SUMMARY

Pyrazolopyrimidines and related fused heterocycles are of interest as potential bioactive molecules. Pyrazolo[4,3-d]pyrimidines were identified as a general class of adenosine receptors, due to the similarity between their structures and purines. Pyrazolo[4,3-d]pyrimidines are also important compounds as a result of their biological activity and structural relationship to azaindoles. A number of pyrazolo[4,3-d]pyrimidines are potentially biologically active compounds as new inhibitors of xantine oxidase. Because of this wide range of activities,we have been interested on ortho-aminocyanopyrazoles or their derivatives as inhibitors of xanthine oxidase. For this purpose we started from the key intermediates and reacted them with malononitrile and diethylmalonate to obtain pyrazolo[4,3-d]pyrimidines.

With the aim of obtaining condensed pyrazolo[4,3-d]pyrimidine systems the condensation has been carried out of a substituted aminopyrazole, which contains a cyano group in the ortho position, with malononitrile and diethylmalonate.

The 5-amino-1-substitutedpyrazole-4-carbonitriles, were used as starting materials, they contain an amino and a cyano group in adjacent positions, which is required for the synthesis of the condensed systems including pyridine and pyrimidine. It has been found that reaction of compound 1a with malononitrile in refluxing ethanol in the presence of triethylamine afforded a yellow crystalline solid of mp 254-256oC. However, the micro-analytical data showed that this product has the molecular formula C20H16N8. Furthermore, the mass spectrum (EI) of this product showed a molecular ion at m/z = 368 and the IR spectrum displays an absorption at 3463 cm-1,corresponding to NH2 stretching,and no CN absorption. The 1H NMR spectrum reveals two singlets for the amino groups at 5.44 and 5.88 ppm and two singlets for the pyrazole H-3 protons. Structure was thus suggested for this product. The formation of compound may be envisaged via initial condensation of the amino group of one molecule of the o-aminonitrile with the cyano group of a second molecule to give an intermediate amidine which then undergoes a second, but intramolecular, amine-nitrile condensation to give the isolated product. To confirm this hypothesis, reflux of compound in ethanol and triethylamine afforded a product completely identical. A similar result had been established by Taylor and Borror.