine 1,1-dioxide. MS (ESI): mass calcd. for C 21 H 19 FN 4 O 3 S, 426.12; m/z found, 426.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.43 (s, 2H), 7.63 (s, 1H), 7.52 (d, J=20.5, 4H), 7.30 (dd, J=16.9, 9.9, 2H), 6.89 (s, 2H), 3.97 (s, 1H), 3.84 (s, 1H), 3.46 (s, 1H), 3.32 (s, 1H), 3.02 (s, 1H), 2.85 (s, 1H), 2.47 (s, 1H), 2.11 (s, 1H).

›Example 517

The title compound was prepared using methods analogous to those described in Step C of Example 504 using (S)-2-aminopropan-1-ol. MS (ESI): mass calcd. for C 20 H 19 FN 4 O 2 , 366.15; m/z found, 366.9 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.46 (s, 2H), 8.00 (d, J=8.1, 1H), 7.62-7.50 (m, 1H), 7.48 (d, J=4.1, 1H), 7.43 (d, J=7.3, 3H), 7.34-7.23 (m, 2H), 6.88 (s, 2H), 4.61 (s, 1H), 3.87-3.75 (m, 1H), 3.38 (s, 1H), 3.14 (s, 1H), 0.96 (d, J=6.6, 3H).

›Example 518

The title compound was prepared using methods analogous to those described in Step C of Example 504 using (R)-1,1,1-trifluoropropan-2-amine. MS (ESI): mass calcd. for C 20 H 16 F 4 N 4 O, 404.13; m/z found, 404.9 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 8.52 (d, J=1.0, 2H), 7.68 (dd, J=7.6, 1.4, 1H), 7.60-7.49 (m, 1H), 7.48-7.38 (m, 3H), 7.28-7.25 (m, 1H), 7.22 (dd, J=11.1, 1.7, 1H), 5.39 (d, J=9.6, 1H), 5.18 (s, 2H), 4.73 (m, 1H), 1.12 (d, J=7.0, 3H).

›Example 519

The title compound was prepared using methods analogous to those described in Step C of Example 504 using 4′-(2-aminopyrazin-5-yl)-3′-fluoro-[1, l-biphenyl]-2-carboxylic acid and piperazin-2-one. MS (ESI): mass calcd. for C 21 H 18 FN 5 O 2 , 391.14; m/z found, 392.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) Complex due to the presence of multiple conformations on the NMR time-scale, peaks listed for identification purposes only: δ 8.58-8.55 (m), 8.50-8.40 (m), 8.10 (d, J=1.5), 8.04-7.98 (m), 7.56-7.41 (m), 7.37-7.27 (m), 6.75 (s), 6.43 (s), 5.06 (s), 4.83 (s), 4.45 (d, J=19.2), 4.05-3.95 (m), 3.72-3.46 (m), 3.27 (s), 3.14 (s), 2.97 (s), 2.67 (s).

›Example 520

The title compound was prepared using methods analogous to those described in Step C of Example 504 using piperazin-2-one. MS (ESI): mass calcd. for C 21 H 18 FN 5 O 2 , 391.14; m/z found, 391.9 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) Complex due to the presence of multiple conformations on the NMR time-scale, peaks listed for identification purposes only: δ 8.47 (d, J=1.2), 8.41 (d, J=1.2), 7.49-7.34 (m), 7.29-7.19 (m), 6.68 (s), 6.35 (s), 5.45 (s), 5.25 (s), 4.38 (d, J=18.7), 4.03 (s), 3.59-3.50 (m), 3.31-2.88 (m), 2.64 (s).

Intermediate HH

2-Bromo-5-(trifluoromethyl)benzoic acid (200 mg, 0.74 mmol) was dissolved in DMF (4.65 mL) and HATU (424 mg, 1.12 mmol) added to the resultant mixture at rt. The solution was stirred for 10 min then treated with N,N-diisopropylethylamine (0.51 mL, 3.0 mmol) and morpholine (0.096 mL, 1.1 mmol). The reaction was stirred for 15 hours then quenched by the addition of saturated NH 4 Cl (5 mL) and EtOAc (5 mL). The aqueous phase was extracted with ethyl acetate (3×10 mL) and the combined organic extracts washed with brine, dried over Na 2 SO 4 and concentrated to dryness. The crude product was purified by FCC to give the title compound. 1 H NMR (500 MHz, CDCl 3 ) δ 7.76-7.71 (m, 1H), 7.55-7.49 (m, 2H), 3.92-3.86 (m, 1H), 3.83-3.69 (m, 4H), 3.66-3.58 (m, 1H), 3.32-3.24 (m, 1H), 3.25-3.17 (m, 1H).

›Example 521

The title compound was prepared in a manner similar to that described in Example 88 using (2-bromo-5-(trifluoromethyl)phenyl)(morpholino)-methanone. MS (ESI): mass calcd. for C 22 H 18 F 4 N 4 O 2 , 446.14; m/z found, 447.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.40 (s, 1H), 8.18 (s, 1H), 8.10-8.01 (m, 1H), 7.90-7.82 (d, J=7.9, 1H), 7.78-7.69 (m, 2H), 7.47-7.35 (m, 2H), 3.72-3.60 (dd, J=10.0, 4.2, 2H), 3.58-3.49 (m, 1H), 3.44-3.36 (m, 1H), 3.15-3.04 (m, 1H), 2.90-2.80 (dd, J=13.4, 5.2, 1H), 2.80-2.72 (m, 1H).

›Example 522

The title compound was prepared in a manner similar to that described in Example 88 using (2-bromo-5-(trifluoromethyl)phenyl)(morpholino)methanone and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 22 H 18 F 4 N 4 O 2 , 446.14; m/z found, 447.0 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.65-8.58 (d, J=1.3, 2H), 7.91-7.85 (dd, J=8.3, 1.9, 1H), 7.78-7.76 (m, 1H), 7.76-7.73 (d, J=8.1, 1H), 7.71-7.63 (m, 1H), 7.46-7.43 (dd, J=2.7, 1.8, 1H), 7.43-7.41 (dd, J=6.2, 1.7, 1H), 3.72-3.60 (m, 2H), 3.60-3.52 (m, 1H), 3.46-3.39 (m, 1H), 3.37-3.33 (m, 1H), 3.16-3.09 (m, 1H), 2.92-2.77 (m, 2H).

›Example 523

›Example 524

›Example 525

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine and 2-(2-bromophenoxy)pyrimidine. MS (ESI): mass calcd. for C 23 H 15 FN 4 O, 382.12: m/z found, 383.1 [M+H] + . 1 H NMR (400 MHz, CDCl 3 ) δ 9.24 (s, 1H), 8.51-8.42 (m, 3H), 8.14-8.05 (m, 1H), 7.57-7.28 (m, 8H), 6.99-6.89 (m, 1H), 6.55 (dd, J=3.6, 1.8, 1H).

Intermediate HI

To a 48 mL pressure tube containing a stirbar were added 2-chloropyrimidine (1.69 g, 14.7 mmol), 2-bromophenol (1.63 mL, 14.0 mmol), Cs 2 CO 3 (5.49 g, 16.8 mmol) and DMSO (30 mL). The vial was sealed and heated at 120° Celsius for 15 hours. The reaction was then diluted with 100 mL of ethyl acetate and extracted with brine (2×50 mL). The organic layer was isolated, dried and concentrated to dryness to provide the crude product which was subsequently purified FCC to provide the title compound. 1 H NMR (500 MHz, CDCl 3 ) δ 8.57 (s, 1H), 8.56 (s, 1H), 7.72-7.60 (dd, J=8.0, 1.6, 1H), 7.45-7.34 (m, 1H), 7.32-7.23 (m, 1H), 7.23-7.11 (m, 1H), 7.10-7.01 (t, J=4.8, 1H).

Intermediate HJ

The title compound was prepared in a manner similar to that described for Intermediate HI using 2-chloropyrimidin-4-amine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.04-7.94 (d, J=5.7, 1H), 7.66-7.58 (dd, J=8.0, 1.5, 1H), 7.41-7.30 (m, 1H), 7.30-7.20 (m, 1H), 7.18-7.05 (m, 1H), 6.20-6.09 (d, J=5.7, 1H), 5.19 (s, 2H).

Intermediate HK

The title compound was prepared in a manner similar to that described for Intermediate HI using 4-chloropyrimidin-2-amine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.15-8.12 (d, J=5.6, 1H), 7.65-7.61 (dd, J=8.0, 1.6, 1H), 7.37-7.32 (m, 1H), 7.20-7.16 (dd, J=8.1, 1.5, 1H), 7.16-7.09 (m, 1H), 6.19-6.14 (d, J=5.7, 1H), 5.21 (s, 2H).

Intermediate HL

The title compound was prepared in a manner similar to that described for Intermediate HI using 6-chloropyrimidin-4-amine. 1 H NMR (500 MHz, DMSO-d) δ 7.95 (d, J=0.8, 1H), 7.67-7.62 (m, 1H), 7.38 (m, 1H), 7.20-7.14 (m, 2H), 6.75 (s, 2H), 5.77 (d, J=0.9, 1H).

Intermediate HM

The title compound was prepared in a manner similar to that described for Intermediate HI using 2-chloro-4-methylpyrimidine. 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.44 (d, J=5.1, 1H), 7.72 (dd, J=8.0, 1.6, 1H), 7.49-7.43 (m, 1H), 7.34 (dd, J=8.0, 1.6, 1H), 7.26-7.20 (m, 1H), 7.17-7.14 (m, 1H), 2.41 (s, 3H).

Intermediate HN

The title compound was prepared in a manner similar to that described for Intermediate HI using 4-chloro-2-methylpyrimidine. 1 H NMR (500 MHz, CDCl 3 ) δ 8.47 (d, J=5.8, 1H), 7.64 (dd, J=8.0, 1.5, 1H), 7.42-7.33 (m, 1H), 7.23-7.10 (m, 2H), 6.64 (d, J=5.7, 1H), 2.55 (s, 3H).

Intermediate HO

The title compound was prepared in a manner similar to that described for Intermediate HI using 2-chloronicotinonitrile. 1 H NMR (500 MHz, CDCl 3 ) δ 8.32-8.21 (dd, J=5.0, 1.9, 1H), 8.09-7.95 (dd, J=7.6, 1.9, 1H), 7.68-7.60 (dd, J=8.0, 1.5, 1H), 7.45-7.36 (m, 1H), 7.29-7.23 (dd, J=8.1, 1.5, 1H), 7.21-7.16 (m, 1H), 7.15-7.09 (dd, J=7.6, 5.0, 1H).

Intermediate HP

The title compound was prepared in a manner similar to that described for Intermediate HI using 4-chloropicolinonitrile. 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.60-8.55 (m, 1H), 7.82-7.77 (m, 1H), 7.73-7.66 (m, 1H), 7.51 (m, 1H), 7.42-7.36 (m, 1H), 7.34-7.27 (m, 1H), 7.11-7.06 (m, 1H).

Intermediate HQ

The title compound was prepared in a manner similar to that described for Intermediate HI using 2-chloro-5-methoxypyrimidine. 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.41 (d, J=0.6, 2H), 7.73 (d, J=8.0, 1H), 7.46 (m, 1H), 7.33 (d, J=8.1, 1H), 7.23 (m, 1H), 3.87 (d, J=0.5, 3H).

Intermediate HR

The title compound was prepared in a manner similar to that described for Intermediate HI using 4-chloro-2-(trifluoromethyl)pyrimidine. 1 H NMR (500 MHz, DMSO-d) δ 8.92 (d, J=5.8, 1H), 7.76 (dd, J=8.0, 1.5, 1H), 7.53-7.40 (m, 3H), 7.29 (m, 1H).

Intermediate HS

The title compound was prepared in a manner similar to that described for Intermediate HI using 4-(azetidin-1-yl)-6-chloropyrimidine. 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.10 (d, J=0.8, 1H), 7.70 (dd, J=8.0, 1.5, 1H), 7.43 (m, 1H), 7.30-7.18 (m, 2H), 5.84 (d, J=0.8, 1H), 4.06-3.97 (m, 4H), 2.41-2.30 (m, 2H).

Intermediate HT

The title compound was prepared in a manner similar to that described for Intermediate HI using 2-bromo-5-(trifluoromethyl)phenol. 1 H NMR (500 MHz, CDCl 3 ) δ 8.62-8.49 (d, J=4.8, 2H), 7.82-7.75 (dd, J=8.4, 0.9, 1H), 7.54-7.51 (d, J=2.0, 1H), 7.44-7.40 (m, 1H), 7.13-7.08 (m, 1H).

Intermediate HU

To a sealable 4 mL vial, containing 6-(chloromethyl)picolinonitrile (100 mg, 0.66 mmol) and 2-bromophenol (113 mg, 0.66 mmol), were added Cs 2 CO 3 (320 mg, 0.98 mmol) and acetonitrile (1.7 mL). The vial was then heated at 80° Celsius for 15 hours. The reaction was then diluted with ethyl acetate, filtered through a celite plug and concentrated to dryness. The material was used without further purification. 1 H NMR (500 MHz, CDCl 3 ) δ 8.02-7.93 (m, 1H), 7.93-7.85 (m, 1H), 7.65-7.59 (dd, J=7.7, 1.1, 1H), 7.58-7.53 (dd, J=7.9, 1.6, 1H), 7.29-7.22 (m, 1H), 6.93-6.90 (dd, J=8.3, 1.3, 1H), 6.90-6.86 (m, 1H), 5.23 (s, 2H).

Intermediate HV

The title compound was prepared in a manner similar to that described for Intermediate HI using 2-(chloromethyl)nicotinonitrile. 1 H NMR (500 MHz, CDCl 3 ) δ 8.83-8.74 (dd, J=4.9, 1.7, 1H), 8.02-7.97 (dd, J=7.9, 1.7, 1H), 7.57-7.49 (dd, J=7.9, 1.6, 1H), 7.42-7.35 (dd, J=7.9, 4.9, 1H), 7.27-7.20 (m, 1H), 7.08-7.01 (dd. J=8.2, 1.3, 1H), 6.91-6.83 (m, 1H), 5.37 (s, 2H).

›Example 526

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)pyrimidine. MS (ESI): mass calcd. for C 20 H 14 FN 5 O, 359.12; m/z found, 360.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.56 (d, J=4.8, 2H), 8.35-8.30 (m, 1H), 7.99 (d, J=1.5, 1H), 7.82 (m, 1H), 7.58 (dd, J=7.6, 1.7, 1H), 7.52-7.46 (m, 1H), 7.42-7.28 (m, 4H), 7.17 (t, J=4.8, 1H), 6.70 (s, 2H).

›Example 527

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)pyrimidine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 20 H 14 FN 5 O, 359.12; m/z found, 360.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.58 (d, J=4.8, 2H), 8.43 (d, J=1.4, 2H), 7.58-7.46 (m, 3H), 7.42-7.27 (m, 4H), 7.20 (t, J=4.8, 1H), 6.88 (s, 2H).

›Example 528

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)pyrimidin-4-amine. MS (ESI): mass calcd. for C 20 H 15 FN 6 O, 374.13; m/z found, 375.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.35-8.28 (dd, J=2.1, 1.5, 1H), 8.08-8.00 (d, J=1.5, 1H), 7.84-7.77 (m, 1H), 7.77-7.71 (d, J=5.9, 1H), 7.52-7.47 (dd, J=7.6, 1.7, 1H), 7.46-7.40 (m, 1H), 7.38-7.32 (m, 2H), 7.32-7.27 (dd, J=12.6, 1.7, 1H), 7.23-7.16 (dd, J=8.1, 1.2, 1H), 6.11-6.09 (d, J=5.9, 1H).

›Example 529

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)pyrimidin-4-amine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 20 H 15 FN 6 O, 374.13; m/z found, 375.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.49-8.43 (d, J=1.4, 2H), 7.79-7.72 (d, J=5.9, 1H), 7.51-7.47 (dd, J=7.6, 1.7, 1H), 7.47-7.41 (m, 2H), 7.39-7.28 (m, 3H), 7.22-7.17 (dd, J=8.1, 1.2, 1H), 6.16-6.05 (d, J=5.9, 1H).

›Example 530

The title compound was prepared in a manner similar to that described in Example 88 using 6-((2-bromophenoxy)methyl)picolinonitrile. MS (ESI): mass calcd. for C 23 H 16 FN 5 O, 397.13; m/z found, 398.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.38-8.29 (d, J=1.5, 1H), 8.24 (s, 1H), 8.01-7.90 (m, 2H), 7.83-7.73 (m, 1H), 7.72-7.64 (dd, J=8.2, 1.0, 1H), 7.52-7.48 (dd, J=8.1, 1.6, 1H), 7.48-7.44 (m, 1H), 7.44-7.40 (dd, J=7.6, 1.7, 1H), 7.40-7.34 (m, 1H), 7.19-7.15 (dd. J=8.3, 1.1, 1H), 7.14-7.07 (m, 1H), 5.26 (s, 2H).

›Example 531

The title compound was prepared in a manner similar to that described in Example 88 using 2-((2-bromophenoxy)methyl)nicotinonitrile. MS (ESI): mass calcd. for C 23 H 16 FN 5 O, 397.13; m/z found, 398.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.80-8.73 (dd, J=5.0, 1.7, 1H), 8.32-8.27 (m, 1H), 8.24-8.22 (d, J=1.4, 1H), 8.22-8.15 (dd, J=7.9, 1.7, 1H), 7.89-7.82 (m, 1H), 7.57-7.49 (dd, J=7.9, 5.0, 1H), 7.45 (s, 1H), 7.44-7.42 (dd, J=4.4, 1.6, 1H), 7.41-7.35 (m, 2H), 7.26-7.22 (dd, J=8.2, 1.0, 1H), 7.14-7.09 (m, 1H), 5.34 (s, 2H).

›Example 532

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)nicotinonitrile. MS (ESI): mass calcd. for C 22 H 14 FN 5 O, 383.12; m/z found, 384.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.28-8.25 (m, 1H), 8.22-8.18 (d, J=1.4, 1H), 8.17-8.13 (dd. J=5.0, 1.9, 1H), 8.10-8.04 (dd, J=7.6, 1.9, 1H), 7.89-7.82 (m, 1H), 7.57-7.53 (dd, J=7.6, 1.7, 1H), 7.53-7.47 (m, 1H), 7.45-7.41 (m, 1H), 7.41-7.37 (dd, J=8.1, 1.7, 1H), 7.34-7.28 (m, 2H), 7.12-7.04 (dd, J=7.6, 5.0, 1H).

›Example 533

The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)pyrimidin-2-amine. MS (ESI): mass calcd. for C 20 H 15 FN 6 O, 374.13; m/z found, 375.2 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.35-8.29 (m, 1H), 8.12-8.07 (d, J=1.5, 1H), 8.05-8.00 (d, J=7.0, 1H), 7.92-7.85 (m, 1H), 7.59-7.55 (dd, J=7.5, 1.8, 1H), 7.55-7.49 (m, 1H), 7.49-7.43 (m, 1H), 7.36-7.33 (dd, J=8.1, 1.7, 1H), 7.33-7.31 (dd, J=8.0, 1.3, 1H), 7.31-7.27 (dd, J=12.5, 1.7, 1H), 6.72-6.42 (d, J=7.0, 1H).

›Example 534

The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)pyrimidin-2-amine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 20 H 15 FN 6 O, 374.13; m/z found, 375.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.46 (s, 2H), 7.98-7.94 (d, J=5.8, 1H), 7.53-7.49 (d, J=7.6, 1H), 7.49-7.42 (m, 2H), 7.41-7.36 (m, 1H), 7.36-7.32 (d, J=8.2, 1H), 7.32-7.27 (m, 1H), 7.26-7.14 (d, J=8.0, 1H), 6.13-6.04 (d, J=5.8, 1H).

›Example 535

The title compound was prepared in a manner similar to that described in Example 88 using 6-(2-bromophenoxy)pyrimidin-4-amine. MS (ESI): mass calcd. for C 20 H 15 FN 6 O, 374.13; m/z found, 375.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.24 (s, 1H), 7.97 (d, J=1.4, 1H), 7.90 (s, 1H), 7.74 (m, 1H), 7.50 (dd, J=7.6, 1.7, 1H), 7.42 (m, 1H), 7.36-7.29 (m, 2H), 7.28-7.22 (m, 1H), 7.13 (d, J=8.1, 1H), 6.65 (s, 2H), 6.52 (s, 2H), 5.67 (s, 1H).

›Example 536

The title compound was prepared in a manner similar to that described in Example 88 using 6-(2-bromophenoxy)pyrimidin-4-amine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 20 H 15 FN 6 O, 374.13; m/z found, 375.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.38 (s, 2H), 7.92 (s, 1H), 7.47 (m, 2H), 7.40 (d, J=6.4, 1H), 7.36-7.23 (m, 3H), 7.11 (d, J=7.7, 1H), 6.68 (br, 4H), 5.68 (s, 1H).

›Example 537

The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)picolinonitrile. MS (ESI): mass calcd. for C 22 H 14 FN 5 O, 383.12; m/z found, 384.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.47 (d, J=5.1, 1H), 8.29 (s, 1H), 7.96 (s, 1H), 7.81 (s, 1H), 7.66-7.56 (m, 2H), 7.48 (dd, J=20.1, 7.3, 2H), 7.39-7.20 (m, 3H), 7.07 (s, 1H), 6.68 (s, 2H).

›Example 538

The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)picolinonitrile and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 22 H 14 FN 5 O, 383.12; m/z found, 384.0 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.50 (d, J=5.7, 1H), 8.40 (d, J=1.3, 2H), 7.61 (dd, J=7.9, 2.0, 2H), 7.53 (dd, J=11.1, 5.0, 2H), 7.48-7.42 (m, 1H), 7.36 (dd, J=12.1, 1.5, 1H), 7.31 (dd, J=11.5, 5.0, 2H), 7.11 (dd, J=5.7, 2.5, 1H), 6.86 (s, 2H).

›Example 539

The title compound was prepared in a manner similar to that described in Example 88 using 4-(azetidin-1-yl)-6-(2-bromophenoxy)pyrimidine. MS (ESI): mass calcd. for C 23 H 19 FN 6 O, 414.16; m/z found, 415.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.39-8.31 (m, 1H), 8.08 (d, J=0.9, 1H), 8.02 (d, J=1.5, 1H), 7.85 (m, 1H), 7.55 (dd, J=7.6, 1.7, 1H), 7.51-7.42 (m, 1H), 7.40-7.29 (m, 3H), 7.18 (dd, J=8.0, 1.2, 1H), 6.71 (s, 2H), 5.71 (d, J=0.9, 1H), 3.96 (t, J=7.5, 4H), 2.39-2.24 (m, 2H).

›Example 540

The title compound was prepared in a manner similar to that described in Example 88 using 4-(azetidin-1-yl)-6-(2-bromophenoxy)pyrimidine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 23 H 19 FN 6 O, 414.16; m/z found, 415.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.46 (d, J=1.5, 2H), 8.11 (d, J=0.9, 1H), 7.60-7.52 (m, 2H), 7.50-7.41 (m, 1H), 7.41-7.31 (m, 3H), 7.17 (dd, J=8.1, 1.2, 1H), 6.89 (s, 2H), 5.73 (d, J=0.9, 1H), 3.98 (t, J=7.5, 4H), 2.41-2.27 (m, 2H).

›Example 541

The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)-2-methylpyrimidine. MS (ESI): mass calcd. for C 21 H 16 FN 5 O, 373.13; m/z found, 374.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.53 (s, 1H), 8.35 (d, J=5.8, 1H), 8.08 (d, J=1.3, 1H), 7.87 (m, 1H), 7.51 (dd, J=7.5, 1.9, 1H), 7.45 (m, 1H), 7.38 (dd, J=7.8, 6.9, 1H), 7.33 (dd, J=7.9, 1.6, 1H), 7.26 (m, 1H), 7.21 (d, J=8.1, 1H), 6.49 (d, J=5.8, 1H), 4.73 (s, 2H), 2.51 (s, 3H).

›Example 542

The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)-2-methylpyrimidine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 16 FN 5 O, 373.13; m/z found, 374.1 [M+H] + . 1 H NMR (500 MHz, CDCl 3 ) δ 8.50 (s, 2H), 8.38 (d, J=5.8, 1H), 7.53-7.28 (m, 6H), 7.21 (d, J=7.9, 1H), 6.51 (d, J=5.7, 1H), 5.30 (s, 2H), 2.52 (s, 3H).

