Versatile Monitoring Tools in Parallel Solid-Phase Synthesis

Parallel synthesis on solid-phase is routinely applied in our combinatorial chemistry efforts for lead finding and lead optimization in drug discovery. The synthetic products are released in solution, isolated individually, and purified, but most of the synthetic process is carried out on solid-phase. This facilitates lab automation and enhances throughput. The vastly increased synthetic productivity poses the question of how to best characterize the quality of compound libraries in an efficient and accurate way. In order to provide maximal information with minimal sample consumption, we have integrated a combination of analytical techniques in our workflow. The techniques, comprising IR, NMR, LC-MS, and HPLC online nitrogen detection (CLND), are illustrated on simple examples, but are usually applied to hundreds of molecules, and recurrently, within the timeframe of a library production.