Chemoselective High-Throughput Purification Mediated by Solid-Supported Reagents Its Application to the First 6,9-Disubstituted Purine Library Synthesis

A new application of solid-supported reagents was developed to separate the alkylated N7 N9 regioisomers derived from commercially available 2-amino-6-chloropurine. Simple filtration through an alumina H positive pad or scavenging by AG Dowex-50W-X8 resin provides diverse N9 regioisomers selectively in moderate yields with high purities (less than90 percent). This purification method can be conveniently used in a high-throughput format and facilitates the synthesis of a purine library without laborious regioisomer separation and aqueous work-up. The first library synthesis of 6,9-disubstituted purines is reported using the combination of this novel separation method in conjunction with polymer-supported reagents.