›Example 543

The title compound was prepared in a manner similar to that described in Example 88 using 5-bromo-1H-benzo[d]imidazole and 2-((3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-yl)oxy)pyrimidine. MS (ESI): mass calcd. for C 23 H 15 FN 4 O, 382.12; m/z found, 383.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 9.31 (s, 1H), 8.52-8.45 (d, J=4.9, 2H), 7.95 (s, 1H), 7.92-7.87 (d, J=8.6, 1H), 7.79-7.70 (d, J=8.6, 1H), 7.59-7.55 (dd, J=7.7, 1.7, 1H), 7.55-7.47 (m, 2H), 7.45-7.39 (m, 2H), 7.38-7.32 (dd, J=12.0, 1.7, 1H), 7.30-7.23 (dd, J=8.1, 1.2, 1H), 7.13-7.08 (t, J=4.8, 1H).

›Example 544

The title compound was prepared in a manner similar to that described in Example 88 using 6-bromo-3H-imidazo[4,5-b]pyridine and 2-((3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-yl)oxy)pyrimidine. MS (ESI): mass calcd. for C 22 H 14 FN 5 O, 383.12; m/z found, 384.1 [M+H] + . 1 H NMR (500 MHz, CD 3 OD) δ 8.55-8.52 (m, 1H), 8.51-8.47 (d, J=4.9, 2H), 8.43 (s, 1H), 8.19-8.14 (t, J=1.7, 1H), 7.59-7.55 (dd, J=7.7, 1.8, 1H), 7.55-7.47 (m, 2H), 7.46-7.40 (m, 2H), 7.39-7.33 (dd, J=11.9, 1.7, 1H), 7.30-7.25 (dd, J=8.0, 1.2, 1H).

›Example 545

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)-4-methylpyrimidine. MS (ESI): mass calcd. for C 21 H 16 FN 5 O, 373.13; m/z found, 374.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.37 (d, J=5.1, 1H), 8.32 (d, J=1.6, 1H), 8.00 (d, J=1.6, 1H), 7.82 (m, 1H), 7.56 (dd, J=7.5, 1.7, 1H), 7.51-7.44 (m, 1H), 7.41-7.24 (m, 4H), 7.05 (d, J=5.1, 1H), 6.70 (s, 2H), 2.34 (s, 3H).

›Example 546

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)-4-methylpyrimidine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 16 FN 5 O, 373.13; m/z found, 374.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.44 (s, 2H), 8.39 (d. J=5.1, 1H), 7.57-7.44 (m, 3H), 7.41-7.31 (m, 3H), 7.25 (d, J=7.2, 1H), 7.07 (d, J=4.9, 1H), 6.89 (s, 2H), 2.35 (s, 3H).

›Example 547

The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)-2-(trifluoromethyl)pyrimidine. MS (ESI): mass calcd. for C 21 H 13 F 4 N 5 O, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.76 (d, J=5.8, 1H), 8.29-8.24 (m, 1H), 7.95 (d, J=1.5, 1H), 7.78 (m, 1H), 7.58 (dd, J=7.5, 1.8, 1H), 7.54-7.48 (m, 1H), 7.45 (m, 1H), 7.39 (dd, J=8.0, 1.3, 1H), 7.27 (m, 3H), 6.66 (s, 2H).

›Example 548

The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)-2-(trifluoromethyl)pyrimidine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 13 F 4 N 5 O, 427.11; m/z found, 428.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.78 (d, J=5.7, 1H), 8.37 (m, 2H), 7.57 (dd, J=7.5, 1.8, 1H), 7.48 (m, 3H), 7.39 (dd, J=8.0, 1.3, 1H), 7.33-7.22 (m, 3H), 6.85 (s, 2H).

›Example 549

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)-5-methoxypyrimidine. MS (ESI): mass calcd. for C 21 H 16 FN 5 O 2 , 389.13; m/z found, 390.1 [M+H] + . 1 H NMR (500 MHz, DMSO-d 6 ) δ 8.45 (s, 1H), 8.35 (s, 1H), 7.55 (m, 2H), 7.46 (m, 1H), 7.42-7.32 (m, 3H), 7.22 (d, J=8.0, 1H), 6.89 (s, 2H), 3.83 (s, 3H).

›Example 550

The title compound was prepared in a manner similar to that described in Example 88 using 2-(2-bromophenoxy)-5-methoxypyrimidine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C 21 H 16 FN 5 O 2 , 389.13;

