Hydrochloric Acid → 1-(4-Amidinophenyl)-3-(4-t-butylphenyl)-4-{[4-(ethoxycarbonylmethyloxy)-1-piperidinyl]carbonyl}-2-methyl-2H-pyrazol-5-one monohydrochloride

HRID 1740080Notes

Reaction equation

HRID 1740080 reaction equation
[ClH:1].[C:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]([CH3:41])[N:14]([C:33]3[CH:38]=[CH:37][C:36]([C:39]#[N:40])=[CH:35][CH:34]=3)[C:15](=[O:32])[C:16]=2[C:17]([N:19]2[CH2:24][CH2:23][CH:22]([O:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]2)=[O:18])=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3].C(=O)([O-])[O-].[NH4+:46].[NH4+]>C(O)C>[ClH:1].[C:39]([C:36]1[CH:35]=[CH:34][C:33]([N:14]2[C:15](=[O:32])[C:16]([C:17]([N:19]3[CH2:20][CH2:21][CH:22]([O:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][CH2:24]3)=[O:18])=[C:12]([C:9]3[CH:8]=[CH:7][C:6]([C:2]([CH3:3])([CH3:4])[CH3:5])=[CH:11][CH:10]=3)[N:13]2[CH3:41])=[CH:38][CH:37]=1)(=[NH:46])[NH2:40]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 517111Ammonium CarbonateHCID 154355023-(4-t-Butylphenyl)-4-{[4-(ethoxycarbonylmethyloxy)-1-piperidinyl]carbonyl}-1-(4-cyanophenyl)-2-methyl-2H-pyrazol-5-one

Product 1

HCID 218376491-(4-Amidinophenyl)-3-(4-t-butylphenyl)-4-{[4-(ethoxycarbonylmethyloxy)-1-piperidinyl]carbonyl}-2-methyl-2H-pyrazol-5-one monohydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Dry hydrogen chloride was introduced into a mixture of 1.19 g of 3-(4-t-butylphenyl)-4-{[4-(ethoxycarbonylmethyloxy)-1-piperidinyl]carbonyl}-1-(4-cyanophenyl)-2-methyl-2H-pyrazol-5-one and 15 ml of absolute ethanol under cooling with ice for 2 hours, and the mixture was stirred under cooling with ice for another 15 hours. 38.5 g of ammonium carbonate was added to adjust the pH to 7-8, and the reaction solution was stirred at room temperature for 22 hours. The precipitated insolubles were filtered off, and hydrochloric acid in ethanol was added to the mother liquor to adjust the pH to 3. The precipitated crystals were filtered off, and the mother liquor was concentrated under reduced pressure. The residue was purified by C-18 reverse phase silica gel chromatography (water/methanol=2:1). The resulting crude crystals were recrystallized in methanol-chloroform-ethyl acetate to give 543 mg of the title compound as colorless crystals.

Workup

  1. temperatureunder cooling with ice for 2 hours
  2. temperatureunder cooling with ice for another 15 hours
  3. stirringthe reaction solution was stirred at room temperature for 22 hours
  4. filtrationThe precipitated insolubles were filtered off
  5. additionhydrochloric acid in ethanol was added to the mother liquor
  6. filtrationThe precipitated crystals were filtered off
  7. concentrationthe mother liquor was concentrated under reduced pressure
  8. customThe residue was purified by C-18 reverse phase silica gel chromatography (water/methanol=2:1)
  9. customThe resulting crude crystals were recrystallized in methanol-chloroform-ethyl acetate

Sources & evidence

ORD record
ord-ca3d266cc1e145bcab3038d715142d62
Source dataset
uspto-grants-1999_10
Patent number
US05968967

Reaction notes

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