Sodium hydride → 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-5-carboxylic acid methyl ester

HRID 460003Notes

Reaction equation

HRID 460003 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14](=[O:25])[NH:15][CH:16]1[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]1)=[CH:8]2)=[O:4].Br[CH2:27][C:28]([NH:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][N:32]=1)=[O:29].[H-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:27][C:28](=[O:29])[NH:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][N:32]=1)[C:9]([C:14](=[O:25])[NH:15][CH:16]1[CH2:17][CH2:18][N:19]([CH:22]([CH3:23])[CH3:24])[CH2:20][CH2:21]1)=[CH:8]2)=[O:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 34211102-Bromo-N-(5-chloro-2-pyridinyl)acetamide2×HCID 685586112-(1-Isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-5-carboxylic acid methyl ester

Product 1

HCID 685649451-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3 g 2-(1-Isopropyl-piperidin-4-ylcarbamoyl)-1H-indole-5-carboxylic acid methyl ester in 80 ml absolute DMF 419 mg NaH (60% in mineral oil) were added under an argon atmosphere. After stirring for 30 min. 2.179 g 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added and the reaction mixture stirred for 2 h at RT. Then additional 105 mg NaH (60% in mineral oil) and 1.089 g 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added and the mixture stirred for 1 h at RT. The solvent was removed in vacuo and the residue purified by chromatography on silica gel using CH2Cl2/MeOH/HOAC/H2O=9/1/0.1/0.1. The fractions containing the product were concentrated and lyophilized in a water/CH3CN mixture. Yield: 3.68 g.

Workup

  1. stirringthe reaction mixture stirred for 2 h at RT
  2. stirringthe mixture stirred for 1 h at RT
  3. customThe solvent was removed in vacuo
  4. customthe residue purified by chromatography on silica gel
  5. additionThe fractions containing the product
  6. concentrationwere concentrated

Sources & evidence

ORD record
ord-322ce36a7c28413ea8da2e6b2b8264eb
Source dataset
uspto-grants-2007_03
Patent number
US07196103B2

Reaction notes

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