反应详情

A mixture of propyl 3-{6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}cyclobutanecarboxylate (5 g), 1N aqueous sodium hydroxide solution (10 mL), methanol (10 mL) and tetrahydrofuran (10 mL) was stirred at room temperature for 2 hr. The reaction mixture was adjusted to pH 4 with water and 1 N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained extract was dissolved in N,N-dimethylformamide (50 mL), N-methoxymethanamine hydrochloride (1.4 g), 1-hydroxybenzotriazole (2.3 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.8 g) and triethylamine (2.1 mL) were added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 N hydrochloric acid and then 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 tetrahydrofuran (20 mL), and methylmagnesium bromide (1.0 M tetrahydrofuran solution, 8.1 mL) was added at room temperature. The reaction mixture was stirred for 3 hr, saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.3 g, 28%).

1. extractionextracted with ethyl acetate
2. washThe organic layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. extractionThe obtained extract
6. dissolutionwas dissolved in N,N-dimethylformamide (50 mL)
7. additionN-methoxymethanamine hydrochloride (1.4 g), 1-hydroxybenzotriazole (2.3 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.8 g) and triethylamine (2.1 mL) were added
8. stirringthe mixture was stirred at room temperature for 16 hr
9. additionThe reaction mixture was diluted with ethyl acetate
10. washwashed with 1 N hydrochloric acid
11. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
12. customThe solvent was evaporated under reduced pressure
13. customThe residue obtained by purification by silica gel column chromatography
14. stirringThe reaction mixture was stirred for 3 hr
15. extractionthe mixture was extracted with ethyl acetate
16. washThe obtained ethyl acetate layer was washed with saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. customThe solvent was evaporated under reduced pressure
19. customThe obtained residue was purified by silica gel column chromatography