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 908601ノート

反応式

HRID 908601 の反応式
[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]

参加物

4

反応物 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

生成物 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 ester収率 77.2%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-41fc43132b2f43b3a3171b0094287d57
出典データセット
uspto-grants-2011_09
特許番号
US08017612B2

反応ノート

読み込み中…