AUTOMATED SYNTHESIS AND PURIFICATION OF AMIDES - EXPLOITATION OF AUTOMATED SOLID-PHASE EXTRACTION IN ORGANIC-SYNTHESIS

Automated parallel synthesis of small organic molecules, either as sin gle entities or as mixtures, offers the potential for the rapid optimi zation of physical and biological properties of a molecule. Currently, emphasis has been placed on solid phase synthesis technology to accom plish the rapid preparation of large numbers of molecules. Automated s olution phase synthesis is an alternative approach which has the advan tages of having shorter development times and being more amenable to s caleup. Utilizing commercially available liquid handlers for reaction setup and exploiting automated solid phase extraction for product puri fication, a procedure has been developed to prepare and purify up to 1 00 amide analogs, simultaneously. Both carbodiimide mediated couplings and p-nitrophhenyl ester displacements have been carried out using th is procedure. Product amides having overall neutral or basic character have been prepared in good yield and with good to excellent purities.