反应详情

A mixture of 4′-{[2-methyl-5-oxo-4-(4-oxocyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (5.0 g), butane-2,3-diol (1.8 g), 4-methylbenzenesulfonic acid (0.19 g) and toluene (20 mL) was heated with a Dean-Stark apparatus under reflux for 8 hr. The reaction mixture was added to saturated aqueous sodium hydrogen carbonate solution, 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. 40% of the residue was dissolved in tetrahydrofuran (30 mL), sodium cyanoborohydride (1.3 g) and boron trifluoride etherate (2.6 mL) were added, and the mixture was heated under reflux for 13 hr. The reaction mixture was added to saturated aqueous sodium hydrogen carbonate solution, 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. The residue obtained by purification by silica gel column chromatography was dissolved in acetonitrile (10 mL), Dess-Martin periodinane (1.7 g) was added, and the mixture was stirred at room temperature for 14 hr. Saturated aqueous sodium hydrogen carbonate solution and aqueous sodium thiosulfate solution were added to the reaction mixture, and the mixture was stirred for 3 hr. The solvent was evaporated under reduced pressure, 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 (10 mL). Methylmagnesium bromide (6.2 mL, 1.0 M tetrahydrofuran solution) was added dropwise at 0° C., and the mixture was stirred at room temperature for 4 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 (0.24 g, 10%).

1. temperaturewas heated with a Dean-Stark apparatus
2. temperatureunder reflux for 8 hr
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe solvent was evaporated under reduced pressure
7. dissolution40% of the residue was dissolved in tetrahydrofuran (30 mL)
8. additionsodium cyanoborohydride (1.3 g) and boron trifluoride etherate (2.6 mL) were added
9. temperaturethe mixture was heated
10. temperatureunder reflux for 13 hr
11. additionThe reaction mixture was added to saturated aqueous sodium hydrogen carbonate solution
12. extractionthe mixture was extracted with ethyl acetate
13. washThe organic layer was washed with saturated brine
14. dry with materialdried over anhydrous magnesium sulfate
15. customThe solvent was evaporated under reduced pressure
16. customThe residue obtained by purification by silica gel column chromatography
17. stirringthe mixture was stirred for 3 hr
18. customThe solvent was evaporated under reduced pressure
19. extractionthe mixture was extracted with ethyl acetate
20. washThe organic layer was washed with saturated brine
21. dry with materialdried over anhydrous magnesium sulfate
22. customThe solvent was evaporated under reduced pressure
23. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
24. additionMethylmagnesium bromide (6.2 mL, 1.0 M tetrahydrofuran solution) was added dropwise at 0° C.
25. stirringthe mixture was stirred at room temperature for 4 hr
26. additionThe reaction mixture was added to 1 M hydrochloric acid
27. extractionthe mixture was extracted with ethyl acetate
28. washThe organic layer was washed with saturated brine
29. dry with materialdried over anhydrous magnesium sulfate
30. customThe solvent was evaporated under reduced pressure
31. customthe residue was purified by silica gel column chromatography