4-bromo-3-fluorobenzenesulfonamide

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 5 mL vial equipped with a magnetic stir bar were added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-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 140° C. 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 H2O (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-d6) δ ppm 7.50 (s, 2H), 7.53 (s, 1H), 7.75-7.80 (m, 1H), 7.92-7.94 (m, 1H), 8.02 (s, 1H), 8.06 (dt, J=8.02, 1.29 Hz, 1H), 8.21 (t, J=1.64 Hz, 1H), 8.40 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H9F4N3O2S, 360.0. found 360.1. To a 5 mL vial equipped with a magnetic stir bar to give an orange suspension The vial was sealed The reaction mixture was subsequently filtered the product was purified by preparative HPLC eluting with a gradient of 35-60% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 5 mL vial equipped with a magnetic stir bar were added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-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 140° C. 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 H2O (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-d6) δ ppm 7.50 (s, 2H), 7.53 (s, 1H), 7.75-7.80 (m, 1H), 7.92-7.94 (m, 1H), 8.02 (s, 1H), 8.06 (dt, J=8.02, 1.29 Hz, 1H), 8.21 (t, J=1.64 Hz, 1H), 8.40 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H9F4N3O2S, 360.0. found 360.1. To a 5 mL vial equipped with a magnetic stir bar to give an orange suspension The vial was sealed The reaction mixture was subsequently filtered the product was purified by preparative HPLC eluting with a gradient of 35-60% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to general procedure B, 4-bromo-3-fluorobenzenesulfonamide (150 mg, 0.59 mmol), 5-cyano-1-methyl-1H-pyrrol-2-ylboronic acid (106 mg, 0.70 mmol), potassium fluoride (113 mg, 1.95 mmol), and tris(dibenzylideneacetone)dipalladium (0) (15 mg, 0.01 mmol) were placed in an oven dried flask under nitrogen and dry THF (1.4 mL) was added. Tri-t-butylphosphine (89 μL, 0.02 mmol, 10 wt % in hexane) was added and the reaction was stirred for 16 hours. 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-3-fluorobenzenesulfonamide (29 mg, 18%) was provided after purification. MS (ESI) m/z 279. HPLC purity 100.0% at 210-370 nm, 8.6 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min. were placed in an oven dried flask under nitrogen dry THF (1.4 mL) was added

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to general procedure B, 4-bromo-3-fluorobenzenesulfonamide (150 mg, 0.59 mmol), 5-cyano-1-methyl-1H-pyrrol-2-ylboronic acid (106 mg, 0.70 mmol), potassium fluoride (113 mg, 1.95 mmol), and tris(dibenzylideneacetone)dipalladium (0) (15 mg, 0.01 mmol) were placed in an oven dried flask under nitrogen and dry THF (1.4 mL) was added. Tri-t-butylphosphine (89 μL, 0.02 mmol, 10 wt % in hexane) was added and the reaction was stirred for 16 hours. 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-3-fluorobenzenesulfonamide (29 mg, 18%) was provided after purification. MS (ESI) m/z 279. HPLC purity 100.0% at 210-370 nm, 8.6 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min. were placed in an oven dried flask under nitrogen dry THF (1.4 mL) was added

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to general procedure B, 4-bromo-3-fluorobenzenesulfonamide (150 mg, 0.59 mmol), 5-cyano-1-methyl-1H-pyrrol-2-ylboronic acid (106 mg, 0.70 mmol), potassium fluoride (113 mg, 1.95 mmol), and tris(dibenzylideneacetone)dipalladium (0) (15 mg, 0.01 mmol) were placed in an oven dried flask under nitrogen and dry THF (1.4 mL) was added. Tri-t-butylphosphine (89 μL, 0.02 mmol, 10 wt % in hexane) was added and the reaction was stirred for 16 hours. 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-3-fluorobenzenesulfonamide (29 mg, 18%) was provided after purification. MS (ESI) m/z 279. HPLC purity 100.0% at 210-370 nm, 8.6 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min. were placed in an oven dried flask under nitrogen dry THF (1.4 mL) was added

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to general procedure A, 4-Bromo-3-fluoro-benzenesulfonyl chloride (0.40 g, 1.46 mmol) and ammonia (20 mL, ca. 7N in methanol) were stirred together for 16 hours. 4-bromo-3-fluorobenzenesulfonamide was provided after purification (0.23 g, 61%). HRMS: calcd for C6H5BrFNO2S, 252.92084; found (EI, M+), 252.9201. HPLC purity 100.0% at 210-370 nm, 7.5 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min.

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 5 mL vial equipped with a magnetic stir bar were added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-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 140° C. 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 H2O (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-d6) δ ppm 7.50 (s, 2H), 7.53 (s, 1H), 7.75-7.80 (m, 1H), 7.92-7.94 (m, 1H), 8.02 (s, 1H), 8.06 (dt, J=8.02, 1.29 Hz, 1H), 8.21 (t, J=1.64 Hz, 1H), 8.40 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H9F4N3O2S, 360.0. found 360.1. To a 5 mL vial equipped with a magnetic stir bar to give an orange suspension The vial was sealed The reaction mixture was subsequently filtered the product was purified by preparative HPLC eluting with a gradient of 35-60% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)