反应详情

Cyclohexyl isocyanate (0.285 mL, 2.20 mmol) was added to a flask containing 4-[8-(chloromethyl)-5,6-dimethyl-7H-imidazo[4,5-c]tetraazolo[1,5-a]pyridin-7-yl]butan-1-amine hydrochloride (680 mg, 1.98 mmol), triethylamine (0.311 mL, 2.2 mmol), and dichloromethane (20 mL). The reaction mixture was stirred at room temperature for 2 hours and additional triethylamine and cyclohexyl isocyanate (1.1 equivalents each) were added. The reaction mixture was stirred overnight at room temperature, then was partitioned between dichloromethane (50 mL) and 2:1 water/saturated aqueous sodium carbonate (30 mL). The aqueous layer was extracted with dichloromethane (3×20 mL). The organic layers were combined, washed with 0.5 M aqueous sodium hydroxide (2×30 mL), and concentrated under reduced pressure. The resulting white solid was triturated with ethyl acetate, isolated by filtration, and washed with ethyl acetate and water to provide 777 mg of N-{4-[8-(chloromethyl)-5,6-dimethyl-7H-imidazo[4,5-c]tetraazolo[1,5-a]pyridin-7-yl]butyl}-N′-cyclohexylurea.

1. stirringThe reaction mixture was stirred overnight at room temperature
2. customwas partitioned between dichloromethane (50 mL) and 2:1 water/saturated aqueous sodium carbonate (30 mL)
3. extractionThe aqueous layer was extracted with dichloromethane (3×20 mL)
4. washwashed with 0.5 M aqueous sodium hydroxide (2×30 mL)
5. concentrationconcentrated under reduced pressure
6. customThe resulting white solid was triturated with ethyl acetate
7. customisolated by filtration
8. washwashed with ethyl acetate and water