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

反応式

HRID 31522 の反応式
[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

参加物

4

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

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)+].

後処理

  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

出典と根拠

ORDレコード
ord-01dd9a7639b64317942fe172285121a7
出典データセット
uspto-grants-2008_09
特許番号
US07425638B2

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