Dimethylformamide → Sorafenib

Participants

Reaction Steps

N-methyl-4-(4-ureidophenoxy)picolinamide (50 g, 0.1746 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (33.95 ml, 0.2270 mol) and 3-trifluoromethyl-4-chloroaniline (34.2 g, 0.1746 mol) were mixed with N,N-dimethyl formamide (200 ml) (DMF) and the reaction mass was heated to reflux for 24 hours. It was then cooled to room temperature and quenched in water (600 ml). The quenched mass was extracted repeatedly with ethyl acetate and the combined ethyl acetate layer was then back washed with water to remove DMF traces. It was then dried over sodium sulfate and evaporated under vacuum to obtain solid. The solid thus obtained was then slurried in ethyl acetate (400 ml) at ambient temperature and filtered to give 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylpicolinamide (sorafenib base) (64 g).

Provenance & Evidence