›Tables in the description — 4

TABLE 3 — COM- POUND

STRUCTURE	#	NAME
1	5-(3-fluoro-2′-(methylsulfonyl)-[1,1′- biphenyl]-4-yl)pyrazin-2-amine
2	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]methanesulfonamide
3	6-Amino-3-[3.-fluoro-2′- (methylsulfonyl)biphenyl-4- yl]pyrazine-2-carbonitrile
4	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl- 3′-fluorobiphenyl-2-sulfonamide
5	4′-(5-aminopyrazin-2-yl)-3′-fluoro- [1.1′-biphenyl]-2-sulfonamide
6	4′-(5-Aminopyrazin-2-yl)-N- cyclohexyl-3′-fluorobiphenyl-2- sulfonamide
7	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (2-methylpropyl)biphenyl-2- sulfonamide
8	(racemic)-4′-(5-Aminopyrazin-2-yl)-3′- fluoro-N-(2,2,2-trifluoro-1- methylethyl)biphenyl-2-sulfonamide racemic
9	4′-(5-Aminopyrazin-2-yl)-N- (cyclobutylmethyl)-3′-fluorobiphenyl- 2-sulfonamide
10	(racemic)-(endo)-4′-(5- Aminopyrazin-2-yl)-N- bicyclo[2.2.1]hept-2-yl-3′- fluorobiphenyl-2-sulfonamide racemic
11	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (1-methylcyclobutyl)biphenyl-2- sulfonamide
12	4′-(5-Aminopyrazin-2-yl)-N-(1,1- dimethylpropyl)-3′-fluorobiphenyl-2- sulfonamide
13	4′-(5-4minopyrazin-2-yl)-3′-fluoro-N- (2,2,2-trifluoro-1,1- dimethylethyl)biphenyl-2-sulfonamide
14	4′-(5-Aminopyrazin-2-yl)-N- cyclopentyl-3′-fluorobiphenyl-2- sulfonamide
15	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- methylbiphenyl-2-sulfonamide
16	4′-(5-Aminopyrazin-2-yl)-N-ethyl-3′- fluorobiphenyl-2-sulfonamide
17	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (2-phenylethyl)biphenyl-2- sulfonamide
18	(R)-4′-5-Aminopyrazin-2-yl)-3′- fluoro-N-[(1R)-2,2,2-trifluoro-1- phenylethyl]biphenyl-2-sulfonamide
19	(S)-4′-(5-Aminopyrazin-2-yl)-3′-fluoro- N-[(1S)-2,2,2-trifluoro-1- phenylethyliblphenyl-2-sulfonamide
20	(S)-4′-(5-Aminopyrazin-2-yl)-3′-fluoro- N-[(S)-2,2,2-trifluoro-1- methylethyl]biphenyl-2-sulfonamide
21	4′-(5-Aminopyrazin-2-yl)-N-(2,3- dihydro-1H-inden-2-yl)-3′- fluorobiphenyl-2-sulfonamide
22	(S)-4′-(5-Aminopyrazin-2-yl)-N-[(1S)- 2,3-dihydro-1H-inden-1-yl]-3′- fluorobiphenyl-2-sulfonamide
23	(R)-4′-(5-Aminopyrazin-2-yl\|)-N-[(1R)- 2,3-dihydro-1H-inden-1-yl]-3′- fluorobiphenyl-2-sulfonamide
24	(R)-4′-(5-Aminopyrazin-2-yl)-3′- fluoro-N-[(1R)-1- phenylethyl]biphenyl-2-sulfonamide
25	(R)-4′-(5-Aminopyrazin-2-yl)-3′- fluoro-N-[(1R)-2-hydroxy-1- methylethyl]piphenyl-2-sulfonamicie
26	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- phenylbiphenyl-2-sulfonamide
27	(S)-4′-(5-Aminopyrazin-2-yl)-N-[((3S)- 1-ethyl-2-oxoazepan-a-y]-3′- fluorobiphenyl-2-sulfonamide
28	(S)-4′-(5-Aminopyrazin-2-yl)-3′-fluoro- N-[(3S)-2-oxoazepan-3-yl]biphenyl-2- sulfonamide
29	(S)-4′-(5-Aminopyrazin-2-yl)-3′-fluoro- N-[(3S)-1-methyl-2-oxoazepan-3- yl]biphenyl-2-sulfonamide
30	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (1,2,2,6,6-pentamethylpiperidin-4- yl)biphenyl-2-sulfonamide
31	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- pyridin-3-ylbiphenyl-2-sulfonamide
32	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1S)-2-hydroxy-1- methylethyl]piphenyl-2-sulfonamide
33	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfamide
34	N-(4′-(5-aminopyrazin-2-yl)-3′-fluoro- [1,1′-biphenyl]-2-yl)propane-2- sulfonamide
35	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]ethanesulfonamide
36	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]propane-1- sulfonamide
37	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-2- methylpropane-1-sulfonamide
38	N-(4′-(5-aminopyrazin-2-yl)-3′-fluoro- [1,1′-biphenyl]-2- yl)cyclopropanesulfonamide
39	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]hexane-1- sulfonamide
40	N-(4′-(5-aminopyrazin-2-yl)-3′-fluoro- [1,1′-biphenyl]-2- yl)cyclobutanesulfonamide
41	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-1,1,1- trifluoromethanesulfonamide
42	4′-(5-Aminopyrazin-2-yl)-3′-fluoro- N,N-dimethylbiphenyl-2-sulfonamide
43	5-[3-fluoro-2′-(piperidin-1- ylsulfonyl)biphenyl-4-yl]pyrazin-2- amine
44	5-[3-Fluoro-2′-(morpholin-4- ylsulfonyl)biphenyl-4-yl]pyrazin-2- amine
45	5-{2′-[(1,1-Dioxidothiomorpholin-4- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
46	5-[3-Fluoro-2′-(piperazin-1- ylsulfonyl)biphenyl-4-yl]pyrazin-2- amine
47	4′-(5-Aminopyrazin-2-yl)-N,N-diethyl- 3′-fluorobiphenyl-2-sulfonamide
48	5-[3-Fluoro-2′-(pyrrolidin-1- ylsulfonyl)biphenyl-4-yl]pyrazin-2- amine
49	5-{2′-[(4,4-Difluoropiperidin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
50	5-{2′-[(3,3-Difluoropiperidin-1- yl)sulfonyl)-3-fluorobiphenyl-4- yl}pyrazin-2-amine
51	5-{2′-[(3,3-Difluoropyrrolidin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
52	5-{2′-[(3,3-Difluoroazetidin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
53	5-[2′-(Azepan-1-ylsulfonyl)-3- fluorobiphenyl-4-yl]pyrazin-2-amine
54	5-{3-Fluoro-2′-[(4-methylpiperazin-1- yl)sulfonyl]biphenyl4-yl}pyrazin-2- amine
55	1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}-4- (trifluoromethyl)piperidin-4-ol
56	5-(3-Fluoro-2′-{[4- (methylsulfonyl)piperazin-1- yl]sulfonyl}biphenyl-4-yl)pyrazin-2- amine
57	5-{2′-[(4-Acetylpiperazin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
58	5-(2′-{[4- (Cyclopropylcarbonyl)piperazin-1- yl]sulfonyl}-3-fluoroblphenyl-4- yl)pyrazin-2-amine
59	2-(4-{[4′-[5-Aminopymzin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}piperazin- 1-yl)ethanol
60	5-{2′-[(4-Cyclopropylpiperazin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
61	racemic 5-[3-Fluoro-2′- (hexahydropyrrolo[1,2-a]pyrazin- 2(1H)-ylsulfonyl)biphenyl-4- yl]pyrazin-2-amine
62	5-{2′-[(3,5-Dimethylpiperazin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
63	racemic 1-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}piperidine-3-carbonitrile
64	1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]sulfonyl}piperidine-4-carbonitrile
65	5-{2′-[(4-Aminopiperidin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
66	4-{1,4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-ylisulfonyl}piperazin- 2-one
67	1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}piperidin- 4-ol
68	(1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}piperidin- 4-yl)methanol
69	2-(1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}piperidin- 4-yl)ethanol
70	racemic 1-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}piperidin-3-ol
71	racemic 2-(1-{[4′-(5-Aminopyrazin-2- yl)-3′-fluorobiphenyl-2- yl]sulfonyl}piperidin-3-yl)ethanol
72	5-{3-Fluoro-2′-{[4- (methylamino)piperidin-1- yl]sulfonyl}biphenyl-4-yl)pyrazin.-2- amine
73	5-(2′-{[4-(Dimethylamino)piperidin-1- yl]sulfonyl}-3-fluorobiphenyl-4- yl)pyrazin-2-amine
74	racemic 5-{2′-[(3-Aminopiperidin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
75	N-(1-{[4′-(5-Aminopyrazin-2′yl)-3′- fluorobiphenyl-2-yl]sulfonyl}piperidin- 4-yl)acetamide
76	racemic (1-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}piperldin-3-yl)methanol
77	racemic tert-Butyl (1-{[4′-(5- aminopyrazin-2-yl)-3′-fluorobiphenyl- 2-yl]sulfonyl}piperidin-3-yl)carbamate
78	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1S,2S)-2-hydroxy-1- (hydroxymethyl)-2- phenylethyl]biphenyl-2-sulfonamide
79	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1S)-1-(hydroxymethyl)-3- methylbutyl]biphenyl-2-sulfonamide
80	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (3-hydroxypropyl)biphenyl-2- sulfonamide
81	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1S)-2-hydroxy-1- phenylethyl]biphenyl-2-sulfonamide
82	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1R)-2-hydroxy-1- phenylethyl]biphenyl-2-sulfonamide
83	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1S,2R)-2-hydroxy-1-methyl-2- phenylethyl]biphenyl-2-sulfonamide
84	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1S,2S)-1-(hydroxymethyl)-2- methylbutyl]blphenyl-2-sulfonamide
85	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1R,2R)-2- hydroxycyclohexyl]biphenyl-2- sulfonamide
86	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1R)-1- (hydroxymethyl)propyl]biphenyl-2- sulfonamide
87	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1R,2S)-2- hydroxycyclohexyl]biphenyl-2- sulfonamide
88	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (2-hydroxyethyl)biphenyl-2- sulfonamide
89	4′-(5-Aminopyrazin-2-yl)-N- cyclopropyl-3′-fluoroblphenyl-2- sulfonamide
90	4′-(5-Aminopyrazin-2-yl)-N- (cyclopropylmethyl)-3′-fluorobiphenyl- 2-sulfonamide
91	(R)-(1-((4′-(5-aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)pyrrolidin-2-yl)methanol
92	(R)-5-(2′-((3-aminopyrrolidin-1- yl)sulfonyl)-3-fluoro-[1,1′-biphenyl]-4- yl)pyrazin-2-amine
93	(S)-5-(2′-((3-aminopyrrolidin-1- yl)sulfonyl)-3-fluoro-[1,1′-biphenyl]-4- yl)pyrazin-2-amine
94	(R) 5-(2′-{[2-(Aminomethyl)pyrrolidin- 1-yl]sulfonyl}-3-fluorobiphenyl-4- yl)pyrazin-2-amine
95	(S)-(1-((4′-(5-aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2′- yl)sulfonyl)pyrrolidin-2-yl)methanol
96	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (methylsulfonyl)biphenyl-2- sulfonamide
97	(R)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(2-hydroxypropyl)-[1,1′-biphenyl]-2- sulfonamide
98	(S)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(2-hydroxypropyl)-[1,1′-biphenyl]-2- sulfonamide
99	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1- hydroxycyclohexyl)methyl]biphenyl- 2-sulfonamide
100	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (2-hydroxy-1,1- dimethylethyl)biphenyl-2-sulfonamide
101	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (2-hydroxy-2-methylpropyl)biphenyl- 2-sulfonamide
102	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (3-hydroxy-1,1- dimethylpropyl)biphenyl-2- sulfonamide
103	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (3-hydroxy-2,2- dimethylpropyl)biphenyl-2- sulfonamide
104	(S)-4′-(5-aminopyrazin-2-yl)-N-(2,3- dihydroxypropyl)-3′-fluoro-[1,1′- biphenyl]-2-sulfonamide
105	(R)-4′-(5-aminopyrazin-2-yl\|)-N-(2,3- dihydroxypropyl)-3′-fluoro-[1,1′- biphenyl]-2-sulfonamide
106	(trans)-1-{[4′-(5-Aminopyrazin-2-yl\|)- 3′-fluorobiphenyl-2- yl]suifonyl}pyrrolidine-3,4-diol
107	(S)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(2-oxopyrrolidin-3-yl)-[1,1′- biphenyl]-2-sulfonamide
108	(S)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(2-oxopiperidin-3-yl)-[1,1′- biphenyl]-2-sulfonamide
109	(R)-4′-(5-Aminopyrazin-2-yl)-3′- fluoro-N-[1-(hydroxymethyl)-2′- methylpropypiphenyl-2-sulfonamide
110	trans 4′-(5-Aminopyrazin-2-yl)-3′- fluoro-N-(4- hydroxycyclohexyl)biphenyl-2- sulfonamide
111	(R)-(1-((4′-(5-aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)pyrrolidin-3-yl)methanol
112	(S)-(1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}pyrrolidin- 3-yl)methanol
113	(R)-4′-(5-Aminopyrazin-2-yl)-3′- fluoro-N-(2-oxopipendin-3- yl)biphenyl-2-sulfonamide
114	(R)-4′-(5-Aminopyrazin-2-yl)-3′- fluoro-N-methyl-N-piperidin-3- ylbiphenyl-2-sulfonamide
115	(S)-4′-(5-Aminopyrazin-2-yl)-3′-fluoro- N-methyl-N-piperidin-3-ylbiphenyl-2′- sulfonamide
116	(3),4-(5-aminopyrazin-2-yl)-3′-fluoro- N-(1-hydroxy-3-phenylpropan-2-yl)- [1,1′-biphenyl]-2-sulfonamide
117	(R)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(2-hydroxy-2-phenylethyl)-[1,1′- biphenyl]-2-sulfonamide
118	4′-(5-aminopyrazin-2-yl)-3′-fluoro-N- ((1S,2S)-1-hydroxy-1-phenylpropan- 2-yl)-N-methyl-[1,1′-biphenyl)-2- sulfonamide
119	1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}azetidin- 3-ol
120	racemic (trans)-4′-(5-Aminopyrazin-2- yl)-3′-fluoro-N-(2- hydroxycyclohexyl)biphenyl-2- sulfonamide
121	racemic (trans)-4′-(5-Aminopyrazin-2- yl)-3′-fluoro-N-[2- (hydroxymethyl)cyclohexyl]biphenyl- 2-sulfonamide
122	racemic (cis)-4′-(5-Aminopyrazin-2- yl)-3′-fluoro-N-[2- (hydroxymethyl)cyclohexyl]biphenyl- 2-sulfonamide
123	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- piperidin-4-ylbiphenyl-2-sulfonamide
124	5-(2′-{[3-(Aminomethyl)azetidin-1- yl]sulfonyl}-fluorobiphenyl-4- yl)pyrazin-2-amine
125	4′-(5-Aminopyrazin-2-yl)-N-(azetidin- 3-ylmethyl)-3′-fluorobiphenyl-2- sulfonamide
126	(R)-5-(3-Fluoro-2′-{[3- (methylamino)pyrrolidin-1- yl]sulfonyl}biphenyl-4-yl)pyrazin-2- amine
127	(R)-4′-(5-Aminopyrazin-2-yl)-3′- fluoro-N-(2,2,2-trifluoro-1- methylethyl)biphenyl-2-sulfonamide
128	5-[3-Fluoro-2′-(1,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5- ylsulfonyl)biphenyl-4-yl]pyrazin-2- amine
129	4-(1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}piperidin- 4-yl)-2,4-dihydro-3H-1,2,4-triazol-3- one
130	5-(2′-((1R,4R)-2,5- diazabicyclo[2.2.1]heptan-2- ylsulfonyl)-3-fluoro-[1,1′-biphenyl]-4- yl)pyrazin-2-amine
131	5-(2′-((1S,4S)-2,5- diazabicyclo[2.2.1]heptan-2- ylsulfonyl)-3-fluoro-[1,1′-biphenyl]-4- yl)pyrazin-2-amine
132	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (5-hydroxypentyl)biphenyl-2- sulfonamide
133	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (6-hydroxyhexyl)biphenyl-2′- sulfonamide
134	N-(4-Aminocyclohexyl)-4′-(5- aminopyrazin-2-yl)-3′-fluorobiphenyl- 2-sulfonamide
135	(S)-(1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}-2,3- dihydro-1H-indol-2-yl)methanol
136	4′-(5-Aminopyrazin-2-yl)-N- cyclohexyl-3′-fluoro-N-(2- hydroxyethyl)biphenyl-2-sulfonamide
137	(S)-5-{2′-[(3-Aminopiperidin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
138	4′-(5-Aminopyrazin-2-yl)-3′-fluoro- N,N-bis(2-hydroxyethyl)biphenyl-2- sulfonamide
139	1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl)sulfonyl}azetidine- 2-carboxamide
140	4′-(5-Aminopyrazin-2-yl)-N- cyclopropyl-3′-fluoro-N-(tetrahydro- 2H-pyran-4-yl)biphenyl-2- sulfonamide
141	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (2-hydroxyethyl)-N-(1- methylethyl)biphenyl-2-sulfonamide
142	racemic (4-{[4′-(5.-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}morpholin-2-yl)methanol
143	(1R,5S)-3-((4′-(5-aminopyrazin-2-yl)- 3′-fluoro-[1,1′-biphenyl]-2-yl)sulfonyl)- 3-azabicyclo[3.1.0]hexan-6-amine
144	(S)-5-(3-fluoro-2′-((2-methylpiperazin- 1-yl)sulfonyl)-[1,1′-biphenyl]-4- yl)pyrazin-2-amine
145	(R)-5-(3-fluoro-2′-((2- methylpiperazin-1-yl)sulfonyl)-[1,1′- biphenyl]-4-yl)pyrazin-2-amine
146	(R)-(1-((4′-(5-aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)piperazin-2-yl)methanol
147	4′-(5-Aminopyrazin-2-yl)-3′-fluora-N- [2-hydroxy-1-(hydroxymethyl)-1- methylethyl]piphenyl-2-sulfonamide
148	(S)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(1-hydroxy-3-methylbutan-2-yl)- [1,1′-biphenyl]-2-sulfonamide
149	(S)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(1-hydroxy-3,3-dimethylbutan-2- yl)-[1,1′-biphenyl]-2-sulfonamide
150	(R)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(1-hydroxy-3,3-dimethylbutan-2- yl)-[1,1′-biphenyl]-2-sulfonamide
151	tert-Butyl [2-({4′-(5-aminopyrazin-2- yl)-3′-fluorobiphenyl-2- yl]sulfonyl}amino)ethyl]carbamate
152	N-(2-Aminoethyl)-4′-(5-aminopyrazin- 2-yl)-3′-fluorobiphenyl-2-sulfonamide
153	(S)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(1-hydroxybutan-2-yl)-[1,1′- biphenyl]-2-suifonamide
154	(S)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(pyrrolidin-3-yl)-[1,1′-biphenyl]-2- sulfonamide
155	N-[2-({(4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]sulfonyl}amino)ethyl]acetamide
156	(S)-2-(4′-(5-aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2- ylsulfonamido)propanoic acid
157	4′-(5-Aminopyrazin-2-yl)-N-[2- (carbamoylamino)ethyl]-3′- fluorobiphenyl-2-sulfonamide
158	4′-(5-aminopyrazin-2-yl)-3′-fluoro-N- ((1S,2S-2-hydroxy-2,3-dihydro-1H- inden-1-yl)-[1,1′-biphenyl]-2- sulfonamide
159	4′-(5-aminopyrazin-2-yl)-3′-fluoro-N- ((1R,2R)-2-hydroxy-2,3-dihydro-1H- inden-1-yl)-[1,1′-biphenyl]-2- sulfonamide
160	4′-(5-aminopyrazin-2-yl)-3′-fluoro-N- ((1S,2R)-2-hydroxy-2,3-dihydro-1H- inden-1-yl)-[1,1′-biphenyl]-2- sulfonamide
161	4′-(5-aminopyrazin-2-yl)-3′-fluoro-N- ((1R,2S)-2-hydroxy-2,3-dihydro-1H- inden-1-yl)-[1,1′-biphenyl]-2- sulfonamide
162	4′-(5-aminopyrazin-2-yl)-3′-fluoro-N- ((1S,2S)-2-hydroxycyclohexyl)-[1,1′- biphenyl]-2-sulfonamide
163	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [6-(trifluoromethyl)pyridin-3- yl]biphenyl-2-sulfonamide
164	5-(3-Fluoro-2′-{[4-(1H-imidazol-4′- yl)piperidin-1-yl]sulfonyl}biphenyl-4- yl)pyrazin-2-amine
165	N-[(4-Amino-2-methylpyrimidin-5- yl)methyl]-4′-(5-aminopyrazin-2-yl)-3′- fluorobiphenyl-2-sulfonamide
166	4′-(5-Aminopyrazin-2-yl)-N-(2,6- dimethoxypyrimidin-4-yl)-3′- fluorobiphenyl-2-sulfonamide
167	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (5-methylpyrazin-2-yl)biphenyl-2- sulfonamide
168	(S)-2-(4′-(5-aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2- ylsulfonamido)-4-methylpentanamide
169	4′-(5-Aminopyrazin-2-yl)-N-(2- cyanoethyl)-3′-fluorobiphenyl-2- sulfanamide
170	(R)-4′-(5-aminopyrazin-2-yl)-N-(1- cyanopropan-2-yl)-3′-fluoro-[1,1′- biphenyl)-2-sulfonamide
171	(S)-4′-(5-aminopyrazin-2-yl)-N-(1- cyanopropan-2-yl)-3′-fluoro-[1,1′- biphenyl]-2-sulfonamide
172	4′-(5-Aminopyrazin-2-yl)-N-(2- cyanoethyl)-N-cyclopropyl-3′- fluorobiphenyl-2-suifonamide
173	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (3-methyloxetan-3-yl)biphenyl-2- sulfonamide
174	3-(4-{[4′-(5-Aminopyrazin-2-yl)-3′- fluoroblphenyl-2-yl]sulfonyl}piperazin- 1-yl)propanenitrile
175	(S)-4′-(5-aminopyrazin-2-yl)-3′-fluoro- N-(1-methoxypropan-2-yl)-[1,1′- biphenyl]-2-sulfonamide
176	5-{3-Fluoro-2′-[(4-pyrazin-2- ylpiperazin-1-yl)sulfonyl]biphenyl-4- yl}pyrazin-2-amine
177	5-{3-Fluoro-2′-(4-pyrimidin-2- ylpiperazin-1-yl)sulfonyl]biphenyl-4- yl}pyrazin-2-amine
178	5-(2′-Amino-3-fluorobiphenyl-4- yl)pyrazin-2-amine
179	4′-(5-Aminepyrazin-2-yl)-3′-fluoro-N- [1- hydroxymethyl)cyclopentyl]biphenyl- 2-sulfonamide
180	1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}-3- phenylpyrrolidin-3-ol
181	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]pyrroildine-1- sulfonamide
182	N′-[4′-(5-Aminopyrazin-2-yl)-3′- fluoroblphenyl-2-yl]-N,N- dimethylsulfamide
183	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]morpholine-4- sulfonamide
184	(3S)-1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}pyrrolidin- 3-ol
185	(3R)-1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluoroblphenyl-2-yl]sulfonyl}pyrrolidin- 3-ol
186	(3′S,4′S)-1′-{[4′-(5-Aminopyrazin-2- yl)-3′-fluorobiphenyl-2-yl]sulfonyl}- 1,3′-bipyrrolidin-4′-ol
187	(3S,4S)-1-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2-yl]sulfonyl}-4- morpholin-4-ylpyrrolidin-3-ol
188	(3S,4S)-1-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2-yl]sulfonyl}-4-(4- methylpiperazin-1-yl)pyrrolidin-3-ol
189	5-{3-Fluoro-2′-[(trifluoromethyl)- sulfanyl]biphenyl-4-yl}pyrazin-2- amine
190	5-[2′-(tert-Butylsulfanyl)-3- fluorobiphenyl-4-yl]pyrazin-2-amine
191	5-[2′-(Ethylsulfonyl)-3-fluorobiphenyl- 4-yl]pyrazin-2-amine
192	5-[3-Fluoro-2′- (propylsulfonyl)biphenyl-4-yl]pyrazin- 2-amine
193	5-{3-Fluoro-2′-[(2- methylpropyl)sulfonyyl]iphenyl-4- yl}pyrazin-2-amine
194	5-[2′-(tert-Butylsulfonyl)-3- fluorobiphenyl-4-yl]pyrazin-2-amine
195	5-[2′-(Cyclopentylsulfonyl)-3- fluorobiphenyl-4-yl]pyrazin-2-amine
196	5-[2′-(Cyclobutylsulfonyl)-3- fluorobiphenyl-4-yl]pyrazin-2-amine
197	5-[2′-(Cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]pyrazin-2-amine
198	5-[3-Fluoro-2′- (hexylsulfonyl)biphenyl-4-yl]pyrazin- 2-amine
199	5{3Fluoro-2′-[(1- methylethyl)sulfonyl]biphenyl-4- yl}pyrazin-2-amine
200	2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]sulfanyl}acetamide
201	2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfanyl}-N,N- diethylacetemide
202	5-{3-Fluoro-2′-[(2-morpholin-4-yl-2- oxoethyl)sulfanyl]biphenyl-4- yl}pyrazin-2-amine
203	(racemic) 5-({[4′-(5-Aminopyrazin-2- yl)-3′-fluorobiphenyl-2- yl]sulfanyl}methyly)-1,3-oxazolidin-2- one
204	N-(2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]sulfanyl}ethyl)benzamide
205	5-(3-Fluoro-2′-{[4- (methylsulfonyl)benzyl]sulfanyl}biphenyl- 4-yl)pyrazin-2-amine
206	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-4- (trifluoromethyl)biphenyl-2- sulfonamide
207	5-[3-Fluoro-2′-(methylsulfonyl)-4′- (trifluoromethyl)biphenyl-4-yl]pyrazin- 2-amine
208	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- methyl-4-(trifluoromethyl)biphenyl-2- sulfonamide
209	4-{[4′-(5-Aminopyrazin-2-yl)-3′-fluoro- 4-(trifluoromethyl)biphenyl-2- yl]sulfonyl}piperazin-2-one
210	4′-(5-aminopyrazin-2-yl)-3′-fluoro-N- (2-hydroxyethyl)-4- (trifluoromethyl)biphenyl-2- sulfonamide
211	4′-(5-Aminopyrazin-2-yl)-N-ethyl-3′- fluoro-4-(trifluoromethyl)biphenyl-2- sulfonamide
212	5-{3-Fluoro-2′-[(4-methylpiperazin-1- yl)sulfonyl]-4′- (trifluoromethyl)biphenyl-4-yl}pyrazin- 2-amine
213	5-[3-Fluoro-2′-(pyrimidin-2- ylsulfanyl)biphenyl-4-yl]pyrazin-2- amine hydrochloride
214	5-[3-Fluoro-2′-(pyrimidin-4- ylsulfanyl)biphenyl-4-yl]pyrimidin-2- amine formate salt
215	6-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfanyl}pyrimidin- 4-amine hydrochloride
216	2-{1,4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfanyl}pyrimidin- 4-amine hydrochloride
217	4-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfanyl}pyrimidin- 5-amine hydrochloride
218	5-[3-Fluoro-2′-(pyrazin-2- ylsulfanyl)biphenyl-4-yl]pyrazin-2′ amine hydrochloride
219	2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfanyl}pyrimidin- 5-amine hydrochloride
220	1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorotiphenyl-2-yl]-N- methylmethanesulfonamide formic acid salt
221	1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N-(2- hydroxyethyl)methanesulfonamide formic acid salt
222	1-({[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]methyl}sulfonyl)azetidin-3-ol formic acid salt
223	4-({[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]methyl}sulfonyl)piperazin-2-one formic acid salt
224	(S)-1-(4′-(5-Aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2-yl)-N-(1- hydroxypropan-2- yl)methanesulfonamide
225	(R)-1-(4′-(5-Aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2-yl)-N-(1- hydroxypropan-2- yl)methanesulfonamide hydrochloride
