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

HRID 1458977Notes

Reaction equation

HRID 1458977 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[N:7]1[C:11]([CH3:12])=[C:10]([C:13](=[O:15])[CH3:14])[CH:9]=[N:8]1.C=O.[ClH:18].[CH2:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21][NH:20]1.Cl.[CH2:30](O)C>C(O)C>[ClH:18].[CH3:12][C:11]1[N:7]([C:2]2[N:1]=[CH:6][CH:5]=[CH:4][N:3]=2)[N:8]=[CH:9][C:10]=1[C:13](=[O:15])[CH2:14][CH2:30][N:20]1[CH2:21][CH2:22][C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:19]1

Participants

6

Reactant 4

HCID 712Formaldehyde2×HCID 27347171,2,3,4-Tetrahydroisoquinoline HydrochlorideHCID 154563751-(2-Pyrimidinyl)-4-acetyl-5-methylpyrazoleHCID 21887872Ethanol hydrochloride

Product 1

HCID 220973011-[5-Methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-3-(1,2,3,4-tetrahydroisoquinolin-2-yl)-1-propanone hydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1.01 g of 1-(2-pyrimidinyl)-4-acetyl-5-methylpyrazole was dissolved in 100 ml of ethanol. After adding 450 mg of paraformaldehyde and 848 mg of 1,2,3,4-tetrahydroisoquinoline hydrochloride, the mixture was heated under reflux overnight. Next, 200 mg of paraformaldehyde was further added to the reaction mixture which was then concentrated by heating under reflux overnight. To the obtained residue was added chloroform. Then 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 subjected to silica gel column chromatography and developed with a solvent mixture (chloroform/methanol, 30:1). A fraction containing the terget compound was concentrated. To the residue thus obtained was added a 1N hydrochloric acid/ethanol solution. After concentration, ethanol was added to the residue. After recrystallization, 550 mg of the title compound was obtained.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux overnight
  3. concentrationwas then concentrated
  4. temperatureby heating
  5. temperatureunder reflux overnight
  6. additionTo the obtained residue was added chloroform
  7. washThen it was washed with a saturated aqueous solution of sodium hydrogencarbonate
  8. dry with materiala saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate
  9. customAfter evaporating the solvent
  10. additionA fraction containing the terget compound
  11. concentrationwas concentrated
  12. customTo the residue thus obtained
  13. concentrationAfter concentration, ethanol
  14. additionwas added to the residue
  15. customAfter recrystallization

Sources & evidence

ORD record
ord-dedaeba456264842b8e448ee80afa6b9
Source dataset
uspto-grants-1998_12
Patent number
US05852019

Reaction notes

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