反应详情

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.

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