反应详情

温度

0 °C

To a solution of (5-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methoxy)-6-(2-fluoro-5-methoxyphenyl)pyridin-3-yl)methanol (930 mg) and ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoate (945 mg) in THF (20 mL) was slowly added, at 0° C., 60% sodium hydride (300 mg) by small portions, and the mixture was stirred at 60° C. for 3 hr. After cooling to 0° C., water (1.0 mL) was added to the reaction mixture, and the mixture was further stirred at 60° C. for 1 hr. The mixture was acidified with 1N hydrochloric acid at 0° C., and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by preparative HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA-containing system)), and saturated aqueous sodium carbonate solution was added to the obtained fraction. The mixture was extracted with ethyl acetate, and the extract was dried over anhydrous sodium sulfate and evaporated under reduced pressure to give the title compound (192 mg) as a white solid.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed with saturated brine
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was evaporated under reduced pressure
5. customthe residue was purified by preparative HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA-containing system)), and saturated aqueous sodium carbonate solution
6. additionwas added to the obtained fraction
7. extractionThe mixture was extracted with ethyl acetate
8. dry with materialthe extract was dried over anhydrous sodium sulfate
9. customevaporated under reduced pressure