Methyl 7-methyl-alpha-oxo-1H-indole-3-acetate → 3-(5-Dimethylaminomethyl-2-methyl-benzofuran-3-yl)-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

HRID 402910Notes

Reaction equation

HRID 402910 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([CH3:13])=[C:10]([CH2:14][C:15]([NH2:17])=[O:16])[C:9]=2[CH:18]=1)[CH3:3].C[O:20][C:21](=O)[C:22]([C:24]1[C:32]2[C:27](=[C:28]([CH3:33])[CH:29]=[CH:30][CH:31]=2)[NH:26][CH:25]=1)=O.CC([O-])(C)C.[K+]>C1COCC1.CCOC(C)=O>[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([CH3:13])=[C:10]([C:14]3[C:15](=[O:16])[NH:17][C:21](=[O:20])[C:22]=3[C:24]3[C:32]4[C:27](=[C:28]([CH3:33])[CH:29]=[CH:30][CH:31]=4)[NH:26][CH:25]=3)[C:9]=2[CH:18]=1)[CH3:3]

Participants

6

Reactant 3

HCID 11241405Methyl 7-methyl-alpha-oxo-1H-indole-3-acetateHCID 23665647Potassium tert-butoxideHCID 591920222-(5-Dimethylaminomethyl-2-methyl-benzofuran-3-yl)-acetamide

Product 1

HCID 249678903-(5-Dimethylaminomethyl-2-methyl-benzofuran-3-yl)-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dioneYield 73%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(5-dimethylaminomethyl-2-methyl-benzofuran-3-yl)-acetamide (111 mg, 0.406 mmol) and (7-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (132 mg, 0.608 mmol) in anhydrous THF (4.0 mL) is added dropwise a 1 M solution of t-BuOK in THF (2.0 mL) at 0° C. under an argon atmosphere. The resulting deep red reaction mixture is stirred for 1 h at 0° C., diluted with EtOAc, washed with a saturated aqueous NH4Cl solution and washed with brine. The combined aqueous phases are extracted with EtOAc and the combined organic phases are 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 (122 mg, 0.295 mmol, 73%). 1H NMR (400 MHz, DMSO-d6, 298 K): δ=11.88 (bs, 1H), 11.07 (bs, 1H), 7.91 (s, 1H), 7.38 (d, J=8.3 Hz, 1H), 7.04 (d, J=8.3 Hz, 1H), 6.93 (s, 1H), 6.75 (d, J=6.8 Hz, 1H), 6.50 (t, J=7.5 Hz, 1H), 6.42 (d, J=7.8 Hz, 1H), 3.40-3.16 (m, 2H), 2.40 (s, 2H), 2.12 (s, 2H), 1.84 (s, 6H). MS (ES+): 414 (M(C26H23N3O3)+H)+.

Workup

  1. customThe resulting deep red reaction mixture
  2. washwashed with a saturated aqueous NH4Cl solution
  3. washwashed with brine
  4. extractionThe combined aqueous phases are extracted with EtOAc
  5. dry with materialthe combined organic phases are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customto afford an orange solid
  9. customPurification by flash column chromatography (silica gel, EtOAc/acetic acid/water 7:1:1)

Sources & evidence

ORD record
ord-01a813394d6f4683b321d21ca28141c9
Source dataset
uspto-grants-2014_06
Patent number
US08742132B2

Reaction notes

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