1,8-Diazabicyclo(5.4.0)undec-7-ene → Sorafenib

HRID 2094791Notes

Reaction equation

HRID 2094791 reaction equation
ClC(Cl)(Cl)[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:7]=1)=[O:4].N12CCCN=C1CCCCC2.[NH2:30][C:31]1[CH:47]=[CH:46][C:34]([O:35][C:36]2[CH:41]=[CH:40][N:39]=[C:38]([C:42]([NH:44][CH3:45])=[O:43])[CH:37]=2)=[CH:33][CH:32]=1>CN(C)C=O.C(OCC)(=O)C>[Cl:12][C:9]1[CH:10]=[CH:11][C:6]([NH:5][C:3](=[O:4])[NH:30][C:31]2[CH:47]=[CH:46][C:34]([O:35][C:36]3[CH:41]=[CH:40][N:39]=[C:38]([C:42]([NH:44][CH3:45])=[O:43])[CH:37]=3)=[CH:33][CH:32]=2)=[CH:7][C:8]=1[C:13]([F:16])([F:15])[F:14]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 166551294-(4-Aminophenoxy)-N-methylpicolinamideHCID 86648442HCID 86648442, compound

Product 1

HCID 216239SorafenibYield 84.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2,2,2-trichloro-N-(4-chloro-3-(trifluoromethyl)phenyl)acetamide (45 g, 0.1319 mol) was refluxed in N,N-dimethyl formamide (100 ml) with 1,8-diazabicyclo[5.4.0]undec-7-ene (24.67 ml, 0.1649 mol) and 4-(4-aminophenoxy)-N-methylpicolinamide (32.07 g, 0.1319 mol) for 24 hours and cooled to room temperature. The reaction mass was quenched in water (1000 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 dried over sodium sulfate and evaporated under vacuum to obtain solid. The obtained solid was slurried in ethyl acetate (1000 ml) at ambient temperature and filtered to give 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl) ureido)phenoxy)-N-methylpicolinamide (sorafenib base) (52 g).

Workup

  1. customThe reaction mass was quenched in water (1000 ml)
  2. extractionThe quenched mass was extracted repeatedly with ethyl acetate
  3. washthe combined ethyl acetate layer was then back washed with water
  4. customto remove DMF traces
  5. dry with materialIt was dried over sodium sulfate
  6. customevaporated under vacuum
  7. customto obtain solid
  8. filtrationfiltered

Sources & evidence

ORD record
ord-2615b9140eb145c6b83962c4ac68c7db
Source dataset
uspto-grants-2013_05
Patent number
US08445687B2

Reaction notes

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