N-bromobutanimide → 2-Propen-1-yl[3-[5-(2-chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-(methyloxy)phenyl]carbamate

HRID 239348Notes

Reaction equation

HRID 239348 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[C:12]([O:24][CH3:25])=[C:13]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:14]=[CH:15][CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[CH3:34][CH:35]([CH3:39])[C:36](=[S:38])[NH2:37]>C(Cl)Cl.CS(C)=O.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:38][C:36]([CH:35]([CH3:39])[CH3:34])=[N:37][C:9]=2[C:11]2[C:12]([O:24][CH3:25])=[C:13]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 67184N-bromobutanimideHCID 109095072-MethylpropanethioamideHCID 579896212-Propen-1-yl [3-[(2-chloro-4-pyrimidinyl)acetyl]-2-(methyloxy)phenyl]carbamate

Product 1

HCID 579896912-Propen-1-yl[3-[5-(2-chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-(methyloxy)phenyl]carbamateYield 64.8%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-propen-1-yl [3-[(2-chloro-4-pyrimidinyl)acetyl]-2-(methyloxy)phenyl]carbamate (15.4 g, 42 mmol) in DCM (150 mL), NBS (7.6 g, 42 mmol) was added and the solution was allowed to stir at rt for 30 min. The reaction mixture was then concentrated in vacuo and the resulting oil was diluted with DMSO (150 mL) and 2-methylpropanethioamide (6.6 g 63.8 mmol) was added at once. The reaction was complete after stirring 1 h at rt. The reaction mixture was diluted with EtOAc and organic layer was washed with water and brine successively, dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product, which was purified by column chromatography on silica gel (DCM:petroleum ether 2:1) to afford the title compound of Step F (12.1 g, 63.8% yield) which was used directly in the next step.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. additionwas added at once
  3. stirringafter stirring 1 h at rt
  4. washwas washed with water and brine successively
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product, which
  9. customwas purified by column chromatography on silica gel (DCM:petroleum ether 2:1)

Sources & evidence

ORD record
ord-59c9973d3f4142c38c8421fe54b5c89b
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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