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

HRID 914663Notes

Reaction equation

HRID 914663 reaction equation
[CH:1]([N:4]([C:29]1[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=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].[F:37][C:38]1[CH:46]=[C:45]2[C:41]([C:42]([CH:47]=O)=[CH:43][NH:44]2)=[CH:40][CH:39]=1.N1CCCCC1>C1(C)C=CC=CC=1.O>[F:37][C:38]1[CH:46]=[C:45]2[C:41]([C:42]([CH:47]=[C:15]3[C:14]4[N:10]([C:11]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)=[N:12][N:13]=4)[C:9]4[CH:24]=[CH:25][CH:26]=[CH:27][C:8]=4[N:7]([CH2:6][C:5]([N:4]([CH:1]([CH3:3])[CH3:2])[C:29]4[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=4)=[O:28])[C:16]3=[O:17])=[CH:43][NH:44]2)=[CH:40][CH:39]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 2629036-Fluoroindole-3-carboxaldehydeHCID 58957931N-isopropyl-N-(6-methoxy-pyridin-3-yl)-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-acetamide

Product 1

HCID 1363477452-[4-(6-fluoro-1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamideYield 80.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

To a solution of N-isopropyl-N-(6-methoxy-pyridin-3-yl)-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-acetamide (Preparation 11) (150 mg, 0.311 mmol) and 6-fluoro-1H-indole-3-carbaldehyde (61 mg, 0.373 mmol) in toluene (20 mL) was added piperidine (100 μL). The reaction vessel was equipped with a Dean-Stark trap that contained toluene and 4A molecular sieves and was heated at reflux for 24 hours. The solution was cooled to room temperature and was diluted with water. The aqueous solution was washed with EtOAc (3×) and the combined organic extracts were dried (MgSO4), filtered and concentrated. The residue was purified by medium pressure chromatography eluting with a solvent gradient (10% EtOAc in hexanes to 100% EtOAc) to yield 158 mg of 2-[4-(6-fluoro-1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-(6-methoxy-pyridin-3-yl)-acetamide. MS 628.3 (M+1), 626.2 (M−1).

Workup

  1. customThe reaction vessel was equipped with a Dean-Stark trap that
  2. temperaturewas heated
  3. temperatureat reflux for 24 hours
  4. washThe aqueous solution was washed with EtOAc (3×)
  5. dry with materialthe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by medium pressure chromatography
  9. washeluting with a solvent gradient (10% EtOAc in hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-8bf0547f6cb647419616da5e4b204203
Source dataset
uspto-grants-2007_09
Patent number
US07265104B2

Reaction notes

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