Methyl iodide → 2-(4-methoxy-pyridin-3-yl)-1-methyl-1H-indole-5-carbonitrile

HRID 593587Notes

Reaction equation

HRID 593587 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[C:9]1[NH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][C:14]([C:18]#[N:19])=[CH:13][CH:12]=2.[H-].[Na+].IC.[C:24]([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[C:9]1[N:10]([CH3:24])[C:11]2[C:16]([CH:17]=1)=[CH:15][C:14]([C:18]#[N:19])=[CH:13][CH:12]=2

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 582156342-(4-methoxy-pyridin-3-yl)-1H-indole-5-carbonitrile

Product 1

HCID 582157182-(4-methoxy-pyridin-3-yl)-1-methyl-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-methoxy-pyridin-3-yl)-1H-indole-5-carbonitrile (Example 90, 178 mg, 0.649 mmol) in DMF (4 mL) is added 60% sodium hydride in mineral oil (78 mg, 1.95 mmol) and the suspension is stirred for 30 min. Iodomethane (138 mg, 0.97 mmol) is then added to the reaction mixture which is stirred at ambient temperature for 1 h. Aqueous NaHCO3 (3 mL) is added to quench the reaction and the mixture is filtered and purified by HPLC using an Xbridge C18 with a gradient of acetonitrile in 0.1% NH4OH to afford 2-(4-methoxy-pyridin-3-yl)-1-methyl-1H-indole-5-carbonitrile as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.59 (s, 3H), 3.89 (s, 3H), 6.67 (s, 1H), 7.27 (d, J=5.8 Hz, 1H), 7.54 (dd, J=8.6, 1.5 Hz, 1H), 7.70 (d, J=8.6 Hz, 1H), 8.11 (d, J=1.1 Hz, 1H), 8.42 (s, 1H), 8.60 (d, J=5.8 Hz, 1H). HRMS (ESI) m/z 264.1138 [(M+H) calcd for C16H14N3O: 264.1137].

Workup

  1. stirringis stirred at ambient temperature for 1 h
  2. customto quench
  3. customthe reaction
  4. filtrationthe mixture is filtered
  5. custompurified by HPLC

Sources & evidence

ORD record
ord-d6e5c317a9784ae88ea64b21e33f60a1
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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