Methyl iodide → 1-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile

HRID 1630832Notes

Reaction equation

HRID 1630832 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[NH:8][C:9]3[C:14]([C:15]=2[C:16]#[N:17])=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:2]=1.[H-].[Na+].IC.[C:22]([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:22][N:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:15]([C:16]#[N:17])=[C:7]1[C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 114473142-pyridin-3-yl-1H-indole-3-carbonitrile

Product 1

HCID 582157791-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-pyridin-3-yl-1H-indole-3-carbonitrile (1.0 g, 4.56 mmol) in DMF (17 mL) is added 60% sodium hydride in mineral oil (547 mg, 13.68 mmol) and the suspension is stirred for 30 min. Iodomethane (971 mg, 6.84 mmol) is then added to the reaction mixture and stirred at ambient temperature for 1 h. Aqueous NaHCO3 (3 mL) is added and the mixture is concentrated in vacuo. The residue is purified by purified by silica gel flash chromatography (dichloromethane-methanol gradient) to give 1-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 3.83 (s, 3H), 7.35 (t, J=7.5 Hz, 1H), 7.40-7.46 (m, 1H), 7.64 (d, J=8.3 Hz, 1H), 7.67-7.74 (m, 2H), 8.16 (dt, J=8.0, 2.0, 1.9 Hz, 1H), 8.76 (dd, J=5.1, 1.5 Hz, 1H), 8.86 (d, J=1.5 Hz, 1H). HRMS (ESI) m/z 234.1029 [(M+H)+ Calcd for C15H12N3: 234.1031].

Workup

  1. stirringstirred at ambient temperature for 1 h
  2. concentrationthe mixture is concentrated in vacuo
  3. customThe residue is purified
  4. customby purified by silica gel flash chromatography (dichloromethane-methanol gradient)

Sources & evidence

ORD record
ord-796c712dfa274a21911fa67eb41ffdd9
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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