Phosphorus oxychloride → 2-Chloro-3-(4-fluorophenyl)pyrido[3,2-d]pyrimidin-4(3H)-one

HRID 1674706Notes

Reaction equation

HRID 1674706 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[N:15]=[CH:16][CH:17]=[CH:18][C:11]=3[NH:10][C:9]2=S)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:22]>>[Cl:22][C:9]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:13](=[O:14])[C:12]2[N:15]=[CH:16][CH:17]=[CH:18][C:11]=2[N:10]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 576141483-(4-Fluorophenyl)-2-thioxo-2,3-dihydropyrido[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 576141462-Chloro-3-(4-fluorophenyl)pyrido[3,2-d]pyrimidin-4(3H)-one

Conditions

Temperature
135 °C

Procedure

A mixture of 3-(4-fluorophenyl)-2-thioxo-2,3-dihydropyrido[3,2-d]pyrimidin-4(1H)-one (2.6 g, 9.5 mmol) in 30 mL of POCl3 is heated to 135° C. and stirred for 2 days. After cooling to RT, the excess POCl3 is removed in vacuo, and the residue is azeotroped twice with toluene. The resulting sticky brown oil/solid mix is dissolved in CH2Cl2 and neutralized to pH 7-8 with saturated NaHCO3. The layers are separated, and the CH2Cl2 layer is dried (Na2SO4), filtered, and evaporated to give a brown sticky solid. Purification by column chromatography (gradient from CH2Cl2 to 20% EtOAc/CH2Cl2) affords the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 8.91 (1H, m), 8.05 (1H, m), 7.74 (1H, m), 7.28 (4H, m).

Workup

  1. temperatureAfter cooling to RT
  2. customthe excess POCl3 is removed in vacuo
  3. customthe residue is azeotroped twice with toluene
  4. additionThe resulting sticky brown oil/solid mix
  5. dissolutionis dissolved in CH2Cl2 and neutralized to pH 7-8 with saturated NaHCO3
  6. customThe layers are separated
  7. dry with materialthe CH2Cl2 layer is dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. customto give a brown sticky solid
  11. customPurification by column chromatography (gradient from CH2Cl2 to 20% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-953a79466c4d440aa4382e8e1a180de8
Source dataset
uspto-grants-2011_08
Patent number
US08003656B2

Reaction notes

Loading…