Phosphorus oxychloride → 7-Chloro-5-methyl-2-phenylpyrazolo(1,5-a)pyrimidine

HRID 928250Notes

Reaction equation

HRID 928250 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[N:5]([N:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:11]=2)[C:6](=O)[CH:7]=1.P(Cl)(Cl)([Cl:20])=O>>[Cl:20][C:6]1[N:5]2[N:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:11]=[C:4]2[N:3]=[C:2]([CH3:1])[CH:7]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178429158HCID 178429158, compound

Product 1

HCID 127261227-Chloro-5-methyl-2-phenylpyrazolo(1,5-a)pyrimidineYield 54.2%

Procedure

5-Methyl-2-phenylpyrazolo[1,5-a]pyrimidin-7(4H)-one (210 mg, 0.932 mmol) is heated in phosphoryl chloride (1.74 mL, 18.6 mmol) in a sealed vial at 100° C. for 2 hr. The reaction mixture is cooled to room temperature and slowly poured over ice. The resulting suspension is extracted with dichloromethane and washed with brine. The organic layer is dried over Na2SO4, filtered and concentrated in vacuo. The crude material is purification by column chromatography (eluent 0-100% ethyl acetate:hexanes) to provide 7-chloro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidine (123 mg, yield 54%). LCMS: (AA) M+1 244; 1H NMR (400 MHz, DMSO) δ 8.07-8.02 (m, 2H), 7.53-7.47 (m, 2H), 7.46-7.41 (m, 1H), 7.32 (s, 1H), 7.23 (s, 1H), 2.53 (s, 3H).

Workup

  1. additionslowly poured over ice
  2. extractionThe resulting suspension is extracted with dichloromethane
  3. washwashed with brine
  4. dry with materialThe organic layer is dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurification by column chromatography (eluent 0-100% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-c5a2fe1bcc714f23b57cddd86eb07df4
Source dataset
uspto-grants-2016_03
Patent number
US09290500B2

Reaction notes

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