反应详情

To a mixture of 4′-{[4-ethyl-5-(4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile (1.5 g) and 2,6-lutidine (0.98 mL) in dichloromethane (10 mL) was added triisopropylsilyl trifluoromethanesulfonate (1.5 mL) at 0° C. After stirring for 2 hr, the reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was dissolved in dimethyl sulfoxide (5 mL), and then hydroxylamine hydrochloride (1.7 g) and sodium hydrogen carbonate (2.5 g) were added. The mixture was stirred overnight at 90° C. After cooling, the reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), and N,N′-carbonyldiimidazole (0.6 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.6 mL) were added. After stirring for 30 min, the reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.3 g, 77%).

1. washwashed with water
2. dry with materialdried over sodium sulfate
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in dimethyl sulfoxide (5 mL)
5. additionhydroxylamine hydrochloride (1.7 g) and sodium hydrogen carbonate (2.5 g) were added
6. stirringThe mixture was stirred overnight at 90° C
7. temperatureAfter cooling
8. additionthe reaction mixture was diluted with ethyl acetate
9. washwashed with water
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated
12. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
13. additionN,N′-carbonyldiimidazole (0.6 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.6 mL) were added
14. stirringAfter stirring for 30 min
15. additionthe reaction mixture was diluted with ethyl acetate
16. washwashed with 1 M hydrochloric acid
17. dry with materialdried over sodium sulfate
18. concentrationconcentrated
19. customThe residue was purified by silica gel column chromatography