反应详情

4′-{[4-(trans-4-Hydroxycyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.20 g), isoxazol-3-ol (0.071 g) and triphenylphosphine (0.22 g) were dissolved in tetrahydrofuran (2 mL), a solution of diisopropyl azodicarboxylate (0.44 mL, 1.9 M toluene solution) in tetrahydrofuran (1 mL) was added dropwise, and the mixture was stirred at room temperature for 18 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. The residue obtained by purification by silica gel column chromatography was added to a mixture of hydroxylammonium chloride (0.43 g), sodium hydrogen carbonate (0.7 g), and dimethyl sulfoxide (3 mL), which had been stirred at 40° C. for 30 min in advance, and the mixture was stirred at 90° C. for 18 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 (1 mL). N,N′-Carbonyldiimidazole (0.081 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.074 mL) were added, and the mixture was stirred at room temperature for 66 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 purified by silica gel column chromatography and recrystallized (ethyl acetate) to give the title compound as a colorless solid (0.055 g, 22%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. customThe residue obtained by purification by silica gel column chromatography
6. stirringhad been stirred at 40° C. for 30 min in advance
7. stirringthe mixture was stirred at 90° C. for 18 hr
8. extractionthe mixture was extracted with ethyl acetate
9. washThe organic layer was washed with saturated brine
10. dry with materialdried over anhydrous magnesium sulfate
11. customThe solvent was evaporated under reduced pressure
12. dissolutionthe residue was dissolved in tetrahydrofuran (1 mL)
13. additionN,N′-Carbonyldiimidazole (0.081 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.074 mL) were added
14. stirringthe mixture was stirred at room temperature for 66 hr
15. additionEthyl acetate and water were added to the reaction mixture
16. extractionextracted with ethyl acetate
17. washThe organic layer was washed with saturated brine
18. dry with materialdried over anhydrous magnesium sulfate
19. customThe solvent was evaporated under reduced pressure
20. customthe residue was purified by silica gel column chromatography
21. customrecrystallized (ethyl acetate)