反应详情

4-{(3S)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-({[2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (4.0 mg, 0.0065 mmol) was mixed with MeOH (77 μL), THF (39 μL) and 1.0 M NaOH (42 μL, 0.042 mmol). The reaction mixture was stirred at room temperature for 30 min. The organic solvents were removed under reduced pressure. The resulting aqueous solution was diluted with aq. NH4Cl and extracted twice with EtOAc. The combined organic layers were dried, filtered and concentrated to give an intermediate. The intermediate was dissolved in a mixture of DCM (0.066 mL) and TFA (0.066 mL, 0.86 mmol). The resulting solution was stirred at room temperature for 30 min., then concentrated under reduced pressure. The residue was diluted with MeOH, neutralized with NH4OH, filtered and purified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min., eluting with a gradient of MeCN and water with 0.15% NH4OH) to give two diastereoisomers of the title compound as white powders.

1. customThe organic solvents were removed under reduced pressure
2. additionThe resulting aqueous solution was diluted with aq. NH4Cl
3. extractionextracted twice with EtOAc
4. customThe combined organic layers were dried
5. filtrationfiltered
6. concentrationconcentrated
7. customto give an intermediate
8. stirringThe resulting solution was stirred at room temperature for 30 min.
9. concentrationconcentrated under reduced pressure
10. additionThe residue was diluted with MeOH
11. filtrationfiltered
12. custompurified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min.
13. washeluting with a gradient of MeCN and water with 0.15% NH4OH)