The use of high-throughput synthesis and purification in the preparation of a directed library of adrenergic agents

Miles G. Siegel, Patrick J. Hahn,
Research Technology & Proteins Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, U.S.A.

Athony J. Shuker, Christine A. Droste, Cynthia D. Jesudason, John H. McDonald III, Donald P. Matthews, Christopher J. Rito, Andrew J. Thorpe
Endocrine Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, U.S.A.

Abstract
A library of potential agonists and antagonists for adrenergic receptors was prepared using high-throughput solution-phase parallel synthesis. Traditional solution-phase reductive amination reactions followed by rapid purification by ion exchange chromatography yielded products with near-analytical purity. An array of ketones and amines, arranged in an 8 × 12 matrix, were combined to form 96 individual compounds.

Keywords
adrenergic agonists and antagonists, ethanolamine library, ion exchange chromatography, parallel synthesis, reductive amination