反应详情

温度

60 °C

A mixture of hydroxylammonium chloride (2.67 g), sodium hydrogen carbonate (4.30 g) and dimethyl sulfoxide (7 mL) was stirred at 60° C. for 30 min, a solution of 4′-[(4-{trans-4-[1-(1-hydroxycyclobutyl)ethoxy]cyclohexyl}-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (1.45 g) in dimethyl sulfoxide (8 mL) was added, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then 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). N,N′-Carbonyldiimidazole (503 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (472 mg) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=50/50→35/65 (volume ratio)] to give the title compound as a colorless amorphous compound (890 mg, 56%).

1. stirringthe mixture was stirred at 90° C. for 18 hr
2. washwashed with water
3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
6. additionN,N′-Carbonyldiimidazole (503 mg) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (472 mg) were added
7. stirringthe mixture was stirred at room temperature for 2 hr
8. additionThe reaction mixture was diluted with ethyl acetate
9. washwashed with saturated aqueous potassium hydrogensulfate solution
10. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
11. customThe solvent was evaporated under reduced pressure
12. customthe residue was purified by silica gel chromatography [eluent: hexane/ethyl acetate=50/50→35/65 (volume ratio)]