An efficient synthesis of new imidazo[1,2- a]pyridine-6-carbohydrazide and pyrido[1,2- a]pyrimidine-7-carbohydrazide derivatives via a five-component cascade reaction

Abstract

A highly efficient and straightforward synthesis of N-fused heterocyclic compounds including N'-(1-(4-nitrophenyl)ethylidene)imidazo[1,2-a]pyridine-6-carbohydrazide and N'-(1-(4-nitrophenyl)ethylidene)pyrido[1,2-a]pyrimidine-7-carbohydrazide derivatives is successfully achieved via a five-component cascade reaction utilizing cyanoacetohydrazide, 4-nitroacetophenone, 1,1-bis(methylthio)-2-nitroethylene and various diamines in a mixture of water and ethanol. The new efficient domino protocol involving a sequence of N,N-acetal formation, Knoevenagel condensation, Michael reaction, imine-enamine tautomerization and N-cyclization as key steps. The merit of this catalyst free approach is highlighted by its easily available starting materials, operational simplicity, clean reaction profile, the use of environmentally benign solvents and tolerance of a wide variety of functional groups.

Fig. 1. Drugs containing the imidazo[1,2-a]pyridine and pyrido[1,2-a]pyrimidine cores.

Scheme 1. Synthetic scheme for the generation of products 6a–q.

Fig. 2. ¹H and ¹³C NMR chemical shifts of 6a.

Scheme 2. Proposed mechanism for the formation of products 6.