4-methyl-2-[(R)-3-(4-propyl-benzylcarbamoyl)-piperazin-1-yl]-thiazole-5-carboxylic acid tert-butyl ester → 2-[(R)-4-(2-fluoro-4-trifluoromethoxy-benzenesulfonyl)-3-(4-propyl-benzylcarbamoyl)-piperazin-1-yl]-4-methyl-thiazole-5-carboxylic acid tert-butyl ester

HRID 908601Notes

Reaction equation

HRID 908601 reaction equation
[C:1]([O:5][C:6]([C:8]1[S:12][C:11]([N:13]2[CH2:18][CH2:17][NH:16][C@@H:15]([C:19](=[O:31])[NH:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][CH3:30])=[CH:24][CH:23]=3)[CH2:14]2)=[N:10][C:9]=1[CH3:32])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:33][C:34]1[CH:39]=[C:38]([O:40][C:41]([F:44])([F:43])[F:42])[CH:37]=[CH:36][C:35]=1[S:45](Cl)(=[O:47])=[O:46]>N1C=CC=CC=1>[C:1]([O:5][C:6]([C:8]1[S:12][C:11]([N:13]2[CH2:18][CH2:17][N:16]([S:45]([C:35]3[CH:36]=[CH:37][C:38]([O:40][C:41]([F:42])([F:43])[F:44])=[CH:39][C:34]=3[F:33])(=[O:47])=[O:46])[C@@H:15]([C:19](=[O:31])[NH:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([CH2:28][CH2:29][CH3:30])=[CH:26][CH:27]=3)[CH2:14]2)=[N:10][C:9]=1[CH3:32])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 597038424-methyl-2-[(R)-3-(4-propyl-benzylcarbamoyl)-piperazin-1-yl]-thiazole-5-carboxylic acid tert-butyl esterHCID 866194812-Fluoro-4-(trifluoromethoxy)benzenesulfonyl chloride

Product 1

HCID 597037082-[(R)-4-(2-fluoro-4-trifluoromethoxy-benzenesulfonyl)-3-(4-propyl-benzylcarbamoyl)-piperazin-1-yl]-4-methyl-thiazole-5-carboxylic acid tert-butyl esterYield 77.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of the compound (50 mg) obtained in Step 6 in pyridine (0.5 ml) was added, with stirring at room temperature, 2-fluoro-4-trifluoromethoxybenzenesulfonyl chloride (46 mg). After stirring overnight at room temperature, the reaction mixture was concentrated under reduced pressure. The residue was partitioned by adding ethyl acetate and water. The organic layer was washed successively with 1N aqueous hydrochloric acid solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by thin layer chromatography (ethyl acetate:n-hexane=1:2) to give the title compound (59 mg).

Workup

  1. stirringAfter stirring overnight at room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe residue was partitioned
  4. additionby adding ethyl acetate and water
  5. washThe organic layer was washed successively with 1N aqueous hydrochloric acid solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by thin layer chromatography (ethyl acetate:n-hexane=1:2)

Sources & evidence

ORD record
ord-41fc43132b2f43b3a3171b0094287d57
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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