反应详情

温度

-78 °C

Ethyl 2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carboxylate (595 mg, 1.25 mmol) was dissolved in dichloromethane (25 mL) under nitrogen atmosphere and cooled at −78° C. Diisobutyl aluminum hydride (1 M in hexane, 4.36 mL, 4.36 mmol) was added over 10 min. After 1 h diisobutyl aluminum hydride (1 M in hexane, 1.4 mL) was added and the mixture was stirred for 2 h. MeOH (3 mL) was added and the mixture was let to rt. Water (5 mL) was added. The slurry was stirred for 20 min and filtrated through a plug of diatomeous earth. The filter plug was washed with 10% MeOH in DCM. The phases were separated and the aqueous phase was extracted with DCM. The combined organic layer was dried over sodium sulfate, filtered and concentrated onto silica. The residue was purified by column chromatography on silica eluting with a gradient of methanol in dichloromethane to give the title compound as a solid, 270 mg (50%).

1. customwas let to rt
2. stirringThe slurry was stirred for 20 min
3. filtrationfiltrated through a plug of diatomeous earth
4. washThe filter plug was washed with 10% MeOH in DCM
5. customThe phases were separated
6. extractionthe aqueous phase was extracted with DCM
7. dry with materialThe combined organic layer was dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated onto silica
10. customThe residue was purified by column chromatography on silica eluting with a gradient of methanol in dichloromethane