Hydrochloric Acid → 4-(3-Chloro-2,4-difluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline

Participants

Reaction Conditions

Reaction Steps

3-Chloro-2,4-difluoroaniline (1.7 g, 10.1 mmol) and 5N hydrogen chloride in isopropanol (2 ml) were added to a suspension of tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate (4 g, 10.1 mmol, PCT Int. Appl. WO2003082831, AstraZeneca) in isopropanol (50 ml). The mixture was stirred at 80° C. for 3 hours. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 5-10% 7N methanolic ammonia in dichloromethane) to give 4-(3-chloro-2,4-difluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline (3.63 g, 85%) as a white solid.

Provenance & Evidence