Dimethylformamide → 5-(6-chloro-1-methyl-1H-indol-2-yl)nicotinaldehyde

HRID 1630862Notes

Reaction equation

HRID 1630862 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]3[CH:12]=[C:13]([CH:17]=[O:18])[CH:14]=[N:15][CH:16]=3)[NH:8]2)=[CH:4][CH:3]=1.CI.[CH3:21]N(C=O)C.[H-].[Na+]>O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]3[CH:16]=[N:15][CH:14]=[C:13]([CH:17]=[O:18])[CH:12]=3)[N:8]2[CH3:21])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 582157125-(6-chloro-1H-indol-2-yl)-pyridine-3-carbaldehyde

Product 1

HCID 454897085-(6-chloro-1-methyl-1H-indol-2-yl)nicotinaldehyde

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A flask is charged with 5-(6-chloro-1H-indol-2-yl)-pyridine-3-carbaldehyde (Example 104, 7.8 g, 28.9 mmol), MeI (5.33 g, 37.5 mmol) and DMF (300 mL), and 60% NaH in mineral oil (1.386 g, 34.6 mmol) is added at 0° C. The mixture is stirred for 2 h. Water (100 mL) is added. The mixture is extracted with EtOAc twice and the combined organic phase is washed with water (2×200 mL) and brine (200 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue is purified by silica gel chromatography with a 0 to 2% methanol-DCM gradient to give 6-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole. MS (ESI) m/z 271.0, 272.9 (M+H)+.

Workup

  1. additionis added at 0° C
  2. extractionThe mixture is extracted with EtOAc twice
  3. washthe combined organic phase is washed with water (2×200 mL) and brine (200 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel chromatography with a 0 to 2% methanol-DCM gradient

Sources & evidence

ORD record
ord-de279948d7af4bef8f740e69f9fc32f5
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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