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 1968724Notes

Reaction equation

HRID 1968724 reaction equation
[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

Participants

5

Reactant 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

Product 1

HCID 594297023-(6-Chloro-3-dimethylaminomethyl-isoquinolin-5-yl)-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-b8fc49dddc7a46c6a66d1609151ee471
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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