4-bromo-N-tert-butylbenzenesulfonamide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromobenzenesulfonyl chloride (100.2 g) in THF (400 mL) was added t-butylamine (125 mL). An exothermic reaction results with gentle refluxing of the solvent. After 30 min, the bath was removed and the mixture was allowed to warm to r.t. Isopropyl acetate (400 mL) was added and the mixture was washed twice with water. The aqueous phase was back-extracted with ethyl acetate and the combined organics were dried (sodium sulfate) and concentrated to provide the title compound as a solid (112.9 g). An exothermic reaction results with gentle refluxing of the solvent the bath was removed Isopropyl acetate (400 mL) was added the mixture was washed twice with water The aqueous phase was back-extracted with ethyl acetate the combined organics were dried (sodium sulfate) concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Place t-butylamine (4.32 mL, 41.1 mmol), triethylamine (8.15 mL, 58.7 mmol) and dichloromethane (75 mL) in a 3-neck round bottom flask. Cool this stirring solution to 0° C. and add a solution of 4-bromobenzenesulfonyl chloride (10.0 g, 39.1 mmol) in dichloromethane (50 mL). Add additional dichloromethane (25 mL) and stir the reaction overnight, allowing it to warm to ambient temperature. Evaporate the reaction in vacuo. Suspend the resulting white solid in ethyl acetate and filter it. Concentrate the filtrate in vacuo and purify the resulting residue by flash chromatography (silica gel; 50%-80% gradient CH2Cl2 in hexanes) to provide 9.85 g of 4-bromo-N-tert-butyl-benzenesulfonamide (86%). the reaction overnight to warm to ambient temperature Evaporate the reaction in vacuo filter it Concentrate the filtrate in vacuo purify the resulting residue by flash chromatography (silica gel; 50%-80% gradient CH2Cl2 in hexanes)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Place t-butylamine (4.32 mL, 41.1 mmol), triethylamine (8.15 mL, 58.7 mmol) and dichloromethane (75 mL) in a 3-neck round bottom flask. Cool this stirring solution to 0° C. and add a solution of 4-bromobenzenesulfonyl chloride (10.0 g, 39.1 mmol) in dichloromethane (50 mL). Add additional dichloromethane (25 mL) and stir the reaction overnight, allowing it to warm to ambient temperature. Evaporate the reaction in vacuo. Suspend the resulting white solid in ethyl acetate and filter it. Concentrate the filtrate in vacuo and purify the resulting residue by flash chromatography (silica gel; 50%-80% gradient CH2Cl2 in hexanes) to provide 9.85 g of 4-bromo-N-tert-butyl-benzenesulfonamide (86%). the reaction overnight to warm to ambient temperature Evaporate the reaction in vacuo filter it Concentrate the filtrate in vacuo purify the resulting residue by flash chromatography (silica gel; 50%-80% gradient CH2Cl2 in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-bromobenzenesulfonyl chloride (200 mg, 0.783 mmol) was dissolved in MC (10 ml), followed by dropwise addition of tert-butylamine (0.41 ml, 3.91 mmol) at 0° C., and then the resulting mixture was stirred at room temperature under nitrogen stream for 1 hour. Distilled water (15 ml) was added to the resulting reaction liquid, followed by extraction with MC (30 ml×2). The organic layer was dried over anhydrous sodium sulfate, followed by filtration and concentration, and then the residue thus obtained was dried under vacuum, to obtain 228 mg of white solid (100%). followed by extraction with MC (30 ml×2) The organic layer was dried over anhydrous sodium sulfate followed by filtration and concentration the residue thus obtained was dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: According to general procedure B, 4-bromo-N-(tert-butyl)benzenesulfonamide (117 mg, 0.40 mmol), 5-cyano-1-methyl-1H-pyrrol-2-ylboronic acid (72 mg, 0.48 mmol), potassium fluoride (76 mg, 1.3 mmol), and tris(dibenzylideneacetone)dipalladium(0) (10 mg, 0.01 mmol) were placed in an oven dried flask under nitrogen and dry THF (1.0 mL) was added. Tri-t-butylphosphine (60 μL, 0.02 mmol, 10 wt % in hexane) was added and the reaction was stirred for 16 hours. N-(tert-butyl)-4-(5-cyano-1-methyl-1H-pyrrol-2-yl)benzenesulfonamide (19 mg, 15%) was provided after purification. MS (ESI) m/z 317. HPLC purity 100.0% at 210-370 nm, 10.5 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. were placed in an oven dried flask under nitrogen dry THF (1.0 mL) was added

