Dimethyl Sulfoxide → Sorafenib

HRID 2094789Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH2:11])=[O:10])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].N12CCCN=C1CCCCC2.N[C:28]1[CH:44]=[CH:43][C:31]([O:32][C:33]2[CH:38]=[CH:37][N:36]=[C:35]([C:39]([NH:41][CH3:42])=[O:40])[CH:34]=2)=[CH:30][CH:29]=1.CS(C)=O>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:10])[NH:11][C:28]2[CH:44]=[CH:43][C:31]([O:32][C:33]3[CH:38]=[CH:37][N:36]=[C:35]([C:39]([NH:41][CH3:42])=[O:40])[CH:34]=3)=[CH:30][CH:29]=2)=[CH:4][C:3]=1[C:12]([F:13])([F:14])[F:15]

Participants

Conditions

Temperature: 115 °C

Procedure

1-(4-chloro-3-(trifluoromethyl)phenyl)urea (15 g, 0.0628 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (11.75 ml, 0.078 mol) and 4-(4-aminophenoxy)-N-methylpicolinamide (15.27 g, 0.0628 mol) were mixed with dimethyl sulfoxide (45 ml) and the reaction mass was then heated to 110-120° C. for 12-18 hours. The reaction mass was cooled to room temperature and quenched in water (250 ml). The quenched mass was extracted repeatedly with ethyl acetate and the combined ethyl acetate layer was then back washed with water. It was dried over sodium sulfate and evaporated under vacuum to obtain solid. The obtained solid was slurried in acetonitrile (150 ml) at ambient temperature and filtered to give 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl) ureido) phenoxy)-N-methylpicolinamide (sorafenib base) (17.5 g).

Workup

temperatureThe reaction mass was cooled to room temperature
customquenched in water (250 ml)
extractionThe quenched mass was extracted repeatedly with ethyl acetate
washthe combined ethyl acetate layer was then back washed with water
dry with materialIt was dried over sodium sulfate
customevaporated under vacuum
customto obtain solid
filtrationfiltered

Sources & evidence

ORD record: ord-238572794da14ee3894610ce64b4a0bc
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445687B2

Reaction notes

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