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

HRID 900111Notes

Reaction equation

HRID 900111 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[C:11]2[C:20]3[N:16]([C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18][N:19]=3)[C:15]3[CH:27]=[CH:28][CH:29]=[CH:30][C:14]=3[N:13]([CH2:31][C:32]([N:34]([CH:41]([CH3:43])[CH3:42])[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:33])[C:12]2=[O:44])=[CH:2]1.C([O-])=O.[NH4+]>[Pd].CCO>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH:11]2[C:20]3[N:16]([C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18][N:19]=3)[C:15]3[CH:27]=[CH:28][CH:29]=[CH:30][C:14]=3[N:13]([CH2:31][C:32]([N:34]([CH:41]([CH3:42])[CH3:43])[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:33])[C:12]2=[O:44])=[CH:2]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 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-acetamide

Product 1

HCID 236606722-[4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamideYield 18.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

To 10% Pd/C and EtOH was added 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 (0.71 g, 1.2 mmol). An additional 25 mL of EtOH was added followed by ammonium formate (0.77 g, 12.2 mmol). The reaction mixture was heated to 80° C. for 6 hours. The catalyst was removed by filtration through Celite® and the filtrate was concentrated. The residue was dissolved in ethyl acetate and the organic solution was washed with saturated NaHCO3. The organic phase was dried over sodium sulfate and concentrated. The crude product was purified by chromatography (0% to 18% acetone/methylene chloride) to give 128 mg of 2-[4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamide as a racemic mixture. 1H NMR (CD2Cl2) δ 8.18 (s, 1H), 7.64 (dd, 2H), 7.55 (dd, 1H), 7.510-7.41 (m, 8H), 7.36 (dd, 1H), 7.25 (m, 3H), 7.09 (m, 2H), 7.027 (m, 1H), 6.85 (dd, 1H), 4.86 (m, 1H), 4.40 (br d, 1H), 4.04 (dd, 1H), 3.79 (m, 3H), 1.03 (dd, 6H); MS 581.4 (M+1).

Workup

  1. customThe catalyst was removed by filtration through Celite®
  2. concentrationthe filtrate was concentrated
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washthe organic solution was washed with saturated NaHCO3
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product was purified by chromatography (0% to 18% acetone/methylene chloride)

Sources & evidence

ORD record
ord-7fbe4a26880d4d0dacc118e66d0ede32
Source dataset
uspto-grants-2008_04
Patent number
US07358242B2

Reaction notes

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