Sodium hydride → 2-pyridin-3-yl-1H-indole-3-carbonitrile

HRID 1630831Notes

Reaction equation

HRID 1630831 reaction equation
[C:1]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=1)#[N:2].[H-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[N:14]1[CH:15]=[CH:16][CH:17]=[C:12]([C:11]2[NH:10][C:5]3[C:4]([C:3]=2[C:1]#[N:2])=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:13]=1

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 59534663N-(2-cyanomethyl-phenyl)-nicotinamide

Product 1

HCID 114473142-pyridin-3-yl-1H-indole-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

N-(2-cyanomethyl-phenyl)-nicotinamide (0.095 g, 0.384 mmol) is dissolved in DMF (3 mL). NaH (60%, 0.015 g, 0.384 mmol) is added and the mixture is heated to 130° C. After 18 h, the mixture is cooled down, diluted with ethyl acetate, and washed with 1M aqueous sodium hydroxide. The combined washings are back-extracted with ethyl acetate. The combined organic phase is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 19:1) to give 2-pyridin-3-yl-1H-indole-3-carbonitrile as a brown solid. 1H NMR (400 MHz, MeOD) δ ppm 7.29-7.32 (m, 1H), 7.34-7.39 (m, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.66 (dd, J=8.0, 4.9 Hz, 1H), 7.70 (d, J=7.8 Hz, 1H), 8.39-8.44 (m, 1H), 8.68 (dd, J=4.8, 1.5 Hz, 1H), 9.15 (d, J=1.5 Hz, 1H).

Workup

  1. temperaturethe mixture is cooled down
  2. washwashed with 1M aqueous sodium hydroxide
  3. extractionThe combined washings are back-extracted with ethyl acetate
  4. dry with materialThe combined organic phase is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 19:1)

Sources & evidence

ORD record
ord-f4ee126a347448179c59627a763a9d0b
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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