Phosphorus oxychloride → HCID 86606795, compound

HRID 42562Notes

Reaction equation

HRID 42562 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12](O)[C:11]([C:15]#[N:16])=[CH:10][C:9]=2[C:17]2[CH:22]=[CH:21][N:20]=[C:19]([S:23][CH3:24])[N:18]=2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:27]>CN(C=O)C>[Cl:27][C:12]1[C:11]([C:15]#[N:16])=[CH:10][C:9]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([S:23][CH3:24])[N:18]=2)=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[N:13]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178503415HCID 178503415, compound

Product 1

HCID 86606795HCID 86606795, compoundYield 60.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(4-fluorophenyl)-2-(hydroxy)-5-(2-methylsulfanylpyrimidin-4-yl)pyridin-3-carbonitrile (48.84 g, 144.6 mmol, obtained in reference example 21), POCl3 (166 mL, 1.8 mol) and DMF (2.2 mL) was heated to 100° C. for 2 h. It was allowed to cool to room temperature and concentrated. It was cooled with an acetone-CO2 bath and EtOAc and ice were subsequently added. The organic phase was decanted, washed with saturated NaHCO3, dried over Na2SO4 and concentrated to dryness. The crude obtained was purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity, to afford 31.00 g of the title compound (yield: 60%).

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated
  3. temperatureIt was cooled with an acetone-CO2 bath
  4. additionEtOAc and ice were subsequently added
  5. customThe organic phase was decanted
  6. washwashed with saturated NaHCO3
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. customThe crude obtained
  10. customwas purified by chromatography on silica gel
  11. temperatureof increasing polarity

Sources & evidence

ORD record
ord-a36059bc6a4848479e03e0bdfd36fd40
Source dataset
uspto-grants-2013_09
Patent number
US08536194B2

Reaction notes

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