Solid/solution Phase Annulation (SPAnTM) technology: Single–step derivatization of primary amines to heterocycles

ORGN 788

Roland E. Dolle, Blanca Martinez-Teipel, and Calum MacLeod. Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341
Amine derivatization is the most widely employed transformation in combinatorial and medicinal chemistry. Numerous streamlined synthesis protocols are available to generate collections of amides, sulfonamides, ureas and amines from primary and secondary amines. These protocols yield acyclic derivatives. Of equal importance is the rapid access to cyclic derivatives. Single–step amine annulation chemistries have been developed as part of the title technology platform to address this void. This first disclosure takes an in–depth look at a novel series of SPAnTM reagents that transform primary amines into diverse arrays of C(O)NR–containing heterocycles. The reagents are well suited for establishing nascent structure–activity relationships in biologically active lead compounds.