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

HRID 2215795Notes

Reaction equation

HRID 2215795 reaction equation
CO[C:3](=[O:18])[C:4]([C:6]1[CH:7]=[CH:8][C:9]([O:16][CH3:17])=[C:10]2[C:14]=1[N:13]([CH3:15])[CH:12]=[CH:11]2)=O.[NH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([CH2:28][C:29]([NH2:31])=[O:30])=[CH:20]1.CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[NH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([C:28]2[C:29](=[O:30])[NH:31][C:3](=[O:18])[C:4]=2[C:6]2[CH:7]=[CH:8][C:9]([O:16][CH3:17])=[C:10]3[C:14]=2[N:13]([CH3:15])[CH:12]=[CH:11]3)=[CH:20]1

Participants

6

Reactant 4

HCID 397Indole-3-acetamideHCID 8028TetrahydrofuranHCID 21055226(1-methyl-4-methoxyl-1H-indol-7-yl)-oxo-acetic acid methyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 219499543-(1H-indol-3-yl)-4-(4-methoxy-1-methyl-1H-indol-7-yl)-pyrrole-2,5-dioneYield 72.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of (1-methyl-4-methoxyl-1H-indol-7-yl)-oxo-acetic acid methyl ester (0.27 g, 1.10 mmol) and 2-(1H-indol-3-yl-acetamide (0.17 g, 1 mmol) in DMF (5 mL) was added a solution of potassium tert-butoxide in THF (1.0 M, 4.0 mL, 4.0 mmol) at room temperature. The reaction mixture was heated at 60° C. for 4 hrs, cooled to room temperature, and quenched with hydrochloric acid (1.0 N). After stirring at room temperature for 30 min, the mixture was extracted with ethyl acetate and the extract was washed with water, saturated aqueous sodium bicarbonate and brine, dried (sodium sulfate), filtered and evaporated. Flash column chromatography on silica gel eluting with chloroform and acetone gave 3-(1H-indol-3-yl)-4-(4-methoxy-1-methyl-1H-indol-7-yl)-pyrrole-2,5-dione (270 mg, 72.7%). 1H NMR (d6-DMSO, 400 MHz) 3.65 (s, 3H), 3.84 (s, 3H), 6.46˜6.55 (m, 4H), 6.78 (d, J=7.6 Hz, 1H), 6.95 (t, J=7.2 Hz, 1H), 7.13 (d, J=3.2 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.86 (d, J=3.2 Hz, 1H), 11.05 (s, 1H), 11.79 (s, 1H); MS (ES, m/z): C22H17FN3O3: 372.19(M++1), 370.29 (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 was washed with water, saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-5f9e035abc2748768dc1459a7bbfa0dc
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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