反应详情

温度

70 °C

To a solution of 1-(4-fluorophenyl)-6-methyltetrahydropyrimidin-2(1H)-one (240 mg, 1.1 mmol) in tetrahydrofuran (5 mL) was added bis(trichloromethyl) carbonate (170 mg, 0.57 mmol), and the mixture was stirred at 70° C. for 3.5 hr. The mixture was cooled to room temperature, a solution of N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (250 mg, 0.76 mmol) in tetrahydrofuran (8 mL) and N,N-diisopropylethylamine (300 mg, 2.3 mmol) were added to the mixture, and the mixture was stirred at room temperature for 1 hr. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution were added to the mixture, and the aqueous layer was extracted 3 times with ethyl acetate/tetrahydrofuran. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=50/50→100/0) to give the title compound (29 mg, 7%) as a white solid.

1. temperatureThe mixture was cooled to room temperature
2. stirringthe mixture was stirred at room temperature for 1 hr
3. extractionthe aqueous layer was extracted 3 times with ethyl acetate/tetrahydrofuran
4. washThe combined organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated under reduced pressure
8. customthe residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=50/50→100/0)