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

HRID 414329Notes

Reaction equation

HRID 414329 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-7a345a46bbf14d529b560089c2128d72
Source dataset
uspto-grants-1988_12
Patent number
US04791203

Reaction notes

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