Microwave-assisted synthesis of 3-bromo-5-aminopyridine derivatives

ORGN 728

Reddeppareddy Dandu, dreddy@cephalon.com, Adam C Rose, N/A, and Robert L. Hudkins. Department of Medicinal Chemistry, Cephalon, Inc, 145 Brandywine Parkway, West Chester, PA 19380
For a medicinal chemistry lead optimization program we required a scalable method to 3-bromo-5-aminopyridine derivatives in multigram quantities. The traditional methods to synthesize 3-bromo-5-aminopyridine derivatives involved either palladium catalyzed or base promoted reactions from 3,5-dibromopyridine and the amine derivatives. These “classical” synthetic methods led to the formation of mixture of products and difficulty in purification. We have developed a microwave-promoted synthetic method to prepare 3-bromo-5-aminopyridine derivatives from commercially available 3,5-dibromopyridine and aliphatic amines in good / high yields and purity without using either metal catalysts or bases. Here we report a facile and rapid synthesis of several 3-bromo-5-aminopyridine derivatives using microwave heating technique.