2-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl ester → 3-(6-Chloro-3-dimethylaminomethyl-isoquinolin-5-yl)-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

HRID 505211ノート

反応式

HRID 505211 の反応式
[Cl:1][C:2]1[C:3]([CH2:16][C:17]([NH2:19])=[O:18])=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([CH2:12][N:13]([CH3:15])[CH3:14])=[CH:5]2.C[O:21][C:22](=O)[C:23]([C:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[N:27]([CH3:34])[CH:26]=1)=O.[K].CC([O-])(C)C.[K+]>C1COCC1>[Cl:1][C:2]1[C:3]([C:16]2[C:17](=[O:18])[NH:19][C:22](=[O:21])[C:23]=2[C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]([CH3:34])[CH:26]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([CH2:12][N:13]([CH3:14])[CH3:15])=[CH:5]2

参加物

5

反応物 3

HCID 44536752-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl esterHCID 668817842-(6-Chloro-3-dimethylaminomethyl-isoquinolin-5-yl)-acetamideHCID 86625790potassium t-BuOK

生成物 1

HCID 594297023-(6-Chloro-3-dimethylaminomethyl-isoquinolin-5-yl)-4-(1-methyl-1H-indol-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-(6-chloro-3-dimethylaminomethyl-isoquinolin-5-yl)-acetamide (47 mg, 0.17 mmol) and (1-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (56 mg, 0.26 mmol) in anhydrous THF was added dropwise a 1 M solution of potassium t-BuOK in THF (1.8 mL) under an argon atmosphere at 0° C. The resulting deep red reaction mixture was stirred for 1.5 h at 0° C., quenched with a saturated aqueous NH4Cl solution and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated at reduced pressure. Purification by flash column chromatography (silica gel, EtOAc/water/acetic acid 7:1:1) afforded the title compound as its acetate salt (61 mg, 0.12 mmol, 70%). MS (ES+): 445 (M(C25H2135ClN4O2)+H)+.

後処理

  1. customThe resulting deep red reaction mixture
  2. customquenched with a saturated aqueous NH4Cl solution
  3. extractionextracted twice with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customPurification by flash column chromatography (silica gel, EtOAc/water/acetic acid 7:1:1)

出典と根拠

ORDレコード
ord-dfcf949b44a64288a799ed6e283923a3
出典データセット
uspto-grants-2010_08
特許番号
US07781438B2

反応ノート

読み込み中…