3-Amino-4-pyrazole carbosamide hemisulfate

Intermediate for the synthesis of allopurinol.

It is one of the 3-amino-4-substituted pyrazole series. It can be used as an intermediate to synthesize many pharmacologically effective organic compounds, such as allopurinol, one of the pyrazolopyrimidine derivatives series, the latter since 1963 Since its clinical use, it has been the main drug for the treatment of gout. At present, there are few known methods for synthesizing

3-aminopyrazole-4-carboxamide hemisulfate in China, mainly by reacting malononitrile and triethyl orthoformate to prepare ethoxymethylene malononitrile, and then with The reaction of hydrazine hydrate yields 3-amino-4-cyanopyrazole, which is finally reacted with concentrated sulfuric acid to produce

3-aminopyrazole-4-carboxamide hemisulfate (Chen Huiru, Xiao Guomin et al. 3-aminopyrazole- Synthesis of 4-formamide hemisulfate [J]. Chemical Industry Times, 2008, 6 (22): 39 40), the total yield of synthesis by this method is about 60% (calculated as malononitrile), this method It involves a three-step reaction, the steps are longer, and the reagents used, such as malononitrile and ethoxymethylene malononitrile, are more toxic and expensive. In addition, the 3-aminopyrazole-4 prepared by this method -Formamide hemisulfate has a color that is difficult to remove and requires additional processing, which is more complicated.

There are reports in foreign literature using pyridylamide hydrazone and ethoxymethylene malononitrile as raw materials to obtain 3-amino-4-cyanopyrazole by addition and cyclization, and then react with concentrated sulfuric acid to obtain the target compound (Reuken G Jones. Reactions of orthoesters with activemethylene compounds[J]. J Am Chem Soc. 1952,74(5) :4889 4891). The main raw materials used in this method are expensive, the reaction yield is not high, and the profit of industrial production is low. It must be difficult.