Methyl 7-methyl-alpha-oxo-1H-indole-3-acetate → 3-(7-Methyl-1H-indol-3-yl)-4-[2-methyl-5-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-pyrrole-2,5-dione

HRID 1992638Notes

Reaction equation

HRID 1992638 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([CH2:17][C:18]([NH2:20])=[O:19])[C:11]([N+]([O-])=O)=[N:12][CH:13]=2)[CH2:4][CH2:3]1.C[O:22][C:23](=O)[C:24]([C:26]1[C:34]2[C:29](=[C:30]([CH3:35])[CH:31]=[CH:32][CH:33]=2)[NH:28][CH:27]=1)=O.[CH3:37]C([O-])(C)C.[K+]>C1COCC1>[CH3:35][C:30]1[CH:31]=[CH:32][CH:33]=[C:34]2[C:29]=1[NH:28][CH:27]=[C:26]2[C:24]1[C:23](=[O:22])[NH:20][C:18](=[O:19])[C:17]=1[C:10]1[C:11]([CH3:37])=[N:12][CH:13]=[C:8]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[CH:9]=1

Participants

5

Reactant 3

HCID 11241405Methyl 7-methyl-alpha-oxo-1H-indole-3-acetateHCID 23665647Potassium tert-butoxideHCID 668689562-[5-(4-Methyl-piperazin-1-yl)-2-nitro-pyridin-3-yl]-acetamide

Product 1

HCID 668690143-(7-Methyl-1H-indol-3-yl)-4-[2-methyl-5-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-pyrrole-2,5-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[5-(4-Methyl-piperazin-1-yl)-2-nitro-pyridin-3-yl]-acetamide (96 mg, 0.34 mmol) and (7-Methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (127 mg, 0.58 mmol) in dry THF (8.0 mL) is added at 0° C. under an atmosphere of argon, a solution of 1.0 M KOtBu in THF (1.7 ml, 1.7 mmol). After stirring for 2 h at 0° C., TLC analysis indicated complete consumption of the starting materials. The reaction mixture is diluted with EtOAc and washed with brine. The aqueous phase is extracted with EtOAc and the combined organic layers are washed with brine, dried over Na2SO4, and concentrated at reduced pressure. The residue is purified by FCC (EtOAc/AcOH/H2O 6:1:1) to afford the title compound as an orange powder. 1H NMR (d6-DMSO 400 MHz): δ 2.05 (s, 3H), 2.04-2.11 (m, 4H), 2.46 (s, 3H), 3.06-3.14 (m, 4H), 6.35 (d, J=8.1 Hz, 1H), 6.65 (dd, J=8.1, 7.2 Hz, 1H), 6.84 (d, J=7.2 Hz, 1H), 6.87 (d, J=2.0 Hz,1H), 7.95 (s, 1H), 8.16 (d, J=2.0 Hz, 1H). ES+−MS: 447 [M+H]+.

Workup

  1. customconsumption of the starting materials
  2. additionThe reaction mixture is diluted with EtOAc
  3. washwashed with brine
  4. extractionThe aqueous phase is extracted with EtOAc
  5. washthe combined organic layers are washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated at reduced pressure
  8. customThe residue is purified by FCC (EtOAc/AcOH/H2O 6:1:1)

Sources & evidence

ORD record
ord-25bd547845e840ee8c32ec2a738f3012
Source dataset
uspto-grants-2010_01
Patent number
US07648989B2

Reaction notes

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