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

반응식

HRID 31522 반응식
[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

참가 물질

4

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

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)+].

후처리

  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

출처 및 근거

ORD 기록
ord-01dd9a7639b64317942fe172285121a7
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425638B2

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