3-氯-4-(二氟甲氧基)苯胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-chloro-4-difluoromethoxyaniline (1.95 g) in methylene chloride (50 ml), triethylamine (1.1 g) was added, and a solution of 1-methylcyclopropanecarbonyl chloride (1.2 g) in methylene chloride was dropwise added while cooling with ice-water. The reaction mixture was stirred at room temperature for 1 hour, admixed with water and extracted with ether. The extract was washed with 1 N hydrochloric acid, sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated to give crude crystals (2.6 g). Recrystallization from ethanol gave N-(3-chloro-4-difluoromethoxyphenyl)-1-methylcyclopropanecarboxamide (2.2 g). M.P., 59°-60° C. extracted with ether The extract was washed with 1 N hydrochloric acid, sodium hydrogen carbonate solution and saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated to give crude crystals (2.6 g) Recrystallization from ethanol

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-chloro-4-(difluoromethoxy)aniline (0.814 g, 4.20 mmol) in butan-1-ol (10 mL), were added DIPEA (2.203 mL, 12.61 mmol) and 2,5-dibromopyrimidine (1 g, 4.20 mmol). The reaction mixture was stirred at 120° C. for 12 h and concentrated. The crude product was purified by flash chromatography on silica gel using 3% ethyl acetate in petroleum ether to give 5-bromo-N-(3-chloro-4-(difluoromethoxy)phenyl)pyrimidin-2-amine (0.8 g, 64%). LCMS (ES-ES), m/z 349.98. concentrated The crude product was purified by flash chromatography on silica gel using 3% ethyl acetate in petroleum ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-chloro-4-difluoromethoxyaniline (1.95 g) in methylene chloride (50 ml), triethylamine (1.1 g) was added, and a solution of 1-methylcyclopropanecarbonyl chloride (1.2 g) in methylene chloride was dropwise added while cooling with ice-water. The reaction mixture was stirred at room temperature for 1 hour, admixed with water and extracted with ether. The extract was washed with 1 N hydrochloric acid, sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated to give crude crystals (2.6 g). Recrystallization from ethanol gave N-(3-chloro-4-difluoromethoxyphenyl)-1-methylcyclopropanecarboxamide (2.2 g). M.P., 59°-60° C. extracted with ether The extract was washed with 1 N hydrochloric acid, sodium hydrogen carbonate solution and saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated to give crude crystals (2.6 g) Recrystallization from ethanol