反应详情

温度

-78 °C

To a solution of ethyl 2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine-4-carboxylate (0.49 g, 1.05 mmol) in dry dichloromethane (25 mL) diisobutyl aluminum hydride (2.63 mL, 1M solution in hexane, 2.63 mmol), was added under nitrogen during 10 min at −78° C. The mixture was stirred at −78° C. for 1 h. Diisobutyl aluminum hydride solution (2.8 mL) was added and the mixture was stirred for 10 min. The mixture was quenched with methanol and allowed to warm to ambient temperature. Water (5 mL) was added, the slurry was stirred for 20 min and filtered through a pad of diatomeous earth. The pad was washed with 10% solution of methanol in dichloromethane. The organic phase was separated and the water phase was extracted with 10% solution of methanol in dichloromethane. The combined organic extracts was dried over sodium sulfate and concentrated in vacuum. The residue was purified by column chromatography on silica eluting with 0-5% gradient of methanol in dichloromethane to yield the title compounds, 318 mg (72%).

1. stirringthe mixture was stirred for 10 min
2. customThe mixture was quenched with methanol
3. temperatureto warm to ambient temperature
4. additionWater (5 mL) was added
5. stirringthe slurry was stirred for 20 min
6. filtrationfiltered through a pad of diatomeous earth
7. washThe pad was washed with 10% solution of methanol in dichloromethane
8. customThe organic phase was separated
9. extractionthe water phase was extracted with 10% solution of methanol in dichloromethane
10. dry with materialThe combined organic extracts was dried over sodium sulfate
11. concentrationconcentrated in vacuum
12. customThe residue was purified by column chromatography on silica eluting with 0-5% gradient of methanol in dichloromethane