Chloroacetic Acid → 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid carboxymethyl ester

HRID 18550

反応式

HRID 18550 の反応式
[Cl:1][C:2]1[S:6][C:5]([C:7]2[O:11][N:10]=[C:9]([CH2:12][N:13]3[C:17]4[CH:18]=[CH:19][CH:20]=[C:21]([C:22]([OH:24])=[O:23])[C:16]=4[N:15]=[C:14]3[C:25](=[O:36])[NH:26][CH:27]3[CH2:32][CH2:31][N:30]([CH:33]([CH3:35])[CH3:34])[CH2:29][CH2:28]3)[CH:8]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:44][C:45]([OH:47])=[O:46]>CN(C=O)C>[C:45]([CH2:44][O:23][C:22]([C:21]1[C:16]2[N:15]=[C:14]([C:25](=[O:36])[NH:26][CH:27]3[CH2:32][CH2:31][N:30]([CH:33]([CH3:34])[CH3:35])[CH2:29][CH2:28]3)[N:13]([CH2:12][C:9]3[CH:8]=[C:7]([C:5]4[S:6][C:2]([Cl:1])=[CH:3][CH:4]=4)[O:11][N:10]=3)[C:17]=2[CH:18]=[CH:19][CH:20]=1)=[O:24])([OH:47])=[O:46]

参加物

5

反応物 3

HCID 300Chloroacetic Acid2 回HCID 11430Potassium Carbonate2 回HCID 112378401-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid

生成物 1

HCID 670126621-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid carboxymethyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

50 mg (0.08 mmol) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid were dissolved in 6 mL DMF. Subsequently 27.6 mg KI, 126.5 mg (0.88 mmol) K2CO3 and 62.8 mg (0.64 mmol) chloro-acetic acid were added. The resulting mixture was stirred for 8 h at 60° C. Further 92 mg K2CO3 and 62.8 mg (0.64 mmol) chloro-acetic acid were added. After further 8 h at 60° C. the reaction mixture was concentrated under removed pressure. The remaining residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid) to give pure 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid carboxymethyl ester as a white amorphous solid. The corresponding dihydrochloride was obtained by treatment with a 0.1 M HCl-solution and following lyophilization.

後処理

  1. concentrationAfter further 8 h at 60° C. the reaction mixture was concentrated
  2. customunder removed pressure
  3. customThe remaining residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid)

出典と根拠

ORDレコード
ord-8c49b626646c445298fe01daa8fba5be
出典データセット
uspto-grants-2010_06
特許番号
US07741341B2

関連ノート

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