Practical synthesis of quinoxalinone scaffolds via palladium-catalyzed intramolecular N-arylations

ORGN 741

Xuehong Luo, xuehong.luo@astrazeneca.com, Etienne Chenard, Peter Martens, Yun-Xing Cheng, and Miroslaw J. Tomaszewski. Department of Medicinal Chemistry, AstraZeneca R&D Montreal, 7171 Frederick Banting, Ville St-Laurent (Montreal), QC H4S 1Z9, Canada
Quinoxalinone and its tricyclic analogues are interesting previleged scaffolds in drug discovery process. They can be found as core structures in many pharmaceutically important compounds. In this poster, a practical method to the synthesis of a series of pharmaceutically interesting quinoxalinone scaffolds (21 examples)will be disclosed. The key step involves intramolecular palladium-catalyzed N-arylation through the use of microwave irradiation. The reaction tolerates many substituted bromo anilides to ensure quick delivery of diversified small molecules in parallel. Conventional heating can also be applied to synthesizethe scaffolds in gram scale. The limitation and scope of this methodology will also be discussed.