Methanol → 6-(4-Chlorophenyl)-5-(phenyl)-2-oxo-1,2-dihydropyridine-3-nitrile

HRID 916922Notes

Reaction equation

HRID 916922 reaction equation
CN(C)[CH:3]=[C:4]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:5]([C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1)=O.[C:21]([CH2:23][C:24]([NH2:26])=[O:25])#[N:22].CO.[H-].[Na+]>CN(C=O)C>[Cl:13][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[NH:26][C:24](=[O:25])[C:23]([C:21]#[N:22])=[CH:3][C:4]=2[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7898CyanoacetamideHCID 24758Sodium hydrideHCID 694161721-(4-Chlorophenyl)-3-(dimethylamino)-2-phenylprop-2-en-1-one

Product 1

HCID 694176906-(4-Chlorophenyl)-5-(phenyl)-2-oxo-1,2-dihydropyridine-3-nitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
95 °C

Procedure

A solution of 3-dimethylamino-1-(4-chlorophenyl)-2-(phenyl)prop-2-en-1-one (43.3 mmol assumed) from Step A, cyanoacetamide (4.0 g, 47.6 mmol), and methanol (3.9 mL, 95 mmol) in DMF (100 mL) was added dropwise to a suspension of sodium hydride (60% in mineral oil) (4.3 g, 108 mmol) in DMF (50 mL) at rt. After the slow addition was complete, the reaction was heated to 95° C. for 2 h. Most of the DMF was then removed in vacuo before the reaction was diluted with aqueous 18% citric acid solution. The mixture was extracted twice with methylene chloride and the organic layers were washed with a portion of brine. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The solid residue was triturated with ether, filtered, and air dried to afford 6-(4-chlorophenyl)-5-(phenyl)-2-oxo-1,2-dihydropyridine-3-nitrile. HPLC/MS: 307 (M+1); Rt=3.0 min;

Workup

  1. additionAfter the slow addition
  2. customMost of the DMF was then removed in vacuo before the reaction
  3. additionwas diluted with aqueous 18% citric acid solution
  4. extractionThe mixture was extracted twice with methylene chloride
  5. washthe organic layers were washed with a portion of brine
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe solid residue was triturated with ether
  9. filtrationfiltered
  10. customair dried

Sources & evidence

ORD record
ord-edaec88e4581469c9a43476314384601
Source dataset
uspto-grants-2007_09
Patent number
US07271266B2

Reaction notes

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