反应详情

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).

1. temperaturethe reaction mass was heated
2. temperatureto reflux for 24 hours
3. customquenched in water (600 ml)
4. extractionThe quenched mass was extracted repeatedly with ethyl acetate
5. washthe combined ethyl acetate layer was then back washed with water
6. customto remove DMF traces
7. dry with materialIt was then dried over sodium sulfate
8. customevaporated under vacuum
9. customto obtain solid
10. customThe solid thus obtained
11. filtrationfiltered