Formaldehyde → 1-[5-Methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-3-[4-(3,5-dichlorophenyl)-1-piperazinyl]-1-propanone hydrochloride

HRID 1458988Notes

Reaction equation

HRID 1458988 reaction equation
[C:1]([C:4]1[CH:5]=[N:6][N:7]([C:10]2[N:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[C:8]=1[CH3:9])(=[O:3])[CH3:2].Cl.[Cl:17][C:18]1[CH:19]=[C:20]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:21]=[C:22]([Cl:24])[CH:23]=1.[CH2:31]=O>C(O)C>[ClH:17].[CH3:9][C:8]1[N:7]([C:10]2[N:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[N:6]=[CH:5][C:4]=1[C:1](=[O:3])[CH2:2][CH2:31][N:28]1[CH2:29][CH2:30][N:25]([C:20]2[CH:19]=[C:18]([Cl:17])[CH:23]=[C:22]([Cl:24])[CH:21]=2)[CH2:26][CH2:27]1

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 13059027HCID 13059027, compoundHCID 154563751-(2-Pyrimidinyl)-4-acetyl-5-methylpyrazole

Product 1

HCID 220972771-[5-Methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-3-[4-(3,5-dichlorophenyl)-1-piperazinyl]-1-propanone hydrochlorideYield 91.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1.75 g of 4-acetyl-1-(2-pyrimidinyl)-5-methylpyrazole was dissolved in 150 ml of ethanol and 2.21 g of 3,5-dichlorophenylpiperazine hydrochloride and 740 mg of paraformaldehyde were added thereto. The obtained mixture was heated under reflux for 24 hours. Further, 300 mg of paraformaldehyde was added and the obtained mixture was heated under reflux for 15 hours. Then the ethanol was almost halved by evaporation and the precipitate was filtered followed by the addition of chloroform thereto. Next, it was washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. After evaporating the solvent, the residue was purified by silica gel column chromatography (silica gel 90 g, chloroform:methanol=50:1). Then the obtained product was converted into hydrochloride by adding 1N hydrochloric acid and recrystallized from ethanol to thereby give 1.82 g of the title compound.

Workup

  1. temperatureThe obtained mixture was heated
  2. temperatureunder reflux for 24 hours
  3. temperaturethe obtained mixture was heated
  4. temperatureunder reflux for 15 hours
  5. customThen the ethanol was almost halved by evaporation
  6. filtrationthe precipitate was filtered
  7. additionfollowed by the addition of chloroform
  8. washNext, it was washed with a saturated aqueous solution of sodium hydrogencarbonate
  9. dry with materiala saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate
  10. customAfter evaporating the solvent
  11. customthe residue was purified by silica gel column chromatography (silica gel 90 g, chloroform:methanol=50:1)
  12. additionby adding 1N hydrochloric acid
  13. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-405e0a590ea44f768d04eadb35cbb06d
Source dataset
uspto-grants-1998_12
Patent number
US05852019

Reaction notes

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