Methyl 3-indoleglyoxylate → 3-(5-Dimethylaminomethyl-benzofuran-3-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione

HRID 402905Notes

Reaction equation

HRID 402905 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]2[O:12][CH:11]=[C:10]([CH2:13][C:14]([NH2:16])=[O:15])[C:9]=2[CH:17]=1)[CH3:3].C[O:19][C:20](=O)[C:21]([C:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[NH:25][CH:24]=1)=O.CC([O-])(C)C.[K+]>C1COCC1>[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]2[O:12][CH:11]=[C:10]([C:13]3[C:14](=[O:15])[NH:16][C:20](=[O:19])[C:21]=3[C:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[NH:25][CH:24]=3)[C:9]=2[CH:17]=1)[CH3:3]

Participants

5

Reactant 3

HCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 591920342-(5-Dimethylaminomethyl-benzofuran-3-yl)-acetamide

Product 1

HCID 249682333-(5-Dimethylaminomethyl-benzofuran-3-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dioneYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(5-dimethylaminomethyl-benzofuran-3-yl)-acetamide (91 mg, 0.39 mmol) and (1H-indol-3-yl)-oxo-acetic acid methyl ester (119 mg, 0.59 mmol) in anhydrous THF (5.0 mL) is added dropwise a 1 M solution of t-BuOK in THF (1.6 mL) under an argon atmosphere at 0° C. The resulting deep red reaction mixture is stirred for 5 min. at 0° C. and 30 min. at room temperature followed by partitioning between brine and EtOAc. The layers are separated and the aqueous layer is extracted twice with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford an orange solid. Purification by flash column chromatography (silica gel, EtOAc/acetic acid/water 7:1:1) affords the title compound as an orange solid (91.4 mg, 0.237 mmol, 63%). 1H NMR (400 MHz, DMSO-d6, 298 K): δ=11.90 (bs, 1H), 11.06 (bs, 1H), 8.28 (s, 1H), 7.89 (s, 1H), 7.47 (d, J=8.4 Hz, 1H), 7.33 (d, J=8.2 Hz, 1H), 7.06 (d, J=8.4 Hz, 1H), 6.94 (t, J=8.2 Hz, 1H), 6.82 (d, J=8.1 Hz, 1 H), 6.63 (d, J=8.2 Hz, 1H), 6.60 (s, 1H), 2.98 (s, 2H), 1.69 (s, 6H). MS (ES+): 386 (M(C23H19N3O3)+H)+.

Workup

  1. customThe resulting deep red reaction mixture
  2. customby partitioning between brine and EtOAc
  3. customThe layers are separated
  4. extractionthe aqueous layer is extracted twice with EtOAc
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated at reduced pressure
  9. customto afford an orange solid
  10. customPurification by flash column chromatography (silica gel, EtOAc/acetic acid/water 7:1:1)

Sources & evidence

ORD record
ord-245d7428811941ae95a98ee62d2298c0
Source dataset
uspto-grants-2014_06
Patent number
US08742132B2

Reaction notes

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