Cyclopropaneacetic acid → 2-Cyclopropyl-1-{4-[6-fluoro-2-phenoxymethyl-3-(4-trifluoromethoxy-benzyl)-3H-benzoimidazol-5-yl]-piperazin-1-yl}-ethanone

HRID 131244

Reaction equation

HRID 131244 reaction equation
[CH:1]1([CH2:4][C:5]([OH:7])=O)[CH2:3][CH2:2]1.[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>[CH:1]1([CH2:4][C:5]([N:41]2[CH2:42][CH2:43][N:38]([C:37]3[C:9]([F:8])=[CH:10][C:11]4[N:15]=[C:14]([CH2:16][O:17][C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)[N:13]([CH2:24][C:25]5[CH:26]=[CH:27][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:29][CH:30]=5)[C:12]=4[CH:36]=3)[CH2:39][CH2:40]2)=[O:7])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 138440Cyclopropaneacetic acidHCID 684671025-fluoro-2-phenoxymethyl-6-piperazin-1-yl-1-(4-trifluoromethoxy-benzyl)-1H-benzoimidazole

Product 1

HCID 684635972-Cyclopropyl-1-{4-[6-fluoro-2-phenoxymethyl-3-(4-trifluoromethoxy-benzyl)-3H-benzoimidazol-5-yl]-piperazin-1-yl}-ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.020 ml of cyclopropyl-acetic acid (0.2 mmol) and 40 mg of 1′1-carbonyldiimidazole (0.24 mmol) were refluxed in 4 ml dichloromethane under nitrogen for 40 minutes. 100 mg 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 26 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 (24 g silicagel, dichloromethane/methanol 24:1) leading to 77 mg light yellow solid (63%). MS (ISP) 583.3 (M+H)+.

Workup

  1. temperaturethe resulting mixture refluxed for additional 26 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 (24 g silicagel, dichloromethane/methanol 24:1)

Sources & evidence

ORD record
ord-bab3d91ddc434dcdbbdbcee6d092dc76
Source dataset
uspto-grants-2008_06
Patent number
US07384945B2

Linked notes

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