A kind of synthetic method of lobaplatin intermediate

Abstract

The invention relates to the technical field of drug synthesis, in particular to a method for synthesizing a lobaplatin intermediate. The method uses low-toxicity dimethyl malonate as a starting material, and undergoes coupling, bromination, cyclization, hydrolysis, Synthesis of high-purity trans-1,2-dicyanocyclobutane after amidation and dehydration reactions. In the synthesis of the whole route, all the raw and auxiliary materials used are easy to purchase, cheap and low in toxicity. The reaction conditions are not harsh and uncontrollable. The reaction conditions of each step can be applied to scale-up production. Although the reaction steps are increased, the yield of the product However, the yield has been greatly improved, thereby greatly reducing the cost, and the obtained trans-1,2-dicyanocyclobutane has improved purity, fully meets the subsequent use requirements, and greatly improves market competitiveness.

Description

A kind of synthetic method of lobaplatin intermediate technical field The present invention relates to the technical field of pharmaceutical synthesis, in particular to a kind of synthetic method of lobaplatin intermediate. Background technique Loplatin: LBP, D-19466, its chemical name is: trans-1,2-diaminomethyl-cyclobutane-lactic acid platinum (II), The structure is as follows: [0003] Loplatin is the third-generation platinum anti-tumor originally developed by Germany ASTA Medica AG drug. Loplatin is an antitumor drug belonging to the alkylating agent class, most of which are used in combination with chemotherapy, and are often used in chronic granulocytic leukemia. disease, advanced breast cancer, and small cell lung cancer. In September 2004, Hainan Changan International Pharmaceutical successfully transformed the knowledge of Loboplatin in China. Intellectual property rights, obtained exclusive production and operation patents, and obtained the national fi...

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Problems solved by technology

[0008] In the reaction process, flammable, explosive and highly toxic acrylonitrile is used, and it must be reacted at high temperature and high pressure, which causes considerable pollution to the environment. Moreover, the first product obtained is a mixed product of cis and trans, which needs to be rectified to obtain the obtained product. trans-1,2-dicyanocyclobutane

Because the reaction conditions are very harsh and the yield is extremely low, it is almost impossible to be used for industrial production and promotion

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