反应详情

温度

80 °C

To a solution of ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (Intermediate 4) (0.5 g, 0.91 mmol) in DMSO (5 mL) was added bis(neopentylglycolato)diboron (0.41 g, 1.82 mmol) and potassium acetate (0.18 g, 1.82 mmol). The reaction was degassed by purging N2 for 15 min followed by addition of dichloro(1,1-bis(diphenylphosphino)ferrocene)palladium (II) (0.07 g, 0.091 mmol) and again degassed for 10-15 min then heated up to 80° C. for 2 h. After completion of reaction (TLC as well as MS monitoring), the reaction was cooled to rt followed by addition of 2-chloro-4-methylpyridine (0.23 g, 1.37 mmol) and an aqueous solution of Cs2CO3 (0.45 g, 1.37 mmol, dissolved in minimum amount of water). The reaction was degassed by purging N2 for 15 min followed by addition of tetrakis (triphenylphosphine)palladium(0) (0.11 g, 0.091 mmol) and again degassed for 10-15 min then heated up to 80° C. for 16 h. After reaction completion, 100 mL of ice-cold water was added then extracted with EtOAc (3×150 mL) and the combined organic layer was washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 1.50% MeOH: DCM to obtain a beige solid, which was further purified through preperative-HPLC to obtain the desired product as an off-white solid (0.016 g, 3%).

1. customThe reaction was degassed
2. customby purging N2 for 15 min
3. customagain degassed for 10-15 min
4. customAfter completion of reaction (TLC as well as MS monitoring), the reaction
5. temperaturewas cooled to rt
6. customThe reaction was degassed
7. customby purging N2 for 15 min
8. customagain degassed for 10-15 min
9. temperaturethen heated up to 80° C. for 16 h
10. customAfter reaction completion, 100 mL of ice-cold water
11. additionwas added
12. extractionthen extracted with EtOAc (3×150 mL)
13. washthe combined organic layer was washed with brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. customevaporated under reduced pressure
17. customThe crude residue was purified over 100-200 M silica-gel
18. customDCM to obtain a beige solid, which
19. customwas further purified through preperative-HPLC