226	1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N-(trans-4- hydroxycyclohexyl)methanesulfon- amide
227	(S)-1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N-[(2S)-2- hydroxypropyl]methanesulfonamide hydrochloride
228	(R)-1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N-[(2S)-2- hydroxypropyl]methanesulfonamide
229	5-(2′-{[(4-Aminopiperidin.-1- yl)sulfonyl]methyl}-3-fluorobiphenyl- 4-yl)pyrazin-2-amine hydrochloride
230	1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]methanesulfonamide hydrochloride
231	1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N- ethylmethanesulfonamide formate salt
232	1-[1-({[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]methyl}sulfonyl)piperidin4-yl]urea hydrochloride
233	N-[1-({[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]methyl}sulfonyl)piperidin-4- yl]acetamide formate salt
234	5-{2′-[(Ethylsulfanyl)methyl-3- fluorobiphenyl-4-yl}pyrazin-2-amine formate salt
235	5-{3-Fluoro-2′- [(methylsulfanyl)methylibiphenyl-4- yl}pyrazin-2-amine hydrochloride
236	5-(3-Fluoro-2-{[(1- methylethyl)sulfanyl]methyl}biphenyl- 4-yl)pyrazin-2-amine hydrochloride
237	2-(((4′-(5-Aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)methyl)thio)pyrimidin-4-amine hydrochloride
238	6-(((4′-(5-aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)methyl)thio)pyrimidin-4-amine hydrochloride
239	5-(3-fluoro-2′-((pyridazin-3- ylthio)methyl)-[1,1′-biphenyl]-4- yl)pyrazin-2-amine hydrochloride
240	6-(((4′-(5-aminopyrazin-2-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)methyl)thio)pyridazin-3-amine hydrochloride
241	5-{2′-[(1,1-Dioxidotatrahydro-2H- thiopyran-4-yl)sulfonyl)-3- fluorobiphenyl-4-yl}pyrazin-2-amine
242	4-{[4′(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]sulfanyl}pyrimidin- 2-amine hydrochloride
243	5-(3-fluoro-2′-((pyrimidin-4- ylthio)methyl)-[1,1′-biphenyl]-4- yl)pyrazin-2-amine hydrochloride
244	5-[3-Fluoro-2′-({[2- (trimethylsilyl)ethoxy]methyl}sulfanyl) biphenyl-4-yl]pyrazin-2-amine
245	5-[3-Fluoro-2′-({[2- (trimethylsilyl)ethoxy]methyl}sulfonyl) biphenyl-4-yl]pyrazin-2-amine hydrochloridee
246	5-(3-Fluoro-2′-{[3- (methylsulfonyl)propyl]sulfonyl}bi- phenyl-4yl)pyrazin-2-amine hydrochloride
247	5-(3-Fluoro-2′-{[(2R)-2- methylpiperazn-1- yl)sulfonyl)biphenyl-4-yl)pyrimidin-2- amine
248	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1S)-1- (hydroxymethyl)propyl]biphenyl-2- sulfonamide
249	4′-(2-Aminopyrimidin-5-yl)-N-(2- cyanoethyl)-N-cyclopropyl-3′- fluorobiphenyl-2-sulfonamide
250	4′-(2-Aminopyrimidin-5-yl)-N-(2- cyanoethyl)-3′-fluorobiphenyl-2- sulfonamide
251	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-(3-hydroxy-2,2- dimethylpropyl)biphenyl-2- sulfonamide
252	racemic (4-{[4′-(2-Aminopyrimidin-5- yl)-3′-fluorobiphenyl-2- yl]sulfonyl}morpholin-2-yl)methanol
253	5-(3-Fluoro-2′-{[(2S)-2- methylpiperazin-1- yl)sulfonyl}biphenyl-4-yl)pyrimidin-2′- amine
254	5-[2′-(Cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]pyrimidin-2-amine
255	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[2-hydroxy-1-(hydroxymethyl)-1- methylethyl]biphenyl-2-sulfonamide
256	4′-(2-aminopyrimidin-5-yl)-3′-fluoro- N-methyl-N-[(3S)-piperidin-3- yl]biphenyl-2-sulfomamide
257	4′-(2-aminopyrimidin-5-yl)-3′-fluoro- N-methyl-N-[(3R)-piperidin-3- yl]biphenyl-2-suifonamide
258	[(2R)-1-{[4′-(2-Aminopyrimidin-5-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}piperazin-2-yl]methanol
259	racemic (cis) 4′-(2-Aminopyrimidin-5- yl)-3′-fluoro-N-[(cis)-2- hydroxycyclohexyl]biphenyl-2- sulfonamide
260	racemic (trans) 4′-(2-Aminopyrimidin- 5-yl)-3′-fluoro-N-[(trans)-2- hydroxycyclohexyl]biphenyl-2- sulfonamide
261	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-(2-hydroxyethyl)-N-(1- methylethyl)biphenyl-2-sulfonamide
262	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-(trans-4- hydroxycyclohexyl)biphenyl-2- sulfonamide
263	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(3S)-2-oxopyrrolidin-3-yl]biphenyl- 2-sulfonamide
264	5-{2′-[(1,1-Dioxidothiomorpholin-4- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine
265	1-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}azetidin- 3-ol trifluoroacetic acid salt
266	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(3R)-2-oxopiperidin-3-yl]biphenyl- 2-sulfonamide trifluoroacetic acid salt
267	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(3S)-2-oxopiperidin-3-yl]biphenyl- 2-sulfonamide trifluoroacetic acid salt
268	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1R)-2,2,2-trifluoro-1- methylethyl]biphenyl-2-sulfonamide trifluoroacetic acid salt
269	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N[(R)-1-(hydroxymethyl)-2,2- dimethylpropyl]biphenyl-2- sulfonamide trifluoroacetic acid salt
270	4′-2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1S)-1-(hydroxymethyl)-2,2- dimethylpropyl]biphenyl-2- sulfonamide trifiuoroacetic acid salt
271	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1S)-1-(hydroxymethyl)-2- methylpropyl]biphenyl-2-sulfonamide trifluoroacetic acid salt
272	4′-(2-Aminopyrimidin-5-y)-3′-fluoro- N-(2-hydroxy-2- methylpropyl)biphenyl-2-sulfonamide trifluoroacetic acid salt
273	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1R)-1-(hydroxymethyl)-2- methylpropyl]biphenyl-2-sulfonamide trifluoroacetic acid salt
274	4′-(2-Aminopyrimidin-5-yl)-N-[(2S)- 2,3-dihydroxypropyl]-3′- fluorobiphenyl-2-sulfonamide trifluoroacetic acid salt
275	4′-(2-.Aminopyrimidin-5-yl)-3′-fluoro- N-(2-hydroxyethyl)biphenyl-2′ sulfonamide trifluoroacetic acid salt
276	[(2R)-1-{[4′-(2-Aminopyrimidin-5-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}pyrrolidin-2-yl]methanol trifluoroacetic acid salt
277	[(2S)-1-{[4′-(2-Aminopyrimidin-5-yl)- 3′-fluorobiphenyl-2- ylisulfonyl}pyrrolidin-2-yl]methanol trifluoroacetic acid salt
278	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(2R)-2-hydroxypropyl]biphenyl-2- sulfonamide
279	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(2S)-2-hydroxypropyl]biphenyl-2- sulfonamide trifluoroacetic acid salt
280	4′-(2-.Aminopyrimidin-5-yl)-3′-fluoro- N-(2-hydroxy-1,1- dimethylethyl)biphenyl-2-sulfonamide trifluoroacetic acid salt
281	5-{2′-[(4-Cyclopropylpiperazin-1- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine trifluoroacetic acid salt
282	2-(4-{(4′-[2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}piperazin- 1-yl)ethanol trifluoroacetic acid salt
283	4′-(2-Aminopyrimidin-5-yl)-N- (cyclopropylmethyl)-3′-fluorobiphenyl- 2-sulfonamide trifiuoroacetic acid
284	4′-(2-Aminopyrimidin-5-yl)-N- cyclopropyl-3′-fluorobiphenyl-2- sulfonamide trifluoroacetic acid salt
285	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-phenylbiphenyl-2-sulfonamide trifluoroacetic acid salt
286	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1S)-2-hydroxy-1- methylethyl]biphenyl-2-sulfonamide trifluoroacetic acid salt
287	4′-(2-Aminopyrimidin-5-yl)-N-tert- butyl-3′-fluoro-3-methylbiphenyl-2- sulfonamide trifluoroacetic acid salt
288	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-methylbiphenyl-2-sulfonamide trifluoroacetic acid salt
289	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1R)-2-hydroxy-1- methylethyl]biphenyl-2-sulfonamide trifluoroacetic acid salt
290	5-[3-Fluoro-2′-(piperazin-1- ylsulfonyl)biphenyl-4-yl]pyrimidin-2- amine trifluoroacetic acid salt
291	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1R)-2,2,2-trifluoro-1- phanylethyl]biphenyl-2-sulfonamide trifluoroacetic acid salt
292	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1S)-2,2,2-trifluoro-1- phenylethyl]biphenyl-2-sulfonamide trifluoroacetic acid salt
293	5-[2′-(tert-Butylsulfonyl)-3- fluorobiphenyl-4-yl]pyrimidin-2-amine trifluoroacetic acid salt
294	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-(2-methylpropyl)biphenyl-2- sulfonamide trifiuoroacetic acid salt
295	4′-(2-Aminopyrimidin-5-yl)-N-ethyl-3′- fluorobiphenyl-2-sulfonamide trifluoroacetic acid salt
296	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-(2,2,2-trifluoro-1,1- dimethylethyl)biphenyl-2-sulfonamide trifluoroacetic acid salt
297	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1S)-2,2,2-trifluoro-1- methylethyl]biphenyl-2-sulfonamide trifluoroacetic acid salt
298	5-[3-Fluoro-2′-(pyrrolidin-1- ylsulfonyl)biphenyl-4-yl]pyrimidin-2- amine trifluoroacetic acid salt
299	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N,N-dimethylbiphenyl-2-sulfonamide trifluoroacetic acid salt
300	4′-(2-Aminopyrimidin-5-yl)-N,N- diethyl-3′-fluorobiphenyl-2- sulfonamide trifiuoroacetic acid salt
301	5-[3-Fluoro-2′-(piperidin-1- ylsulfonyl)biphenyl-4-yl]pyrimidin-2- amine trifluoroacetic acid salt
302	4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-sulfonamide trifluoroacetic acid salt
303	5-[3-Fluoro-2′-(morpholin-4- ylsulfonyl)biphenyl-4-yl]pyrimidin-2- amine trifluoroacetic acid salt
304	5-[3-Fluoro-2′- (methylsulfonyl)biphenyl-4- yl]pyrimidin-2-amine trifluoroacetic acid salt
305	4′-(2-aminopyrimidin-5-yl)-N-(tert- butyl)-3′-fluoro[1,1′-biphenyl]-2- sulfonamide trifluoroacetic acid salt
306	4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}piperazin- 2-one trifluoroacetic acid salt
307	tert-Butyl N-{[4′-(2-aminopyrimidin-5- yl)-3′-fluorobiphenyl-2-yl]sulfonyl}-L- alaninate
308	N-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}-L- alanine
309	N-[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]pyrrolidine-1- sulfonamide
310	N-[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]morpholine-4- sulfonamide
311	N′-[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]-N,N- dimethylsulfamide
312	5-(2′-(2-oxa-6-azaspiro[3.3]heptan-6- ylsulfonyl)-3-fluoro-[1,1′-biphenyl]-4- yl)pyrimidin-2-amine
313	6-((4′-(2-aminopyrimidin-5-yl)-3′- fluoro-[1,1′-biphenyl]-2-yl)sulfonyl)-2- thia-6-azaspiro[3.3]heptane 2,2- dioxide
314	1-((4′-(2-aminopyrimidin-5-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)azetidine-3-carbonitrile
315	1-((4-(2-aminopyrimidin-5-yl)-3′- fluoro-[1,1′-biphenyl]-2-yl)sulfonyl)-3- (trifluoromethyl)azetidin-3-ol
316	5-{2′-[(1,1-Dioxidotetrahydro-2H- thiopyran-4-yl)sulfonyl]-3- fluorobiphenyl-4-yl}pyrimidin.-2-amine hydrochloride
317	2-(((4′-(2-aminopyrimidin-5-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)methyl)quinazolin-4(3H)- one
318	1-(3-((4′-(2-aminopyrimidin-5-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)propyl)-1H- benzo[d]imidazol-2(3H)-one
319	5-(2′-{[3- (Cyclohexylsulfonyl)propyl]sulfonyl}- 3-fluorobiphenyl-4-yl)pyrimidin-2- amine
320	5-{3-Fluoro-2′-[(1-methyl-1H- benzimidazol-2-yl)sulfonyl]biphenyl- 4-yl}pyrimidin-2-amine
321	5-(2′-{[(3-Cyclopropyl-1,2,4- oxadiazol-5-yl)methyl]sulfonyl}-3- fluorobiphenyl-4-yl)pyrimidin-2-amine
322	4′-(2-aminopyrimidin-5-yl)-3′-fuoro-4- (trifluoromethyl)biphenyl-2- sulfonamide
323	5-[3-fluoro-2′-(methylsulfonyl)-4′- (trifluoromethyl)biphenyl-4- yl]pyrimidin-2-amine
324	4-{[4′-(2-aminopyrimidin-5-yl)-3′- fluoro-4-(trifluoromethyl)biphenyl-2- yl]sulfonyl}piperazin-2-one
325	4′-(2-aminopyrimidin-5-yl)-3′-fluoro- N-methyl-4-(trifluoromethyl)biphenyl- 2-sulfonamide
326	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-(2-hydroxyethyl)-4- (trifluoromethyl)biphenyl-2- sulfonamide
327	4′-(2-Aminopyrimidin-5-yl)-N-ethyl-3′- fluoro-4-(trifluoromethyl)biphenyl-2′- sulfonamide
328	5-{3-Fluoro-2′-[(4-methylpiperazin-1- yl)sulfonyl]-4′- (trifluoromethyl)biphenyl-4- yl}pyrimidin-2-amine
329	5-{2′-[(5-Aminopyrimidin-2- yl)sulfanyl)-3-fluorobiphenyl-4- yl)pyrimidin-2-amine formate salt
330	5-{2′-[(4-Aminopyrimidin-2- yl)sulfanyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine formate salt
331	5-{2′-[(5-Aminopyrimidin-4- yl)sulfanyl]-3-fluorobiphenyl-4- yl)pyrimidin-2-amine formate salt
332	5-[3-Fluoro-2′-(pyrimidin-2- ylsulfanyl)biphenyl-4-yl]pyrimidin-2- amine hydrochloride
333	5-[3-Fluoro-2′-(pyrazin-2- ylsulfanyl)biphenyl-4-yl]pyrimidin-2- amine hydrochloride
334	5-{2′-[(6-Aminopyrimidin-4- yl)sulfanyl)-3-fluorobiphenyl-4- yl}pyrimidin-2-amine formate salt
335	4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfanyl}pyrimidin- 2-amine formate salt
336	5-{2′-[(6-Aminopyrazin-2-yl)sulfanyl]- 3-fluorobiphenyl-4-yl}pyrimidin-2- amine formate salt
337	5-{2′-[(5-Aminopyrimidin-4- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine hydrochloride
338	5-[3-Fluoro-2′-({[2- trimethylsilyl)ethoxy]methyl}sulfonyl) biphenyl-4-yl]pyrimidin-2-amine formate salt
339	5-{2′-[(5-Aminopyrimidin-2- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine hydrochloride
340	5-[3-Fluoro-2′-({[2- (trimethylsilyl)ethoxy]methyl}sulfanyl) biphanyl-4-yl]pyrimidin-2-amine
341	5-(3-Fluoro-2′-(methylsulfonyl)-[1,1′- biphenyl]-4-yl)pyridin-2-amine
342	4′-(6-aminopyridin-3-yl)-N-((tert-butyl)- 3′-fluoro-[1,1′-biphenyl]-2- sulfonamide
343	4′-(6-aminopyridin-3-yl)-N,N-diethyl- 3′-fluoro-[1,1′-biphenyl]-2- sulfonamide
344	5-(3-fluoro-2′-(pyrrolidin-1-ylsulfonyl)- [1,1′-biphenyl]-4-yl)pyridin-2-amine
345	5-(3-fluoro-2′-(piperidin-1-ylsulfonyl)- [1,1′-biphenyl]-4-yl)pyridin-2-amine
346	4′-(6-aminopyridin-3-yl)-N-cyclohexyl- 3′-fluoro-[1,1′-biphenyl]-2- sulfonamide
347	(S)-4′-(6-aminopyridin-3-yl)-3′-fluoro- N-(1-hydroxypropan-2-yl)-[1,1′- biphenyl]-2-sulfonamide
348	4′-(6-aminopyridin-3-yl)-3′-fluoro-N- isobutyl-[1,1′-biphenyl]-2-sulfonamide
349	4′-(6-aminopyridin-3-yl)-3′-fluoro-N- (tert-pentyl)-[1,1′-biphenyl]-2- sulfonamide
350	4′-(6-aminopyridin-3-yl)-3′-fluoro-N- (1,1,1-trifluoro-2-methylpropan-2-yl)- [1,1′-biphenyl]-2-sulfonamide
351	(S)-4′-(6-aminopyridin-3-yl)-3′-fluoro- N-(2,2,2-trifluoro-1-phenylethyl)-[1,1′- biphenyl]-2-sulfonamide
352	(R)-4′-(6-aminopyridin-3-yl)-3-fluoro- N-(1-hydroxypropan-2-yl)-[1,1′- biphenyl]-2-sulfonamide
353	4′-(6-aminopyridin-3-yl)-3′-fluoro-N- (1-methylcyclobutyl)-[1,1′-biphenyl]- 2-sulfonamide
354	4-((4′-(6-aminopyridin-3-yl)-3′-fluoro- [1,1′-biphenyl]-2- yl)sulfonyl)thiomorpholine 1,1-dioxide
355	(S)-4′-(6-aminopyridin-3-yl)-3′-fluoro- N-(1,1,1-trifluoropropan-2-yl)-[1,1′- biphenyl]-2-sulfonamide
356	5-(2′-((1S,4S)-2-oxa-5- azabicyclo[2.2.1]heptan-5-ylsulfonyl)- 3-fluoro-[1,1′-biphenyl]-4-yl)pyridin-2- amine
357	tert-butyl 3-((4′-(6-aminopyridin-3-yl)- 3′-fluoro-[1,1′-biphenyl]-2- ylsulfonamido)methyl)-3- hydroxyazetidine-1-carboxylate
358	4′-(6-aminopyridin-3-yl)-3′-fluoro-N- ((3-hydroxyazetidin-3-yl)methyl)-[1,1′- biphenyl]-2-sulfonamide
359	2-(1-(4′-(6-aminopyridin-3-yl)-3′- fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)piperidin-4-yl)ethanol
360	1-((4′-(6-aminopyridin-3-yl)-3′-fluoro- [1,1′-biphenyl]-2-yl)sulfonyl)piperidin- 4-ol
361	(1-((4′-(6-aminopyridin-3-yl)-3′-fluoro- [1,1′-biphenyl]-2-yl)sulfonyl)piperidin- 4-yl)methanol
362	3′-Fluoro-N-[(1S)-2-hydroxy-1- methylethyl]-4′-(1H-pyrrolo[2,3- b]pyridin-5-yl)biphenyl-2-sulfonamide
363	3′-Fluoro-N-[(1R)-2-hydroxy-1- methylethyl]-4′-(1H-pyrrolo[2,3- b]pyridin-5-yl)biphenyl-2-sulfonamide
364	3′-Fluoro-N-[(3S)-2-oxopyrrolidin-3- yl]-4′-(1H-pyrrolo[2,3-b]pyridin-5- yl)biphenyl-2-sulfonamide
365	5-[2′-(Cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]-1H-pyrrolo[2,3- b]pyridine
366	3′-Fluoro-N-(2-hydroxyethyl)-4′-(1H- pyrrolo[2,3-b]pyridin-5-yl)biphenyl-2- sulfonamide
367	N-tert-Butyl-3′-fluoro-4′-(1H- pyrrolo[2,3-b]pyridin-5-yl)biphenyl-2- sulfonamide
368	3′-Fluoro-4′-(1H-pyrrolo[2,3-b]pyridin 5-yl)biphenyl-2-sulfonamide
369	N-[3′-Fluoro-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2- yl]methanesulfonamide
370	3′-Fluoro-N,N-dimethyl-4′-(5H- pyrrolo[2,3-b]pyrazin-2-yl)biphenyl-2- sulfonamide
371	N-tert-Butyl-3′-fluoro-4′-(5H- pyrrolo[2,3-b]pyrazin-2-yl)biphenyl-2- sulfonamide
372	2-[3-Fluoro-2′-(pyrrolidin-1- ylsulfonyl)biphenyl-4-yl]-5H- pyrrolo[2,3-b]pyrazine
373	N-Diethyl-3′-fluoro-4′-(5H- pyrrolo[2,3-b]pyrazin-2-yl)biphenyl-2- sulfonamide
374	2-[3-Fluoro-2′-(piperidin-1- ylsulfonyl)biphenyl-4-yl)-5H- pyrrolo[2,3-b]pyrazine
375	2-[3.-Fluoro-2′-(morpholin-4- ylsulfonyl)biphenyl-4-yl]-5H- pyrrolo[2,3-b]pyrazine
376	3′-Fluoro-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)N-N-(2,2,2-trifluoro-1- methylethyl)biphenyl-2-sulfonamide
377	2-[3-Fluoro-2′- (methylsulfonyl)biphenyl-4-yl]-5H- pyrrolo[2,3-b]pyrazine
378	3′-Fluoro-N-[(1R)-2-hydroxy-1- methylethyl]-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2- sulfonamide
379	3′-Fluoro-N-methyl-4′-(5H- pyrrolo[2,3-b]pyrazin-2-yl)biphenyl-2- sulfonamide
380	3′-Fluoro-N-[(1S)-2-hydroxy-1- methylethyl]4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2- sulfonamide
381	1-{[3′-Fluoro-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2- yl]sulfonyl}piperidin-4-amine
382	2-{2′-[(1,1-Dioxidothiomorpholin-4- yl)sulfonyl]-3-fluorobiphenyl-4-yl}-5H- pyrrolo[2,3-b]pyrazine
383	2-[3,5-Difiuoro-2′- (methylsulfanyl)biphenyl-4-yl]-5H- pyrrolo[2,3-b]pyrazine
384	2-[2′-(Ethylsulfanyl)-3-fluorobiphenyl- 4-yl]-5H-pyrrolo[2,3-b]pyrazine
385	7-[3-Fluoro-2′- (methylsulfonyl)biphenyl-4-yl]-3,4- dihydro-2H-pyrido[3,2-b][1,4]oxazine
386	7-[3-Fluoro-2′-(piperidin-1- ylsulfonyl)biphenyl-4-yl]-3,4-dihydro- 2H-pyrido[3,2-b][1,4]oxazine
387	4′-(3,4-Dihydro-2H-pyrido[3,2- b][1,4]oxazin-7-yl)-3′-fluorobiphenyl- 2-sulfonamide
388	4′-(3,4-Dihydro-2H-pyrido[3,2- b]l[1,4]oxazin-7-yl)-3′-fluoro-N-[(1S)- 2-hydroxy-1-methylethyl]biphenyl-2- sulfonamide
389	1-{[4′-(3,4-Dihydro-2H-pyrido[3,2- b][1,4]oxazin-7-yl)-3′-fluorobiphenyl- 2-yl]sulfonyl}piperidin-4-amine
390	4′-(3,4-Dihydro-2H-pyrido[3,2- b][1,4]oxazin-7-yl)-3′-fluoro-N-[(1R)- 2-hydroxy-1-methylethyl]biphenyl-2- sulfonamide
391	4′-(3,4-Dihydro-2H-pyrido[3,2- b][1,4]oxazin-7-yl)-N,N-diethyl-3′- fluorobiphenyl-2-sulfonamide
392	7-{2′-[(1,1-Dioxidothiomorpholin-4- yl)sulfonyl]-3-fluorobiphenyl-4-yl]-3,4- dihydro-2H-pyrido[3,2-b][1,4]oxazine
393	N-tert-Butyl-4′-(3,4-dihydro-2H- pyrido[3,2-b][1,4]oxazin-7-yl)-3′- fluorobiphenyl-2-sulfonamide
394	2-(2-Fluoro-4-{2-[(1- methylethyl)sulfanyl]-5- (trifluoromethyl)pyridin-3-yl}phenyl)- 5H-pyrrolo[2,3-b]pyrazine
395	5-(2-Fluoro-4-{2-[(1- methylethyl)sulfonyl]pyridin-3- yl}phenyl)pyrazin-2-amine
396	5-(2-Fluoro-4-{2-[(1- methylethyl)sulfanyl]pyridin-3- yl}phenyl)pyrazin-2-amine
397	2-{2-Fluoro-4-[2-(2,2,2- trifluoroethoxy)pyridin-3-yl]phenyl}- 5H-pyrrolo[2,3-b]pyrazine
398	2-{2-Fluoro-4-[2-(2- methylpropoxy)pyridin-3-yl]phenyl)- 5H-pyrrolo[2,3-b]pyrazine
399	2-{2-Fluoro-4-[2-(1- methylethoxy)pyridin-3-yl]phenyl}- 5H-pyrrolo[2,3-b]pyrazine
400	2-{4-[2-(Cyclopropylmethoxy)pyridin- 3-yl]-2-fluorophenyl}-5H-pyrrolo[2,3- b]pyrazine
401	5-{2-Fluoro-4-[2-(1- methylethoxy)pyridin-3- yl]phenyl}pyrazin-2-amine
402	5-{4-[2-(Cyclopentyloxy)pyridin-3-yl]- 2-fluorophenyl}pyrazin-2-amine
403	5-{4-[2-(Cyclohexyloxy)pyridin-3-yl]- 2-fluorophenyl}pyrazin-2-amine
404	5-[2-Fluoro-4-(2-methoxypyridin-3- yl)phenyl]pyrazin-2-amine
405	5-{4-[2-(Cyclobutyloxy)pyridin-3-yl]-2- fluorophenyl}pyrazin-2-amine
406	tert-Butyl 3-[({3-[4-(5-aminopyrazin-2- yl)-3-fluorophenyl]pyridin-2- yl}oxy)methyl]pyrrolidine-1- carboxylate
407	5-{2-Fluoro-4-[2-(pyrrolidin-3′- ylmethoxy)pyridin-3- yl]phenyl}pyrazin-2-amine
408	5-{2-Fluoro-4-[2-(1- methylethoxy)pyridin-3- yl]phenyl}pyrimidin-2-amine
409	5-[4-(2-Aminopyridin-3-yl)-2- fluorophenyl]pyrimidin-2-amine
410	4′-(5-amino-6-cyanopyrazin-2-yl)-3′- fluoro-N-[(1R)-2-hydroxy-1- methylethypiphenyl-2-sulfonamide
411	3-Amino-6-[2′-(cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]pyrazine-2- carbonitrile
412	4′-(5-Amino-6-cyanopyrazin-2-yl)-3′- fluoro-N-[(1S)-2-hydroxy-1- methylethyl]biphenyl-2-sulfonamide
413	4′-(5-Amino-6-cyanopyrazin-2-yl)-3′- fluoro-N-(2-hydroxyethyl)biphenyl-2- sulfonamide
414	3-Amino-6-{3-fluoro-2′-[(3- oxopiperazin-1-yl)sulfonyl]biphenyl-4- yl}pyrazine-2-carbontrile
415	4′-(5-Amine-6-cyanopyrazin-2-yl)-3′- fluoro-N-[(R)-2- hydroxypropyl]biphenyl-2- sulfonamide
416	3-Amino-6-[3-fluoro-2′-(morpholin-4- ylcarbonyl)biphenyl-4-yl]pyrazine-2- carbonitrile
417	4′-(6-Aminopyridazin-3-yl)-N-tert- butyl-3′-fluorobiphenyl-2-sulfonamide
418	N-tert-Butyl-3′-fluoro-4′-(7H- pyrrolo[2,3-d]pyrimidin-2-yl)biphenyl- 2-sulfonamide
419	N-tert-Butyl-3′-fluoro-4′-(1,8- naphthyridin-3-yl)biphenyl-2- sulfonamide
420	N-tert-Butyl-3′-fluoro-4′-quinoxalin-6- ylbiphenyl-2-sulfonamide
421	N-tert-Butyl-3′-fluoro-4′-(1H-indol-5- yl)biphenyl-2-sulfonamide
422	4′-(1H-Benzimidazol-5-yl)-N-tert- butyl-3′-fluorobiphenyl-2-sulfonamide
423	4′-1H-Benzimidazol-5-yl)-3′-fluoro-N- methylbiphenyl-2-sulfonamide
424	4′-(1,3-Benzothiazol-5-yl)-N-tert- butyl-3′-fluorobiphenyl-2-sulfonamide
425	N-tert-Butyl-3′-fluoro-4′-(1H- pyrrolo[3,2-b]pyridin-6-yl)biphenyl-2- sulfonamide
426	3′-Fluoro-N-methyl-4′-(1H- pyrrolo[2,3-b]pyridin-5-yl)biphenyl-2- sulfonamide
427	4′-(5-Aminepyridin-2-yl)-N-tert-butyl- 3′-fluoro-biphenyl-2-sulfonamide
428	N-tert-Butyl-4′-(5,6-diaminopyrazin-2- yl)-3′-fluorobiphenyl-2-sulfonamide
429	N-tert-Butyl-3′-fluoro-4′-(2-oxo-2,3- dihydro-1H-imidazo[4,5-b]pyrazin-5- yl)biphenyl-2-sulfonamide
430	4′-(6-Amino-5-fluoropyridin-3-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide
431	N-tert-Butyl-4′-(2,3-dihydro-1H- pyrrolo[2,3-b]pyridin-5-yl)-3′- fluorobiphenyl-2-sulfonamide
432	N-tert-Butyl-3′-fluoro-4′-(3H- imidazo[4,5-b]pyridin-6-yl)biphenyl-2- sulfonamide
433	4′-(5-Amino-6-methoxypyrazin-2-yl)- N-tert-butyl-3′-fluorobiphenyl-2- sulfonamide
434	4′-(5-Amino-6-cyanopyrazin-2-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide
435	4′-(5-Amino-3-cyanopyrazin-2-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide
436	4′-(6-Amino-4-cyanopyridin-3-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide
437	4′-(6-amino-2-cyanopyridin-3-yl)-N- (tert-butyl)-3′-fluoro-[1,1′-biphenyl]-2- sulfonamide
438	4′-(5-amino-1,3,4-thiadiazol-2-yl)-N- (tert-butyl)-3′-fluoro-[1,1′-biphenyl]-2- sulfonamide
