Preparation method of high-purity dexrazoxane

Abstract

The invention relates to a preparation method of high-purity dexrazoxane, which comprises the following steps of: (1) cyclization reaction: carrying out cyclization reaction between (S)-1, 2-propane diamine-N, N, N', N'-tetracetic acid or disodium salt of (S)-1, 2-propane diamine-N, N, N', N'-tetracetic acid and formamide, wherein a high boiling point solvent is used; (2) preparation of salt-containing crude product: evaporating the mixture, which is obtained after reaction, for removing the formamide by pressure reduction and concentration, adding organic solvent into the mixture, and filtering to obtain solid; (3) preparation of crude product: adding dioxane into the salt-containing crude product, heating for backflow, filtering, concentrating the filtrate, adding organic solvent into the filtrate to obtain the crude product of dexrazoxane; and (4) refining: adding the crude product of dexrazoxane into N, N'-dimethyl formamide, heating for dissolving, dropwise adding the solvent, carrying out crystallization, filtering to obtain solid, washing the obtained solid with the solvent, drying to finally obtain the high-purity dexrazoxane. The method for synthesizing dexrazoxane is stable in yield and easy in condition control; the product purity is higher than 99.5% and residual organic solvent is little, and the synthesis cost can be reduced.

Description

technical field [0001] The invention relates to a preparation method of high-purity dextropropylimine, which belongs to the field of medicine and chemical industry, and more specifically relates to a synthesis process of high-purity dextropropylimine, including a preparation method and a refining method. Background technique [0002] The chemical name of dexrazoxane is (S)-4,4'-(1-methyl-1,2-ethanediyl)-bis-(2,6-piperazinedione), as shown in the structural formula ( i) as shown: [0003] [0004] Dextropropyl imine is the d-isomer of razoxane, also known as dexrazoxane or derazoxa or ICRF-187, which is a lipophilic derivative of chelating agent ethylenediaminetetraacetic acid, produced by the United States Developed by Chiron Company, it was first launched in Italy in 1992, and was approved by the FDA in July 1995. At present, dextromethyridine is the only drug clinically used to reduce the cardiotoxicity induced by anthracycline antineoplastic drugs. After intracellul...

AI Technical Summary

Problems solved by technology

And the method for dioxane refining, only need the dioxane of 5 times weight of crude product weight to be dissolved under reflux condition, use this method to obtain the product with higher content, but product crystallization needs longer time, and Due to the high solubility of dioxane, the refined yield is not very high

More importantly, the residue of dioxane solvent is relatively high. In the actual test, its content is higher than 0.2%, while the pharmacopoeia maximum is 0.038%. It is difficult to drop to the limit specified in the pharmacopoeia by various means. Larger, and there is a more serious accumulation in the human body, the use of dextropropimine injection containing dioxane will have unpredictable toxic side effects on patients

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