反应详情

温度

105 °C

In a 50 mL 3-neck flask with a magnetic stir bar and condenser was placed (R)-4-((R)-1-((6-bromo-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-on (125 mg, 0.34 mmol), 2-(4-(2,2-difluoroethoxy)-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (135 mg, 0.43 mmol) and Pd(PPh3)4 (40 mg, 0.027 mmol). Evacuated and filled with nitrogen 3×. Added 2.5 mL DME and 2N sodium carbonate (0.51 ml, 1.03 mmol) via syringe and heated in a 105° C. oil bath for 2 hrs at which time LC-MS indicated a complete reaction. Let cool, added EtOAc and water, separated, washed with brine, dried over Na2SO4, filtered and concentrated. Purified by chromatography: ISCO 50 g C18 reverse phase 0-30% water/acetonitrile/0.1% TFA. Partially concentrated under reduced pressure added EtOAc and sat.aq.bicarb, separated, washed with brine, dried over Na2SO4, filtered and concentrated to give a white solid.

1. customIn a 50 mL 3-neck flask with a magnetic stir bar and condenser was placed
2. customEvacuated
3. additionfilled with nitrogen 3×
4. customa complete reaction
5. temperatureLet cool
6. customseparated
7. washwashed with brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customPurified by chromatography
12. concentrationPartially concentrated under reduced pressure
13. additionadded EtOAc and sat.aq.bicarb
14. customseparated
15. washwashed with brine
16. dry with materialdried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated
19. customto give a white solid