The preparation method of 5-azacytosine

Abstract

The invention relates to a preparation method for 5-azacytosine. The preparation method comprises: firstly reacting formic acid with a part of dicyandiamide at 50-60 DEG C, adding the residual dicyandiamide in batches after the reaction is steady, reacting at a constant temperature of 50-60 DEG C for 4 h, then heating to 100-110 DEG C and reacting for 1 h, adding acetic anhydride by dividing into two times, raising the temperature and performing refluxing reaction for 2 h, cooling to 60-70 DEG C, adding ethanol, continuing to cool to room temperature, filtering to obtain a 5-azacytosine crude product, then adding a mixed solution of ethyl acetate and ethanol, filtering and baking to dry, so as to obtain the 5-azacytosine finished product. The beneficial effects comprise that the prepared 5-azacytosine has the HPLC purity of 98.5% or more, has the impurity 1 content less than 0.5% and the impurity 2 content less than 0.1%, and the preparation method is good in technological safety, free of technological wastewater and suitable for large-scale industrialized production.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a preparation method of 5-azacytosine. Background technique [0002] Nucleoside drugs can interfere or directly act on the metabolic process of nucleic acid in the body, and block the synthesis of protein and nucleic acid. Therefore, these compounds have very obvious advantages in the fields of anti-virus and anti-tumor, and have attracted global scientists and pharmaceuticals. The research and development in this area has been very fast in the past ten years, and it is one of the first-choice drugs for the treatment of human epidemics (such as AIDS, hepatitis B, and influenza). The common structural feature of nucleoside compounds is composed of sugar groups and bases. It is possible to obtain new antiviral and antitumor drugs by modifying or transforming the structure of nucleosides. The base part of the nucleoside mainly includes purine and pyrimidine, and base mod...

AI Technical Summary

Problems solved by technology

The preparation of decitabine and azacitidine by using 5-azacytosine of this kind of purity as an intermediate requires repeated refining of the product quality, resulting in an increase in the raw material cost of the final product

[0008] In addition, due to the exothermic heat of the above-mentioned reaction, heating up the reaction after putting all the materials in at one time will bring a very large safety hazard, and it is not suitable for industrial application; the use of batch feeding, and then directly heating up to reflux reaction can partially solve the safety problem. However, the probability of impurity 1 and impurity 2 cannot be reduced, and the purity of 5-azacytosine needs to be refined many times to reach more than 98%.

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