Potassium Carbonate → 3-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

HRID 18577ノート

反応式

HRID 18577 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:25]=[CH:24][C:8]2[NH:9][C:10]([C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:22][CH2:21]4)[CH2:16][CH2:15]3)=[N:11][C:7]=2[CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[Cl:32][C:33]1[S:37][C:36]([C:38]2[O:42][N:41]=[C:40]([CH2:43]OS(C)(=O)=O)[CH:39]=2)=[CH:35][CH:34]=1>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:25]=[CH:24][C:8]2[N:9]=[C:10]([C:12](=[O:23])[NH:13][CH:14]3[CH2:15][CH2:16][N:17]([CH:20]4[CH2:22][CH2:21]4)[CH2:18][CH2:19]3)[N:11]([CH2:43][C:40]3[CH:39]=[C:38]([C:36]4[S:37][C:33]([Cl:32])=[CH:34][CH:35]=4)[O:42][N:41]=3)[C:7]=2[CH:6]=1)=[O:4]

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 865958785-(5-Chlorothiophen-2-yl)isoxazol-3-ylmethyl methanesulfonateHCID 178497372HCID 178497372、化合物

生成物 1

HCID 670117253-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

17.3 g (50.52 mmol) 2-(1-Cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester were dissolved in 800 mL DMF. Subsequently 10.47 g (75.8 mmol) K2CO3 and 14.84 g (50.52 mmol) methanesulfonic acid 5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl ester were added and the resulting mixture was stirred for 2 h at 80° C. The mixture was concentrated under reduced pressure. The residue was suspended in 800 mL ethyl acetate. The next day the resulting precipitate was filtered off and washed with 100 mL ethyl acetate to give 3-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-3H-benzoimidazole-5-carboxylic acid methyl ester. The filtrate was concentrated to a volume of approx. 100 mL. Again the formed precipitate was filtered off. That procedure was repeated once again. The remaining filtrate was concentrated under reduced pressure and finally purified by flash-chromatography on silica gel using ethyl acetate as eluent. The product containing fractions were concentrated under vacuo to give pure (>98%) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester as a light brown crystalline solid.

後処理

  1. concentrationThe mixture was concentrated under reduced pressure
  2. filtrationThe next day the resulting precipitate was filtered off
  3. washwashed with 100 mL ethyl acetate

出典と根拠

ORDレコード
ord-539ee90945854d658e7a37df7d6e73b7
出典データセット
uspto-grants-2010_06
特許番号
US07741341B2

反応ノート

読み込み中…