3-Methoxypropionic acid → 1-{4-[6-Fluoro-2-phenoxymethyl-3-(4-trifluoromethoxy-benzyl)-3H-benzoimidazol-5-yl]-piperazin-1-yl}-3-methoxy-propan-1-one

HRID 507220

反応式

HRID 507220 の反応式
[CH3:1][O:2][CH2:3][CH2:4][C:5]([OH:7])=O.[F:8][C:9]1[C:37]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[CH:36][C:12]2[N:13]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=3)[C:14]([CH2:16][O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:15][C:11]=2[CH:10]=1>ClCCl>[F:8][C:9]1[C:37]([N:38]2[CH2:39][CH2:40][N:41]([C:5](=[O:7])[CH2:4][CH2:3][O:2][CH3:1])[CH2:42][CH2:43]2)=[CH:36][C:12]2[N:13]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][C:32]([F:34])([F:35])[F:33])=[CH:27][CH:26]=3)[C:14]([CH2:16][O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:15][C:11]=2[CH:10]=1

参加物

4

反応物 2

HCID 1344423-Methoxypropionic acidHCID 684671025-fluoro-2-phenoxymethyl-6-piperazin-1-yl-1-(4-trifluoromethoxy-benzyl)-1H-benzoimidazole

生成物 1

HCID 684631841-{4-[6-Fluoro-2-phenoxymethyl-3-(4-trifluoromethoxy-benzyl)-3H-benzoimidazol-5-yl]-piperazin-1-yl}-3-methoxy-propan-1-one

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

0.020 ml 3-methoxy-propionic acid (0.2 mmol) and 40 mg 1,1-carbonyldiimidazole (0.24 mmol) were refluxed in 4 ml dichloromethane under nitrogen for 40 minutes. 100 mg of 5-fluoro-2-phenoxymethyl-6-piperazin-1-yl-1-(4-trifluoromethoxy-benzyl)-1H-benzoimidazole (0.2 mmol) were added and the resulting mixture refluxed for additional 4.5 h. The reaction mixture was then diluted with dichloromethane, washed with water, saturated sodium bicarbonate and brine, dried with magnesium sulfate, filtered and concentrated in vacuo, leading to 129 mg yellow solid. This residue was purified by column chromatography (40 g silicagel, dichloromethane/methanol 24:1) leading to 44 mg off-white solid (37%). MS (ISP) 587.2 (M+H)+.

後処理

  1. temperaturethe resulting mixture refluxed for additional 4.5 h
  2. washwashed with water, saturated sodium bicarbonate and brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThis residue was purified by column chromatography (40 g silicagel, dichloromethane/methanol 24:1)

出典と根拠

ORDレコード
ord-7458c47ec90a4cfaa8b347e0ce32ea42
出典データセット
uspto-grants-2010_08
特許番号
US07786128B2

関連ノート

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