Formic Acid → 1-{4-[4-(5-Cyclopropyl-3-methylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-methylimidazolidine-2,4-dione

HRID 2411887Notes

Reaction equation

HRID 2411887 reaction equation
C(OC[N:10]1[C:14](=[O:15])[CH:13]([CH3:16])[N:12]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([N:25]3[CH2:30][CH2:29][N:28]([C:31]4[C:36]([CH3:37])=[CH:35][C:34]([CH:38]5[CH2:40][CH2:39]5)=[CH:33][N:32]=4)[CH2:27][CH2:26]3)=[O:24])=[C:19]([F:41])[CH:18]=2)[C:11]1=[O:42])C1C=CC=CC=1.C(O)=O>CO.[C].[Pd]>[CH:38]1([C:34]2[CH:35]=[C:36]([CH3:37])[C:31]([N:28]3[CH2:29][CH2:30][N:25]([C:23]([C:20]4[CH:21]=[CH:22][C:17]([N:12]5[CH:13]([CH3:16])[C:14](=[O:15])[NH:10][C:11]5=[O:42])=[CH:18][C:19]=4[F:41])=[O:24])[CH2:26][CH2:27]3)=[N:32][CH:33]=2)[CH2:40][CH2:39]1

Participants

5

Reactant 2

HCID 284Formic AcidHCID 712520443-Benzyloxymethyl-1-{4-[4-(5-cyclopropyl-3-methylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-methylimidazolidine-2,4-dione

Product 1

HCID 712530421-{4-[4-(5-Cyclopropyl-3-methylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-methylimidazolidine-2,4-dioneYield 18.8%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolvent

Procedure

3-Benzyloxymethyl-1-{4-[4-(5-cyclopropyl-3-methylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-methylimidazolidine-2,4-dione (270 mg) described in Example 536 was dissolved in methanol (20 mL), formic acid (0.36 ml) and 10% palladium carbon catalyst (108 mg) were added, and the mixture was stirred with heating under reflux for 16 hr. The reaction mixture was cooled, the catalyst was removed by celite filtration, and the solvent was evaporated. To the residue were added methanol and 0.5N aqueous sodium hydroxide solution, and the mixture was stirred at room temperature. The reaction solution was neutralized with acetic acid, and the solvent was evaporated. Water was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (chloroform:methanol) to give the title compound (40 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 16 hr
  3. temperatureThe reaction mixture was cooled
  4. customthe catalyst was removed by celite filtration
  5. customthe solvent was evaporated
  6. additionTo the residue were added methanol and 0.5N aqueous sodium hydroxide solution
  7. stirringthe mixture was stirred at room temperature
  8. customthe solvent was evaporated
  9. additionWater was added to the residue
  10. extractionthe mixture was extracted with chloroform
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. customthe solvent was evaporated
  13. customThe obtained residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-453ba0717cb447539e4153f516a3aa66
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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