N[[Equation]]N’ Acyl Migration in the Context of a Medicinal Chemistry Program

Abstract

A series of tertiary amides was identified as lead matter for a new medicinal chemistry program. Analysis of analogs made for structure activity studies and physicochemical property measurements revealed that some of these tertiary amides were prone to acyl migration. A series of compounds designed to assess the propensity for acyl migration was synthesized. Qualitative time and temperature kinetics were followed up with quantitative kinetic measurements using 1 H NMR techniques. Many of the examined tertiary amides from this series were shown to migrate under range of pHs and temperatures. Our finding serves as a cautionary note for others working with amides of a similar nature.

Keywords: Amide, acyl migration