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 131240

Reaction equation

HRID 131240 reaction equation
[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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-ef38517339294e56aee289edbdaba8b4
Source dataset
uspto-grants-2008_06
Patent number
US07384945B2

Linked notes

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