439	(R)-4′-(5-amino-1,3,4-thiadiazol-2-yl)- 3-fluoro-N-(1-hydroxypropan-2-yl)- [1,1′-biphenyl]-2-sulfonamide
440	4-((4′-(5-amino-1,3,4-thiadiazol-2-yl)- 3′-fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)thiomorpholine 1,1-dioxide
441	4′-(5-Amino-6-chloropyrazin-2-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide
442	4′-(5-Amino-6-bromopyrazin-2-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide
443	6-amino-3-(2′-(cyclopropylsulfonyl)-3- fluoro-[1,1′-biphenyl]-4- yl)picolinonitrile
444	N-tert-Butyl-3′-fluoro-4′- [1,2,4]triazolo[4,3-a]pyridin-7- ylbiphenyl-2-sulfonamide
445	4′-(5-Amino-6-methylpyrazin-2-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide
446	4′-(5-Amino-6-methylpyrazin-2-yl)-3′- fluorobiphenyl-2-sulfonamide
447	N-tert-Butyl-3′-fluoro-4′-(1H- imidazo[4,5-b]pyrazin-5-yl)biphenyl- 2-sulfonamide
448	N-tert-Butyl-4′-(5,6-diaminopyridin-3- yl)-3′-fluorobiphenyl-2-sulfonamide
449	4′-(5-Amino-6-methylpyrazin-2-yl)-3′- fluoro-N-methylbiphenyl-2- sulfonamide
450	4′-(6-Amino-5-cyanopyridin-3-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide trifluoroacetic acid salt
451	4′-(6-Amino-5-chloropyridin-3-yl)-N- tert-butyl-3′-fluorobiphenyl-2- sulfonamide trifluoroacetic acid salt
452	4′-[6-Amino-5-(trifluoromethyl)pyridin- 3-yl]-N-tert-butyl-3′-fluorobiphenyl-2- sulfonamide trifiuoroacetic acid salt
453	4′-[2-Amino-4- (trifluoromethyl)pyrimidin-5-yl]-N-tert- butyl-3′-fluorobiphenyl-2-sulfonamide trifluoroacetic acid salt
454	4′-(2-Amino-4-methylpyrimidin-5-yl)- N-tert-butyl-3′-fluorobiphenyl-2- sulfonamide trifluoroacetic acid salt
455	N-tert-Butyl-3′-fluoro-4′-[3- (hydroxymethyl)-1H-pyrrolo[2,3- b]pyridin-5-yl]biphenyl-2-sulfonamide
456	4′-(7-Amino-1H-indol-5-yl)-3′-fluoro- N-[1- (hydroxymethyl)cyclopentyl]biphenyl- 2-sulfonamide
457	3′-Fluoro-4′-[3-(hydroxymethyl)-1H- pyrrolo[2,3-b]pyridin-5-yl]-N- methylbiphenyl-2-sulfonamide
458	4′-(7-Amino-1H-indol-5-yl)-N-tert- butyl-3′-fluorobiphenyl-2-sulfonamide
459	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]acetamide
460	1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]urea
461	5-[2,3-Difluoro-2′- (methylsulfonyl)biphenyl-4-yl]pyrazin- 2-amine
462	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl- 2′,3′-difluorobipnenyl-2-sulfonamide
463	N-[4′-(5-Aminopyrazin-2-y)-3′-fluoro- 2′-methylbiphenyl-2- yl]methanesulfonamide
464	4′-(5-Aminopyrazin-2-yl)-2′,3′- difluorobiphenyl-2-sulfonamide
465	4′-(2-Aminopyrimidin-5-yl)-2′,3′- difluoro-N-methylbiphenyl-2- sulfonamide trifluoroacetic acid salt
466	4′-(2-Aminopyrimidin-5-yl)-N-tert- butyl-2′,3′-difluorobipenyl-2- sulfonamide trifluoroacetic acid salt
467	5-[2′,3-Difluoro-4′- (trifluoromethoxy)biphenyl-4- yl]pyrazin-2-amine
468	5-(2′,3-Difluorobiphenyl-4-yl)pyrazin- 2-amine
469	5-(2′-Chloro-3-fluorobiphenyl-4- yl)pyrazin-2-amine
470	5-(3-Fluoro-2′-methylbiphenyl-4- yl)pyrazin-2-amine
471	5-[2′,3-Difiuoro-4′- (trifluoromethyl)biphenyl-4-yl]pyrazin- 2-amine
472	5-[3-Fluoro-2′- (trifluoromethyl)biphenyl-4-yl]pyrazin- 2-amine
473	5-(3-Fluoro-2′-methoxybiphenyl-4- yl)pyrazin-2-amine
474	5-[3-Fluoro-2′- (methylsulfanyl)biphenyl-4-yl]pyrazin- 2-amine
475	5-[3-Fluoro-2′- (trifluoromethoxy)biphenyl-4- yl]pyrazin-2-amine
476	4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-ol
477	5-[3-Fluoro-2′- (phenylsulfonyl)biphenyl-4-yl]pyrazin- 2-amine
478	5-(2′,3,6′-Trifluorobiphenyl-4- yl)pyrazin-2-amine
479	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]benzenesulfonamide
480	5-(2′-Ethyl-3-fluorobiphenyl-4- yl)pyrazin-2-amine
481	{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}acetic acid
482	5-[3-Fluoro-2′-(1- methylethyl)biphenyl-4-yl]pyrazin-2- amine
483	1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]ethanone
484	5-[3-Fluoro-2′-(2,2,2- trifluoroethoxy)biphenyl-4-yl]pyrazin- 2-amine
485	4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-carboxylic acid
486	4′-(5-Aminopyrazin-2′-yl)-3′- fluorobiphenyl-2-carboxamide
487	5-[3-Fluoro-2′-(1- methylethoxy)biphenyl-4-yl]pyrazin- 2-amine
488	5-{4-[2-(Cyclopropylmethoxy)pyridin- 3-yl]-2-fluorophenyl}pyrazin-2-amine
489	2-[3,4′-Difluoro-2′- (methylsulfonyl)biphenyl-4-yl]-5H- pyrrolo[2,3-b]pyrazine
490	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N- methylmethanesulfonmide
491	N-[3′-Fluoro-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2- yl]ethanesulfonamide
492	N-[3′-Fluoro-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2-yl]-N-N- methylmethanesulfonamide
493	N-[3′-Fluoro-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2-yl]-N- methylethanesulfonamide
494	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N- methylethanesulfonamide
495	N-[3′-Fluoro-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2-yl]-2- methylpropane-1-sulfonamide
496	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N- ethylmethanesulfonamide
497	N-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N,2- dimethylpropane-1-sulfonamide
498	5-[3-Fluoro-2′-(morpholin-4- ylcarbonyl)biphenyl-4-yl]-1H- pyrrolo[2,3-b]pyridine
499	5-[3-Fluoro-2′-(morpholin-4- ylcarbonyl)biphenyl-4-yl]pyrimidin-2- amine
500	2-[3-Fluoro-2′-(morpholin-4- ylcarbonyl)biphenyl-4-yl]-5H- pyrrolo[2,3-b]pyrazine
501	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl- 3′-fluorobiphenyl-2-carboxamide
502	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl- 3′,4-difluorobiphenyl-2-carboxamide
503	4′-(5-Aminopyrazin-2-yl)-N,N-diethyl- 3′-fluorobiphenyl-2-carboxamide
504	4′-(2-Aminopyrimidin-5-yl)-3-fluoro- N-[(1S)-2,2,2-trifluoro-1- methylethyl]piphenyl-2-carboxamide
505	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1S)-2,2,2-trifluoro-1- methylethyl]biphenyl-2-carboxamide
506	5-[3-Fluoro-2′-(piperazin-1- ylcarbonyl)biphenyl-4-yl]pyrazin-2- amine
507	5-{2′-[(4-Acetylpiperazin-1- yl)carbonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
508	4′-(5-Aminopyrazin-2-yl)-N- cyclohexyl-3′-fluorobiphenyl-2- carboxamide
509	5-{2′-[(1,1-Dioxidathiomorpholin-4- yl)carbonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
510	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- methylbiphenyl-2-carboxamide
511	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1R)-2,2,2-trifluoro-1- methylethyl]biphenyl-2-carboxamide
512	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1R)-2-hydroxy-1- methylethyl]biphenyl-2-carboxamide
513	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- [(1S)-2-hydroxy-1- methylethyl]biphenyl-2-carboxamide
514	1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]carbonyl)piperidin-4-ol
515	5-{2′-[(4-Aminopiperidin-1- yl)carbonyl]-3-fluorobiphenyl-4- yl}pyrazin-2-amine
516	5-{2′-[(1,1-Dioxidothiomorpholin-4- yl)carbonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine
517	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N-[(1S)-2-hydroxy-1- methylethyl]biphenyl-2-carboxamide
518	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro- N[(1R)-2,2,2-trifluoro-1- methylethypiphenyl-2-carboxamide
519	4-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]carbonyl}piperazin-2-one
520	4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2- yl]carbonyl}piperazin-2-one
521	5-[3-Fluoro-2′-(morpholin-4- ylcarbonyl)-4′- (trifluoromethyl)biphenyl-4-yl]pyrazin- 2-amine
522	5-[3-Fluoro-2′-(morpholin-4- ylcarbonyl)-4′- (trifluoromethyl)biphenyl-4- yl]pyrimidin-2-amine
523	4-{[3′-Fluoro-4′-(1H-pyrrolo[2,3- b]pyridin-5-yl)biphenyl-2- yl]oxy}pyrimidin-2-amine
524	2-{[3′-Fluoro-4′-(1H-pyrrolo[2,3- b]pyridin-5-yl)biphenyl-2- yl]oxy}pyrimidin-4-amine
525	5-[3-Fluoro-2′-(pyrimidin-2- yloxy)biphenyl-4-yl]-1H-pyrrolo[2,3- b]pyridine
526	5-[3-Fluoro-2′-(pyrimidin-2- yloxy)biphenyl-4-yl]pyrazin-2-amine
527	5-[3-Fluoro-2′-(pyrimidin-2- yloxy)biphenyl-4-yl]pyrimidin-2-amine
528	2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}pyrimidin-4- amine
529	5-{2′-[(4-Aminopyrimidin-2-yl)oxy]-3- fluorobiphenyl-4-yllpyrimidin-2-amine
530	6-({[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]oxy}methyl)pyridine-2-carbonitrile
531	2-({[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]oxy}methyl)pyridine-3-carbonitrile
532	2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}pyridine-3- carbonitrile
533	4-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}pyrimidin-2- amine
534	4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy}pyrimidin-2- amine
535	6-{[4′-(5-Aminopyrazin-2′yl)-3′- fluorobiphenyl-2-yl]oxy}pyrimidin-4′- amine
536	5-{2′-[(6-Aminopyrimidin-4-yl)oxy]-3- fluorobiphenyl-4-yl}pyrimidin-2-amine
537	4-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}pyridine-2- carbonitrile
538	4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy}pyridine-2- carbonitrile
539	5-{2′-[(6-Azetidin-1-ylpyrimidin-4- yl)oxy]-3-fluorobiphenyl-4-yl}pyrazin- 2-amine
540	5-{2′-[(6-Azetidin-1-ylpyrimidin-4- yl)oxy]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine
541	5-{3-Fluoro-2′-[(2-methylpyrimidin-4- yl)oxy]biphenyl-4-yl}pyrazin-2-amine
542	5-{3-Fluoro-2′-[(2-methylpyrimidin-4- yl)oxy]biphenyl-4-yl}pyrimidin-2- amine
543	5-[3-Fluoro-2′-(pyrimidin-2- yloxy)biphenyl-4-yl]-1H- benzimidazole
544	6-[3-Fluoro-2′-(pyrimidin-2- yloxy)biphenyl-4-yl]-3H-imidazo[4,5- b]pyridine
545	5-{3-Fluoro-2′-[(4-methylpyrimidin-2- yl)oxy]biphenyl-4-yl}pyrazin-2-amine
546	5-{3-Fluoro-2′-[(4-methylpyrimidin-2- yl)oxy]biphenyl-4-yl}pyrimidin-2- amine
547	5-(3-Fluoro-2′-{(2- (trifluoromethyl)pyrimidin-4- yl]oxy}biphenyl-4-yl)pyrazin-2-amine
548	5-(3-Fluoro-2′-{(2- (trifluoromethyl)pyrimidin-4- yl]oxylbiphenyl-4-yl)pyrimidin-2- amine
549	5-{3-Fluoro-2′-[(5-methoxypyrimidin- 2-yl)oxy]biphenyl-4-yl}pyrazin-2- amine
550	5-{3-Fluoro-2′-[(5-methoxypyrimidin- 2-yl)oxy]biphenyl-4-yl}pyrimidin-2- amine
551	5-[3-Fluoro-2′-(pyrimidin-2-yloxy)-4′- (trifluoromethyl)biphenyl-4-yl]pyrazin- 2-amine
552	5-[3-Fluoro-2′-(pyrimidin-2-yloxy)-4′- (trifluoromethyl)biphenyl-4- yl]pyrimidin-2-amine
553	5-[3-Fluoro-2′-methoxy-4′- (trifluoromethyl)biphenyl-4-yl]pyrazin- 2-amine
554	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-4- (trifluoromethyl)biphenyl-2-ol
555	4-{[4′-(5-Aminopyrazin-2-yl)-3′-fluoro- 4-(trifluoromethyl)biphenyl-2- yl]oxy}pyrimidin-2-amine
556	2-{[4′-(5-Aminopyrazin-2-yl)-3′-fluoro- 4-(trifluoromethyl)biphenyl-2- yl]oxy}pyrimidin-4-amine
557	5-[3-Fluoro-4′-(trifluoromethyl)-2′-{[2- (trimethylsilyl)ethoxy]methoxy}biphenyl- yl-4-yl]pyrimidin-2-amine
558	4′-(2-Aminopyrimidin-5-yl)-3′-fluoro-4- (trifluoromethyl)biphenyl-2-ol
559	5-{2′-[(4-Aminopyrimidin-2-yl)oxy]-3- fluoro-4′-(trifluoromethyl)biphenyl-4- yl}pyrimidin-2-amine
560	4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluoro-4-(trifluoromethyl)biphenyl-2- yl]oxy}pyrimidin-2-amine
561	5-{2′-[(6-Aminopyrimidin-4-yl)oxy]-3- fluoro-4′-(trifluoromethyl)biphenyl-4- yl}pyrimidin-2-amine
562	5-[3-Fluoro-2′,4′- bis(trifluoromethyl)biphenyl-4- yl]pyrazin-2-amine
563	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-4- (trifluoromethyl)biphenyl-2- carbonitrile
564	5-{5-[2-(Pyrimidin-2-yloxy)-4- (trifluoromethyl)phenyl]pyridin-2- yl}pyrimidin-2-amine
565	4-{2-[6-(2-Aminopyrimidin-5- yl)pyridin-3-yl]-5- (trifluoromethyl)phenoxy}pyrimidin-2- amine
566	5-{5-[2-(Pyrimidin-2- yloxy)phenyl]pyridin-2-yl}pyrimidin-2- amine
567	4-{2-[6-(2-Aminopyrimidin-5- yl)pyridin-3-yl]phenoxy}pyrimidin-2- amine
568	5-(5-{2-[(4-Aminopyrimidin-2- yl)oxy]phenyl}pyridin-2-yl)pyrimidin- 2-amine
569	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl- 3′-methylbiphenyl-2-sulfonamide
570	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl- 3′-methoxybiphenyl-2-sulfonamide
571	4′-(5-Aminopyrazin-2-yl)-N-tert- butylbiphenyl-2-sulfonamide
572	4′-(5-Aminopyrazin-2-yl)-N,N- dimethylbiphenyl-2-sulfonamide
573	5-[2′-(Morpholin-4- ylsulfonyl)biphenyl-4-yl]pyrazin-2′- amine
574	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl- 2′-fluorobiphenyl-sultonamide
575	4′-(5-Aminopyrazin-2-yl)-2′-fluoro- N,N-dimethylbiphenyl-2-sulfonamide
576	4′-(2-Amino-1,3-oxazol-4-yl)-N-tert- butyl-3′-fluorobiphenyl-2-sulfonamide
577	4′-(2-Amino-1,3-thiazol-4-yl)-N-tert- butyl-3′-fluorobiphenyl-2-sulfonamide
578	4′-(2-Amino-1,3-thiazol-4-yl)-N,N- diethyl-3′-fluorobiphenyl-2- sulfonamide
579	4-[3-Fluoro-2′-(pyrrolidin-1- ylsulfonyl)biphenyl-4-yl]-1,3-thiazol-2- amine
580	N-tert-Butyl-3′-fluoro-4′-(8- fluoroimidazo[1,2-a]pyridin-2- yl)biphenyl-2-sulfonamide
581	4′-(5-Aminoimidazo[1,2-a]pyridin-2- yl)-N-tert-butyl-3′-fluorobiphenyl-2- sulfonamide
582	2-[2′-(tert-Butylsulfamoyl)-3- fluorobiphenyl-4-yl]imidazo[1,2- a]pyridine-6-carboxamide
583	2-[2′-(tert-Butylsulfamoyl)-3- fluorobiphenyl-4-yl]imidazo[1,2- a]pyridine-6-carboxamide
584	N-tert-Butyl-4′-(5-cyanoimidazo[1,2- a]pyridin-2-yl)-3′-fluorobiphenyl-2- sulfonamide
585	N-tert-Butyl-4′-(6-cyanoimidazo[1,2- a]pyridin-2-yl)-3′-fluorobiphenyl-2- sulfonamide
586	N-tert-Butyl-3′-fluoro-4′-[6- (trifluoromethyl)imidazo[1,2-a]pyridin- 2-yl]biphenyl-2-sulfonamide
587	Ethyl 2-[2′-(tert-butylsulfamoyl)-3- fluorobiphenyl-4-yl]imidazo[1,2- a]pyridine-5-carboxylate
588	N-tert-Butyl-3-fluoro-4′-(5- methoxyimidazo[1,2-a]pyridin-2- yl)biphenyl-2-sulfonamide
589	5-[2′-(Methylsulfonyl)biphenyl-4- yl]pyrazin-2-amine.
590	5-[3-Methyl-2′- (methylsulfonyl)biphenyl-4-yl]pyrazin- 2-amine.
591	4′-(5-Aminopyrazin-2-yl)-N,N,3′- trimethylbiphenyl-2-sulfonamide.
592	4′-(5-Aminopyrazin-2-yl)-3′- hydroxybiphenyl-2-sulfonamide.
593	n-[4′-(5-Aminopyrazin-2-yl)biphenyl- 2-yl]methanesulfonamide.
594	4′-(5-Aminopyrazin-2-yl)biphenyl-2- sulfonamide.
595	N-tert-Butyl-3′-fluoro-4′-(2-oxo-2,3- dihydro-1H-indol-5-yl)biphenyl-2- sulfonamide.
596	N-tert-Butyl-4′-(2,4-dioxo-1,2,3,4- tetrahydroquinazolin-6-yl)-3′- fluorobiphenyl-2-sulfonamide.
597	4′-(3-Amino-1H-indazol-5-yl)-N-tert- butyl-3′-fluorobiphenyl-2- sulfonamide.
598	3-Amino-6-[2′-(tert-butylsulfamoyl)-3- fluorobiphenyl-4-yl]pyrazine-2- carboxylic acid.
599	2-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2- yl]sulfonyl}acetamide.
600	2-{4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}-N,N- diethylacetamide.
601	5-{3-Fluoro-2′-[(2-morpholin-4-yl-2- oxoethyl)sulfonyl]biphenyl-4- yl}pyrimidin-2-amine.
602	5,5′-(3,3′-Difluoro-1,1′:2′,1″- terphenyl-4,4″-diyl)dipyrazin-2- amine.
603	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-4- (trifluoromethyl)biphenyl-2-carboxylic acid.
604	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-4- (trifluoromethyl)biphenyl-2- carbaldehyde.
605	5-[3-Fluoro-2′-(morpholin-4-ylmethyl)- 4′-(trifluoromethyl)biphenyl-4- yl]pyrazin-2-amine.
606	5-{2′-[(4-Aminopiperidin-1-yl)methyl]- 3-fluoro-4′-(trifluoromethyl)biphenyl- 4-yl}pyrazin-2-amine.
607	2-({[4′-(5-Aminopyrazin-2-yl)-3′- fluoro-4-(trifluoromethyl)biphenyl-2- yl]methyl}amino)ethanol.
608	5-{2′-[(4,6-Dimethylpyrimidin-2- yl)oxy]-3-fluorobiphenyl-4-yl}pyrazin- 2-amine.
609	5-{2′-[(4,6-Dimethylpyrimidin-2- yl)oxy]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine.
610	5-(3-Fluoro-2′-{(2- (trifluoromethyl)pyridin-4- yl]oxy}biphenyl-4-yl)pyrazin-2-amine.
611	5-(3-Fluore-2′-{[2- (trifluoromethyl)pyridin-4- yl)oxy}biphenyl-4-yl)pyrimidin-2- amine.
612	5-(3-Fluoro-2′-{[4- (trifluoromethyl)pyrimidin-2- yl]oxy}biphenyl-4-yl)pyrazin-2-amine.
613	5-(3-Fluoro-2′-{[4- (trifluoromethyl)pyrimidin-2- yl]oxy}biphenyl-4-yl)pyrimidin-2- amine.
614	2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}pyrimidin-5- amine.
615	5-{2′-[(5-Aminopyrimidin-2-yl)oxy]-3- fluorobiphenyl-4-yl}pyrimidin-2- amine.
616	2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}-6- methylpyrimidin-4-amine.
617	5-{2′-[(4-Amino-6-methylpyrimidin-2- yl)oxy]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine.
618	6-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy}pyridine-2- carbonitrile.
619	6-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}pyridine-2- carbonitrile.
620	5-{2′-[(5-Aminopyridin-2-yl)oxy]-3- fluorobiphenyl-4-yl}pyrazin-2-amine.
621	5-{2′-[(5-Aminopyridin-2-yl)oxy]-3- fluorobiphenyl-4-yl}pyrimidin-2- amine.
622	5-{2′-[(6-Amino-2-methylpyrimidin-4- yl)oxy]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine.
623	6-{[4′-(5-Aminopyrazin-2-yl)-(3′ fluorobiphenyl-2-yl]oxy}-2- methylpyrimidin4-amine.
624	5-(3-Fluoro-2′-{[6- (trifluoromethyl)pyridin-2- yl]oxy}biphenyl-4-yl)pyrimidin-2- amine.
625	5-(3-Fluoro-2′-{[6- (trifluoromethyl)pyridin-2- yl]oxy}biphenyl-4-yl)pyrazin-2-amine.
626	6-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}pyridine-3- carbonitrile.
627	6-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy}pyridine-3- carbonitrile.
628	2-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}ethanol.
629	2-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy}ethanol.
630	5-[3-Fluoro-2′-(piperidin-4- yloxy)biphenyl-4-yl]pyrazin-2-amine.
631	5-[3-fluoro-2′-(piperidin-4- yloxy)biphenyl-4-yl]pyrimidin-2- amine.
632	5-{3-Fluoro-2′-[(3R)-piperidin-3- yloxy]biphenyl-4-yl}pyrazin-2-amine
633	5-{3-Fluoro-2′-[(3R)-piperidin-3- yloxy]biphenyl-4-yl}pyrimidin-2- amine.
634	5-{3-Fluoro-2′-[(3S)-piperidin-3- yloxy]biphenyl-4-yl}pyrazin-2-amine.
635	5-{3-Fluoro-2′-[(3S)-piperidin-3- yloxy]biphenyl-4-yl}pyrimidin-2- amine.
636	5-{2′-[(6-Cyclopropylpyrimidin-4- yl)oxy]-3-fluorobiphenyl-4-yl}pyrazin- 2-amine.
637	5-{2′-[(6-Cyclopropylpyrimidin-4- yl)oxy]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine.
638	5-{2′-[(2-Aminopyridin-4-yl)oxy]-3- fluorobiphenyl-4-yl}pyrazin-2-amine.
639	5-{2′-[(2-Aminopyridin-4-yl)oxy]-3- fluorobiphenyl-4-yl}pyrimidin-2- amine.
640	5-[2′-(2-Aminoethoxy)-3- fluorobiphenyl-4-yl]pyrazin-2-amine.
641	5-[2′-(2-Aminoethoxy)-3- fluorobiphenyl-4-yl]pyrimidin-2- amine.
642	{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}acetonitrile.
643	{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy}acetonitrile.
644	{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy}acetic acid.
645	5-{2-Fluoro-4-[2-(piperidin-4- yloxy)pyridin-3-ylphenyl}pyrazin-2- amine.
646	5-{2-Fluoro-4-[2-(piperidin-4- yloxy)pyridin-3-yl]phenyl}pyrimidin-2- amine.
647	5-(4-{2-[(1,1-Dioxidotetrahydro-2H- thiopyran4-yl)oxy]pyridin-3-yl}-2- fluorophenyl)pyrazin-2-amine.
648	5-(4-{2-[(1,1-Dioxidotetranydro-2H- thiopyran-4-yl)oxy]pyridin-3-yl}-2- fluorophenyl)pyrimidin-2-amine.
649	2-({3-[4-(2-Aminopyrimidin-5-yl)-3- fluorophenyl]pyridin-2-yl}oxy)ethanol.
650	2-({3-[4-(5-Aminopyrazin-2-yl)-3- fluorophenyl]pyridin-2-yl}oxy)ethanol.
651	5-(4-{2-[(trans-4- Aminocyclohexyl)oxy]pyridin-3-yl}-2- fluorophenyl)pyrimidin-2-amine.
652	5-(4-{2-[(trans-4- Aminocyclohexyl)oxy]pyridin-3-yl}-2- fluorophenyl)pyrazin-2-amine formic acid salt
653	5-{2-Fluoro-4-[2-(tetrahydro-2H- pyran-4-yloxy)pyridin-3- yl]phenyl}pyrazin-2-amine.
654	5-{2-Fluoro-4-[2-(tetrahydro-2H- pyran-4-yloxy)pyridin-3- yl]phenyl}pyrimidin-2-amine
655	(2R)-2-({3-[4-(5-Aminopyrazin-2-yl)- 3-fluorophenyl]pyridin-2- yl}oxy)propan-1-ol.
656	(2R)-2-({3-[4-(2-Aminopyrimidin-5-yl- 3-fluorophenyl]pyridin-2- yl}oxy)propan-1-ol.
657	(2S)-2-({3-[4-(5-Aminopyrazin-2-yl)- 3-fluorophenyl]pyridin-2- yl}oxy)propan-1-ol.
658	(2I)-2-({3-[4-(2-Aminopyrimidin-5-yl)- 3-fluorophenyl]pyridin-2- yl}oxy)propan-1-ol
659	N-(4′-(6-Aminopyridin-3-yl)-3′-fluoro- [1,1′-biphenyl]-2- yl)methanesulfonamide
660	5-(3-Fluoro-2′-(morpholinosulfonyl)- [1,1′-biphenyl]-4-yl)pyridin-2-amine
661	4′-(6.-Aminopyridin-3-yl)-3′-fluoro-N- methyl-[1,1′-biphenyl]-2-sulfonamide
662	4′-(6-Aminopyridin-3-yl)-3′-fluoro- [1,1′-biphenyl]-2-sulforiamide trifluoroacetate
663	5-(2′-((1S,4S)-2-Oxa-5- azabicyclo[2.2.1]heptan-5-ylsulfonyl)- 3-fluoro-[1,1′-biphenyl]-4-yl)pyridin-2- amine
664	4′-(6-Aminopyrazin-2-yl)-3′-fluoro-N- ((3-hydroxyazetidin-3-yl)methyl)-[1,1′- biphenyl]-2-sulfonamide
665	4′-(6-Aminopyridin-3-yl)-3′-fluoro-N- (1-hydroxy-2-methylpropan-2-yl)- [1,1′-biphenyl]-2-sulfonamide
666	4′-(6-Aminopyridin-3-yl)-3′-fluoro-N- ((1S,2S)-1-hydroxy-1-phenylpropan- 2-yl)-N-methyl-[1,1′-biphenyl]-2- sulfonamide
667	4′-(6-Amino-5-fluoropyridin-3-yl)-3′- fluoro-N-(1-hydroxy-2-methylpropan- 2-yl)-[1,1′-biphenyl]-2-sulfonamide
668	(racemic)-1-((4′-(6-Amino-5- fluoropyridin-3-yl)-3′-fluoro-[1,1′- biphenyl]-2-yl)sulfonyl)piperidin-3-ol
669	4′-(6-Amino-5-fluoropyridin-3-yl)-3′- fluoro-N-((1S,2S)-1-hydroxy-1- phenylpropan-2-yl)-N-methyl-[1,1′- biphenyl]-2-sulfonamide
670	N-(1-((4′-(6-Amino-5-fluoropyridin-3- yl)-3′-fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)piperidin-4-yl)acetamide
671	racemic 2-(1-((4′-(6-Amino-5- fluoropyridin-3-yl)-3′-fluoro-[1,1′- biphenyl]-2-yl)sulfonyl)piperidin-3- yl)ethanol.
672	racemic 1-(4′-(6-Amino-5- fluoropyridin-3-yl)-3′-fluoro-[1,1′- biphenyl]-2-yl)sulfonyl)piperidin-3- yl)methanol.
673	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3-yl]-N-[(2R)-2- hydroxypropyl]benzenesulfonamide.
674	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3-yl]-N-ethyl-5- (trifluoromethyl)benzenesulfonamide.
675	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3-yl]-N-tert- butylbenzenesulfonamide.
676	5-{5-[2-(Morpholin-4-ylmethyl)-4- (trifluoromethyl)phenyl]pyridin-2- yl}pyrimidin-2-amine.
677	5-{5-[2-(Morpholin-4- ylcarbonyl)phenyl]pyridin-2- yl}pyrimidin-2-amine.
678	5-[5-(2-Methoxyphenyl)pyridin-2- yl]pyrimidin-2-amine.
679	5-(5-{2-[(3,3Difluoropiperidin-1- yl)sulfonyl]phenyl}pyridin-2- yl)pyrimidin-2-amine trifluoroacetic acid salt.
680	5-(5-{2-[(3,3-Difluoropyrrolidin-1- yl)sulfonyl]phenyl}pyridin-2- yl)pyrimidin-2-amine trifluoroacetic acid salt.
681	5-{5-[2-(Azepan-1- ylsulfonyl)phenyl]pyridin-2- yl}pyrimidin-2-amine trifluoroacetic acid salt.
682	5-(5-{2-[(4,4-Difluoropiperidin-1- yl)sulfonyl]phenyl}pyridin-2- yl)pyrimidin-2-amine trifluoroacetic acid salt.
683	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-ethylbenzenesulfonamide trifluoroacetic acid salt.
684	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N- (dicyclopropylmethyl)benzene- sulfonamide trifluoroacetic acid salt.
