ORGN 776

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.