反应详情

温度

125 °C

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-hydroxyurea (5 g, 0.0196 mol) was suspended in N,N-dimethyl formamide (15 ml) with triethyl amine (8.2 ml, 0.0589 mol) and 4-(4-aminophenoxy)-N-methylpicolinamide (4.7 g, 0.0196 mol). The reaction mass was then heated to 125° C. for 4 days. The reaction mass was concentrated under reduced pressure and the obtained residue was quenched with water (50 ml) at room temperature. The aqueous layer was extracted repeatedly with ethyl acetate and the combined ethyl acetate layer was back washed with water. Degassing of the ethyl acetate gave semisolid which upon agitation in acetonitrile (50 ml) at ambient temperature for 2-3 hours gave desired product. The product was filtered and vacuum dried to obtain 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylpicolinamide (sorafenib base) (2.5 g).

1. concentrationThe reaction mass was concentrated under reduced pressure
2. customthe obtained residue was quenched with water (50 ml) at room temperature
3. extractionThe aqueous layer was extracted repeatedly with ethyl acetate
4. washthe combined ethyl acetate layer was back washed with water
5. customDegassing of the ethyl acetate
6. customgave semisolid which upon agitation in acetonitrile (50 ml) at ambient temperature for 2-3 hours