HCID 13412531, compound → Sorafenib

HRID 2094787Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:17])OC2C=CC=CC=2)=[CH:4][C:3]=1[C:18]([F:21])([F:20])[F:19].[NH2:22][C:23]1[CH:39]=[CH:38][C:26]([O:27][C:28]2[CH:33]=[CH:32][N:31]=[C:30]([C:34]([NH:36][CH3:37])=[O:35])[CH:29]=2)=[CH:25][CH:24]=1>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:17])[NH:22][C:23]2[CH:39]=[CH:38][C:26]([O:27][C:28]3[CH:33]=[CH:32][N:31]=[C:30]([C:34]([NH:36][CH3:37])=[O:35])[CH:29]=3)=[CH:25][CH:24]=2)=[CH:4][C:3]=1[C:18]([F:19])([F:20])[F:21]

Participants

Conditions

Temperature: 42.5 °C

Procedure

Phenyl 4-chloro-3-(trifluoromethyl)phenylcarbamate (100 g, 0.3174 mol) and 4-(4-aminophenoxy)-N-methylpicolinamide (77.14 g, 0.3174 mol) were dissolved in N,N-dimethyl formamide (300 ml) to obtain a clear reaction mass. The reaction mass was agitated at 40-45° C. for 2-3 hours, cooled to room temperature and diluted with ethyl acetate (1000 ml). The organic layer was washed with water (250 ml) followed by 1N HCl (250 ml) and finally with brine (250 ml). The organic layer was separated, dried over sodium sulfate and degassed to obtain solid. This solid was stripped with ethyl acetate and finally slurried in ethyl acetate (1000 ml) at room temperature. It was then filtered and vacuum dried to give (118 g) of 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylpicolinamide (sorafenib base).

Workup

customto obtain a clear reaction mass
temperaturecooled to room temperature
washThe organic layer was washed with water (250 ml)
customThe organic layer was separated
dry with materialdried over sodium sulfate
customdegassed
customto obtain solid
filtrationIt was then filtered
customvacuum dried

Sources & evidence

ORD record: ord-b2b2b5ac6e344c02a5267d935b94889d
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445687B2

Reaction notes

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