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 1992638ノート

反応式

HRID 1992638 の反応式
[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

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-25bd547845e840ee8c32ec2a738f3012
出典データセット
uspto-grants-2010_01
特許番号
US07648989B2

反応ノート

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