Thesis describes the Authors’ development of methods for the synthesis of low molecular weight partially hydrogenated aliphatic substituted azolopyrimidines with a nodular nitrogen atom. The novel multicomponent approach to the synthesis of partially hydrogenated azolopyrimidines containing exclusively aliphatic substituents in an aqueous medium has been proposed. This approach is based on the theoretical principles and the requirements for potential drug-like compounds, analysis of known methods for the synthesis of aryl-substituted azolopyrimidine systems, involving priority areas of "green chemistry" (use of non-toxic solvents).
Three-component condensation of 3-amino-1,2,4-triazole and its derivatives with aliphatic aldehydes and β-dicarbonyl methylene-active compounds in water yielded 4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines. Formaldehyde was introduced into the reaction in the form of paraformaldehyde, which proved to be more convenient from a practical point of view, compared with a solution of formalin, and at the same time had almost no effect on the reaction time. Introduction of other binucleophiles into three-component condensation with aliphatic aldehydes and 1,3-dicarbonyl compounds, namely 5-amino-2H-tetrazole and 1,2,3-triazole-4-carboxamide, in an aqueous medium without any catalyst under microwave or thermal activation also led to the selective formation of 4,7-dihydrotetrazolo(-1,2,3-triazolo)[1,5-a]pyrimidines. The chemical structure of these compounds was confirmed by spectral methods of analysis and by X-ray diffraction studies. Cyclocondensation of aminoazoles with acetaldehyde and trifluoroacetoacetic ester results in formation the mixture of two diastereomers of the corresponding stable 5-hydroxy-substituted 4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines without elimination of their hydroxy-group. The dehydration of the tetrahydroderivatives obtained in more severe conditions took place. Their spatial structure was established using spectral analysis methods. The compounds were obtained in an aqueous medium in catalyst-free conditions. Their synthesis satisfies the principles of "green chemistry".
It was found that the three-component condensation of 5-amino-1,2,3-triazole-4-carboxamide with malononitrile and cyclohexanone led to the formation of a spiro-derivative of 1,2,3-triazolo[1,5-a]pyrimidine. It was shown that the interaction of 3-amino-1,2,4-triazole and 5-amino-1,2,3-triazole-4-carboxamide with cyclohexanone and malononitrile have the opposite direction of the formation of the pyrimidine ring; this phenomenon is explained by the rearrangement of Dimroth at one of the stages of cyclocondensation with the participation of 5-amino-1,2,3-triazole-4-carboxamide.
