Automated Synthesis and Purification of Amides: Exploitation of Automated Solid Phase Extraction in Organic Synthesis

R. Michael Lawrence; Scott A. Biller; Olga M. Fryszman; Michael A. Poss

doi:10.1055/s-1997-1232

Synthesis 1997; 1997(5): 553-558
DOI: 10.1055/s-1997-1232

paper

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Automated Synthesis and Purification of Amides: Exploitation of Automated Solid Phase Extraction in Organic Synthesis

R. Michael Lawrence¹ , Scott A. Biller² , Olga M. Fryszman³ , Michael A. Poss³

¹Department of Combinatorial Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 08543, USA, Fax +1(609)2527446; E-mail: lawrence_m@bms.com
²Department of Metabolic Disease Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute
³Department of Combinatorial Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 08543, USA

Abstract

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Automated parallel synthesis of small organic molecules, either as single entities or as mixtures, offers the potential for the rapid optimization of physical and biological properties of a molecule. Currently, emphasis has been placed on solid phase synthesis technology to accomplish the rapid preparation of large numbers of molecules. Automated solution phase synthesis is an alternative approach which has the advantages of having shorter development times and being more amenable to scaleup. Utilizing commercially available liquid handlers for reaction setup and exploiting automated solid phase extraction for product purification, a procedure has been developed to prepare and purify up to 100 amide analogs, simultaneously. Both carbodiimide mediated couplings and p-nitrophenyl ester displacements have been carried out using this procedure. Product amides having overall neutral or basic character have been prepared in good yield and with good to excellent purities.

amides - automation - ion exchange - solid phase extraction - combinatorial libraries

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