Ammonia → 6-Chloro-2-(4-fluorophenyl)-3,4'-bipyridine-5-carbonitrile

HRID 42559Notes

Reaction equation

HRID 42559 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)=[CH:12][C:11]([C:20]#[N:21])=[C:10](O)[N:9]=2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:25].N>CN(C=O)C>[Cl:25][C:10]1[N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:13]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[CH:12][C:11]=1[C:20]#[N:21]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 24813Phosphorus oxychlorideHCID 178509481HCID 178509481, compound

Product 1

HCID 859950346-Chloro-2-(4-fluorophenyl)-3,4'-bipyridine-5-carbonitrileYield 55.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(4-fluorophenyl)-6-hydroxy-3,4′-bipyridine-5-carbonitrile (6.57 g, 22.5 mmol, obtained in reference example 10), POCl3 (26.3 mL, 287.5 mmol) and DMF (0.37 mL) was heated to reflux under argon atmosphere for 2 h. It was cooled with an ice bath and basified by adding 30% aqueous NH3. The precipitate obtained was filtered and washed with water. The product was purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity as eluent, to afford 3.86 g of the desired product as a yellow solid (yield: 55%).

Workup

  1. temperaturewas heated
  2. temperatureto reflux under argon atmosphere for 2 h
  3. temperatureIt was cooled with an ice bath
  4. customThe precipitate obtained
  5. filtrationwas filtered
  6. washwashed with water
  7. customThe product was purified by chromatography on silica gel
  8. temperatureof increasing polarity as eluent

Sources & evidence

ORD record
ord-7f298eeb3f4f4482b7cad256a8bf217b
Source dataset
uspto-grants-2013_09
Patent number
US08536194B2

Reaction notes

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