Method for synthesizing Lomerizine Hydrochlortde

Abstract

This invention synthesis process consists of steps: (1) 2,3,4-trimethoxy benzaldehyde and di(4-fluorobenzyl) methyl piperazne, in molar ratio of (1:1) to (1:2.5) are fed in, heating to melt; (2) dropping-in formic acid, in mole ratio of (1:1) to 2,3,4-trimethoxy benzaldehyde, reacting for 1-3 hrs; (3) after cooled, adding concentrate hydrochloride acid-anhydrous alcohole mixed solution reacting for 1-5 hrs, to obtain crude product; (4) recrystallization of said product, by adding acetonitrile-methanol mixed solution or acetonitrile-ethanol mixed solution, refluxing for 1 hr. to obtain the final product. Advantages are: no need of salification, directly to obtain final product, high yield (more than 80%), to obtain pharmaceutical product after recrystallization, commercial (ton-scale) prodn.

Description

technical field

[0001] The invention relates to a method for synthesizing lomerizine hydrochloride (1-(2,3,4-trimethoxybenzyl)-4-[bis(4-fluorophenyl)methyl]piperazine dihydrochloride) method. Background technique

[0002] Migraine is a common chronic recurrent unilateral headache. my country is an area with a high incidence of migraine. Lomerizine hydrochloride (Lomerizine hydrochloride) is a new type of diphenylpiperazine calcium channel blocker, it can selectively increase the blood flow of cerebral blood vessels with little effect on peripheral blood vessels, and can also inhibit the diffusion inhibition ( Spreadingdepression) and neuritis, protect people and animals from the damage of cerebral ischemia and hypoxia, so developing lomerizine hydrochloride to treat migraine has broad market prospect. In view of the obvious economic and social benefits of lomerizine hydrochloride, many different synthetic methods have been developed. Although there are many methods for s...

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