685	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-[(1S)-2,2,2-trifluoro-1- methylethyl]benzenesulfonamide trifluoroacetic acid salt.
686	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-[(1R)-2,2,2-trifluoro-1- methylethyl]benzenesulfonamide trifluoroacetic acid salt.
687	4-({2-[6-(2-Aminopyrimidin-5- yl)pyridin-3- yl]phenyl}sulfonyl)piperazin-2-one.
688	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-[(2S)-2- hydroxypropyl]benzenesulfonamide.
689	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-[(2R)-2- hydroxypropyl]benzenesulfonamide.
690	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-(2-hydroxyethyl)-5- (trifluoromethyl)benzenesulfonamide.
691	5-{5-[2- (Cyclopropylsulfonyl)phenyl]pyridin- 2yl}pyrimidin-2-amine trifluoroacetic acid salt.
692	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-ethyl-5- (trifluoromethyl)benzenesulfonamide trifluoroacetic acid salt.
693	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-tert-butylbenzenesulfonamide.
694	2-[6-(2-Aminopyrimidin-5-yl)pyridin-3- yl]-N-[(1R)-2-hydroxy-1- methylethyl]benzenesulfonamide.
695	3-Amino-6-{2′-[(4-aminopyrimidin-2- yl)oxy]-3-fluorobiphenyl-4- yl}pyrazine-2-carbonitrile trifluoroacetic acid salt.
696	5-(4′-Bromo-2′,3-difluoroblphenyl-4- yl)pyrazin-2-amine.
697	5-(4′-Bromo-2′,3-difluorobiphenyl-4- yl)-1H-pyrrolo[2,3-b]pyridine.
698	5-(3-fluoro-2-methoxy-4′- (trifluoromethyl)-[1,1′-biphenyl]-4- yl)pyrazin-2-amine.
699	5-(2′,3,4′-Trifluorobiphenyl-4- yl)pyrazin-2-amine
700	racemic 5-[3-Fluoro-2′- (methylsulfinyl)biphenyl-4-yl]pyrazin- 2-amine
701	4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-carbonitrile
702	1-(4′-(5-Aminopyrazin-2-yl)- 3′-fluoro-[1,1′-biphenyl]-2- yl)imidazolidin-2-one
703	4′-(2-Amino-4- cyanopyrimidin-5-yl)-N-tert-butyl-3′- fluorobiphanyl-2-sulfonamide
704	6-Amino-3-{2′-[(1,1- dioxidothiomorpholin-4-yl)sulfonyl]-3- fluorobiphenyl4-yl}pyrazine-2- carbonitrile
705	1-{[4′-(2-Aminopyrimidin-5- yl)-3′-fluorobiphenyl-2-yl]sulfonyl}-N- methylazetidine-3-carboxamide
706	4′-(5-Amino-3-cyanopyrazin- 2-yl)-3′-fluoro-N-(2- hydroxyethyl)biphenyl-2-sulfonamide
707	4′-(5-Amino-3-cyanopyrazin- 2-yl)-3′-fluoro-N-[(2S)-2- hydroxypropyl]biphenyl-2- sulfonamide
708	4′-(5-Amino-3-cyanopyrazin- 2-yl)-3′-fluoro-N-[(2R)-2- hydroxypropyl]biphenyl-2- sulfonamide
709	1-((4′-(2-Aminopyrimidin-5- yl)-3′-fluoro-[1,1′-biphenyl]-2- yl)sulfonyl)piperidine-4-carboxamide
710	4′-(5-Amino-3-cyanopyrazin- 2-yl)-3′-fluora-N-[(1R)-2-hydroxy-1- methylethyl]piphenyl-2-sulfonamide
711	4′-(5-Amino-3-cyanopyrazin- 2-yl)-3′-fluoro-N-[(1S)-2-hydroxy-1- methylethypiphenyl-2-sulfonamide
712	4′-(5-Amino-3-cyanopyrazin- 2-yl)-3′-fluoro-N-(2-hydroxyethyl)-4- (trifluoromethyl)biphenyl-2- sulfonamide
713	4′-(5-Amino-3-cyanopyrazin- 2-yl)-N-ethyl-3′-fluoro-4- (trifluoromethyl)-[1,1′-biphenyl]-2- sulfonamide
714	4′-(5-Amino-3-cyanopyrazin- 2-yl)-3′-fluoro-N-(3-hydroxy-2,2- dimethylpropyl)biphenyl-2- sulfonamide
715	6-Amino-3-{3-fluoro-2′-[(3- oxopiperazin-1-yl)sulfonyl]-4′- (trifluoromethyl)biphenyl-4- yl}pyrazine-2-carbonitrile
716	N-(2-{[4′-(2-Aminopyrimidin- 5-yl)-3′-fluorobiphenyl-2- yl]sulfonyl}ethyl)benzamide
717	1-{[4′-(2-Aminopyrimidin-5- yl)-3′-fluorobiphenyl-2-yl]sulfonyl)- 3,3-dimethylbutan-2-one
718	5-[3-Fluoro-2′-(pyrimidin-2- ylsulfonyl)biphenyl-4-yl]pyrimidin-2- amine
719	5-[3-Fluoro-2′-(pyrazin-2- ylsulfonyl)biphenyl-4-yl]pyrimidin-2- amine
720	5-[3-Fluoro-2′-(pyrimidin-4- ylsulfonyl)biphenyl-4-yl]pyrimidin-2- amine
721	5-{2′-[(6-Aminopyrimidin-4- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine
722	5-{2′-[(4-Aminopyrimidin-2- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine
723	5-{2′-[(5-Aminopyrazin-2- yl)sulfonyl]-3-fluorobiphenyl-4′- yl}pyrimidin-2-amine
724	4-{[4′-(2-Aminopyrimidin-5- yl)-3′-fluorobiphenyl-2- yl]sulfonyl}pyrimidin-2-amine
725	5-{2′-[(6-Aminopyrazin-2- yl)sulfonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine
726	6-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}pyrimidin-4-amine
727	2.-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}pyrimidin-4-amine
728	5-{2′- [(Cyclopropylmethyl)sulfonyl]-3- fluorobiphenyl-4-yl}pyrimidin-2-amine
729	6-Amino-3-[2′- (cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]pyrazine-2- carbonitrile
730	1-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}cyclopentanecarbonitrile
731	1-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]sulfonyl}cyclopentanecarboxamide
732	2-{[4′-(2-Aminopyrimidin-5- yl)-3′-fluorobiphenyl-2-yl]sulfonyl}-2- methylpropanenitrile
733	2-{[4′-(2-Aminopyridin-5- yl)-3′-fluorobiphenyl-2-yl]sulfonyl}-2- methylpropanamide
734	5--{2′-[(2-Amino-1,1- dimethylethyl)sulfonyl]-3- fluorobiphenyl-4-yl}pyrimidin-2-amine
735	2-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2-yl]sulfonyl}-2- methylpropanenitrile
736	2-{[4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2-yl]sulfonyl}-2- methylpropanamide
737	5-{2′-[(2-Amino-1,1- dimethylethyl)sulfonyl]-3- fluorobiphenyl-4-yl}pyrazin-2-amine
738	1-{[4′-(2-Aminopyrimidin-5- yl)-3′-fluorobiphenyl-2- yl]sulfonyl}cyclopentanecarbonitrile
739	1-{[4′-(2-Aminopyrimidin-5- yl)-3′-fluorobiphenyl-2- yl]sulfonyl}cyclopentanecarboxamide
740	5-(2′-{[1- (Aminomethyl)cyclopentyl]sulfonyl}- 3-fluorobiphenyl-4-yl)pyrimidin-2- amine
741	5-{[4′-(5-Aminopyrazin-2′-yl)-3′- fluorobiphenyl-2-yl]sulfanyl}pyrazin- 2-amine
742	5-{2′-[(6-Aminopyrazin-2- yl)sulfanyl]-fluorobiphenyl-4- yl}pyrazin-2-amine
743	5-(3-Fluoro-2′-(pyrimidin-4- ylthio)-[1,1′-biphenyl]-4-yl)pyrazin-2- amine
744	5-{2′-[(5-Aminopyrazin-2- yl)sulfanyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine
745	6-Amino-3-{2′-[(4-aminopyrimidin-2- yl)oxy]-3-fluorobiphenyl-4- yl}pyrazine-2-carbanitrile
746	6-Amino-3-[3-fluoro-2′-(pyrimidin-2- yloxy)-4′-(trifluoramethyl)biphenyl-4- yl]pyrazine-2-carbonitrile
747	6-Amino-3-[3-fluoro-2′- (pyrimidin-2-yloxy)biphenyl-4- yl]pyrazine-2-carbonitrile
748	N-(tert-Butyl)-3′-fluoro-4′-(5- (methylsulfonamido)pyrazin-2-yl)- [1,1′-biphenyl]-2-sulfonamide
749	5-{2′-[(Ethylsulfonyl)methyl]-3- fluorobiphenyl-4-yl}pyrazin-2-amine hydrogen chloride salt
750	5-{3-Fluoro-2′- [(methylsulfonyl)methyl]biphenyl-4- yl}pyrazin-2-amine
751	5-(3-Fluoro-2′-{[(1- methylethyl)sulfonyl]methyl}biphenyl- 4-yl)pyrazin-2-amine
752	5-{3-Fluoro-2′-(pyrimidin-2- ylsulfonyl)methyl]biphenyl-4- yl}pyrazin-2-amine
753	2-({(4′-(5-Aminopyrazin-2-yl)- 3′-fluorobiphenyl-2- yl]methyl}sulfanyl)pyrimidin-4-amine
754	racemic 5-(3-Fluoro-2′-{[2- {trifluoromethyl)morpholin-4- yl]carbonyl}biphenyl-4-yl)pyrazin-2- amine
755	1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]carbonyl}azetidin- 3-ol
756	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (tetrahydro-2H-pyran-4-yl)biphenyl-2- carboxamide
757	5-{2′-[(1,1-Dioxidothiomorpholin-4- yl)carbonyl]-3-fluoro-4′- (trifluoromethyl)biphenyl-4-yl}pyrazin- 2-amine
758	1-(4-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]carbonyl)morpholin-2-yl)ethanol (diastereomeric mixture).
759	1-(4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2- yl]carbonyl}morpholin-2-yl)ethanol (diastereomeric mixture).
760	4′-(5-Aminopyrazin-2-yl)-3′-fluoro-N- (2-hydroxyethyl)biphenyl-2- carboxamide
761	4′-(2-4minopyrimidin-5-yl)-3′-fluoro- N-(2-hydroxyethyl)biphenyl-2- carboxamide
762	(3R)-1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]carbonyl}piperidin-3-ol
763	(cis/trans) 4′-(5-Aminopyrazin-2-yl)- 3′-fluoro-N-(4- hydroxycyclohexyl)biphenyl-2- carboxamide
764	(3R)-1-{[4′-(2-Aminopyrimidin-5-yl)- 3′-fluorobiphenyl-2- yl]carbonyl}piperidin-3-ol
765	(cis/trans) 4′-(2-Aminopyrimidin-5-yl)- 3′-fluoro-N-(4- hydroxycyclohexyl)biphenyl-2- carboxamide
766	racemic 5-(3-Fluoro-2′-{[2- (trifluoromethyl)morpholin-4- yl]carbonyl}biphenyl-4-yl)pyrimidin-2- amine
767	(3S)-1-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2- yl]carbonyl}piperidin-3-ol
768	(3S)-1-{[4-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]carbonyl}piperidin-3-ol
769	(3R)-1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]carbonyl}pyrrolidin-3-ol
770	(3R)-1-{[4′-(2-Aminopyrimidin-5-yl)- 3′-fluorobiphenyl-2- yl]carbonyl}pyrrolidin-3-ol
771	(3S)-1-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]carbonyl}pyrrolidin-3-ol
772	(3S)-1-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2- yl]carbonyl}pyrrolidin-3-ol
773	5-{2′-[(2,6-Dimethylmorpholin-4- yl)carbonyl]-3-fluorobiphenyl-4- yl)pyrazin-2-amine (diastereoisomeric mixture).
774	5-(3-Fluoro-2′-{[(3S)-3- methylmorpholin-4- yl]carbonyl}biphenyl-4-yl)pyrazin-2- amine
775	5-(3-Fluoro-2′-{[(3R)-3- methylmorpholin-4- yl]carbonyl}biphenyyl-4-yl)pyrazin-2- amine
776	5-(3-Fluoro-2′-{[(2S)-2- methylmorpholin-4- yl]carbonyl}biphenyl-4-yl)pyrazin-2- amine
777	5-(3-Fluoro-2′-{[(2S)-2- methylmorpholin-4- yl]carbonyl}biphenyl-4-yl)pyrimidin-2- amine
778	5-(3-Fluoro-2′-{[(3S)-3- methylmorpholin-4- yl]carbonyl}biphenyl-4-yl)pyrimidin-2′- amine
779	5-(3-Fluoro-2′-{[(3R)-3- methylmorpholin-4- yl]carbonyl}biphenyl-4-yl)pyrimidin-2- amine
780	5-{2′-[(2,6-Dimethylmorpholin-4- yl)carbonyl]-3-fluorobiphenyl-4- yl}pyrimidin-2-amine (diastereoisomeric mixture)
781	5-{2-Fluoro-4-[2-(morpholin-4- ylcarbonyl)pyridin-3-yl]phenyl]-1H- pyrrolo[2,3-b]pyridine
782	5-{2-Fluoro-4-[2-(morpholin-4- ylcarbonyl)pyridin-3- yl]phenyl}pyrimidin-2-amine
783	5-{2-Fluoro-4-[2-(morpholin-4- ylcarbonyl)pyridin-3- yl]phenyl}pyrazin-2-amine
784	2-[4-(5-Aminopyrazin-2-yl)-3-fluoro- phenyl]-N-tert-butyl-5- (trifluoromethyl)benzamide
785	2-[4-(5-Aminopyrazin-2-yl)-3-fluoro- phenyl]-N-[(1R)-2-hydroxy-1-methyl- ethyl]-5-(trifluoromethyl)benzamide
786	2-[4-(5-Aminopyrazin-2-yl)-3-fluoro- phenyl]-N-[(1S)-2-hydroxy-1-methyl- ethyl]-5-(trifluoromethyl)benzamide
787	2-[4-(5-Aminopyrazin-2-yl)-3-fluoro- phenyl]-5-(trifluoromethyl)-N-[(1R)- 2,2,2-trifluoro-1-methyl- ethyl]enzamide
788	2-[4-(2-Aminopyrimidin-5-yl)-3-fluoro- phenyl]-5-(trifuoromethyl)-N-[(1S)- 2,2,2-trifluoro-1-methyl- ethyl]enzamide
789	2-[4-(2-Aminopyrimidin-5-yl)-3-fluoro- phenyl]-5-(trifluoromethyl)-N-(1R)- 2,2,2-trifluoro-1-methyl- ethyl)benzamide
790	2-[4-(5-Aminopyrazin-2-yl)-3-fluoro- phenyl]-5-(trifiuoromethyl)-N-[(1S)- 2,2,2-trifluoro-1-methyl- ethyl]benzamide
791	[2-[4-(2-Aminopyrimidin-5-yl)-3- fluoro-phenyl]phenyl]-(3- hydroxyazetidin-1-yl)methanone
792	[2-[4-(2-Aminopyrimidin-5-yl)-3- fluoro-phenyl]phenyl]-[4- (methylamino)-1-piperidyl]methanone
793	[2-[4-(2-Aminopyrimidin-5-yl)-3- fluoro-phenyl]-5- (trifluoromethyl)phenyl]-(1,1-dioxo- 1,4-thiazinan-4-yl)methanone
794	2-[4-(2-Aminopyrimidin-5-yl)-3-fluoro- phenyl]-N-tert-butyl-5- (trifluoromethyl)benzamide
795	[2-[4-(5-Aminopyrazin-2-yl)-3-fluoro- phenyl]-5-(trifluoromethyl)phenyl]-(4- hydroxy-1-piperidyl)methanone
796	[2-[4-(2-Aminopyrimidin-5-yl)-3- fluoro-phenyl]-5- (trifluoromethyl)phenyl]-(4-hydroxy-1- piperidyl)methanone
797	2-[4-(2-Aminopyrimidin-5-yl)-3-fluoro- phenyl]-N-tetrahydropyran-4-yl- benzamide
798	racemic [2-]4-(5-Aminopyrazin-2-yl)- 3-fluoro-phenyl]phenyl]-[2- (hydroxymethyl)morpholin-4- yl]methanone
799	racemic [2-[4-(2-Aminopyrimidin-5- yl)-3-fluoro-phenyl]phenyl]-2- (hydroxymethyl)morpholin-4- yl]methanone
800	N-[3-[4-(2-Aminopyrimidin-5-yl)-3- fluorophenyl]pyridin-2-yl}-2,2- dimethylpropanamide
801	N-{3-[4-(5-Aminopyrazin-2-yl)-3- fluorophenyl]pyridin-2-yl}-2,2- dimethylpropanamide
802	N-{3-[3-Fluoro-4-(1H-pyrrolo[2,3- b]pyridin-5-yl)phenyl]pyridin-2-yl}-2,2- dimethylpropanamide
803	racemic 5-(2-Fluoro-4-(2- (pyrrolidin-3-ylsulfonyl)pyridin-3- yl)phenyl)pyrazin-2-amine hydrochloride
804	5-(2-Fluoro-4-(2- (pyrrolidin-3- ylsulfonyl)pyridin-3- yl)phenyl)pyrimidin-2-amine formic acid salt.
805	5-(4-(2- (Cyclobutylsulfonyl)pyridin-3- yl)-2-fluorophenyl)pyrimidin- 2-amine hydrochloride.
806	5-(4-(2- (Cyclobutylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrazin-2-amine hydrochloride
807	5-(4-(2- (Cyclohexylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrimidin-2-amine hydrochloride
808	5-(4-(2- (Cyclohexylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrazin-2-amine hydrochloride
809	5-(4-2- (Cyclopentylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrimidine-2-amine hydrochloride
810	5-(4-(2- (Cyclopentylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrazin-2-amine hydrochloride
811	5-(4-(2-(tert- Butylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrimidin-2-amine formic acid salt.
812	5-(4-(2-(tert- Butylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrazin-2-amine formic acid salt.
813	racemic 5-(4-(2-(sec- Butylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrimidin-2-amine formate
814	racemic 5-(4-(2-(sec- Butylsulfonyl)pyridin-3-yl)-2- fluorophenyl)pyrazin-2-amine formate
815	1-((3-(4-(2-Aminopyrimidin-5- yl)-3-fluorophenyl)pyridine-2- yl)sulfonyl)piperidin-1-yl)ethanone
816	1-((3-(4-(2-Aminopyrazin-5- yl)-3-fluorophenyl)pyridine-2- yl)sulfonyl)piperidin-1-yl)ethanone hydrogen chloride salt
817	5-(2-Fluoro-4-(2-((3- methoxypropyl)sulfonyl)pyridine-3- yl)phenyl)pyrimidin-2-amine hydrogen chloride salt.
818	5-(2-Fluoro-4-(2-((3- methoxypropyl)sulfonyl)pyridine-3- yl)phenyl)pyrazin-2-amine hydrogen chloride salt.
819	4-((3-(4-(2-aminopyrimidin-5- yl)-3-fluorophenyl)pyridine-2- yl)sulfonyl)tetrahydro-2H-thiopyran 1,1-dioxide
820	4-((3-(4-(2-Aminopyrazin-5- yl)-3-fluorophenyl)pyridine-2- yl)sulfonyl)tetrahydro-2H-thiopyran 1,1-dioxide
821	5-(2-Fluoro-4-(2-((2- morpholinoethyl)sulfonyl)pyridine- 3-yl)phenyl)pyrimidin-2- amine formic acid salt.
822	5-(2-Fluoro-4-(2-((2- morpholinoethyl)sulfonyl)pyridine-3- yl)phenyl)pyrazin-2-amine
823	5-(2-Fluoro-4-(2- (((tetrahydro-2H-pyran-4- yl)methyl)sulfonyl)pyridine-3- yl)pyrimidin-2-amine formic acid salt.
824	5-(2-Fluoro-4-(2- (((tetrahydro-2H-pyran-4- yl)methyl)sulfonyl)pyridine-3- yl)pyrazin-2-amine formic acid salt.
825	5-(2-Fluoro-4-{2-[(1- methylethyl)sulfonyl]pyridin-3- yl}phenyl)pyrimidin-2-amine
826	5-(2-Fluoro-4-(2- (isopropylsulfonyl)pyridine-3- yl)phenyl)-1H-pyrrolo[2,3-b]pyridine
827	5-{2-Fluoro-4-[2-(piperidin-4- ylsulfonyl)pyridin-3- yl]phenyl)pyrimidin-2-amine formic acid salt.
828	5-{4-[2-(Cyclopropylsulfonyl)pyridin- 3-yl]-2-fluorophenyl}pyrimidin-2- amine formic acid salt.
829	5-{4-[2-(Cyclopropylsulfonyl)pyridin- 3-yl]-2-fluorophenyl}pyrazin-2-amine formic acid salt.
830	5-{2-Fluoro-4-[2-(tetrahydro-2H- pyran-4-ylsulfonyl)pyridin-3- yl]phenyl}pyrazin-2-amine hydrochloride
831	5-{2-Fluoro-4-[2-(tetrahydro-2H- pyran-4-ylsulfonyl)pyridin-3- yl]phenyl}pyrimidin-2-amine formic acid salt.
832	5-{2-Fluoro-4-[2-(piperidin-4- ylsulfonyl)pyridin-3-yl]phenyl}pyrazin- 2-amine hydrochloride
833	5-(2,3-Difluorobiphenyl-4-yl)pyrazin- 2-amine.
834	5-(3-Fluoro-2-methoxybiphenyl-4- yl)pyrazin-2-amine.
835	5-[3-Fluoro-2-methoxy-2′- (methylsulfonyl)biphenyl-4-yl]pyrazin- 2-amine.
836	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl- 3′-fluoro-2′-methoxybiphenyl-2- sulfonamide.
837	N-[4′-(5-Aminopyrazin-2-yl)-3′-fluoro- 2′-methoxybiphenyl-2- yl]methanesulfonamide.
838	5-(3-fluoro-2′-(pyrazin-2-yl-[1,1′- biphenyl]-4-yl)pyrazin-2-amine
839	5-(3-Fluoro-2′-pyrazin-2-ylbiphenyl-4- yl)pyrimidin-2-amine.
840	5,5′-(3′-Fluorobiphenyl-2,4′- diyl)dipyrazin-2-amine.
841	5-[2′-(5-Aminopyrazin-2-yl)-3- fluorobiphenyl-4-yl]pyrimidin-2- amine.
842	5-[2′-(6-Aminopyrazin-2-yl)-3- fluorobiphenyl-4-yl]pyrazin-2-amine.
843	5-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]pyrimidin-2- amine.
844	5-5′-(3′-Fluorobiphenyl-2,4′- diyl)dipyrimidin-2-amine.
845	5-[4′-(5-Aminopyrazin-2-yl)-3′-fluoro- 5-(trifluoromethyl)biphenyl-2- yl]pyrimidin-2-amine.
846	5-[3-Fluoro-2′-(2-methoxypyrimidin-5- yl)biphenyl-4-yl]pyrazin-2-amine.
847	5-[3-Fluoro-2′-(1-methyl-1H-pyrazol- 4,yl)biphenyl-4-yl]pyrazin-2-amine.
848	5-(3-Fluoro-2′-pyrimidin-5-ylbiphenyl- 4-yl)pyrazin-2-amine.
849	5-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]pyrimidine-2- carbonitrile.
850	5-[3-Fluoro-2′-(2-morpholin-4- ylpyrimidin-5-yl)biphenyl-4-yl]pyrazin- 2-amine.
851	1-{4-[4-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl)-1H-pyrazol-1-yl}- 2-methylpropan-2-ol.
852	5-[3-Fluoro-2′-(1,2,3,6- tetrahydropyridin-4-yl)-4′- (trifluoromethyl)biphenyl-4-yl]pyrazin- 2-amine.
853	5-[4′-(5-Aminopyrazin-2-yl)-3′-fluoro- 4-(trifluoromethyl)biphenyl-2- yl]pyrimidin-2-amine.
854	5-{2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3-yl]phenyl}pyrimidin-2- amine.
855	5-{5-[2-(2-Aminopyrimidin-5- yl)phenyl]pyridin-2-yl}pyrimidin-2- amine.
856	5-[2′-(1,1-Dioxidoisothiazolidin-2-yl)- 3-fluorobiphenyl-4-yl]pyrazin-2-amine
857	5-[2′-(1,1-Dioxido-1,2-thiazinan-2-yl)- 3-fluorobiphenyl-4-yl]pyrazin-2-amine
858	5-[2′-(1,1-Dioxidoisothiazolidin-2-yl)- 3-fluorobiphenyl-4-yl]pyrimidin-2- amine
859	5-[2-Fluoro-4-(2-pyrrolidin-1- ylpyridin-3-yl)phenyl]pyrazin-2-amine
860	1-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]pyrrolidin-2-one
861	5-[2′-(6-Aminopyridin-3-yl)-3- fluorobiphenyl-4-yl]pyrazin-2-amine
862	5-[3-Fluoro-2′-(2-piperazin-1- ylpyrimidin-5-yl)biphenyl-4-yl]pyrazin- 2-amine
863	6-[4-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]pyridazin-3-amine
864	5-{2′-[1-(2-Aminoethyl)-1H-pyrazol-4- yl]-3-fluorobiphenyl-4-yl]pyrazin-2- amine
865	5-[2′-(6-Aminopyridin-3-yl)-3- fluorobiphenyl-4-yl]pyrimidin-2-amine
866	5-[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]-N- methylpyrimidin-2-amine
867	4-[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]pyrimidin-2-amine
868	4-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]pyrimidin-2-amine
869	5-{3-Fluoro-2′-[1-(2-methoxyethyl)- 1H-pyrazol-4-yl]biphenyl-4- yl}pyrazin-2-amine
870	5-[3-Fluoro-2′-(1H-pyrazol-4- yl)biphenyl-4-yl]pyrazin-2-amine
871	{4-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-1H-pyrazol-1- yl}acetonitrile
872	5-[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]-N- methylpyrimidin-2-amine
873	5-(3-Fluoro-2′-isothiazol-4-ylbiphenyl- 4-yl)pyrazin-2-amine
874	2-{4-[4′-(5-Aminopyrazin-2-yl)-3′- flluoroblphenyl-2-yl-1H-pyrazol-1- yl}ethanol
875	{4-[4′-(2-Aminopyrimidin.-5-yl)-3′- fluorobiphenyl-2-yl]-1H-pyrazol- yl}acetonitrile
876	5-[3-Fluoro-2′-(1H-pyrazo-4- yl)biphenyl-4-yl]pyrimidin-2-amine
877	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3-yl]-N-[(1S)-2,2,2- trifluoro-1- methylethyl]penzenesulfonamide as the hydrochloride salt
878	5-{5-[2-(Cyclopropylsulfonyl)phenyl]- 3-fluoropyridin-2-yl}pyrimidin-2-amine
879	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3-yl]-N-[(2S)-2- hydroxypropyl]benzenesulfonamide
880	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3-yl]-N-[(1S)-2-hydroxy- 1-methylethyl]benzenesulfonamide
881	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-a-yl]-N-[(1R)-2-hydroxy- 1-methylethyl]benzenesulfonamide
882	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3-yl]-N-(2- hydroxyethyl)benzenesulfonamide.
883	2-[6-(2-Aminopyrimidin-5-yl)-5- fluoropyridin-3yl]-N-[(1R)-2,2,2- trifluoro-1- methylethyl]benzenesulfonamide
884	5-{2′-[(1,1-Dioxidotetrahydro-2H- thiopyran-4-yl)methoxy]-3- fluorobiphenyl-4-yl}pyrazin-2-amine
885	5-{2′-[(1,1-Dioxidotetrahydro-2H- thiopyran-4-yl)oxy]-3-fluorobiphenyl- 4-yl}pyrazin-2-amine
886	4-(([4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2- yl]oxy}methyl)benzoic acid
887	4-({[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2- yl]oxy}methyl)benzoic acid
888	4-{[4′-(5-Aminopyrazin-2-yl)-3′- fluorobiphenyl-2-yl]oxy}benzoic acid
889	4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy}benzoic acid
890	4-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]oxy)benzamide
891	5-{2′-1(trans-4-Aminocyclohexyl)oxy]- 3-fluorobiphenyl-4-yl}pyrazin-2-amine
892	5-[2′-Amino-3-fluoro-4′- (trifluoromethyl)biphenyl-4-yl]pyrazin- 2-amine
893	5-[2-Fluoro-4-(2-phenylpyridin-3- yl)phenyl]pyrazin-2-amine
894	5-[2-Fluoro-4-(2-phenoxypyridin-3- yl)phenyl]pyrazin-2-amine
895	5-[2-Fluoro-4-(2-phenoxypyridin-3- yl)phenyl]pyrimidin-2-amine
896	5-{2-Fluoro-4-[2-(pyridin-3- yloxy)pyridin-3-yl]phenyl}pyrazin-2- amine
897	5-{2-Fluoro-4-[2- (phenylsulfonyl)pyridin-3- yl]phenyl}pyrazin-2-amine
898	5-{2-fluoro-4-[2- (phenylsulfonyl)pyridin-3- yl]phenyl}pyrimidin-2-amine
899	5-{2-Fluoro-4-[2-(pyridin-3- ylsulfonyl)pyridin-3-yl]phenyl}pyrazin- 2-amine
900	5-(2-Fluoro-4-{2-[(1-methylpyrrolidin- 3-yl)sulfonyl]pyridin-3- yl}phenyl)pyrazin-2-amine
901	5-(2-Fluoro-4-{2-[(1- methylethyl)sulfonyl]-6- (trifluoromethyl)pyridin-3- yl}phenyl)pyrazin-2-amine
902	5-(2-Fluoro-4-{2-[(1- methylethyl)sulfonyl]-6- (trifluoromethyl)pyridin-3- yl}phenyl)pyrimidin-2-amine
903	5-(4-{2-[(1-Acetylpiperidin-3- yl)sulfonyl]pyridin-3-yl}-2- fluorophenyl)pyrazin-2-amine
904	2-[4-({3-[4-(5-Aminopyrazin-2-yl)-3- fluorophenyl]pyridin-2- yl}sulfonyl)pipendin-1-yl]ethanol
905	(racemic)-1-[4({3-[4-(5- Aminopyrazin-2-yl)-3- fluorophenyl]pyridin-2- yl}sulfonyl)piperidin-1-yl]propan-2-ol
906	5-{2-Fluoro-4-[2-tetrahydro-2H- pyran-4-ylsulfonyl)-6- (trifluoromethyl)pyridin-3- yl]phenyl}pyrazin-2-amine
907	5-{2-Fluoro-4-[2-(tetrahydro-2H- pyran-4-ylsulfonyl)-6- (trifluoromethyl)pyridin-3- yl]phenyl}pyrimidin-2-amine
908	5-(2-Fluoro-4-(2-{[1- (methylsulfonyl)piperidin-4- yl]sulfonyl}pyridin-3- yl)phenyl]pyrazin-2-amine
909	5-(2-Fluoro-4-(2-{[1- (methylsulfonyl)piperidin-4- yl]sulfonyl}pyridin-3- yl)phenyl]pyrimidin-2-amine
910	5-(4-{2-[(1-Acetylpiperidin-4- yl)sulfonyl]-6-(trifluoromethyl)pyridin- 3-yl}-2-fluorophenyl)pyrazin-2-amine
911	5-(4-{2-[(1-Acetylpiperidin-4- yl)sulfonyl]-6-(trifluoromethyl)pyridin- 3-yl}-2-fluorophenyl)pyrimidin-2- amine
912	5-(4-{2-[(1,1-Dioxidotetrahydra-2H- thiopyran-4-yl)sulfonyl]-6- (trifluoromethyl)pyridin-3-yl}-2- fluorophenyl)pyrazin-2-amine
913	5-(4-{2-[(1,1-Dioxidotetrahydro-2H- thiopyran-4-yl)sulfonyl]-6- (trifluoromethyl)pyridin-3-yl}-2- fluorophenyl)pyrimidin-2-amine

