Efficient synthesis of thiazolo[3,2-c] pyrimidinones via multicomponent reactions

Thiazolo[5,4-d]-, [4,5-d]-, and [3,2-a]-pyrimidines are known to have variety of biological properties which were well-documented in recent literature and they can be produced over variety of synthetic routes. As the last thiazolopyrimidine core structure, thiazolo[3,2-c]pyrimidines are quite unknown in the sense of their synthesis or biological properties in the literature. Novel synthetic examples of thiazolo[3,2-c]pyrimidines and their biological activity results were reported for the first time by our group in 2014, 2015 and 2018. In order to advance the chemistry and biology of thiazolo[3,2-c]pyrimidines, synthesis of new potentially bioactive 3-oxothiazolo[3,2-c]pyridimine derivaties were aimed in the current dissertation work. To achieve the goal, first of all, the heterocyclic enamines as convenient precursors were prepared and characterized by IR and NMR analyses. In the second and third parts of the work, 3-oxothiazolo[3,2-c]pyrimidines were efficiently synthesized via Mannich cyclizations of the heterocyclic enamines, ethyl 2-(4-oxothiazolidin-2-ylidene) acetate and ethyl 2-((Z)-5-benzylidene-4-oxothiazolidin-2-ylidene) acetate, with formaldehyde or acetaldehyde and primary amines under mild conditions. After the characterization of all title compounds by IR, NMR and HRMS measurements, a preliminary antibacterial activity study for new 3-oxothiazolo[3,2-c]pyridimines were performed in the last part of the work. It was found that only one derivative exhibited bacteriostatic and moderate antibacterial activity against tested bacteria.