反应详情

温度

40 °C

A suspension of hydroxylamine hydrochloride (661 mg) and sodium hydrogen carbonate (941 mg) in dimethyl sulfoxide (5 mL) was stirred at 40° C. for 30 min, and then 4′-[(1-{4-[(4,4-difluorocyclohexyl)oxy]phenyl}-2-ethyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (635 mg) was added to the mixture, and the mixture was stirred at 90° C. for 12 hr. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was dissolved in ethyl acetate. The solution was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (20 mL), and then 1,1′-carbonyldiimidazole (272 mg) and 1,8-diazabicyclo[5,4,0]undec-7-ene (0.25 mL) were added thereto. The mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was successively washed with water and saturated brine (20 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give the title compound as a pale yellow amorphous solid (12.1 mg, 2%).

1. stirringthe mixture was stirred at 90° C. for 12 hr
2. filtrationthe precipitated solid was collected by filtration
3. dissolutionThe obtained solid was dissolved in ethyl acetate
4. washThe solution was washed with saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. customthe solvent was evaporated
7. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
8. addition1,1′-carbonyldiimidazole (272 mg) and 1,8-diazabicyclo[5,4,0]undec-7-ene (0.25 mL) were added
9. stirringThe mixture was stirred at room temperature for 2 hr
10. additionThe reaction mixture was diluted with ethyl acetate
11. washthe mixture was successively washed with water and saturated brine (20 mL)
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated in vacuo
14. customThe residue was purified by column chromatography on silica gel