HCID 66727008, compound → HCID 59278181, compound

HRID 559746Notes

Reaction equation

HRID 559746 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([C@@H:17]([NH:20][C:21]([C:23]2[C:24]3[CH:31]=[N:30][N:29]([C:32]4[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=4)[C:25]=3[CH:26]=[N:27][CH:28]=2)=[O:22])[CH2:18][CH3:19])[CH2:13][CH:12]1[C:39](=[O:41])[NH2:40])=O)C1C=CC=CC=1.[H][H]>CO.[Pd]>[C:39]([CH:12]1[CH2:13][CH:14]([C@@H:17]([NH:20][C:21]([C:23]2[C:24]3[CH:31]=[N:30][N:29]([C:32]4[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=4)[C:25]=3[CH:26]=[N:27][CH:28]=2)=[O:22])[CH2:18][CH3:19])[CH2:15][CH2:16][NH:11]1)(=[O:41])[NH2:40]

Participants

5

Reactant 2

HCID 66727008HCID 66727008, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 59278181HCID 59278181, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of 2-carbamoyl-4-((S)-1-{[1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-propyl)-piperidine-1-carboxylic acid benzyl ester (340 mg, 0.61 mmol) in MeOH (10 mL) was added to a flask containing 10% palladium on carbon (52 mg, 0.05 mmol) under nitrogen and then the mixture was placed under 1 atmosphere of hydrogen. The reaction was monitored by HPLC-MS indicating 50% conversion. After stirring overnight, the mixture was filtered, and concentrated. The reaction was re-subjected to the above condition for an additional 5 hours at which time the mixture was filtered through diatomaceous earth, rinsed with MeOH, filtered and concentrated. The crude material was purified by reversed-phase HPLC (Sunfire PrepC18 OBD 5 uM 30×150 mm column, eluted with 15-85% acetonitrile in water, with 0.1% TFA). Fractions containing the desired product were concentrated in vacuo, made basic with a few drops of saturated sodium bicarbonate solution and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to afford the title compound as a white solid.

Workup

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated
  3. waitThe reaction was re-subjected to the above condition for an additional 5 hours at which time
  4. filtrationthe mixture was filtered through diatomaceous earth
  5. washrinsed with MeOH
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by reversed-phase HPLC (Sunfire PrepC18 OBD 5 uM 30×150 mm column, eluted with 15-85% acetonitrile in water, with 0.1% TFA)
  9. additionFractions containing the desired product
  10. concentrationwere concentrated in vacuo
  11. extractionextracted with EtOAc
  12. washThe organic layer was washed with brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-d26acbf89aa64f89a9aff06b66fe9215
Source dataset
uspto-grants-2011_11
Patent number
US08063065B2

Reaction notes

Loading…