TABLE 4 — Prophetic Examples

STRUCTURE	No.	NAME
1	4′-(6-Aminopyridazin-3-yl)-3′- fluorobiphenyl-2-sulfonamide
2	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl-3′- fluoro-5-(trifluoromethyl)biphenyl-2- sulfonamide
4	N-[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]methanesulfonamide
5	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl-3′- fluoro-5-methoxybiphenyl-2-sulfonamide
6	(3S)-1-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}pyrrolidine-3- carboxamide
7	(3R)-1-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}pyrrolidine-3- carboxamide
8	5-[3-Fluoro-2′-(morpholin-4- ylcarbonyl)biphenyl-4-yl]pyrazin-2-amine
9	5-{2′-[(Cyclopropylmethyl)sulfonyl]-3- fluorobiphenyl-4-yl}pyrazin-2-amine
10	1-{[4′-(2-Aminopyrimidin-5-yl)-3′- fluorobiphenyl-2-yl]sulfonyl}-4- (pentafluoroethyl)piperidin-4-ol
11	tert-Butyl (1-{[3′-fluoro-4′-(5H-pyrrolo[2,3- b]pyrazin-2-yl)biphenyl-2- yl]sulfonyl}piperidin-4-yl)carbamate
12	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl-3′,4- difluorobiphenyl-2-sulfonamide
13	4′-(5-Aminopyrazin-2-yl)-N-tert-butyl-3′- fluoro-4-(trifluoromethyl)biphenyl-2- sulfonamide

TABLE 5 — FLAP binding and Human Whole Blood assay data

Cmp	FLAP Binding wild type HTRF	Human Whole Blood LTB4 IC 50
No.	K i (μM)	1:1 (μM)
1	0.217	0.860
2	0.286	0.358
3	>10
4	0.001	0.018
5	0.035	0.370
6	0.001	0.033
7	0.002	0.014
8	0.001	0.012
9	0.003	0.060
10	0.003	0.053
11	0.002	0.015
12	0.002	0.021
13	0.001	0.018
14	0.003	0.032
15	0.010	0.059
16	0.006	0.018
17	0.002	0.025
18	0.002	0.070
19	0.002	0.050
20	0.001	0.009
21	0.002	0.035
22	0.002	0.048
23	0.001	0.013
24	0.002	0.048
25	0.003	0.023
26	0.001	0.026
27	0.029	10.000
28	0.090	0.325
29	0.059	0.030
30	0.095
31	0.004	0.036
32	0.008	0.030
33	0.304
34	0.031	0.334
35	0.036	0.094
36	0.010	0.120
37	0.030	0.676
38	0.033	0.177
39	0.008	0.075
40	0.014	0.112
41	0.014	2.687
42	0.011	0.149
43	0.002	0.111
44	0.007	0.058
45	0.003	0.010
46	0.057	0.194
47	0.001	0.017
48	0.011	0.158
49	0.002	0.021
50	0.001	0.015
51	0.004	0.042
52	0.004	0.155
53	0.003	0.238
54	0.020	0.023
55	0.001	1.232
56	0.011	3.516
57	0.015	0.252
58	0.005	0.991
59	0.020	1.017
60	0.028	0.464
61	0.011	0.117
62	0.142	0.111
63	0.006	0.028
64	0.002	0.006
65	0.049	0.322
66	0.021	0.069
67	0.003	0.012
68	0.001	0.006
69	0.001	0.008
70	0.002	0.010
71	0.002	0.023
72	0.111	0.168
73	0.062	0.077
74	0.006	0.061
75	0.012	0.185
76	0.002	0.027
77	0.003	0.342
78	0.001	0.166
79	0.005	0.150
80	0.004	0.088
81	0.006	0.152
82	0.001	0.018
83	0.001	0.019
84	0.003	0.097
85	0.002	0.020
86	0.003	0.027
87	0.003	0.075
88	0.007	0.036
89	0.006	0.043
90	0.001	0.012
91	0.005	0.028
92	0.325	0.222
93	0.127	0.128
94	0.076	0.235
95	0.010	0.053
96	0.354	>10
97	0.008	0.042
98	0.008	0.039
99	0.002	0.030
100	0.001	0.024
101	0.002	0.014
102	0.000	0.035
103	0.000	0.017
104	0.012	>1
105	0.025	0.481
106	0.019	>1
107	0.016	0.132
108	0.010	0.049
109	0.001	0.018
110	0.003	0.029
111	0.004	0.058
112	0.007	0.154
113	0.010	0.145
114	0.012	0.221
115	0.004	0.108
116	0.001	0.012
117	0.001	0.007
118	0.000	0.006
119	0.003	0.022
120	0.001	0.017
121	0.000	0.010
122	0.001	0.018
123	0.083	1.125
124	0.035	0.217
125	0.050	>10
126	0.141	0.572
127	0.002	0.035
128	0.001	0.038
129	0.004	0.534
130	0.129	0.633
131	0.144	0.695
132	0.002	0.011
133	0.001	0.032
134	0.001	>1
135	0.000	0.016
136	0.001	0.015
137	0.003	0.044
138	0.011	0.174
139	0.133	0.341
140	0.001	0.011
141	0.001	0.003
142	0.015	0.041
143	0.008	0.049
144	0.015	0.097
145	0.017	0.021
146	0.019	0.168
147	0.001	0.102
148	0.002	0.008
149	0.005	0.082
150	0.001	0.011
151	0.001	0.114
152	0.081	0.537
153	0.003	0.007
154	0.029	1.044
155	0.012	0.103
156	0.351	>10
157	0.010	1.841
158	0.001	0.001
159	0.001	0.001
160	0.000	0.005
161	0.000	0.048
162	0.005	0.122
163	0.001	0.595
164	0.001	0.333
165	0.018	0.879
166	0.164	4.463
167	0.047	0.442
168	0.014	0.135
169	0.003	0.023
170	0.001	0.012
171	0.002	0.013
172	0.004	0.020
173	0.001	0.017
174	0.002	0.023
175	0.001	0.017
176	0.000	0.010
177	0.000	0.302
178	1.323
179	0.000	0.002
180	0.002	0.037
181	0.007	0.240
182	0.020	0.217
183	0.034	0.130
184	0.009	0.021
185	0.010	0.051
186	0.019	0.021
187	0.066	0.069
188	0.201	1.185
189	0.173	1.649
190	0.058	0.471
191	0.658
192	0.058	0.171
193	0.026	0.144
194	0.733
195	0.003	0.093
196	0.010	0.104
197	0.010	0.083
198	0.083	0.375
199	0.039	0.250
200	0.035	0.176
201	0.021	0.358
202	0.072	0.172
203	0.005	0.052
204	0.004	0.128
205	0.008	0.066
206	0.002	0.043
207	0.017	0.205
208	0.000	0.014
209	0.001	0.034
210	0.000	0.020
211	0.001	0.006
212	0.001	0.005
213	0.002	0.025
214	0.012	0.138
215	0.002	0.012
216	0.002	0.016
217	0.001	0.009
218	0.003	0.029
219	0.005	0.031
220	0.205	0.219
221	0.300	0.854
222	0.118	0.638
223	0.663
224	0.293	0.516
225	0.856
226	0.211	0.329
227	0.670
228	1.055
229	1.067
230	1.205	5.000
231	0.135	0.564
232	0.358
233	0.637
234	0.025	0.238
235	0.036	0.285
236	0.057	0.443
237	0.008	0.134
238	0.005	0.038
239	0.006
240	0.002	0.021
241	0.015	0.061
242	0.001	0.004
243	0.003	0.120
244	0.029	0.211
245	0.045	0.233
246	0.199	0.302
247	0.089	0.197
248	0.050	0.124
249	0.059	0.094
250	0.038	0.077
251	0.005	0.068
252	0.127	0.206
253	0.134	0.191
254	0.080	0.586
255	0.008	0.076
256	0.035	0.073
257	0.154	1.125
258	0.243	0.202
259	0.005	0.034
260	0.010	0.057
261	0.006	0.075
262	0.018	0.046
263	0.169	0.207
264	0.028	0.144
265	0.045	0.160
266	0.184	0.464
267	0.154	0.350
268	0.011	0.056
269	0.015	0.087
270	0.057	1.065
271	0.051	0.606
272	0.032	0.125
273	0.009	0.105
274
275	0.065	0.192
276	0.023	0.325
277	0.052	>1
278	0.036	0.095
279	0.070	0.149
280	0.003	0.087
281	0.061	0.044
282	0.750	0.280
283	0.009	0.119
284	0.042	1.037
285	0.003	0.111
286	0.142	0.206
287	0.009	0.074
288	0.103	0.420
289	0.022	0.036
290	0.940
291	0.007	0.421
292	0.012	1.029
293	>10
294	0.002	0.248
295	0.025	0.110
296	0.005	0.066
297	0.005	0.045
298	0.081	1.166
299	0.121
300	0.013	0.120
301	0.013	0.204
302	2.500
303	0.612
304	>10
305	0.002	0.078
306	0.397
307	0.004	0.416
308	>10
309	0.214	1.785
310	0.492
311	0.747
312	0.262	0.376
313	0.397	0.574
314	0.089	0.178
315	0.001	0.027
316	0.746
317	0.335	>10
318	0.689	2.001
319	0.204	3.263
320	0.129	1.084
321	0.505	8.486
322	0.032	0.138
323	0.770	6.644
324	0.019	0.101
325	0.004	0.091
326	0.003	0.029
327	0.002	0.039
328	0.015	0.119
329	0.012	0.066
330	0.012	0.088
331	0.014	0.062
332	0.065	0.125
333	0.045	0.671
334	0.012	0.067
335	0.002	0.037
336	0.004	0.065
337	2.500
338	0.199	1.094
339	2.500
340	0.104	0.321
341	>10
342	0.002	0.117
343	0.004	0.057
344	0.081	>10
345	0.028	0.259
346	0.005	0.095
347	0.077	0.161
348	0.005	0.106
349	0.001	0.013
350	0.002	0.026
351	0.017	0.297
352	0.016	0.064
353	0.001	0.020
354	0.037	0.093
355	0.005	0.029
356	0.032	0.107
357	0.114	1.128
358	0.055	>10
359	0.004	0.054
360	0.022	0.067
361	0.005	0.026
362	0.001	0.047
363	0.001	0.184
364	0.003	0.150
365	0.003	0.060
366	0.001	0.040
367	0.001	0.006
368	0.013	0.178
369	0.017	0.375
370	0.002	0.088
371	0.001	0.015
372	0.025	0.031
373	0.001	0.007
374	0.001	0.011
375	0.002	0.031
376	0.000	0.010
377	0.033	0.979
378	0.001	0.016
379	0.001	0.033
380	0.001	0.046
381	0.005	0.141
382	0.000	0.011
383	0.008	1.633
384	0.004	0.082
385	0.042	1.083
386	0.002	0.077
387	0.008	0.253
388	0.002	0.037
389	0.013	0.137
390	0.000	0.010
391	0.002	0.056
392	0.001	0.016
393	0.001	0.012
394	>10
395	0.009	0.032
396	0.008	0.137
397	>10
398	0.034	1.132
399	0.028	0.358
400	0.014	0.729
401	0.158	0.538
402	0.092	0.522
403	0.070	0.389
404	0.155	1.490
405	0.100	2.708
406	0.135	4.314
407	>10
408	0.128	1.142
409	>10
410	0.004	0.088
411	0.036	1.968
412	0.019	0.509
413	0.019	0.448
414	0.065	0.120
415	0.011	0.037
416	1.249
417	0.108	0.726
418	1.250
419	1.369
420	0.086	3.280
421	0.028	>10
422	0.003	0.146
423	0.284	4.795
424	0.010	>10
425	0.002	0.111
426	0.002	0.073
427	0.054	1.599
428	0.004	0.004
429	0.013	0.209
430	0.005	0.059
431	0.001	0.009
432	0.004	0.019
433	0.001	0.025
434	0.001	0.036
435	0.009	0.166
436	0.308	3.277
437	0.023	0.381
438	0.001	0.017
439	0.063	0.300
440	0.031	0.215
441	0.001	0.006
442	0.001	0.009
443	0.343	3.331
444	0.183	>10
445	0.001	0.008
446	0.304	1.371
447	0.003	0.144
448	0.010	0.112
449	0.022	0.079
450	0.074	0.340
451	0.002	0.038
452	0.081	1.954
453	>10	>10
454	0.012	0.345
455	0.001	0.094
456	0.003	0.114
457	0.003	0.140
458	0.004	0.053
459	>10
460	>10
461	0.041	0.209
462	0.002	0.062
463	0.982
464	0.121	>10
465	0.186	0.957
466	0.254	0.990
467	0.250	2.827
468	0.620
469	0.250	2.347
470	0.620
471	0.250	3.395
472	0.145	2.524
473	0.113	1.411
474	0.021	2.653
475	0.750
476	0.032	0.891
477	0.016	0.738
478	0.250
479	0.006	0.571
480	0.354
481	1.912
482	0.120
483	0.354
484	0.078	3.465
485	>10
486	2.500
487	0.054	0.444
488	0.097	1.653
489	0.020	0.307
490	0.354	0.269
491	0.015	0.215
492	0.015	0.155
493	0.007	0.303
494	0.032	0.099
495	0.004	0.509
496	0.019	0.165
497	0.025	0.510
498	0.016	0.111
499	0.433
500	0.048	0.139
501	0.359
502	0.083	0.363
503	0.014	0.092
504	0.768
505	0.018	0.071
506	>10
507	>10
508	0.790
509	0.147	0.093
510	1.939
511	0.213	0.323
512	0.443	0.470
513	>10
514	0.132	0.148
515	>10
516	>10
517	>10
518	>10
519	>10
520	>10
521	0.005	0.013
522	0.348	0.393
523	0.001	0.025
524	0.001	0.018
525	0.003	0.036
526	0.008	0.019
527	0.074	0.183
528	0.005	0.034
529	0.036	0.090
530	0.034	1.112
531	0.008	0.323
532	0.006	0.032
533	0.005	0.023
534	0.012	0.069
535	0.001	0.017
536	0.021	0.068
537	0.003	0.042
538	0.020	0.330
539	0.002	0.052
540	0.016	0.085
541	0.012	0.066
542	0.107	0.311
543	0.444	4.165
544	0.028	1.652
545	0.012	0.050
546	0.148	0.253
547	0.035	0.104
548	0.467	0.741
549	0.009	0.123
550	0.002	0.016
551	0.000	0.021
552	0.005	0.102
553	0.019	0.430
554	0.002	0.039
555	0.002	0.024
556	0.001	0.013
557	0.147	1.066
558	0.012	0.210
559	0.002	0.055
560	0.005	0.095
561	0.004	0.043
562	0.055	0.226
563	0.020	0.328
564	0.200	0.583
565	0.081	0.984
566	>10
567	1.135
568	2.500
569	0.070	0.335
570	0.035	1.183
571	0.002	0.091
572	0.370
573	0.114
574	0.015	0.494
575	0.750
576	0.008	0.116
577	0.010	0.091
578	0.025	0.956
579	0.095	1.544
580	0.055	5.000
581	0.060	2.823
582	>10
583	>10
584	>10
585	>10
586	>10
587	>10
588	0.133	>10
589	>10
590	>10
591	~2.49
592	>10
593	>10
594	>10
595	~2.49
596	>10
597	~2.49
598	>10
599	>10
600	>10
601	>10
602	0.0006	0.0167
603	0.0276	>10
604	0.0050	0.0894
605	0.0019	0.0978
606	0.0463	2.624
607	0.1384	0.1520
608	0.0287	0.0539
609	0.2464	0.7677
610	0.0274	0.1170
611	0.2489	0.5626
612	0.0146	0.0420
613	0.2146	0.5565
614
615
616
617
618	0.0146	0.2109
619	0.0034	0.0451
620	0.0019	0.0132
621	0.0050	0.1006
622	0.0461	0.3401
623	0.0049	0.0935
624
625	0.0078	0.1727
626	0.0062	0.0453
627	0.0437	0.3661
628	0.3362
629	0.8358
630	1.8950
631	>10
632	1.2677
633	>10
634	0.3108	1.470
635	1.0869
636	0.0046	0.1072
637	0.0188	0.3975
638	0.0014	0.0148
639	0.0072	0.0670
640	1.3397
641	>10
642	0.0788	0.9806
643	0.3225	4.2874
644	>10
645
646
647
648
649	>10
650	0.8316
651	0.3062	1.5363
652	0.0627	0.8425
653	0.0173	0.5267
654	0.1303	1.0459
655	0.5034	1.8302
656	1.3957
657	0.0735	2.3415
658	0.5717
659	~0.7500
660	0.0833	>10
661	~2.49
662	~1.22
663	0.0058	0.0347
664	0.0050	>1
665	0.0026	0.0224
666	0.0032	0.0361
667	0.0060	0.0396
668	0.0230	0.1897
669	0.0040	0.1064
670	0.0977	0.5255
671	0.0157	0.1645
672	0.0137	0.1964
673	0.1343	0.1013
674	0.0024	0.0174
675	0.0007	0.0551
676	0.2339	3.7145
677	>10
678	>10
679	0.1316	0.2054
680	0.6097	1.0502
681	0.0522	0.1057
682	0.2239	0.2638
683	0.6021	0.2800
684	0.0463	0.1342
685	0.0523	0.1148
686	0.3343	1.4900
687	0.7399	3.5456
688	0.6955	1.1844
689	0.4846	0.7872
690	0.1771	0.1175
691	>10
692	0.0533	0.1097
693	0.0495	0.1032
694	0.6762	1.0115
695	0.0084	0.3355
696	~0.2499	3.27492
697	>10
698	0.0087	0.1117
699
700	>10
701	~1.41
702	~0.3041
703	>10
704	0.1025	0.1906
705	0.0869	0.2891
706	0.0796	0.3620
707	0.0327	0.1266
708	0.0235	0.1416
709	0.0054	0.2682
710	0.0137	0.05651
711	0.0417	0.1420
712	0.0019	0.05233
713	0.0017	0.05339
714	0.0024	0.03311
715	0.0082	0.1858
716	>10
717	1.0083
718	>10
719	>10
720	>10
721	>10
722	>10
723	>10
724	>10
725	1.2960
726	0.9041
727	0.4838	1.1740
728	0.7813
729	0.0647	0.8609
730	0.0067	0.1359
731	0.0147	0.05132
732	0.5571
733	>10
734	>10
735	0.0320	0.2722
736	0.3303	0.4144
737	0.9842
738	0.2400	2.9546
739	0.3701	1.1132
740	>10
741	0.0046	0.02633
742	0.0029	0.02572
743	0.0016	0.02165
744	0.0155	0.13173
745	0.0117	0.11073
746	0.0020	0.13699
747	0.0271	0.26224
748	>10
749	0.2455	0.46752
750	1.1582
751	0.0809	1.05657
752	0.1352	0.29915
753	0.0044	0.02130
754	0.0699	0.37722
755	0.9395
756	>10
757	0.0052	0.016206
758	0.5569
759	>10
760	1.1559
761	>10
762	0.1589	0.44177
763	1.1148
764	>10
765	>10
766	1.9090
767	>10
768	0.5728
769	1.5449
770	>10
771	>10
772	>10
773	0.2227	0.63899
774
775
776
777
778	>10
779	~2.49
780	>10
781	0.7295
782	>10
783	>10
784	0.0079	0.1105
785	0.0085	0.0575
786	0.0607	0.10485
787	0.0091	0.0979
788	0.0178	0.2715
789	0.1303	0.9392
790	0.0015	0.02533
791	>10
792	>10
793	0.2795	0.6419
794	0.0328	3.9355
795	0.0085	0.0686
796	0.3912
797	>10
798	0.2573	0.220039
799	>10
800	>10
801	>10
802	>10	0.000993574
803	0.1065	0.241268
804	0.6359
805	0.0297	0.352777
806	0.0018	0.048395
807	0.0058	0.0721606
808	0.0004	0.00637236
809	0.0038	0.0376964
810	0.0006	0.00563897
811	0.3149	0.541252
812	0.0085	0.0120393
813	0.0339	0.0750585
814	0.0028	0.0209218
815	0.2555	0.128115
816	0.0218	0.0460044
817	0.4629
818	0.0272	0.051606
819	0.0405	0.0474898
820	0.0033	0.041639
821	>10
822	0.2804	0.099106
823	0.1923	0.0950605
824	0.0103	0.0180053
825	0.2732	0.122321
826	0.0007	0.0199205
827	>10
828	0.1153	0.259777
829	0.0032	0.00596486
830	0.0029	0.00555393
831	0.1309	0.0791589
832	1.3119
833	~0.500034
834	0.0489	1.09069
835	~0.35359	0.417157
836	0.0255	0.595114
837	~1.74985
838	0.0286	0.350106
839	0.8297	2.78805
840	0.0127	0.0995864
841	0.1458	0.369658
842	0.0053	0.061038
843	0.0156	0.0442792
844	0.5093	0.907193
845	>10
846	0.0105	0.0418215
847	0.0081	0.0991289
848	0.0968	0.321736
849	0.0356	>1
850	0.0377	0.195434
851	0.0326	0.359335
852	0.1179	1.34555
853	0.0047	0.0456037
854	1.2773
855	>10
856	0.0605	0.083888
857	0.0280	0.205494
858	0.2097	0.369743
859	~1.249
860	~1.479

