3-Acetylpyridine → 1-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-one

HRID 483800Notes

Reaction equation

HRID 483800 reaction equation
[C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].CO[CH:12](OC)[N:13]([CH3:15])[CH3:14]>CN(C)C=O>[CH3:12][N:13]([CH3:15])[CH:14]=[CH:2][C:1](=[O:3])[C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 95893-AcetylpyridineHCID 78373Dimethylformamide dimethyl acetal

Product 1

HCID 5670331-(3-Pyridyl)-3-(dimethylamino)-2-propen-1-oneYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 125 g of 3-acetylpyridine and 138 g of N,N-dimethylformamide-dimethylacetal in dry dimethyl-formamide was refluxed for 3 h, after which the solution was evaporated to dryness and the product triturated with ether to give N,N-dimethyl-3-oxo-3-(3-pyridinyl)-prop-1-enamine in 72% yield. To a solution of 10.2 g of this product in 2-methoxyethanol 3.2 g of hydrazine were added under nitrogen and the mixture was heated. After 2 h the solvent was removed in vacuo to give quantitatively 3-(lH-pyrazol-3-yl)pyridine, which was dissolved in dimethylformamide. To this solution 22.8 g of N-bromosuccinimide were added in small portions over a period of 30 min, maintaining the temperature at 0°-5° C. The mixture was stirred for 3 h, poured into water, extracted with ethyl acetate, dried over sodium sulfate and evaporated to dryness, to obtain crude 3-(4-bromo-1H-pyrazol-3-yl)pyridine. To a solution of 13.5 g of this product in 190 ml of acetonitrile were added 17.5 g of methyl iodide under nitrogen, after which the solution was refluxed for 3 h. After cooling the crystalline material was filtered to give 3-(4-bromo-1H-pyrazol-3-yl)-1-methylpyridinium iodide in 71% yield. 15.6 g of this product was suspended in methanol and 5.7 g of sodium borohydride were added in small portions over 20 min at 0° C. After 1 h of stirring glacial acetic acid was added and the pH was adjusted to 6. The solvent was removed in vacuo, the residue suspended in brine and basified, and the product extracted with ethyl acetate. After drying over sodium sulfate and evaporation to dryness 3-(4-bromo-1H-pyrazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine was obtained in 93% yield, and converted into its fumaric salt, which was recrystallized from methanol to give 3-(4-bromo-1H-pyrazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine (E)-2-butenedioate. mp 228° C.

Workup

  1. customafter which the solution was evaporated to dryness
  2. customthe product triturated with ether

Sources & evidence

ORD record
ord-4f6d75a84f6040dcafa1fc797b472e80
Source dataset
uspto-grants-1993_07
Patent number
US05227394

Reaction notes

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