反应详情

温度

40 °C

A mixture of hydroxylammonium chloride (1.4 g), sodium hydrogen carbonate (2.3 g) and dimethyl sulfoxide (3 mL) was stirred at 40° C. for 30 min, 4′-{[4-(3-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dioxaspiro[5.5]undec-9-yl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.91 g) was added, and the mixture was stirred at 90° C. for 15 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 mL). N,N′-Carbonyldiimidazole (0.27 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.24 mL) were added, and the mixture was stirred at room temperature for 1.5 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was acidified with 1 M hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (10 mL). Tetrabutylammonium fluoride (3.4 mL, 1.0 M tetrahydrofuran solution) was added and the mixture was stirred at 70° C. for 3.5 hr. The reaction mixture was added to 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.426 g, 51%).

1. stirringthe mixture was stirred at 90° C. for 15 hr
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customThe solvent was evaporated under reduced pressure
6. dissolutionthe residue was dissolved in tetrahydrofuran (5 mL)
7. additionN,N′-Carbonyldiimidazole (0.27 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.24 mL) were added
8. stirringthe mixture was stirred at room temperature for 1.5 hr
9. additionEthyl acetate and water were added to the reaction mixture
10. extractionextracted with ethyl acetate
11. washThe organic layer was washed with saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. customThe solvent was evaporated under reduced pressure
14. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
15. additionTetrabutylammonium fluoride (3.4 mL, 1.0 M tetrahydrofuran solution) was added
16. stirringthe mixture was stirred at 70° C. for 3.5 hr
17. additionThe reaction mixture was added to 1 M hydrochloric acid
18. extractionthe mixture was extracted with ethyl acetate
19. washThe organic layer was washed with saturated brine
20. dry with materialdried over anhydrous magnesium sulfate
21. customThe solvent was evaporated under reduced pressure
22. customthe residue was purified by silica gel column chromatography