N → N’ acyl migration in the context of a medicinal chemistry program

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 fol-lowed up with quantitative kinetic measurements using 1H 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.(c) 2022 Elsevier Ltd. All rights reserved.