Piperidine → 2-[4-(1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamide

HRID 914688Notes

Reaction equation

HRID 914688 reaction equation
[CH:1]([N:4]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:5](=[O:28])[CH2:6][N:7]1[C:16](=[O:17])[CH2:15][C:14]2[N:10]([C:11]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:12][N:13]=2)[C:9]2[CH:24]=[CH:25][CH:26]=[CH:27][C:8]1=2)([CH3:3])[CH3:2].[NH:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:37]([CH:44]=O)=[CH:36]1.N1CCCCC1>C1(C)C=CC=CC=1>[NH:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:37]([CH:44]=[C:15]2[C:14]3[N:10]([C:11]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:12][N:13]=3)[C:9]3[CH:24]=[CH:25][CH:26]=[CH:27][C:8]=3[N:7]([CH2:6][C:5]([N:4]([CH:1]([CH3:3])[CH3:2])[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:28])[C:16]2=[O:17])=[CH:36]1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 10256Indole-3-CarboxaldehydeHCID 58957944N-isopropyl-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-phenyl-acetamide

Product 1

HCID 1363524502-[4-(1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamideYield 96%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of N-isopropyl-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-phenyl-acetamide (Preparation 7(A)) (1.2 g, 2.7 mmol) in toluene (15 mL) was added 1H-indole-3-carbaldehyde (0.46 g, 3.2 mmol) and piperidine (0.4 mL). The reaction mixture was heated to reflux for 14 hours. Activated 4 Å molecular sieves (2 g) were added and the reaction mixture was refluxed for 24 hours. The sieves were removed by filtration and the filtrate was concentrated. The residue was triturated with methylene chloride and the solid was collected via filtration and was dried in vacuo to give 1.5 g of 2-[4-(1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamide. The filtrate was concentrated and was purified by chromatography (20% acetone/methylene chloride) to afford an additional 320 mg of 2-[4-(1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamide. MS 579.2 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 14 hours
  3. additionActivated 4 Å molecular sieves (2 g) were added
  4. temperaturethe reaction mixture was refluxed for 24 hours
  5. customThe sieves were removed by filtration
  6. concentrationthe filtrate was concentrated
  7. customThe residue was triturated with methylene chloride
  8. filtrationthe solid was collected via filtration
  9. customwas dried in vacuo

Sources & evidence

ORD record
ord-67ed07b53e9b4f63a02abc22d880446f
Source dataset
uspto-grants-2007_09
Patent number
US07265104B2

Reaction notes

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