Phosphorus oxychloride → 4-Chloro-2-(pyridin-2-yl)-6-(pyridin-3-yl)pyrimidine

HRID 1668661Notes

Reaction equation

HRID 1668661 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[NH:10][C:9](=O)[CH:8]=2)[CH:2]=1.P(Cl)(Cl)([Cl:22])=O.P(Cl)(Cl)(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>>[Cl:22][C:9]1[CH:8]=[C:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[N:10]=1

Participants

5

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 516892Sodium BicarbonateHCID 1363493296-pyridin-3-yl-2-pyridin-2-yl-3H-pyrimidin-4-one

Product 1

HCID 283091114-Chloro-2-(pyridin-2-yl)-6-(pyridin-3-yl)pyrimidine

Procedure

To 6-pyridin-3-yl-2-pyridin-2-yl-3H-pyrimidin-4-one (1 eq, 0.26 mmol, 0.035 g) under inert atmosphere, is added dropwise phosphorus oxychloride (15 eq, 3.9 mmol, 0.36 ml) followed by cautious addition of phosphorus pentachloride (1 eq, 0.26 mmol, 0.054 g). After 4 hours at reflux, the reaction mixture is added slowly to ice/water. The pH is adjusted to pH 7 using NaHCO3 and the aqueous portion is extracted with EtOAc. The combined organic extracts are separated, washed with brine, dried (MgSO4) and concentrated in vacuo. The crude product is purified by flash chromatography eluting with 0-100% MeOH in DCM to afford 4-chloro-6-pyridin-3-yl-2-pyridin-2-yl-pyrimidine as a white solid; [M+H]+=269/271.

Workup

  1. temperatureAfter 4 hours at reflux
  2. extractionthe aqueous portion is extracted with EtOAc
  3. customThe combined organic extracts are separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product is purified by flash chromatography
  8. washeluting with 0-100% MeOH in DCM

Sources & evidence

ORD record
ord-0ee63029df014bb8a1693eeb3a2b4778
Source dataset
uspto-grants-2011_08
Patent number
US07989458B2

Reaction notes

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