The invention discloses a preparation method of
palbociclib. The preparation method comprises the following steps: 1) dissolving 4-(6-aminopyridine-3-yl)-
piperazine-1-
tertiary butyl
carboxylate into asolvent A, adding an alkali
reagent, activating at 0-20 DEG C, adding 6-
bromine-2-
chlorine-8-cyclopentyl-5-methyl-pyridino-[2,3-D]-
pyrimidine-7(8H)-
ketone, adjusting the solution to acid after a reaction is completed, cooling and filtering, taking filter cakes, and
drying the filter cakes to obtain an intermediate I; 2) in the presence of an
inert atmosphere, dissolving the intermediate I and
butyl vinyl ether into a
solvent B, catalyzing with a catalyst at 95-105 DEG C, cooling and separating a
crystal after the reaction is completed, filtering, and taking the filter cakes, and
drying the filter cakes to obtain an intermediate II; 3) dissolving the intermediate II into a
solvent C, adding an acid, adjusting the solution to acid after the reaction is completed, filtering, and taking and centrifuging filtrate to obtain a target product, namely
palbociclib. By adjusting reaction parameters and optimizing preparation process procedures, the preparation method is high in product yield, good in purity, simple and mild in
process conditions and applicable to industrial large-scale production.