反应详情

温度

50 °C

To a stirred solution of N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine (4.39 g, 9.37 mmol) in tetrahydrofuran (40 mL) under ice cooling was added sodium hydride (50% in oil, 1.80 g, 37.5 mmol), and the mixture was stirred at 50° C. for 1 hour. After cooling to −78° C., to the reaction mixture was added a solution of 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane (6.02 g, 18.7 mmol) obtained in Step 2 in N,N-dimethylformamide (40 mL), and the mixture was stirred for 2.5 hours with warming to room temperature. The reaction mixture was added with water and extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1) to obtain the target compound, N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine (6.03 g, 91%), as a pale yellow oil.

1. temperatureAfter cooling to −78° C., to the reaction mixture
2. stirringthe mixture was stirred for 2.5 hours
3. temperaturewith warming to room temperature
4. extractionextracted with ethyl acetate
5. washthe organic layer was washed with saturated brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1)