Propanedioyl dichloride → 5,7-Dichloro-2-(4-methylphenyl)pyrazolo[1,5-a]pyrimidine

HRID 1878518Notes

Reaction equation

HRID 1878518 reaction equation
[NH2:1][C:2]1[NH:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[CH:3]=1.[C:14]([Cl:20])(=O)[CH2:15][C:16]([Cl:18])=O>C(#N)C.[OH-].[Na+]>[Cl:18][C:16]1[CH:15]=[C:14]([Cl:20])[N:6]2[N:5]=[C:4]([C:7]3[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=3)[CH:3]=[C:2]2[N:1]=1

Participants

5

Reactant 2

HCID 74269Propanedioyl dichloride2×HCID 178423837HCID 178423837, compound

Product 1

HCID 497615355,7-Dichloro-2-(4-methylphenyl)pyrazolo[1,5-a]pyrimidine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 14798Sodium HydroxideSolvent

Procedure

There was dissolved, in acetonitrile (40 mL), 5-amino-3-(4-methyl-phenyl)-pyrazole (2.00 g, 11.5 mM) in an argon gas atmosphere, malonyl chloride (1.34 mL, 13.8 mM) was added to the resulting solution with ice-cooling and the mixture was stirred at room temperature for 30 minutes. To this reaction liquid, there was added malonyl chloride (134 μL, 1.38 mM) followed by the further stirring of the mixture for 30 minutes. This reaction liquid was diluted with a 1M aqueous sodium hydroxide solution, washed with methylene chloride, and hydrochloric acid was added to the aqueous phase to make the same acidic (pH 2), followed by the extraction with ethyl acetate. The resulting extracts were combined and then concentrated, and the resulting solid was washed with diethyl ether. After the addition of phosphoryl chloride (5 mL) to the resulting solid with ice-cooling, the resulting suspension was stirred for 3 hours, while refluxing the same with heating. The phosphoryl chloride was distilled off from the reaction liquid, ethanol was added to the residue thus obtained with ice-cooling and then the mixture was stirred for 15 minutes. The reaction liquid was concentrated and then the resulting residue was purified by the silica gel column chromatography (ethyl acetate/hexane=1:10) to thus give the title compound (153 mg, overall yield of these two steps: 4%).

Workup

  1. temperaturecooling
  2. customTo this reaction liquid, there
  3. stirringfurther stirring of the mixture for 30 minutes
  4. customThis reaction liquid
  5. washwashed with methylene chloride, and hydrochloric acid
  6. additionwas added to the aqueous phase
  7. extractionfollowed by the extraction with ethyl acetate
  8. concentrationconcentrated
  9. washthe resulting solid was washed with diethyl ether
  10. additionAfter the addition of phosphoryl chloride (5 mL) to the resulting solid with ice-
  11. temperaturecooling
  12. stirringthe resulting suspension was stirred for 3 hours
  13. temperaturewhile refluxing the same
  14. temperaturewith heating
  15. distillationThe phosphoryl chloride was distilled off from the reaction liquid, ethanol
  16. additionwas added to the residue
  17. customthus obtained with ice-
  18. temperaturecooling
  19. stirringthe mixture was stirred for 15 minutes
  20. customThe reaction liquid
  21. concentrationwas concentrated
  22. customthe resulting residue was purified by the silica gel column chromatography (ethyl acetate/hexane=1:10)

Sources & evidence

ORD record
ord-324c190a70ab44debaeef5f75bd6574b
Source dataset
uspto-grants-2012_11
Patent number
US08314098B2

Reaction notes

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