Diisopropylethylamine → 2-{(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-piperazin-4-yl}-ethanal O-[2-(morpholin-4-yl)ethyl]oxime

HRID 10167

반응식

HRID 10167 반응식
[N:1]1([CH2:7][CH2:8][O:9][N:10]=[CH:11][CH2:12]Cl)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:14][C:15]([F:45])([F:44])[C:16]1[CH:17]=[C:18]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[C:19]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][C@H:22]1[CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:20].C(N(C(C)C)CC)(C)C>C(#N)C>[N:1]1([CH2:7][CH2:8][O:9][N:10]=[CH:11][CH2:12][N:24]2[CH2:25][CH2:26][N:21]([C:19](=[O:20])[C:18]3[CH:17]=[C:16]([C:15]([F:14])([F:45])[F:44])[CH:39]=[C:38]([C:40]([F:42])([F:43])[F:41])[CH:37]=3)[C@H:22]([CH2:27][C:28]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[NH:30][CH:29]=3)[CH2:23]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 10972505(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)piperazineHCID 738572932-chloroethanal O-[2-(morpholin-4-yl)ethyl]oxime

생성물 1

HCID 867601842-{(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-piperazin-4-yl}-ethanal O-[2-(morpholin-4-yl)ethyl]oxime수율 96.6%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A mixture of 2-chloroethanal O-[2-(morpholin-4-yl)ethyl]oxime (0.13 g), (2R)-1-[3,5-bis(trifluoromethyl)-benzoyl]-2-(1H-indol-3-ylmethyl)piperazine (0.29 g), diisopropylethylamine (0.11 mL), and acetonitrile (10 mL) was heated under reflux overnight. After cooling to room temperature the solvent was removed in vacuo, and the residue treated with dichloromethane and K2CO3 (aq). The layers were separated, the organic layer was dried (Na2SO4), and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH/NH4OH 92/7.5/0.5) to afford 2-{(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-piperazin-4-yl}-ethanal O-[2-(morpholin-4-yl)ethyl]oxime 0.38 g (95%) as an E/Z mixture. MH+ 626, Rf 0.53+0.66 (E+Z isomer) (CH2Cl2/MeOH/NH4OH 92/7.5/0.5).

후처리

  1. temperaturewas heated
  2. temperatureunder reflux overnight
  3. customwas removed in vacuo
  4. additionthe residue treated with dichloromethane and K2CO3 (aq)
  5. customThe layers were separated
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH/NH4OH 92/7.5/0.5)

출처 및 근거

ORD 기록
ord-ae023882c9984179bbf5210487a49852
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094779B2

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