Olprinone → 2-Chloro-5-(imidazo[1,2-a]pyridin-6-yl)-6-methylpyridine-3-carbonitrile

HRID 579962Notes

Reaction equation

HRID 579962 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[C:8]([C:10]3[CH:11]=[C:12]([C:18]#[N:19])[C:13](=O)[NH:14][C:15]=3[CH3:16])[CH:7]=[CH:6][C:5]=12.P(Cl)(Cl)([Cl:22])=O>CN(C)C=O>[Cl:22][C:13]1[C:12]([C:18]#[N:19])=[CH:11][C:10]([C:8]2[CH:7]=[CH:6][C:5]3[N:4]([CH:3]=[CH:2][N:1]=3)[CH:9]=2)=[C:15]([CH3:16])[N:14]=1

Participants

4

Reactant 2

HCID 4593OlprinoneHCID 24813Phosphorus oxychloride

Product 1

HCID 138523142-Chloro-5-(imidazo[1,2-a]pyridin-6-yl)-6-methylpyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

A mixture of 3.1 g of 1,2-dihydro-5-(imidazo[1,2-a]pyridin-6-yl)-6-methyl-2-oxo-3-pyridinecarbonitrile, 30 ml of phosphorous oxychloride and 5 drops of dimethylformamide was stirred under reflux for 2 hours. An excess of phosphorous oxychloride was removed by distillation under reduced pressure and upon cooling, chloroform, a 20% NaOH solution and then an aqueous sodium carbonate solution were added to the residue to render it alkaline. The organic layer was taken by fractionation. After the chloroform layer was dried over magnesium sulfate, chloroform was removed by distillation. The residue was purified by column chromatography to obtain 1.9 g of 2-chloro-5-(imidazo[1,2-a]pyridin-6-yl)-6-methyl-3-pyridinecarbonitrile.

Workup

  1. temperatureunder reflux for 2 hours
  2. customAn excess of phosphorous oxychloride was removed by distillation under reduced pressure
  3. temperatureupon cooling
  4. additionchloroform, a 20% NaOH solution and then an aqueous sodium carbonate solution were added to the residue
  5. dry with materialAfter the chloroform layer was dried over magnesium sulfate, chloroform
  6. customwas removed by distillation
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-e692604bf7f649d9a4acfd81ee305092
Source dataset
uspto-grants-1988_06
Patent number
US04751227

Reaction notes

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