Synthesis of 6-aryl-1,6-dihydro-dipyrazolo[3,4-b:4,3-c]pyridines

Abstract

Keywords: N-aryl-6-azido-1H-pyrazolo [3,4-b]pyridine-5-carbaldimines, 6-aryl-1,6-dihydrodipyrazolo- [3,4-b:4,3-e]pyridines, thermolysis.Dipyrazolo [3,4-b:4,3-e]pyridines are examples of condensed heterocyclic compounds with notable pharmacological activity, for example bactericidal [1], sedative [2], and antiasthmathic [3]. Substances with electroluminescent properties are also found among them [4,5]. Only 1,7-disubstituted dipyrazolo[3,4-b:4,3-e]-pyridines can be synthesized by the reported cyclization of 2,6-dichloro-3,5-diformylpyridine with hydrazines [6], 5-aminopyrazoles with carbonyl compounds [7-10], and pyrazolin-5-ones with aldehydes and arylimines [11]. The intramolecular cyclocondensation of the hydrazone of 6-chloropyrazolo[3,4-b]pyridine-5-carbaldehyde was used to prepare 3-methyl-1-phenyl-1,7-dihydrodipyrazolo[3,4-b:4,3-e]pyridine [12]. N N N C H Cl Me Ph NNH 2 N N N N H N Me Ph EtOH, ∆, 18 hThere are no reports of 1,6-dihydro analogs of these heterocyclic systems in the literature. It is for this reason that we examine preparatively suitable routes to their synthesis in this paper.6-Chloro-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde (1), synthesized from 5-acetylamino-3-methyl-1-phenylpyrazole by the Vilsmeier-Haack method [12] was proposed as the starting material for the synthesis of the desired materials. Compound 1, like 5-chloropyrazole-4-carbaldehyde [13][14][15], was converted in 85% yield to 6-azidopyrazolo[3,4-b]pyridine-5-carbaldehyde 2 by reaction with NaN 3 in DMSO in the presence of the phase transfer catalyst Bu 4 N + I -.An investigation of the thermal properties of compound 2 showed that, in contrast to its close analog, 2-azido-7-methylquinoline-3-carbaldehyde, which is converted into the corresponding tetrazoloquinoline even at 40°C, it is quite stable and only underwent cyclization to pyrazolo[3,4-e][1,2,3,4]tetrazolo[1,5-a]pyridine 3 on refluxing in toluene for 6 h. It was therefore suggested that when the condensation of the azidoaldehyde 2 with