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

Reaction equation

HRID 10167 reaction equation
[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

Participants

5

Reactant 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

Product 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]oximeYield 96.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-ae023882c9984179bbf5210487a49852
Source dataset
uspto-grants-2006_08
Patent number
US07094779B2

Linked notes

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