Preparation method of dexrazolone

Abstract

The invention provides a preparation method of dexrazolone, which comprises the following step: carrying out ring closing reaction on (S)-1, 2-propylene diamine tetraacetic acid and urea to obtain the dexrazolone. The preparation method has the following beneficial effects: 1, urea is adopted as an amination nitrogen source, high-purity dexrazoxane can be obtained through conventional reaction operation, harsh reaction conditions are avoided, the process operability is high, and process production is facilitated; 2, the reaction is fast, the generation of partial process impurities is avoided, the purification pressure of the final product is reduced, the purity and yield of the prepared dexrazoxane are high, the production cost is greatly reduced, and the method is economical and environment-friendly; 3, post-treatment is simple, convenient and easy to operate, and stable production of a high-quality dexrazoxane raw material medicine is facilitated; and 4, the operation is simple, the process conditions are easy to control, the cost is lower, the yield of products among batches is stable, the refined dexrazoxane is white powder, the purity reaches 99.9% or above, and the maximum individual impurity is 0.05% or below.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a preparation method of dexrazoxane. Background technique [0002] Dexrazoxane is an anti-tumor adjuvant drug, clinically used to alleviate or reduce the cardiotoxicity caused by anthracycline (such as doxorubicin) chemotherapy. The mechanism by which dexrazoxane exerts its cytoprotective activity is not fully understood. Dexrazoxane is a lipophilic derivative of the chelating agent ethylenediaminetetraacetic acid (EDTA), which can rapidly penetrate the cell membrane to reduce the cardiotoxicity of anthracycline antitumor antibiotics such as doxorubicin. Dexrazoxane is hydrolyzed to TCRE in cells -198, and then chelate with intracellular iron, reduce the complex of ferric ions and anthracycline antitumor drugs such as doxorubicin, and prevent the formation of free radicals. [0003] Dexrazoxane for injection was developed by Chiron Corporation of the United States. It was firs...

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Problems solved by technology

CN104177301A, CN101563329A etc. also disclose can be in methanol or dioxane, use sodium methoxide or sodium hydride to catalyze the reaction, but the yield is lower

[0011] Wherein, chloroacetic acid or its derivatives are used as substrates to react with the resolved (S)-1,2-propanediamine to form (S)-1,2-propanediaminetetraacetic acid or its corresponding derivatives, Finally, in the process of ring-closing reaction to prepare dexrazoxane, it is necessary to carry out a decompression reaction at about 150°C. At high temperature, dexrazoxane is very easy to react to form impurities, so the yield and purity of the reaction are poor, and the operation fluctuates between batches. High reliability and uncontrollable product quality limit the industrial application of this route

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