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: According to general procedure C, 4-Bromobenzene sulfonyl chloride (0.40 g, 1.56 mmol) and tert-butylamine (0.41 mL, 3.90 mmol) were stirred together in dry dichloromethane (5 mL) for 16 hours. 4-bromo-N-(tert-butyl)benzenesulfonamide (0.12 g) was provided after purification. MS (ESI) m/z 292. HPLC purity 100.0% at 210-370 nm, 9.2 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.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Procedure R′: A 15 m-1L DMF mixture of 4-bromo-N-tert-butyl-benzenesulfonamide (1022 mg, 3.5 mmol), iodomethane (0.44 mL, 7 mmol), and K2CO3 (987 mg, 7 mmol) is stirred at room temperature overnight. Water and ethyl acetate are added to the mixture. The aqueous layer is extracted several times with ethyl acetate. The combined organic layers are washed with H2O and brine, then dried over Na2SO4 and evaporated. The crude product is purified by silica-gel column chromatography (gradient: 100% CH2Cl2 to 20% EtOAc/CH2Cl2) give the intermediate 4-bromo-N-tert-butyl-N-methyl-benzenesulfonamide (1040 mg, 97% yield). MS (ES+) 251.9 (M-tBu)+, NMR (CDCl3). The aqueous layer is extracted several times with ethyl acetate The combined organic layers are washed with H2O and brine dried over Na2SO4 evaporated The crude product is purified by silica-gel column chromatography (gradient: 100% CH2Cl2 to 20% EtOAc/CH2Cl2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Procedure R′: A 15 mL DMF mixture of 4-bromo-N-tert-butyl-benzenesulfonamide (1022 mg, 3.5 mmol), iodomethane (0.44 mL, 7 mmol), and K2CO3 (987 mg, 7 mmol) is stirred at room temperature overnight. Water and ethyl acetate are added to the mixture. The aqueous layer is extracted several times with ethyl acetate. The combined organic layers are washed with H2O and brine, then dried over Na2SO4 and evaporated. The crude product is purified by silica-gel column chromatography (gradient: 100% CH2Cl2 to 20% EtOAc/CH2Cl2) give the intermediate 4-bromo-N-tert-butyl-N-methyl-benzenesulfonamide (1040 mg, 97% yield). MS (ES+) 251.9 (M-tBu)+, NMR (CDCl3). The aqueous layer is extracted several times with ethyl acetate The combined organic layers are washed with H2O and brine dried over Na2SO4 evaporated The crude product is purified by silica-gel column chromatography (gradient: 100% CH2Cl2 to 20% EtOAc/CH2Cl2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-bromobenzenesulfonyl chloride (100.2 g) in THF (400 mL) was added t-butylamine (125 mL). An exothermic reaction results with gentle refluxing of the solvent. After 30 min, the bath was removed and the mixture was allowed to warm to r.t. Isopropyl acetate (400 mL) was added and the mixture was washed twice with water. The aqueous phase was back-extracted with ethyl acetate and the combined organics were dried (sodium sulfate) and concentrated to provide the title compound as a solid (112.9 g). An exothermic reaction results with gentle refluxing of the solvent the bath was removed Isopropyl acetate (400 mL) was added the mixture was washed twice with water The aqueous phase was back-extracted with ethyl acetate the combined organics were dried (sodium sulfate) concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Place t-butylamine (4.32 mL, 41.1 mmol), triethylamine (8.15 mL, 58.7 mmol) and dichloromethane (75 mL) in a 3-neck round bottom flask. Cool this stirring solution to 0° C. and add a solution of 4-bromobenzenesulfonyl chloride (10.0 g, 39.1 mmol) in dichloromethane (50 mL). Add additional dichloromethane (25 mL) and stir the reaction overnight, allowing it to warm to ambient temperature. Evaporate the reaction in vacuo. Suspend the resulting white solid in ethyl acetate and filter it. Concentrate the filtrate in vacuo and purify the resulting residue by flash chromatography (silica gel; 50%-80% gradient CH2Cl2 in hexanes) to provide 9.85 g of 4-bromo-N-tert-butyl-benzenesulfonamide (86%). the reaction overnight to warm to ambient temperature Evaporate the reaction in vacuo filter it Concentrate the filtrate in vacuo purify the resulting residue by flash chromatography (silica gel; 50%-80% gradient CH2Cl2 in hexanes)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Place t-butylamine (4.32 mL, 41.1 mmol), triethylamine (8.15 mL, 58.7 mmol) and dichloromethane (75 mL) in a 3-neck round bottom flask. Cool this stirring solution to 0° C. and add a solution of 4-bromobenzenesulfonyl chloride (10.0 g, 39.1 mmol) in dichloromethane (50 mL). Add additional dichloromethane (25 mL) and stir the reaction overnight, allowing it to warm to ambient temperature. Evaporate the reaction in vacuo. Suspend the resulting white solid in ethyl acetate and filter it. Concentrate the filtrate in vacuo and purify the resulting residue by flash chromatography (silica gel; 50%-80% gradient CH2Cl2 in hexanes) to provide 9.85 g of 4-bromo-N-tert-butyl-benzenesulfonamide (86%). the reaction overnight to warm to ambient temperature Evaporate the reaction in vacuo filter it Concentrate the filtrate in vacuo purify the resulting residue by flash chromatography (silica gel; 50%-80% gradient CH2Cl2 in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-bromobenzenesulfonyl chloride (200 mg, 0.783 mmol) was dissolved in MC (10 ml), followed by dropwise addition of tert-butylamine (0.41 ml, 3.91 mmol) at 0° C., and then the resulting mixture was stirred at room temperature under nitrogen stream for 1 hour. Distilled water (15 ml) was added to the resulting reaction liquid, followed by extraction with MC (30 ml×2). The organic layer was dried over anhydrous sodium sulfate, followed by filtration and concentration, and then the residue thus obtained was dried under vacuum, to obtain 228 mg of white solid (100%). followed by extraction with MC (30 ml×2) The organic layer was dried over anhydrous sodium sulfate followed by filtration and concentration the residue thus obtained was dried under vacuum