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

HRID 1673201Notes

Reaction equation

HRID 1673201 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

To a solution of the product of Step A, cyanoacetamide (1.33 g, 15.8 mmol), and MeOH (1.3 mL, 32 mmol) in DMF (35 mL) was added dropwise to a suspension of NaH (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 aq 18% citric acid solution. The mixture was extracted twice with CH2Cl2 and the organic layers were washed with brine. The combined organic layers were dried (Na2SO4) and concentrated. The solid residue was triturated with ether, filtered, and air dried to afford the product. (LC-2) HPLC/MS: 375 (M+1), 377 (M+3); Rt=3.47 min.

Workup

  1. additionAfter the slow addition
  2. customMost of the DMF was then removed in vacuo before the reaction
  3. additionwas diluted with aq 18% citric acid solution
  4. extractionThe mixture was extracted twice with CH2Cl2
  5. washthe organic layers were washed with brine
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe solid residue was triturated with ether
  9. filtrationfiltered
  10. customair dried
  11. customto afford the product

Sources & evidence

ORD record
ord-ac691826278c4a68ac342761e6480b74
Source dataset
uspto-grants-2011_08
Patent number
US07999107B2

Reaction notes

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