Pyridine → 5-Chloro-7-(3,5-difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidine

HRID 872097Notes

Reaction equation

HRID 872097 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]3[N:15]=[C:16]([CH3:18])[CH:17]=[C:13]3[NH:12][C:11](=O)[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.N1C=CC=CC=1.O=P(Cl)(Cl)[Cl:28]>>[Cl:28][C:11]1[CH:10]=[C:9]([C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=2)[N:14]2[N:15]=[C:16]([CH3:18])[CH:17]=[C:13]2[N:12]=1

Participants

4

Reactant 3

HCID 1049PyridineHCID 24813Phosphorus oxychlorideHCID 1363939087-(3,5-difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5(4H)-one

Product 1

HCID 866880055-Chloro-7-(3,5-difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidine

Conditions

Temperature
100 °C

Procedure

7-(3,5-Difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5(4H)-one (521 mg) is dissolved in POCl3 (15 mL) and pyridine (0.2 mL) and stirred overnight while heating at 100° C. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The extracted organic layer is washed with 1 M NaHCO3 aqueous solution and brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure and purified by column chromatography to yield the target compound (327 mg). 1H NMR (CDCl3, 300 MHz) δ 7.63 (m, 2H), 7.02 (m, 1H), 6.82 (m, 1H), 6.52 (m, 1H), 2.52 (s, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction solvent is removed by distillation under reduced pressure
  3. extractionThe remainder is extracted with ethyl acetate and water
  4. washThe extracted organic layer is washed with 1 M NaHCO3 aqueous solution and brine
  5. distillationThe dehydrated organic layer is distilled under reduced pressure
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-7e2118b5f89f4503aa5924b5603874c1
Source dataset
uspto-grants-2015_03
Patent number
US08975264B2

Reaction notes

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