Synthesis of tetra-substituted pyrazines and pyrazine N-oxides using palladium-catalyzed cross-coupling reactions

ORGN 776

Jae Uk Jeong, Jae_U_Jeong@gsk.com, Xiaoyang Dong, Attiq Rahman, and Robert W. Marquis, Robert_W_Marquis@GSK.com. Department of Medicinal Chemistry, GlaxoSmithKline Pharm, 1250 South Collegeville Road, Collegeville, PA 19426

Pyrazines are important pharmacophores present in many biologically active compounds.  Several methods have been disclosed for the synthesis of unsymmetrical pyrazines from various starting materials such as epoxides, azirines, and chloropyrazines.  However, efficient synthetic methods for the synthesis of unsymmetrical pyrazines containing four different substituents are limited in scope. The synthesis of tetrasubstituted unsymmetrical pyrazines as well as pyrazine N-oxides has been developed from commercially available 2-chloro-3-methylpyrazine. The procedure and scope of these synthetic routes will be discussed.