4-Bromo-3-fluorobenzenesulfonamide

To an ice cooled solution of 4-bromo-3-fluorobenzenesulfonyl chloride (1, 1.03 g, 3.77 mmol) in acetonitrile (1.88 mL) was added 25% ammonia solution (1.46 mL, 9.41 mmol) dropwise. The mixture was stirred for 10 min at RT, diluted with water and extracted with diethyl ether. The extract was washed with brine, dried over Na2SO4, filtered and the solvent removed under reduced pressure to yield 4-bromo-3-fluorobenzenesulfonamide (0.780 g, 3, 07 mmol, 82% yield). (0840) Analytical data: (0841) 1H NMR (200 MHz, DMSO) delta 7.95 (dd, J = 8.2, 6.9 Hz, 1H), 7.75 (dd, J = 8.4, 2.1 Hz, 1H), 7.64- 7.57 (m, 3H); (0842) 13C NMR (50 MHz, DMSO) delta 157.9 (d, J = 249.0 Hz), 145.5 (d, J = 6.1 Hz), 134.6, 123.2 (d, J = 3.8 Hz), 114.1 (d, J = 25.3 Hz), 112.3 (d, J = 20.8 Hz).A vessel was charged with A solution of 1, 1-dimethoxy-N, N-dimethyl-methanamine (CAS-RN 4637-24-5; 170 mg, 1.38mmol) in acetonitrile (1 mL) was added dropwise at room temperature to a stirring solution of EXAMPLE 342: 3-fluoro-4-(6-(trifluoromethyl)-lH-indazol-4- yl)benzenesulfonamide [0976] To a 5 mL vial equipped with a magnetic stir bar were added 4-(4, 4, 5, 5-tetramethyl- l, 3, 2-dioxaborolan-2-yl)-6-(trifluoromethyl)-lH-indazole (40 mg, 0.128 mmol), 4-bromo-3- fluorobenzenesulfonamide (39.1 mg, 0.154 mmol), aqueous saturated sodium bicarbonate (0.274 mL, 0.513 mmol), PdCl2(dppf) (9.38 mg, 0.013 mmol), and dioxane (2 mL) to give an orange suspension. The vial was sealed and then heated in a microwave reactor at 140C for 30 minutes. The reaction mixture was subsequently filtered and the product was purified by preparative HPLC, eluting with a gradient of 35-60% ACN (containing 0.035% TFA) in H20 (containing 0.05% TFA). The pure fractions were lyophilized to give a TFA salt of the title compound as a white solid (13.7 mg, 22.6%). 1H NMR (400 MHz, DMSO-Step 2: 4-(4-(4-chlorophenyl)-2-(piperidine- l-carbonyl)thiazol-5-yl)-3- fluorobenzenesulfonamide To a solution of (4-(4-chlorophenyl)thiazol-2-yl)(piperidin- l-yl)methanone (Step 1 of compound 50, 0.66 g, 2.16 mmol) in dimethyl acetamide (8 ml) were added 4- bromobenzenesulfonamide (0.55 g, 2.16 mmol) and potassium acetate (0.53 g, 5.41 mmol) at 25C in a tube, the nitrogen gas was bubbled through reaction mixture for 15 minutes. To this was added palladium (II) acetate (0.049 g, 0.21 mmol) under nitrogen and the tube was sealed. The reaction mixture was heated at 150C for 15 hr with stirring. The progress of reaction was monitored by TLC; the reaction mixture was cooled to 25C and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 ml). The reaction mixture was washed with water (2 x 10 ml), dried over sodium sulphate and concentrated under reduced pressure to obtain a crude product; which was purified by column chromatography over silica gel (100-200 mesh) using 55% ethyl acetate in hexanes as an eluent to obtain the title compound (0.31 g, 29.8 %). MS: m/z 480 (M+ l). iHNMR (DMSO-de, 400 MHz): delta 7.76-7.69 (m, 3H), 7.63 (bs-exchanges with D20, 2H), 7.48-7.44 (m, 4H), 4.32-4.20 (m, 2H), 3.72-3.62 (m, 2H), 1.68- 1.52 (m, 6H).(Example 75) 2-Fluoro-3'-[2-isopropyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-y1]-1, 1'-biphenyl-4-sulfonamide (Compound No. 1-680)2-{2-Isopropyl-4-[3-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)phenyl]-1H-imidazol-5-yl}-6-methylpyridine (0.12 g, 0.30 mmol) obtained in Example (35a) and

Molecular Weight:254.08
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:252.92084
Monoisotopic Mass:252.92084
Topological Polar Surface Area:68.5
Heavy Atom Count:12
Complexity:251
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes