Sodium Carbonate → 3-(5-Ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrile

HRID 1921317Notes

Reaction equation

HRID 1921317 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:10][CH3:11])[C:5](=[O:9])[NH:6][C:7]=1[CH3:8].[C:12]([C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1)#[N:13].C(=O)([O-])[O-].[Na+].[Na+]>C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].C1(C)C=CC=CC=1>[CH2:10]([C:4]1[C:5](=[O:9])[NH:6][C:7]([CH3:8])=[C:2]([C:18]2[CH:19]=[C:14]([CH:15]=[CH:16][CH:17]=2)[C:12]#[N:13])[CH:3]=1)[CH3:11]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 207792745-bromo-3-ethyl-6-methyl-1H-pyridin-2-one

Product 1

HCID 116300653-(5-Ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrileYield 36%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A stirred mixture of 5-bromo-3-ethyl-6-methyl-1H-pyridin-2-one, prepared in accordance with the procedures of PREPARATION 1, Step 2, (100 mg, 0.46 mmol), 3-cyanophenylboronic acid (88 mg, 0.6 mmol), 2M aq sodium carbonate (0.69 mL, 1.38 mmol), palladium tetrakis(triphenylphosphine) (16 mg, 0.014 mmol) and toluene (5 mL) is heated at reflux under a nitrogen atmosphere. After 2 hr, more catalyst (16 mg) is added and heating is continued overnight. The reaction is cooled and the mixture is partitioned between water and dichloromethane. The organic layer is separated and the solvents are removed. The residue is purified by chromatography eluting with ethyl acetate and with dichloromethane-5% methanol. Fractions containing product are combined, concentrated and the residue is triturated with hot ether to afford 3-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)benzonitrile (40 mg, 36%) as a white solid. LC/MS: MS m/e=239 (M+H); RT 2.83 min.

Workup

  1. temperatureis heated
  2. temperatureat reflux under a nitrogen atmosphere
  3. temperatureheating
  4. waitis continued overnight
  5. temperatureThe reaction is cooled
  6. customthe mixture is partitioned between water and dichloromethane
  7. customThe organic layer is separated
  8. customthe solvents are removed
  9. customThe residue is purified by chromatography
  10. washeluting with ethyl acetate and with dichloromethane-5% methanol
  11. additionFractions containing product
  12. concentrationconcentrated
  13. customthe residue is triturated with hot ether

Sources & evidence

ORD record
ord-b129b93d2bf245c28e7122e626a47e52
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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