Phosphorus oxychloride → 4-chloro-N-(3,5-dimethylphenyl)pyrimidin-2-amine

HRID 968254Notes

Reaction equation

HRID 968254 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[NH:15][C:14](=O)[CH:13]=[CH:12][N:11]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1.O=P(Cl)(Cl)[Cl:19]>>[Cl:19][C:14]1[CH:13]=[CH:12][N:11]=[C:10]([NH:9][C:4]2[CH:3]=[C:2]([CH3:1])[CH:7]=[C:6]([CH3:8])[CH:5]=2)[N:15]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 14038592-(3,5-dimethylphenylamino)-3H-pyrimidin-4-one

Product 1

HCID 222884124-chloro-N-(3,5-dimethylphenyl)pyrimidin-2-amine

Conditions

Temperature
100 °C

Procedure

2-(3,5-Dimethyl-phenylamino)-3H-pyrimidin-4-one (2.01 g, 9.34 mmol) was dissolved in POCl3 (8.70 ml, 93.4 mmol) and the mixture was heated to 100° C. in a round bottom flask equipped with a reflux condenser and a drying tube. After 5 hours the reaction was cooled to room temperature and concentrated in vacuo. The residue was quenched by the addition of sat NaHCO3 (aq) and was extracted 3× with DCM. The combined organic extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (dissolved sample in DCM, eluted with 85:15 hexane/EtOAc) to afford 4-chloro-N-(3,5-dimethylphenyl)pyrimidin-2-amine (4-3).

Workup

  1. customequipped with a reflux condenser and a drying tube
  2. temperatureAfter 5 hours the reaction was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe residue was quenched by the addition of sat NaHCO3 (aq)
  5. extractionwas extracted 3× with DCM
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (dissolved sample in DCM, eluted with 85:15 hexane/EtOAc)

Sources & evidence

ORD record
ord-afc888e2ccc9446f894e8863ebd9fc93
Source dataset
uspto-grants-2005_10
Patent number
US06958340B2

Reaction notes

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