Water → HCID 21265997, compound

Participants

Reaction Conditions

Reaction Steps

0.38 g of lithium aluminium hydride was added portionwise to a suspension of 2.06 g of ethyl 8-bromo-6-(2-pyridyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-2-carboxylate in 250 ml of tetrahydrofuran at −40° C. while stirring vigorously. A dark green solution thereby formed and this was stirred at −7 to −10° C. for 45 min. Then, the mixture was cooled to −35° C. and treated dropwise with 2 ml of water. After stirring at room temperature for 2 h. a further 6.0 ml of water were added slowly. The reaction mixture was filtered clear over Dicalite and the filtrate was evaporated in a vacuum. The residue was partitioned between 100 ml of chloroform and 50 ml of saturated aqueous sodium hydrogen carbonate solution. The chloroform phase was separated, dried over sodium sulphate and evaporated in a vacuum. The residue (1.9 g) was dissolved in 100 ml of tert-butanol and 50 ml of pyridine, treated with 1.0 g of selenium dioxide and stirred at 65° C. for 30 min. The mixture was evaporated in a vacuum, the residue was dissolved in chloroform, with a small amount of insoluble impurity being filtered off. The solution was chromatographed over 250 g of aluminium oxide (activity 1). A small amount of impurity was eluted with dichloromethane/etanol 98:2, then 0.95 g of the desired 8-bromo-6-(2-pyridyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol was eluted with dichloromethane/ethanol 95:5, 90:10 and 80:20. After recrystallization from ethyl acetate there was obtained 0.80 g of 8-bromo-6-(2-pyridyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol of m.p. 176-178° C. which was converted into the hydrochloride (m.p. above 300° C.).

Provenance & Evidence