反应详情

温度

98 °C

A solution of 10.9 g of 2-amino-7-chloro-5-phenyl-3H-1,4-benzodiazepine (K. Meguro, H. Tawada & Y. Kuwada, Yakugaku Zasshi, 1973, 93, 1253-1262) and 5.2 g of 1,3-dichloroacetone in 200 ml of dioxan was treated with 3.13 g of anhydrous sodium hydrogen carbonate and stirred at 98° C. for 22 h. After cooling the inorganic salts were filtered off, the filtrate was treated with 0.93 g of p-toluenesulphonic acid and stirred at 98° C. for 1.5 h. 74.5 ml of 1N aqueous sodium hydroxide solution and 2.5 g of active charcoal were added to this solution and the mixture was stirred at 80° C. for 2 h. After cooling the mixture was filtered over Dicalite and the filtrate was concentrated in a vacuum. The residue was taken up in dichloromethane and water and the aqueous phase was extracted four times with chloroform. The chloroform was evaporated in a vacuum. The residue (about 8 g) was crystallized from ethyl acetate. The crystals (7.3 g) were filtered off, dissolved in dichloromethane and chromatographed over 180 g of silica gel. The desired product was eluted with dichloromethane containing 2 to 4% ethanol and was recrystallized from ethyl acetate/ethanol 2:1. There were obtained 3.4 g of 8-chloro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol of m.p. 203-204° C., which was converted into the hydrochloride, m.p. 252-254° C.

1. temperatureAfter cooling the inorganic salts
2. filtrationwere filtered off
3. additionthe filtrate was treated with 0.93 g of p-toluenesulphonic acid
4. stirringstirred at 98° C. for 1.5 h
5. addition74.5 ml of 1N aqueous sodium hydroxide solution and 2.5 g of active charcoal were added to this solution
6. stirringthe mixture was stirred at 80° C. for 2 h
7. temperatureAfter cooling the mixture
8. filtrationwas filtered over Dicalite
9. concentrationthe filtrate was concentrated in a vacuum
10. extractionwater and the aqueous phase was extracted four times with chloroform
11. customThe chloroform was evaporated in a vacuum
12. customThe residue (about 8 g) was crystallized from ethyl acetate
13. filtrationThe crystals (7.3 g) were filtered off
14. dissolutiondissolved in dichloromethane
15. customchromatographed over 180 g of silica gel
16. washThe desired product was eluted with dichloromethane containing 2 to 4% ethanol
17. customwas recrystallized from ethyl acetate/ethanol 2:1