TABLE 6 — FLAP binding and Human Whole Blood assay data

Cmp	FLAP Binding wild type HTRF	Human Whole Blood LTB4 IC 50
No.	K i (μM)	1:1 (μM)
1	0.3521	0.8596
2	0.1785	0.3582
3	>10
4	0.0004	0.0184
5	0.0366	0.3698
6	0.0011	0.0328
7	0.0008	0.0136
8	0.0013	0.0120
9	0.0015	0.0603
10	0.0027	0.0531
11	0.0016	0.0154
12	0.0019	0.0213
13	0.0012	0.0178
14	0.0035	0.0324
15	0.0111	0.0590
16	0.0050	0.0184
17	0.0017	0.0251
18	0.0018	0.0703
19	0.0022	0.0498
20	0.0009	0.0085
21	0.0021	0.0347
22	0.0021	0.0481
23	0.0012	0.0129
24	0.0023	0.0482
25	0.0032	0.0263
26	0.0009	0.0258
27	0.0263	~10
28	0.0822	0.3246
29	0.0632	0.0301
30	0.0950
31	0.0040	0.0358
32	0.0062	0.0299
33	~0.3041
34	0.0308	0.3340
35	0.0361	0.0944
36	0.0081	0.1366
37	0.0296	0.6761
38	0.0288	0.1773
39	0.0081	0.0751
40	0.0144	0.1118
41	0.0106	2.6866
42	0.0102	0.1493
43	0.0030	0.0381
44	0.0065	0.0582
45	0.0031	0.0102
46	0.0615	0.1774
47	0.0016	0.0166
48	0.0070	0.1583
49	0.0020	0.0211
50	0.0013	0.0154
51	0.0038	0.0424
52	0.0037	0.1551
53	0.0033	0.2377
54	0.0249	0.0413
55	0.0011	1.2317
56	0.0088	3.5164
57	0.0134	0.2517
58	0.0046	0.9911
59	0.0204	1.0170
60	0.0280	0.4638
61	0.0159	0.1173
62	0.1418	0.1111
63	0.0061	0.0284
64	0.0019	0.0131
65	0.0633	0.3224
66	0.0266	0.0689
67	0.0042	0.0168
68	0.0011	0.0109
69	0.0009	0.0081
70	0.0023	0.0100
71	0.0019	0.0227
72	0.1200	0.1682
73	0.0620	0.0769
74	0.0057	0.0610
75	0.0107	0.1851
76	0.0017	0.0267
77	0.0032	0.3416
78	0.0007	0.1663
79	0.0053	0.1498
80	0.0039	0.0881
81	0.0064	0.1518
82	0.0007	0.0181
83	0.0007	0.0191
84	0.0031	0.0975
85	0.0019	0.0199
86	0.0026	0.0266
87	0.0032	0.0752
88	0.0062	0.0364
89	0.0049	0.0432
90	0.0009	0.0125
91	0.0047	0.0383
92	0.2802	0.3092
93	0.0833	0.1275
94	0.0760	0.2347
95	0.0097	0.0515
96	0.3537	>10
97	0.0066	0.0422
98	0.0061	0.0391
99	0.0016	0.0301
100	0.0008	0.0245
101	0.0018	0.0137
102	0.0004	0.0345
103	0.0003	0.0165
104	0.0117	>1
105	0.0247	0.4805
106	0.0191	>1
107	0.0164	0.1316
108	0.0095	0.0486
109	0.0015	0.0181
110	0.0026	0.0294
111	0.0042	0.0576
112	0.0069	0.1543
113	0.0105	0.1451
114	0.0120	0.2215
115	0.0041	0.1080
116	0.0007	0.0122
117	0.0007	0.0066
118	0.0004	0.0063
119	0.0027	0.0217
120	0.0011	0.0171
121	0.0005	0.0096
122	0.0007	0.0179
123	0.0827	1.1249
124	0.0353	0.2172
125	0.0497	>10
126	0.1408	0.5717
127	0.0020	0.0346
128	0.0008	0.0382
129	0.0039	0.5341
130	0.1295	0.6326
131	0.1438	0.6947
132	0.0024	0.0111
133	0.0010	0.0320
134	0.0013	>1
135	0.0004	0.0161
136	0.0005	0.0155
137	0.0029	0.0438
138	0.0114	0.1737
139	0.1330	0.3409
140	0.0014	0.0106
141	0.0007	0.0033
142	0.0151	0.0406
143	0.0085	0.0488
144	0.0148	0.0971
145	0.0167	0.0209
146	0.0191	0.1684
147	0.0006	0.1021
148	0.0025	0.0083
149	0.0052	0.0824
150	0.0015	0.0113
151	0.0013	0.1140
152	0.0807	0.5365
153	0.0025	0.0069
154	0.0293	1.0445
155	0.0116	0.1025
156	0.3513	>10
157	0.0098	1.8408
158	0.0006	0.0014
159	0.0008	0.0013
160	0.0004	0.0053
161	0.0004	0.0478
162	0.0051	0.1223
163	0.0005	0.5953
164	0.0008	0.3332
165	0.0184	0.8790
166	0.1645	4.4627
167	0.0468	0.4416
168	0.0143	0.1348
169	0.0029	0.0229
170	0.0013	0.0118
171	0.0020	0.0135
172	0.0036	0.0201
173	0.0008	0.0165
174	0.0024	0.0231
175	0.0014	0.0170
176	0.0005	0.0100
177	0.0005	0.3016
178	~1.3228
179	0.0004	0.0021
180	0.0021	0.0369
181	0.0067	0.2397
182	0.0199	0.2171
183	0.0344	0.1300
184	0.0089	0.0206
185	0.0095	0.0507
186	0.0188	0.0207
187	0.0657	0.0689
188	0.2014	1.1849
189	0.0632	1.6493
190	0.0662	0.4710
191	~0.6579
192	0.0483	0.1708
193	0.0309	0.1439
194	0.1558
195	0.0023	0.0690
196	0.0078	0.0963
197	0.0071	0.0831
198	0.0721	0.8194
199	0.0386	0.2518
200	0.0349	0.1762
201	0.0207	0.3582
202	0.0716	0.1721
203	0.0050	0.0523
204	0.0045	0.1282
205	0.0076	0.0656
206	0.0020	0.0427
207	0.0171	0.2046
208	0.0004	0.0137
209	0.0010	0.0340
210	0.0004	0.0196
211	0.0005	0.0058
212	0.0008	0.0053
213	0.0024	0.0246
214	0.0116	0.1378
215	0.0024	0.0116
216	0.0022	0.0160
217	0.0012	0.0089
218	0.0033	0.0291
219	0.0048	0.0312
220	0.2052	0.2186
221	0.3001	0.8543
222	0.1176	0.6381
223	0.6628
224	0.2926	0.5158
225	0.8561
226	0.2108	0.3289
227	0.6699
228	1.0554
229	1.0673
230	1.2050	~5.00034
231	0.1354	0.5639
232	0.3575
233	0.6365
234	0.0255	0.2382
235	0.0357	0.2848
236	0.0571	0.4431
237	0.0078	0.1338
238	0.0050	0.0379
239	0.0059
240	0.0024	0.0215
241	0.0146	0.0605
242	0.0007	0.0039
243	0.0033	0.1199
244	0.0294	0.2109
245	0.0453	0.2330
246	0.1990	0.3017
247	0.0894	0.1968
248	0.0568	0.1237
249	0.0595	0.0940
250	0.0382	0.0774
251	0.0045	0.0678
252	0.1267	0.2055
253	0.1344	0.1906
254	0.0800	0.5856
255	0.0081	0.0761
256	0.0350	0.0734
257	0.1537	1.1249
258	0.2430	0.2021
259	0.0078	0.0340
260	0.0089	0.0566
261	0.0056	0.0749
262	0.0183	0.0456
263	0.1272	0.2074
264	0.0276	0.1439
265	0.0355	0.1600
266	0.1330	0.4639
267	0.1854	0.3504
268	0.0114	0.0559
269	0.0149	0.0873
270	0.0573	1.0654
271	0.0505	0.6062
272	0.0269	0.1246
273	0.0093	0.1047
274
275	0.0648	0.1921
276	0.0235	0.3248
277	0.0516	>1
278	0.0356	0.0945
279	0.0700	0.1176
280	0.0033	0.0872
281	0.0608	0.0445
282	~0.7500	0.2799
283	0.0090	0.1187
284	0.0423	1.0373
285	0.0033	0.1110
286	0.1419	0.2060
287	0.0085	0.0744
288	0.1028	0.4201
289	0.0216	0.0361
290	~0.9401
291	0.0067	0.4205
292	0.0099	1.0294
293	>10
294	0.0024	0.2477
295	0.0200	0.1097
296	0.0031	0.0660
297	0.0032	0.0446
298	0.0806	1.1657
299	0.1212
300	0.0128	0.1205
301	0.0126	0.2044
302	~2.4997
303	~0.612351
304	>10
305	0.0016	0.0776
306	0.3974
307	0.0045	0.4158
308	>10
309	0.2143	1.7848
310	0.4919
311	0.7466
312	0.3226	0.3764
313	0.3877	0.5739
314	0.0888	0.1776
315	0.0013	0.0272
316	0.7456
317	0.3346	>10
318	0.6890	2.0012
319	0.2036	3.2629
320	0.1293	1.0839
321	0.5055	8.4859
322	0.0324	0.1382
323	0.7702	6.6435
324	0.0188	0.1014
325	0.0047	0.0908
326	0.0031	0.0287
327	0.0018	0.0386
328	0.0154	0.1187
329	0.0120	0.0658
330	0.0119	0.0883
331	0.0144	0.0619
332	0.0654	0.1245
333	0.0448	0.6710
334	0.0117	0.0672
335	0.0019	0.0370
336	0.0042	0.0651
337	~2.49977
338	0.1992	1.0937
339	~2.49977
340	0.1043	0.3210
341	>10
342	0.0018	0.1167
343	0.0043	0.0568
344	0.0812	>10
345	0.0277	0.2591
346	0.0045	0.0946
347	0.0769	0.1612
348	0.0050	0.1059
349	0.0009	0.0128
350	0.0024	0.0259
351	0.0165	0.2966
352	0.0158	0.0642
353	0.0014	0.0198
354	0.0365	0.0930
355	0.0049	0.0294
356	0.0320	0.1066
357	0.1139	1.1282
358	0.0550	>10
359	0.0043	0.0541
360	0.0216	0.0675
361	0.0052	0.0262
362	0.0012	0.0472
363	0.0006	0.1840
364	0.0025	0.1498
365	0.0029	0.0600
366	0.0010	0.0399
367	0.0009	0.0056
368	0.0132	0.1780
369	0.0173	0.3751
370	0.0019	0.0880
371	0.0007	0.0150
372	~0.0249977	0.0313
373	0.0008	0.0066
374	0.0012	0.0115
375	0.0021	0.0313
376	0.0005	0.0099
377	0.0330	0.9786
378	0.0006	0.0163
379	0.0013	0.0334
380	0.0011	0.0460
381	0.0048	0.1405
382	0.0005	0.0110
383	0.0079	1.6334
384	0.0039	0.0819
385	0.0419	1.0829
386	0.0018	0.0773
387	0.0080	0.2528
388	0.0017	0.0367
389	0.0131	0.1371
390	0.0004	0.0096
391	0.0020	0.0563
392	0.0009	0.0163
393	0.0010	0.0124
394	>10
395	0.0088	0.0269
396	0.0076	0.1372
397	>10
398	0.0344	1.1316
399	0.0285	0.3583
400	0.0141	0.7291
401	0.1581	0.5379
402	0.0921	0.5223
403	0.0698	0.3889
404	0.1547	1.4904
405	0.0998	2.7077
406	0.1347	4.3142
407	>10
408	0.1284	1.1424
409	>10
410	0.0037	0.0884
411	0.0360	1.9679
412	0.0193	0.5087
413	0.0186	0.4476
414	0.0655	0.1204
415	0.0109	0.0370
416	1.2485
417	0.1082	0.7264
418	~1.2499
419	~1.3693
420	0.0856	3.2802
421	0.0283	>10
422	0.0031	0.1460
423	0.2841	4.7951
424	0.0103	>10
425	0.0023	0.1108
426	0.0020	0.0731
427	0.0439	1.5992
428	0.0043	0.0044
429	0.0131	0.2089
430	0.0051	0.0592
431	0.0008	0.0094
432	0.0042	0.0188
433	0.0011	0.0254
434	0.0011	0.0362
435	0.0094	0.1657
436	0.3075	3.2772
437	0.0233	0.3809
438	0.0007	0.0166
439	0.0629	0.3005
440	0.0309	0.2155
441	0.0008	0.0065
442	0.0009	0.0090
443	0.3430	3.3312
444	0.1826	>10
445	0.0005	0.0077
446	0.3044	1.3709
447	0.0031	0.1441
448	0.0101	0.1119
449	0.0216	0.0788
450	~0.0740	0.3398
451	0.0024	0.0385
452	~0.0805	1.9543
453	>10	>10
454	0.0115	0.3450
455	0.0007	0.0943
456	0.0026	0.1139
457	0.0027	0.1400
458	0.0042	0.0530
459	>10
460	>10
461	0.0405	0.2088
462	0.0023	0.0616
463	~0.9819
464	0.1209	>10
465	0.1860	0.9565
466	~0.2544	0.9901
467	0.0535	2.8275
468	0.3317
469	0.1790	2.3469
470	0.3973
471	0.0558	3.3947
472	0.1360	2.5241
473	0.0730	1.4109
474	0.0215	2.6534
475	0.0896	4.1812
476	0.0241	0.3500
477	0.0147	0.2678
478	~0.2499
479	0.0077	0.5710
480	~0.3535
481	1.9116
482	0.0609	0.3203
483	~0.35359
484	0.0759	3.4650
485	>10
486	~2.4997
487	0.0543	0.4443
488	0.0975	1.6527
489	0.0196	0.3069
490	~0.3535	0.2691
491	0.0146	0.2147
492	0.0154	0.1555
493	0.0069	0.3030
494	0.0316	0.0993
495	0.0041	0.5091
496	0.0188	0.1653
497	0.0251	0.5103
498	0.0157	0.1113
499	0.4330
500	0.0485	0.1386
501	0.3591
502	0.0833	0.3626
503	0.0140	0.0923
504	0.7679
505	0.0181	0.0705
506	>10
507	>10
508	0.7905
509	0.1473	0.1598
510	1.9387
511	0.2128	0.3231
512	0.4430	0.4699
513	>10
514	0.1319	0.1477
515	>10
516	>10
517	>10
518	>10
519	>10
520	>10
521	0.0054	0.0133
522	0.2861	0.2639
523	0.0013	0.0251
524	0.0007	0.0182
525	0.0030	0.0365
526	0.0083	0.0188
527	0.0743	0.1829
528	0.0055	0.0340
529	0.0362	0.0796
530	0.0344	1.1117
531	0.0085	0.3234
532	0.0060	0.0318
533	0.0045	0.0227
534	0.0118	0.0689
535	0.0015	0.0155
536	0.0214	0.0678
537	0.0030	0.0421
538	0.0202	0.3298
539	0.0016	0.0521
540	0.0163	0.0850
541	0.0118	0.0660
542	0.1070	0.3112
543	0.4438	4.1649
544	0.0282	1.6516
545	0.0115	0.0504
546	0.1480	0.2531
547	0.0348	0.1042
548	0.4672	0.7408
549	0.0094	0.1228
550	0.0017	0.0160
551	0.0004	0.0209
552	0.0055	0.1020
553	0.0193	0.4304
554	0.0021	0.0390
555	0.0016	0.0245
556	0.0007	0.0131
557	0.1471	1.0659
558	0.0120	0.2100
559	0.0015	0.0547
560	0.0052	0.0951
561	0.0044	0.0429
562	0.0548	0.2259
563	0.0197	0.3276
564	0.2001	0.5828
565	0.0813	0.9836
566	>10
567	1.1347
568	~2.499
569	~0.0700	0.3345
570	0.0355	1.1833
571	0.0017	0.0907
572	~0.3699
573	0.1136
574	0.0139	0.4942
575	~0.7500
576	0.0079	0.1157
577	0.0102	0.0907
578	0.0252	0.9557
579	0.0951	1.5442
580	0.0548	~5.00034
581	0.0596	2.8229
582	>10
583	>10
584	>10
585	>10
586	>10
587	>10
588	0.1333	>10
589	>10
590	>10
591	~2.4997
592	>10
593	>10
594	>10
595	~2.4997
596	>10
597	~2.4997
598	>10
599	>10
600	>10
601	>10
602	0.0006	0.0167
603	0.0276	>10
604	0.0050	0.0895
605	0.0019	0.0979
606	0.0463	2.6242
607	0.1384	0.1521
608	0.0287	0.0539
609	0.2464	0.7677
610	0.0274	0.1171
611	0.2489	0.5626
612	0.0146	0.0420
613	0.2146	0.5565
614	0.0098
615	0.0509
616	0.0164
617	0.1615
618	0.0146	0.2109
619	0.0034	0.0451
620	0.0019	0.0132
621	0.0050	0.1007
622	0.0461	0.3402
623	0.0049	0.0935
624	0.0327
625	0.0078	0.1727
626	0.0062	0.0454
627	0.0437	0.3662
628	0.3362
629	0.8358
630	1.8950
631	>10
632	1.2677
633	>10
634	0.3108	1.4706
635	1.0869
636	0.0046	0.1073
637	0.0188	0.3976
638	0.0014	0.0148
639	0.0072	0.0671
640	1.3397
641	>10
642	0.0788	0.9806
643	0.3225	4.2875
644	>10
645	>10
646	>10
647	0.2271
648	0.8339
649	>10
650	0.8316
651	0.3062	1.5364
652	0.0627	0.8426
653	0.0173	0.5267
654	0.1303	1.0459
655	0.5034	1.8302
656	1.3957
657	0.0735	2.3415
658	0.5717
659	~0.7500
660	0.0833	>10
661	~2.4997
662	~1.2246
663	0.0058	0.0347
664	0.0050	>1
665	0.0026	0.0224
666	0.0032	0.0361
667	0.0060	0.0396
668	0.0230	0.1897
669	0.0040	0.1064
670	0.0977	0.5255
671	0.0157	0.1646
672	0.0137	0.1965
673	0.1343	0.1013
674	0.0036	0.0133
675	0.0010	0.0551
676	0.2339	3.7145
677	>10
678	>10
679	0.1316	0.2054
680	0.6097	1.0503
681	0.0522	0.1058
682	0.2239	0.2638
683	0.6021	0.2800
684	0.0463	0.1343
685	0.0592	0.1150
686	0.3343	1.4900
687	0.7399	3.5457
688	0.6955	1.1844
689	0.4846	0.7872
690	0.1771	0.1175
691	>10
692	0.0533	0.1098
693	0.0495	0.1033
694	0.6762	1.0116
695	0.0084	0.3356
696	0.1410	3.2749
697	>10
698	0.0087	0.1117
699
700	>10
701	0.1318
702	~0.3041
703	>10
704	0.1025	0.1907
705	0.0869	0.2891
706	0.0796	0.3621
707	0.0327	0.1267
708	0.0235	0.1416
709	0.0054	0.2682
710	0.0137	0.0565
711	0.0417	0.1420
712	0.0019	0.0523
713	0.0017	0.0534
714	0.0024	0.0331
715	0.0082	0.1858
716	>10
717	1.0083
718	>10
719	>10
720	>10
721	>10
722	>10
723	>10
724	>10
725	1.2960
726	0.9041
727	0.4838	1.1741
728	0.7813
729	0.0647	0.8610
730	0.0067	0.1359
731	0.0147	0.0513
732	0.5571
733	>10
734	>10
735	0.0320	0.2723
736	0.3303	0.4145
737	0.9842
738	0.2400	2.9546
739	0.3701	1.1133
740	>10
741	0.0046	0.0263
742	0.0029	0.0257
743	0.0016	0.0217
744	0.0155	0.1317
745	0.0117	0.1107
746	0.0020	0.1370
747	0.0271	0.2622
748	>10
749	0.2455	0.4675
750	1.1582
751	0.0809	1.0566
752	0.1352	0.2992
753	0.0044	0.0213
754	0.0699	0.3772
755	0.9395
756	>10
757	0.0052	0.0162
758	0.5569
759	>10
760	1.1558
761	>10
762	0.1589	0.4418
763	1.1148
764	>10
765	>10
766	1.9090
767	>10
768	0.5728
769	1.5449
770	>10
771	>10
772	>10
773	0.2227	0.6390
774	1.2975
775	0.0304
776	0.1497
777	1.6211
778	>10
779	~2.4997
780	>10
781	0.7295
782	>10
783	>10
784	0.0079	0.1105
785	0.0085	0.0576
786	0.0607	0.1049
787	0.0091	0.0980
788	0.0178	1.8026
789	0.1303	0.9386
790	0.0015	0.0253
791	>10
792	>10
793	0.2795	0.6419
794	0.0328	3.9355
795	0.0085	0.0686
796	0.3912
797	>10
798	0.2573	0.2200
799	>10
800	>10
801	>10
802	>10	>1
803	0.1065	0.2413
804	0.6359
805	0.0297	0.3528
806	0.0018	0.0484
807	0.0058	0.0722
808	0.0004	0.0064
809	0.0038	0.0377
810	0.0006	0.0056
811	0.3149	0.5413
812	0.0085	0.0120
813	0.0339	0.0751
814	0.0028	0.0209
815	0.2555	0.1281
816	0.0370	0.0610
817	0.4629
818	0.0272	0.0516
819	0.0743	0.0475
820	0.0033	0.0416
821	>10
822	0.2804	0.0991
823	0.1923	0.0951
824	0.0103	0.0180
825	0.2732	0.1223
826	0.0007	0.0199
827	>10
828	0.1153	0.2598
829	0.0057	0.0090
830	0.0029	0.0056
831	0.1492	0.0725
832	1.3119
833	~0.5000
834	0.0489	1.0907
835	~0.35359	0.4172
836	0.0255	0.5951
837	~1.74985
838	0.0286	0.3501
839	0.8297	2.7880
840	0.0127	0.0996
841	0.1458	0.3697
842	0.0053	0.0610
843	0.0156	0.0443
844	0.5093	0.9072
845	>10
846	0.0105	0.0418
847	0.0081	0.0991
848	0.0968	0.3217
849	0.0383	3.9030
850	0.0377	0.1954
851	0.0326	0.3593
852	0.1179	1.3456
853	0.0047	0.0456
854	1.2773
855	>10
856	0.0605	0.0839
857	0.0280	0.2055
858	0.2097	0.3697
859	~1.2499
860	~1.4791
861	0.0040	0.0449
862	0.1221	0.1210
863	0.0411	0.1401
864	0.2164	0.4128
865	0.0962	0.1924
866	0.1705	0.5388
867	0.2463	0.7930
868	0.0215	0.3446
869	0.1412	0.8437
870	0.0143	0.0867
871	0.0250	0.3714
872	0.0083	0.0530
873	0.0231	0.3355
874	0.0511	0.3588
875	0.1699	0.8511
876	0.0803	1.0770
877	0.0047	0.0105
878	0.2762	0.3202
879	0.1681	0.1064
880	0.0867	0.1796
881	0.0760	0.1282
882	0.1666	0.0688
883	0.0342	0.0695
884	0.2387	0.7055
885	0.0408	1.0573
886	0.0058	>1
887	0.0304	>1
888	0.0007	0.3666
889	0.0039	0.2358
890	0.0037	0.0623
891	0.0315	0.7516
892	0.0774	0.7311
893	0.0303	0.6027
894	0.0038	0.1411
895	0.0132	0.2220
896	0.0221	0.4664
897	0.0070	0.0903
898	0.0797	0.9281
899	0.0770	0.0873
900	0.0351	0.0408
901	0.0018	0.0016
902	0.0184	0.0886
903	0.0387	0.0634
904	0.2547	0.1046
905	0.0579	0.0529
906	0.0003	0.0020
907	0.0060	0.0120
908	0.0266	0.0437
909	0.2528	0.1166
910	0.0029	0.0092
911	0.1663	0.0287
912	0.0005	0.0088
913	0.0063	0.0119

description truncated at 500,000 characters

Stored text is truncated at the source; the tail of the description is not held.

Claims as granted

16 claims

Classifications

36 codes

IPC · International Patent Classification

Section A — Human necessities

A61K31/55
A61K31/506
A61K31/422

Section C — Chemistry; metallurgy

C07D491/10
C07D405/14
C07D487/08
C07D405/12
C07D413/12
C07D235/10
C07D495/10
C07D401/10
C07D491/107
C07F5/02
C07D277/62
C07D263/48
C07D413/10
C07D401/14
C07D487/04
C07D498/04
C07D241/26
C07D285/12
C07D403/10
C07D471/04
C07D209/08
C07D417/10
C07D413/14
C07D409/12
C07D401/12
C07D403/12
C07D241/20
C07D237/20
C07D491/08
C07D213/73
C07D403/14
C07F7/08
C07D401/04

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Pendency

3.6 y

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1 RCE

Examiner

Samantha Shterengarts

art unit 1625 · TC 1600

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