Palladium-Catalyzed C-H activation of 2-Amino thiazol and Maleimide to synthesize pharmacologically active compounds

Substituted thiazoles as well as maleimeides are one of the important core structures encompassing interesting biological activities. The strategies for efficient, chemoselective and regioselective synthesis of these building blocks are, therefore, highly desired. We are particularly interested in the synthesis of 4- and 5-aryl aminothiazole derivatives and in addition functionalization of maleimide as they have the potential of outstanding activities against various viruses including HCV, HBV and particularly maleimide has anti-cancer activities. In a scenario where the classical methods reported for the synthesis of thiazolide derivatives and functionalization of maleimide are complex and limited only to a few substrates, palladium catalyzed C-H activations can be exceptionally suitable for a single regioselective substitution to make several and easily accessible analogues of thiazolide and maleimide class. The methodology will be explored and exploited for making a variety of the relevant 4- and 5- arylated thiazole, maleimide analogues and subsequently transformed to the corresponding benzoylated derivatives. The project will also provide an opportunity to have a mechanistic comparison of aryl coupling at all the available potential sites of the substrate rings i.e., C-4, C-5, NH and NH2. Once established, the methodology will also be applicable for the regioselective arylation of aminothiazole ring for multiple applications appreciating the inherent advantages of direct arylation i.e., simplicity, economy, more functional group tolerance, wider substrate scope, and minimum waste. The synthesized compounds will be evaluated against various biological targets such as HCV, HBV, Mycobacterium tuberculosis, Sarcocytis neurona etc. and as anti-cancer agents at collaborative institutions in Europe where PI has strong collaboration and has done a great work in the past