Paper
LI Shumin1, WU Tingting1, WANG Xinglan1, ZHANG Jiquan1,2, TANG Lei2*
The antitumor drug gedatolisib was prepared by taking cyanuric chloride (2) as the starting material. Compound 2 reacted with morpholine in acetone/water to give 2-chloro-4,6-bis(morpholin-4-yl)-1,3,5-triazine, which was followed by a Suzuki coupling with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline in the presence of Pd(PPh3)4 to afford 4-[4,6-bis(morpholin-4-yl)-1,3,5-triazine-2-yl]aniline. In this step, the amount of the catalyst Pd(PPh3)4 was reduced from 5％ to 0.8％, the crude was purified by recrystallization in ethyl acetate. Then the latter was subjected to an amidation with N,N'-carbonyl diimidazole and a condensation with (4-aminophenyl)[4-(dimethylamino)- piperidin-1-yl]methanone to prepare the target compound with a total yield of 40.1％(based on 2). This process has short synthetic route, accessible materials, mild conditions and handy operations, which makes it suitables for the scale-up preparation.
