Citric Acid → N-(2-cyano-5-phenylphenyl)-5-phenylpyridine-3-carboxamide

HRID 454516Notes

Reaction equation

HRID 454516 reaction equation
[C:1]1(OB=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:19]1[CH:20]=[CH:21][C:22]([C:40]#[N:41])=[C:23]([NH:25][C:26]([C:28]2[CH:29]=[N:30][CH:31]=[C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:33]=2)=[O:27])[CH:24]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:40]([C:22]1[CH:21]=[CH:20][C:19]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:24][C:23]=1[NH:25][C:26]([C:28]1[CH:29]=[N:30][CH:31]=[C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:33]=1)=[O:27])#[N:41]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 62657Potassium Phosphate, TribasicHCID 14438906HCID 14438906, compoundHCID 58508508N-(5-chloro-2-cyanophenyl)-5-phenylpyridine-3-carboxamide

Product 1

HCID 58508437N-(2-cyano-5-phenylphenyl)-5-phenylpyridine-3-carboxamideYield 102.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phenylboranic acid (88 mg), tripotassium phosphate (0.28 g), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (2.5 mg), and palladium(II) acetate (2.7 mg) were added to a toluene (3.0 mL) suspension of N-(5-chloro-2-cyanophenyl)-5-phenylpyridine-3-carboxamide (0.20 g), followed by heating to reflux under a nitrogen atmosphere for 1 hour and 30 minutes. The reaction mixture was cooled to room temperature, and then 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (2.5 mg) and palladium(II) acetate (2.7 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 6 hours. After cooling the reaction mixture to room temperature, ethyl acetate and a 10% aqueous solution of citric acid were added thereto, and the insoluble substance was removed by filtration. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Diisopropyl ether was added to the obtained residue, and the solid substance was collected by filtration to obtain 0.23 g of N-(2-cyano-5-phenylphenyl)-5-phenylpyridine-3-carboxamide as a light yellow solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour and 30 minutes
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 6 hours
  5. temperatureAfter cooling the reaction mixture to room temperature
  6. customthe insoluble substance was removed by filtration
  7. customThe organic layer was separated
  8. washwashed with a saturated aqueous solution of sodium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. additionDiisopropyl ether was added to the obtained residue
  12. filtrationthe solid substance was collected by filtration

Sources & evidence

ORD record
ord-db590438e2744b75b530e827c9701dc6
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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