Indole-3-acetamide → 3-(1,5-dimethyl-1H-indol-7-yl)-4-(1H-indol-3-yl]-pyrrole-2,5-dione

HRID 2215782Notes

Reaction equation

HRID 2215782 reaction equation
CO[C:3](=[O:17])[C:4]([C:6]1[CH:7]=[C:8]([CH3:16])[CH:9]=[C:10]2[C:14]=1[N:13]([CH3:15])[CH:12]=[CH:11]2)=O.[NH:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([CH2:27][C:28]([NH2:30])=[O:29])=[CH:19]1.CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[CH3:15][N:13]1[C:14]2[C:10](=[CH:9][C:8]([CH3:16])=[CH:7][C:6]=2[C:4]2[C:3](=[O:17])[NH:30][C:28](=[O:29])[C:27]=2[C:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[NH:18][CH:19]=2)[CH:11]=[CH:12]1

Participants

6

Reactant 4

HCID 397Indole-3-acetamideHCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 69642519(1,5-dimethyl-1H-indol-7-yl)-oxo-acetic acid methyl ester

Product 1

HCID 219500073-(1,5-dimethyl-1H-indol-7-yl)-4-(1H-indol-3-yl]-pyrrole-2,5-dioneYield 56.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of (1,5-dimethyl-1H-indol-7-yl)-oxo-acetic acid methyl ester (0.51 g, 2.21 mmol) and 2-(1H-indol-3-yl-acetamide (0.35 g, 2 mmol) in DMF (20 mL) was added a solution of potassium tert-butoxide in THF (1.0 M, 8.0 mL, 8.0 mmol) at room temperature. The reaction mixture was heated at 50° C. for 18 h, cooled to room temperature, and quenched with hydrochloric acid (1.0 N). After 30 min at room temperature, the mixture was extracted with ethyl acetate and the extract washed with water, saturated aqueous sodium bicarbonate and brine, dried (sodium sulfate), filtered and concentrated. Flash column chromatography on silica gel eluting with chloroform and acetone gave 3-(1,5-dimethyl-1H-indol-7-yl)-4-(1H-indol-3-yl]-pyrrole-2,5-dione (400 mg, 56.3%). 1HNMR (DMSO-d6, 400 MHz) 2.28 (s, 3H), 3.64 (s, 3H), 6.39 (d, J=3.07 Hz, 1H), 6.50 (t, J=7.66 Hz, 1H), 6.53 (t, J=7.00 Hz, 1H), 6.74 (d, J=1.4 Hz, 1H), 7.0 (t, J=7.47 Hz, 1H), 7.20 (d, J=3.09 Hz, 1H), 7.35 (d, J=8.11 Hz, 1H), 7.41 (s, 1H), 7.88 (d, J=3.0 Hz, 1H), 11.13 (s, 1H), 11.84 (s, 1H); MS (ES, m/z): C22H17N3O2: 356.2 (M++1); 354.2 (M+−1).

Workup

  1. temperaturecooled to room temperature
  2. customquenched with hydrochloric acid (1.0 N)
  3. extractionthe mixture was extracted with ethyl acetate
  4. washthe extract washed with water, saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-7affac4fc6834928bda62db3a117e1cf
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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