Regiospecific coupling of dehydroacetic acid and hydrazines leading to bioactive heterocycles

The reaction of dehydroacetic acid with hydrazines provides two types of pyranopyrazoles and a bipyrazole.Earlier studies typically missed the detection or isolation of one or more products and did not investigate their ratio systematically.Consequently, current literature data suggest that virtually same reaction conditions led to different products.In this work, we therefore attempted to investigate the effect of reaction conditions and reactants to the distribution of the products such as pyrano[4,3-c]pyrazole-4(1H)-one, pyrano[2,3c]pyrazole-4(1H)-one, and 1'H,2H-[3,4'-bipyrazole]-5'-ol.Product ratio, reaction rate and the conversion depended on the applied solvent and the acidic additive.Optimized conditions allowed us to expand the limited chemical space of these pyranopyrazoles by enumerating a virtual library synthetically sampled by pilot building blocks.Finally, the biological activity of the isolated compounds was confirmed against the non-receptor tyrosine phosphatase SHP2.