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Microwave-assisted C-H arylation of Quinazolin-4-one-type Precursors of Bioactive Heterocycles
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1  Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRA UMR 6014, F-76000 Rouen, France

Published: 02 November 2015 by MDPI in 1st International Electronic Conference on Medicinal Chemistry session ECMC-1

Our group is focused on the synthesis of C,N,S- or C,N,O-containing heterocyclic precursors of bioactive molecules able to modulate the activity of kinases involved to some extent in Alzheimer's disease.1 Previous biological results lead us to intensively study thiazoloquinazolin-4-one backbone especially modulations of positions 1 and 2. Following our effort for the construction of a broad range of substituted thiazoloquinazolin-4-one derivatives as potential kinase inhibitors,2 modulating the position 3 was further explored. As an efficient and versatile approach in complex molecules synthesis palladium-catalyzed, C–H functionalization of heteroarenes3 represents an extremely attractive approach.

Our presentation describes the first extensive study of palladium-catalyzed direct C-H (hetero)-arylation of quinazolin-4(3H)-ones with aryl iodides, bromides and chlorides under microwave irradiation.4 This innovative methodology tolerates a broad range of heteroaryl and aryl halides substituted by electronically different groups. The scope of substrates was extended to pyridinopyrimidin-4-ones. This method provides an efficient, versatile, and rapid access to 2-arylquinazolin-4-one backbone and will be extended to our thiazoloquinazolin-4-one derivatives.


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Keywords: palladium-catalyzed C-H (hetero)-arylation, quinazolin-4(3H)-ones