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

HRID 1961846Notes

Reaction equation

HRID 1961846 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.[N:34]1([C:40](=[S:42])[NH2:41])[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>C(Cl)Cl.CS(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:42][C:40]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[N:41][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

6

Reactant 3

HCID 67184N-bromobutanimideHCID 23935444-MorpholinecarbothioamideHCID 579896212-Propen-1-yl [3-[(2-chloro-4-pyrimidinyl)acetyl]-2-(methyloxy)phenyl]carbamate

Product 1

HCID 579897552-Propen-1-yl[3-[5-(2-chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-(methyloxy)phenyl]carbamateYield 98.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-propen-1-yl [3-[(2-chloro-4-pyrimidinyl)acetyl]-2-(methyloxy)phenyl]carbamate (30 g, 82.9 mmol) in DCM (300 mL), NBS (14.8 g, 82.9 mmol) was added and the solution was allowed to stir at rt for 30 min. The reaction mixture was then concentrated on the rotovap and the resulting oil was diluted with DMSO (240 mL) and 4-morpholinecarbothioamide (14.8 g 101 mmol) was added at once. The reaction was complete after stirring 1 h at rt. The combined organic layers were 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 product of Step A (40 g, 98.8% yield) which was used directly in the next step.

Workup

  1. concentrationThe reaction mixture was then concentrated on the rotovap
  2. additionwas added at once
  3. stirringafter stirring 1 h at rt
  4. washThe combined organic layers were 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-5909f4cce19b43e595799ed8d3f79abe
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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