N,N-Diethylaniline → 3-Bromo-7-chloro-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidine

HRID 1026890Notes

Reaction equation

HRID 1026890 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[C:10](O)=[C:9]([C:12]([N:14]3[CH2:19][CH2:18][CH:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:16][CH2:15]3)=[O:13])[CH:8]=[N:7][C:6]=12.C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:39])=O>>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[C:10]([Cl:39])=[C:9]([C:12]([N:14]3[CH2:19][CH2:18][CH:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:16][CH2:15]3)=[O:13])[CH:8]=[N:7][C:6]=12

Participants

4

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178519790HCID 178519790, compound

Product 1

HCID 866462893-Bromo-7-chloro-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidineYield 93%

Procedure

To 3-bromo-7-hydroxy-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidine (7.7 g, 19.1 mmol) obtained in step 2 were added phosphorus oxychloride (100 mL) and N,N-diethylaniline (6.1 mL, 38.3 mmol), and the mixture was heated under reflux for 5 hr. The reaction mixture was concentrated under reduced pressure, the residue was diluted with ethyl acetate (100 mL) and neutralized with saturated aqueous sodium hydrogen carbonate solution (300 mL) under ice-cooling, and the organic layer and the aqueous layer were separated. The organic layer was washed with 10% aqueous citric acid solution (50 mL) and saturated brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1) to give the title compound (7.5 g, 93%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 5 hr
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was diluted with ethyl acetate (100 mL)
  5. temperaturecooling
  6. customthe organic layer and the aqueous layer were separated
  7. washThe organic layer was washed with 10% aqueous citric acid solution (50 mL) and saturated brine (100 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-ad8f826c53f04cd59868c281a17cb0c4
Source dataset
uspto-grants-2014_05
Patent number
US08729264B2

Reaction notes

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