Methanol → 6-(2,4-Dichlorophenyl)-5-(4-chlorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile

HRID 8781

Reaction equation

HRID 8781 reaction equation
CN(C)[CH:3]=[C:4]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)[C:5]([C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[Cl:14])=O.[C:23]([CH2:25][C:26]([NH2:28])=[O:27])#[N:24].CO.[H-].[Na+]>CN(C=O)C>[Cl:14][C:8]1[CH:9]=[C:10]([Cl:13])[CH:11]=[CH:12][C:7]=1[C:5]1[NH:28][C:26](=[O:27])[C:25]([C:23]#[N:24])=[CH:3][C:4]=1[C:15]1[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7898CyanoacetamideHCID 24758Sodium hydrideHCID 670199243-Dimethylamino-1-(2,4-dichlorophenyl)-2-(4-chlorophenyl)prop-2-en-1-one

Product 1

HCID 219848256-(2,4-Dichlorophenyl)-5-(4-chlorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
95 °C

Procedure

A solution of 3-dimethylamino-1-(2,4-dichlorophenyl)-2-(4-chlorophenyl)prop-2-en-1-one (14.4 mmol assumed) from Step A, cyanoacetamide (1.33 g, 15.8 mmol), and methanol (1.3 mL, 32 mmol) in DMF (35 mL) was added dropwise to a suspension of sodium hydride (60% in mineral oil) (1.45 g, 36 mmol) in DMF (16 mL) at rt. After the slow addition was complete, the reaction was heated to 95° C. for 2.5 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 the product. HPLC/MS: 375 (M+1), 377 (M+3); Rt=3.47 min; 1H NMR (CDCl3): δ 6.96 (br d, J=8.4 Hz,2H), 7.14 (d, J=8.2 Hz, 1H), 7.25 (br d, J=8.4 Hz, 2H), 7.31 (dd, J=1.9 and 8.2 Hz, 1H), 7.50 (d, J=2.0 Hz, 1H), 7.996 (s, 1H).

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
  11. customto afford the product

Sources & evidence

ORD record
ord-69b20dddb4ce4c1fbef670bef6b342b4
Source dataset
uspto-grants-2006_08
Patent number
US07091216B2

Linked notes

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