Dichloromethane → HCID 18753482, compound

Participants

Reaction Steps

Diethyl azodicarboxylate (283 μl, 1.8 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (218 mg, 0.6 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (95 μl, 0.84 mmol) and 1-(2-hydroxyethyl)-2-pyrrolidinone (95 μl, 0.84 mmol) in methylene chloride (8 ml) under nitrogen. The mixture was stirred for 4 hours at ambient temperature, and then purified by pouring it directly on to a column of silica and eluting with methylene chloride/acetonitrile/methanol (60/32.5/7.5). The purified product was triturated with ether and collected by filtration. The solid was dissolved in methylene chloride/methanol (1/1) and 2M ethereal hydrogen chloride (1 ml) was added. The volatiles were removed by evaporation, the residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(2-oxopyrrolidin-1-yl)ethoxy)quinazoline hydrochloride (182 mg, 60%).

Provenance & Evidence