Cyanoacetamide → 4-methyl-2-oxo-6-pyridin-4-yl-1H-pyridine-3-carbonitrile

HRID 593852Notes

Reaction equation

HRID 593852 reaction equation
O/[C:2](/[CH3:12])=[CH:3]\[C:4]([C:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1)=O.[C:13]([CH2:15][C:16]([NH2:18])=[O:17])#[N:14].N1CCCCC1>CCO>[CH3:12][C:2]1[CH:3]=[C:4]([C:6]2[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=2)[NH:18][C:16](=[O:17])[C:15]=1[C:13]#[N:14]

Participants

5

Reactant 3

HCID 7898CyanoacetamideHCID 8082PiperidineHCID 178467987HCID 178467987, compound

Product 1

HCID 141992554-methyl-2-oxo-6-pyridin-4-yl-1H-pyridine-3-carbonitrileYield 11.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of (2Z)-3-hydroxy-1-(4-pyridinyl)-2-buten-1-one (8 g, crude, 49 mmol) and cyanoacetamide (4.12 g, 49 mmol) in anhydrous EtOH (100 mL) was added piperidine (4.17 g, 49 mmol) under N2 at 75° C. The mixture was heated at reflux for 1 h, and then cooled to room temperature. After filtration, the solid was collected and washed with H2O to give the crude product (4 g) as two isomers. After separation by HPLC, 1.8 g of 6-methyl-2-oxo-1,2-dihydro-4,4′-bipyridine-3-carbonitrile and 1.2 g of 4-methyl-6-oxo-1,6-dihydro-2,4′-bipyridine-5-carbonitrile were obtained. The identity of 6-methyl-2-oxo-1,2-dihydro-4,4′-bipyridine-3-carbonitrile was established by nOE analysis. 1H NMR (400 MHz, DMSO-d6) δ 12.79 (br. s., 1H), 8.75 (d, 2H), 7.58 (d, 2H), 6.37 (s, 1H), 2.31 (s, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 h
  3. filtrationAfter filtration
  4. customthe solid was collected
  5. washwashed with H2O
  6. customto give the crude product (4 g) as two isomers
  7. customAfter separation by HPLC, 1.8 g of 6-methyl-2-oxo-1,2-dihydro-4,4′-bipyridine-3-carbonitrile

Sources & evidence

ORD record
ord-36b5d59b34de46a99063d6523de6802e
Source dataset
uspto-grants-2016_01
Patent number
US09242962B2

Reaction notes

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