The invention provides a preparation method of a diacylglycerol
kinase inhibitor, which comprises the following steps: S1, reacting 4-fluorobenzyl
bromide with
magnesium under
inert gas by taking
iodine as an initiator to obtain a
Grignard reagent B; s2, the
Grignard reagent B and N-tert-butyloxycarbonyl-4-piperidone are subjected to an
addition reaction, and an intermediate C is obtained through
hydrolysis and deprotection; s3, carrying out Heck
coupling reaction on the intermediate C, 4-fluorophenyl
trifluoromethanesulfonate and a catalyst in the presence of alkali to obtain an intermediate D; s4, carrying out
substitution reaction on the intermediate D and chloroethanol in the presence of alkali to obtain an intermediate E; s5, carrying out
Mitsunobu reaction on the intermediate E to obtain an intermediate F; s6, carrying out
addition reaction on the intermediate F and N, N '-thiocarbonyldiimidazole to obtain an intermediate G; and S7, carrying out cyclization reaction on the intermediate G, 2-methyl aminobenzoate and alkali to obtain the diacylglycerol
kinase inhibitor R59949. The synthesis
route disclosed for the first time has the characteristics of mild
reaction conditions, reasonable design, cheap and easily available raw materials, high yield and the like, and provides theoretical support for
biological evaluation and clinical application of R59949.