Study On Synthesis And Application Of 5-Azacytosine

Azacytidine and decitabine have been approved for the myelodysplastic syndrome, they are new anticancer drugs of DNA methyltransferases inhibitors which were successful developmented based on tumor express genetic abnormalities. But their applications are still limited to the cost. This paper studied on the synthesis of their common drug intermediates 5-azacytosine. By using simple and accessible materials, mild reaction conditions, simple post-process of synthetic route got high yield and purity of target compound 5-azacytosine.Guanylureaformate was synthesized by hydrolysis of dicyandiamide in formic acid, and then it reacted with triethyl orthoformate via cyclization to give 5-azacytosine. In this paper, stepwise and one pot synthesis of 5-azacytosine was studied. The best ratio, reaction temperature and reaction time to get 5-azacytosine with high yield and high purity were summarized in this paper.6-Methyl-5-azacytosine,6-ethyl-5-azacytosine,6-propyl-5-azacytosine were synthesized by replacing triethyl orthoformate with triethyl orthoacetate, triethyl orthopropionate and triethyl orthobutyrate using the optimized conditions of stepwise synthesis of 5-azacytosine.The application of 5-azacytosine in organic synthesis was also studied in this paper. 5-Azacytosine can react with n-propylamine, n-butylamine, furfuryl amine and benzylamine through one step reaction to get N-n-propyl-1,3,5-triazine-2,4-diamine, N-n-butyl-1,3,5-triazine-2,4-diamine, N-(2-furanylmethyl)-1,3,5-triazine-2,4-diamine, N-benzyl-1,3,5-triazine-2,4-diamine. The above drug intermediates have important research significance in the field of medicine and chemical industry. The title compounds and intermediates were certified by NMR, MS and IR.