Preparation method of Ozagrel sodium

Abstract

The invention discloses a preparation method of Ozagrel sodium. The method comprises the following steps: performing a bromination reaction on ethyl 4-methylcinnamate and N-bromo-succinimide by takingacetonitrile as a solvent under the triggering of azodiisobutyronitrile, so as to obtain ethyl 4-bromomethylcinnamate; performing a condensation cyclization reaction on the ethyl 4-bromomethylcinnamate and imidazole by taking sodium hydroxide as an acid-binding agent and taking tetrahydrofuran as a solvent, so as to obtain imidazole ethyl 4-methylcinnamate; performing alkali hydrolysis on the imidazole ethyl 4-methylcinnamate, so as to obtain the Ozagrel sodium. According to the preparation method, the condensation cyclization reaction is performed by taking the sodium hydroxide as the acid-binding agent and taking the tetrahydrofuran as the solvent, so that the finally obtained product does not contain toxic components, the yield and the purity of the product can be effectively improved,and the content of genotoxic impurities (the ethyl 4-bromomethylcinnamate and ethyl 4-dibromomethylcinnamate) in the product is zero.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a preparation method of ozagrel sodium. Background technique [0002] Sodium ozagrel, whose chemical name is trans-3-[4-(1H-imidazole-1-methyl)phenyl]-2-sodium acrylate, was established in 1989 by Japan Ono Pharmaceutical Co., Ltd. The first thromboxane synthase inhibitor to be marketed under the trade name Cataclot; it blocks prostaglandin (PGH 2 ) generates thromboxane (TXA 2 ), promote platelet-derived PGH 2 Turn to endothelial cells, which synthesize PGI 2 , thus improving the TXA 2 PGI 2 abnormal balance. Ozagrel sodium has the effect of inhibiting platelet aggregation and dilating blood vessels. Clinically, Ozagrena is mainly used for the treatment of acute thrombotic cerebral infarction and the movement disorder associated with cerebral infarction. [0003] At present, there are several synthesis routes of ozagrel sodium, the commonly used one is to bromide the p-...

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Problems solved by technology

[0005] But, p-bromomethyl cinnamate ethyl and imidazole are the reaction carried out in the acetone solution in the above-mentioned method, and acetone belongs to precursor, and purchase and management all have larger problem; Secondly, p-bromomethyl cinnamate and imidazole In the reaction of imidazole, imidazole methyl cinnamate dimer will be produced, which affects the yield and purity of ozagrel ethyl ester and increases the difficulty of post-processing; in addition, the synthetic reaction time of imidazole methyl cinnamate Too long, low production efficiency

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