Piperazin-2-one → [4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(piperazin-2-one-4-yl-methyl)-piperidin-1-yl]-methanone

HRID 31522

Reaction equation

HRID 31522 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][C:2]1=[O:7].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:18]([C:27]([N:29]3[CH2:34][CH2:33][CH:32]([CH2:35]Br)[CH2:31][CH2:30]3)=[O:28])[C:17]([C:37]3[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][C:38]=3[O:47][CH2:48][CH3:49])=[N:16]2)=[CH:11][CH:10]=1>CN(C)C=O>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH:19]([C:20]3[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=3)[N:18]([C:27]([N:29]3[CH2:34][CH2:33][CH:32]([CH2:35][N:4]4[CH2:5][CH2:6][NH:1][C:2](=[O:7])[CH2:3]4)[CH2:31][CH2:30]3)=[O:28])[C:17]([C:37]3[CH:42]=[CH:41][C:40]([C:43]([F:44])([F:45])[F:46])=[CH:39][C:38]=3[O:47][CH2:48][CH3:49])=[N:16]2)=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 231360Piperazin-2-oneHCID 86595530[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-bromomethyl-piperidin-1-yl]-methanone

Product 1

HCID 69273762[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(piperazin-2-one-4-yl-methyl)-piperidin-1-yl]-methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Piperazine-2-one (21 mg, 0.21 mmol) was added to a solution [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-bromomethyl-piperidin-1-yl]-methanone (48 mg, 0.07 mmol) in anhydrous dimethylformamide (2.0 mL). The mixture was stirred overnight at 70° C. The reaction mixture was cooled to ambient temperature and partitioned between methylene chloride and a saturated aqueous solution of ammonium chloride. The aqueous phase was extracted with methylene chloride and the combined organic extracts were washed with brine, and dried over anhydrous sodium sulfate. Evaporation of the solvents and chromatography of the residue over silica gel using 1-5% methanol in methylene chloride gave [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(piperazin-2-one-4-yl-methyl)-piperidin-1-yl]-methanone, which was dissolved in dilute hydrochloric acid (0.5 N, 1 mL) and lyophilized to give [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(piperazin-2-one-4-yl-methyl)-piperidin-1-yl]-methanone hydrochloride as an off-white powder (23 mg, 45%). LR-MS (APCI): 702.4 [(M+H)+].

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. custompartitioned between methylene chloride
  3. extractionThe aqueous phase was extracted with methylene chloride
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customEvaporation of the solvents and chromatography of the residue over silica gel using 1-5% methanol in methylene chloride

Sources & evidence

ORD record
ord-01dd9a7639b64317942fe172285121a7
Source dataset
uspto-grants-2008_09
Patent number
US07425638B2

Linked notes

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