Phosphorus oxychloride → 4-Chloro-5-(4-fluorophenyl)-2-methylthio-6-(4-pyridyl)pyrimidine

HRID 897392Notes

Reaction equation

HRID 897392 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=O)[N:10](C)[C:11]([S:20][CH3:21])=[N:12][C:13]=2[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:9]1[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)[N:12]=[C:11]([S:20][CH3:21])[N:10]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 223466205-(4-fluorophenyl)-3-methyl-2-methylthio-6-(4-pyridyl)-4(3H)-pyrimidinone

Product 1

HCID 223466344-Chloro-5-(4-fluorophenyl)-2-methylthio-6-(4-pyridyl)pyrimidine

Procedure

5-(4-fluorophenyl)-3-methyl-2-methylthio-6-(4-pyridyl)-3H-pyrimidin-4-one (0.327 g, 1 mmol) and 5 ml of POCl3 in a 15-ml r.b.flask with a stir bar was stirred at 120° C. for 16 h. The remaining POCL3 was evaporated in vacuo. The dark brown residue was mixed with ice-water. The resulting acidic dark brown solution was neutralized to pH 7-8 with sat'd NaHCO3 and extracted by EtOAc (2×10 ml). The combined organic layers were washed with brine (10 ml) and dried over Na2SO4. 4-chloro-5-(4-fluorophenyl)-2-methylthio-6-(4-pyridyl)pyrimidine was isolated by flash chromatography with 50% EtOAc in hexane; MS: m/z (M+H)+ 332; C16H11ClFN3S requir.331.8.

Workup

  1. customThe remaining POCL3 was evaporated in vacuo
  2. additionThe dark brown residue was mixed with ice-water
  3. extractionextracted by EtOAc (2×10 ml)
  4. washThe combined organic layers were washed with brine (10 ml)
  5. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-3a8d7d0f41e64312b52e8805add46bbe
Source dataset
uspto-grants-2005_07
Patent number
US06921762B2

Reaction notes

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