Tert-Butylamine → N-{3-[4-(2-amino-pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2,4-difluoro-phenyl}-2,5-difluoro-benzenesulfonamide

Participants

Reaction Steps

N-[3-(1-ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide (123 mg, 0.217 mmol) was dissolved in dry DCM, mCPBA (75 mg, 2 eq) was added and the reaction mixture was stirred at room temperature for 3 hours. A further addition of mCPBA was made (50 mg) and the mixture was stirred for 2 more hours. It was then diluted with DCM, washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and evaporated to dryness. The crude intermediate N-oxide (130 mg) was dissolved in dry trifluoromethylbenzene (1.5 mL), the solution was cooled to 0° C. and t-butyl amine (0.118 mL 1.12 mmol, 5 eq) was added. Tosylanhydride (150 mg, 0.448 mmol, 2 eq) was then added in portions. After 1 h stirring at 0° C., further additions of t-butyl amine (0.03 mL, 1.25 eq) and tosylanhydride (40 mg, 0.5 eq) were made and the reaction mixture was stirred at 0° C. for 30 more minutes. Trifluoroacetic acid (1.5 mL) was then added and the mixture was hated to 70° C. and stirred at this temperature for 1.5 h. The solvent was evaporated and the residue taken up with DCM and water. The aqueous phase was neutralized with 32% aq. NaOH and extracted 3 times with DCM. The combined organic layers were washed with brine, dried over Na2SO4 and evaporated to dryness. The crude product was purified by chromatography on silica gel (DCM/MeOH 95:5) to give 46 mg of N-{3-[4-(2-amino-pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2,4-difluoro-phenyl}-2,5-difluoro-benzenesulfonamide as a white solid.

Provenance & Evidence