Cesium carbonate → Ethyl 1-(5-(2-(3-ethylureido)-7-(4-methylpyridin-2-yl)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

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%).

Provenance & Evidence