Pyridine → 5-Chloro-7-(3,4-difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidine

HRID 872087Notes

Reaction equation

HRID 872087 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]=[CH:6][C:7]=1[F:8].N1C=CC=CC=1.O=P(Cl)(Cl)[Cl:28]>>[Cl:28][C:11]1[CH:10]=[C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=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 1363939327-(3,4-Difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5(4H)-one

Product 1

HCID 866880035-Chloro-7-(3,4-difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidine

Procedure

7-(3,4-Difluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5(4H)-one (821 mg) is dissolved in POCl3 (15 mL) and pyridine (0.2 mL) and stirred overnight while heating. 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 the target compound (301 mg) is yielded by column chromatography. 1H NMR (CDCl3, 300 MHz) δ 8.08 (m, 1H), 7.78 (m, 1H), 7.36 (q, J=8.7 Hz, 1H), 6.73 (s, 1H), 6.40 (s, 1H), 2.51 (s, 3H).

Workup

  1. temperaturewhile heating
  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

Sources & evidence

ORD record
ord-bdb6a5a1460a4d8fa2e02c0f11aa8d11
Source dataset
uspto-grants-2015_03
Patent number
US08975264B2

Reaction notes

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