Tetrahydrofuran → 3-(6-Bromo-1H-indol-3-yl)-4-(1-methy-1H-indol-7-yl)-pyrrole-2,5-dione

HRID 2215764

Reaction equation

HRID 2215764 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH2:11][C:12]([NH2:14])=[O:13])[CH:4]=[CH:3]1.CC(C)([O-])C.[K+].C1COCC1.C[O:27][C:28](=O)[C:29]([C:31]1[C:39]2[C:34](=[CH:35][C:36]([Br:40])=[CH:37][CH:38]=2)[NH:33][CH:32]=1)=O>CN(C=O)C>[Br:40][C:36]1[CH:35]=[C:34]2[C:39]([C:31]([C:29]3[C:28](=[O:27])[NH:14][C:12](=[O:13])[C:11]=3[C:9]3[CH:8]=[CH:7][CH:6]=[C:5]4[C:10]=3[N:2]([CH3:1])[CH:3]=[CH:4]4)=[CH:32][NH:33]2)=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 114353972-(1-methyl-1H-indol-7-yl)acetamideHCID 23665647Potassium tert-butoxide3×HCID 28916741methyl 2-(6-bromo-1H-indol-3-yl)-2-oxoacetate2×

Product 1

HCID 696426173-(6-Bromo-1H-indol-3-yl)-4-(1-methy-1H-indol-7-yl)-pyrrole-2,5-dioneYield 73.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
50 °C

Procedure

To solution of 2-(1-methyl-1H-indol-7-yl)-acetamide (0.300 g, 1.59 mmol) in DMF (15 mL) was added a 1.0 M solution of potassium tert-butoxide in THF (1.59 mL, 1.59 mmol), followed after 5 minutes by (6-bromo-1H-indol-3-yl)-oxo-acetic acid methyl ester (0.235 g, 0.83 mmol) in DMF (1.25 mL). After another 5 minutes additional potassium tert-butoxide (1.59 mL) was introduced followed by the additional (6-bromo-1H-indol-3-yl)-oxo-acetic acid methyl ester (0.235 g, 0.83 mmol) in DMF (1.25 mL). The reaction was stirred for 5 minutes and an additional potassium tert-butoxide (1.59 mL) was introduced. After heating at 50° C. over night, then deep red solution and was cooled to room temperature, quenched with 1N HCl and poured in EtOAc. The two layers were separated and the organic layer was washed with H2O, saturated aq NaHCO3, and brine (×3), dried (MgSO4), filtered, and concentrated. Flash chromatography (80% EtOAc/hexane) gave the title compound (0.256 g, 38%) as a red solid. 1H NMR (400 MHz, DMSO-d6) 3.64 (s, 3H), 6.26 (d, J=4.4 Hz, 1H), 6.47 (d, J=2.8 Hz, 1H), 6.60 (dd, J=2, 8.8 Hz, 1H), 6.88 (d, J=7.2 Hz, 1H), 6.98 (dd, J=7.2, 7.2 Hz, 1H), 7.24 (d, J=3.6 Hz, 1H), 7.61 (dd, J=1.2, 8 Hz, 1H), 7.87 (d, J=2.8 Hz, 1H), 11.18 (s, 1H), 11.91 (s, 1H). MS (electrospray, m/z) 420/418 (M−−1).

Workup

  1. temperaturedeep red solution and was cooled to room temperature
  2. customquenched with 1N HCl
  3. additionpoured in EtOAc
  4. customThe two layers were separated
  5. washthe organic layer was washed with H2O, saturated aq NaHCO3, and brine (×3)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-f790b61639bf494b9f1738a8817378fa
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Linked notes

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