Three-Component Synthesis of 4-Aroyl-2(1),4,5,7-Tetrahydropyrazolo[3,4-b]Pyridin-6-Ones and Their Properties

Abstract

Inspired by the concept of multicomponent reactions, a novel one-pot synthesis involving arylglyoxals, 5-aminopyrazoles, and Meldrum's acid has been developed and employed for the creation of a small library of 4-aroyl-2(1),4,5,7-tetrahydropyrazolo- (3,4-b)pyridin-6-ones. The alkylation, acylation, reduction, and oxidation reactions of 4-aroyl-3-methyl-2,4,5,7-tetrahydropyrazolo(3,4-b)pyridin-6-ones have been studied. In last two decades the multicomponent reactions (MCRs) have been recognized as a highly powerful synthetic strategy for the combinatorial synthesis of compound libraries and have received significant attention (1-6). A central issue in MCRs research is the synthesis of nitrogen heterocycles, since this group of organic compounds holds a special place among pharmaceutically and agro- chemically important natural and synthetic products. Pyrazolopyridines among different azoloazines have received more attention as one of the "privileged medicinal scaffolds" which are used for the development of new drug candidates of various applications. Numerous methods for the synthesis of systems incorporating a pyrazolopyridine moiety have been reported with respect to their different structures (7-17). In the past several years, we and others have developed various MCRs based on interaction Meldrum's acid or its derivatives with carbonyl compounds and different nitrogen-containing 1,3-binucleophiles that can provide facile route to partially hydrogenated fused heterocyclic systems for chemical and biomedical purposes, some natural alkaloids and their analogs (4-6, 17, 18). For example, three-component reactions of 5-aminopyrazoles with aromatic, heterocyclic, or some aliphatic aldehydes and Meldrum's acid were shown to provide facile access to 4-aryl-4,5,6,7-tetrahydropyrazolo(3,4-b)pyridin-6-ones (17, 19-22). Unfortu- nately, there are only two reaction centers suitable for further chemical modification in their structure (21). For this reason, the introduction of a new chemically active group, such as carbonyl moiety, in tetrahydropyrazolo(3,4-b)- pyridin-6-one scaffold is a prioritary synthetic task for us. We have selected arylglyoxals as possible building blocks to be used in MCR with 5-aminopyrazoles and Meldrum's acid. They would be able to provide an additional carbonyl group in target heterocycles. These 1,2-dicarbonyl compounds are widely used in the design of different heterocycles (23). Nevertheless, in scientific literature there are no publications concerning one-pot synthesis of tetrahydropyrazolo(3,4-b)pyridin- 6-one derivatives on the base of glyoxals, 5-aminopyrazoles, and Meldrum's acid.