A New, One-Pot, Multicomponent Synthesis of Bioactive N-Pyrazolylformamidines under Microwave Irradiation

Abstract

A one-pot, three-component, microwave-assisted reaction of polysubstituted 5-aminopyrazoles, triethyl orthoformate, and a series of cyclic secondary amines was developed and successfully employed for the synthesis of novel N-pyrazolylformamidines. Under catalyst-free conditions, the reaction proceeded in a chemo-and regioselective manner, resulting in the formation of unsymmetric formamidines, which were isolated in high yields and purity. Some of the prepared compounds were found to inhibit interleukin-17 secretion in phenotypic in vitro assays.

3,4-Diaminopyrazolo[3,4-d]pyrimidines: a new three-component microwave-assisted synthesis and anti-leukemic properties

“…Recently, we reported 42 a multi-component reaction for the pyrimidinone ring annulation onto 5-aminopyrazole-4-carboxylates using microwave-assisted condensation of these compounds with primary amines and trimethyl orthoformate. It is also known 43 that the reaction of 5-aminopyrazole-4-carbonitriles with secondary amines and triethyl orthoformate under microwave irradiation resulted in the formation of formamidines structurally similar to the intermediates in the proposed synthesis of N 3 , N 4 -disubstituted 3,4-diaminopyrazolo[3,4- d ]pyrimidines. Therefore, we decided to employ controlled microwave irradiation to facilitate our proposed multi-component reaction.…”