Trifluoroacetic anhydride → HCID 68984682, compound

Participants

Reaction Steps

A mixture of N-{5-[(1-(2-amino-2-oxoethyl)-6-{[(4-methylphenyl)sulfonyl]amino}-1,6-dihydropyridin-3-yl)oxy]-2-chlorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (300 mg, 0.527 mmol), trifluoroacetic anhydride (2 mL) and dichloromethane (2.5 mL) was stirred at room temperature for 5 hr. The reaction solution was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with ethyl acetate (×3). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, 1N aqueous sodium hydroxide solution (10 mL) and ethanol (10 mL) were added to the residue, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate (×3). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (NH silica gel, ethyl acetate) and recrystallized from ethyl acetate-hexane to give N-{5-[(2-aminoimidazo[1,2-a]pyridin-6-yl)oxy]-2-chlorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (134 mg, 64%) as a white solid. To a solution of N-{5-[(2-aminoimidazo[1,2-a]pyridin-6-yl)oxy]-2-chlorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (130 mg, 0.328 mmol) thus-obtained and triethylamine (136 μL, 0.984 mmol) in tetrahydrofuran (4 mL) was added with stirring under ice-cooling cyclopropanecarbonyl chloride (38.7 μL, 0.426 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=50/50→0/100) and recrystallized from ethyl acetate-tetrahydrofuran to give the title compound (83.0 mg, 54%) as a white solid.

Provenance & Evidence