反应详情

A solution of 16.3 g of 2-amino-7-chloro-5-(2-pyridyl)-3H-1,4-benzodiazepine and 8.4 g of 1,3-dichloroacetone in 600 ml of dioxan was treated with 5.6 g of anhydrous sodium hydrogen carbonate and stirred at 100°0 C. for 16 h. A further 0.84 g of dichloroacetone and 0.56 g of anhydrous sodium hydrogen carbonate were added and the mixture was stirred at 100° C. for a further 8 h. The mixture was evaporated in a vacuum and the residue was partitioned between chloroform and water. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were evaporated in a vacuum. The residue was dissolved in dichloromethane and chromatographed over 800 g of silica gel. With dichloromethane/ethanol 197:3 there were eluted small amounts of impurities, with dichloromethane/ethanol 196:4 there were eluted 10.2 g of the desired product. After recrystallization from ethyl acetate there were obtained 9.0 g of 2-chloromethyl-8-chloro-6-(2-pyridyl)-4H-imidazo[1,2-a][1,4]benzodiazepine of m.p. 161° C.

1. stirringthe mixture was stirred at 100° C. for a further 8 h
2. customThe mixture was evaporated in a vacuum
3. customthe residue was partitioned between chloroform and water
4. extractionThe aqueous phase was extracted twice with dichloromethane
5. customThe combined organic phases were evaporated in a vacuum
6. dissolutionThe residue was dissolved in dichloromethane
7. customchromatographed over 800 g of silica gel
8. washWith dichloromethane/ethanol 197:3 there were eluted small amounts of impurities
9. washwith dichloromethane/ethanol 196:4 there were eluted 10.2 g of the desired product
10. customAfter recrystallization from ethyl acetate