Synthesis Of Cinepazide Maleate

Calcium channel blocker (CCB) also called calcium antagonist, it is one of the drugsoften used for heart and blood vessels, mainly indicated for treating cardiovascular diseasesuch as hypertension, coronary heart disease, arrhythmia and so on, it is widely used andwith high frequency. It is classified to four kinds according to its bonding point:(1)Dihydropiridine;(2) Benzothiazepine;(3) Phenylalkylamine;(4) Triphenyl piperazine.Cinepazide maleate belongs to new generation of piperazine drug, with good curativeeffect and it has become the first line drug for curing cardio-cerebrovascular disease. Inview of its treatment status, it will have a good market prospect to develop the cinepazidemaleate.This thesis is to study the synthesis route of cinepazide maleate and optimization ofthe synthesis parameter, and three steps are included in this trial. The first step:3,4,5-trimethoxy cinnamoyl chloride is prepared by3,4,5-trimethoxy cinnamic acid andthionyl chloride. The second step: Cinepazide is prepared by condensation reaction which3,4,5-trimethoxy cinnamoyl chloride with l-[1-(nafoxidine carbonyl) methyl] piperazine.Then cinepazide maleate salt is prepared by cinepazide with maleic acid, thenre-crystallized, cinepazide maleate with high melting point and stable quality is obtained.Each step is screened and optimized in this thesis. Reaction temperature, time, ratio ofeach material, adding time are mainly studied, and at last product with high purity andhigh yield are screened through the trials. The yield of the final step reaches71.6%aftercrude cinepazide maleate is refined.