N,N-Dimethylaniline → 7-Chloro-2,5-dimethylpyrazolo(1,5-a)pyrimidine

HRID 1639653Notes

Reaction equation

HRID 1639653 reaction equation
[CH3:1][C:2]1[CH:12]=[C:5]2[NH:6][C:7]([CH3:11])=[CH:8][C:9](=O)[N:4]2[N:3]=1.CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:24])=O.[OH-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:24][C:9]1[N:4]2[N:3]=[C:2]([CH3:1])[CH:12]=[C:5]2[N:6]=[C:7]([CH3:11])[CH:8]=1

Participants

7

Reactant 4

HCID 949N,N-DimethylanilineHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 178422355HCID 178422355, compound

Product 1

HCID 184069877-Chloro-2,5-dimethylpyrazolo(1,5-a)pyrimidineYield 59.7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 2,5-dimethyl-4H-pyrazolo[1,5-a]pyrimidin-7-one (10.0 g, 61.3 mmol) in toluene (150 mL), add N,N-dimethylaniline (9.7 mL, 76.7 mmol). Add phosphorus oxychloride (11.2 mL, 122.6 mmol) dropwise to this white suspension. Reflux for 3 h under an inert atmosphere, cool to room temperature, and concentrate the reaction to a brown oil using reduced pressure. Dissolve the oil in ethyl acetate (250 mL) and basify with 1 N NaOH. Separate and extract the basic aqueous phase with additional ethyl acetate (2×100 mL). Combine the organic phases, dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure to yield a brown solid. Purify the material using flash chromatography, eluting with 80% hexane/20% (30% THF/hexane) to 0% hexane/100% (30% THF/hexane) in a step gradient of 20% increments to provide a light green solid (6.65 g, 59%). ES/MS m/z (35Cl) 182.3 (M+1)+.

Workup

  1. temperatureReflux for 3 h under an inert atmosphere
  2. concentrationconcentrate
  3. customthe reaction to a brown oil
  4. customSeparate
  5. extractionextract the basic aqueous phase with additional ethyl acetate (2×100 mL)
  6. dry with materialCombine the organic phases, dry over anhydrous magnesium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customto yield a brown solid
  10. customPurify the material
  11. washeluting with 80% hexane/20% (30% THF/hexane) to 0% hexane/100% (30% THF/hexane) in a step gradient of 20% increments

Sources & evidence

ORD record
ord-9fc98d642564481ba870ceadaba4a25d
Source dataset
uspto-grants-2012_02
Patent number
US08110580B2

Reaction notes

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