N-bromobutanimide → N-(3-(5-(2-chloro-4-pyrimidinyl)-2-(1,1-diethylethyl)-1,3-thiazol-4-yl)-2-fluoraphenyl)-2,6-difluorobenzenesulfonamide

HRID 239256Notes

Reaction equation

HRID 239256 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[CH3:38][C:39]([CH3:44])([CH3:43])[C:40](=[S:42])[NH2:41]>CC(N(C)C)=O.O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:42][C:40]([C:39]([CH3:44])([CH3:43])[CH3:38])=[N:41][C:9]=2[C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 67184N-bromobutanimideHCID 30311302,2-DimethylpropanethioamideHCID 57989720N-(3-(2-(2-chloropyriMidin-4-yl)acetyl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide

Product 1

HCID 57989782N-(3-(5-(2-chloro-4-pyrimidinyl)-2-(1,1-diethylethyl)-1,3-thiazol-4-yl)-2-fluoraphenyl)-2,6-difluorobenzenesulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-{3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (2.0 g, 4.53 mmol) in 40 mL DMA, 1.0 eq. NBS (0.806 g, 4.53 mmol) was added and the solution was allowed to stir 15 min at rt. 2,2-dimethylpropanethioamide (0.531 g, 4.53 mmol) was then added at rt. The reaction was heated to 60° C. for 2 hours. The reaction was not complete by LC-MS. The reaction mixture was then heated to 80° C. for an additional hour. The reaction mixture was diluted with water and extracted×2 with EtOAc. The combined EtOAc washings were washed with water×3 to remove DMA, dried over MgSO4, filtered and concentrated onto silica gel. The crude material was chromatographed in 10-80% EtOAc in Hexanes to give the desired product, 1.6 g (64%). MS (ESI): 539.1 [M+H]+.

Workup

  1. temperatureThe reaction was heated to 60° C. for 2 hours
  2. temperatureThe reaction mixture was then heated to 80° C. for an additional hour
  3. extractionextracted×2 with EtOAc
  4. washThe combined EtOAc washings were washed with water×3
  5. customto remove DMA
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated onto silica gel
  9. customThe crude material was chromatographed in 10-80% EtOAc in Hexanes

Sources & evidence

ORD record
ord-c39d8f945a7a41a09cbeaa053d72f205
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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