反应详情

温度

50 °C

To a solution of 1-benzyl-4-(4-fluoro-2-methyl-phenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester (4.0 g, 10.3 mmol) in EtOH (20 mL) and THF (20 mL) was added an aqueous solution of NaOH (1N, 20 mL, 20.0 mmol) and the mixture was heated at 50° C. for 3 hours. After cooling down to RT, the mixture was acidified with aqueous HCl (1N) until pH reached 3 and the product extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated to give the crude acid which was used directly in the next step without further purification. The residue was taken up in THF (20 mL) before Et3N (1.42 mL, 10.3 mmol), DPPA (diphenyl phosphorazidate, 2.83 g, 10.3 mmol) and tBuOH (3.85 mL, 41.1 mmol) were added. The reaction mixture was heated at 60° C. for 7 hours, volatiles were then partially evaporated, and the concentrated solution poured onto EtOAc (200 mL) and washed with H2O. The organic layer was dried over Na2SO4, and purification by column chromatography (SiO2, EtOAc/Heptane 1/5) yielded 2.6 g (58%) of the title compound as a white solid.

1. temperatureAfter cooling down to RT
2. extractionthe product extracted with EtOAc
3. dry with materialThe combined organic phases were dried over Na2SO4
4. concentrationconcentrated
5. customto give the crude acid which
6. customwas used directly in the next step without further purification
7. additionwere added
8. temperatureThe reaction mixture was heated at 60° C. for 7 hours
9. customvolatiles were then partially evaporated
10. additionthe concentrated solution poured onto EtOAc (200 mL)
11. washwashed with H2O
12. dry with materialThe organic layer was dried over Na2SO4, and purification by column chromatography (SiO2, EtOAc/Heptane 1/5)