Stereodynamics of Ar–CO rotation and conformational preferences of 2-amino-3-(2,4-difluorobenzoyl)-imidazo[1,2-a]pyridine

Abstract The dynamic NMR analysis of 2 , a subunit of a new class of cyclic-dependent kinase inhibitors, reveals that the compound exists as two conformational isomers, Z and E , in acetone, as a consequence of the restricted rotation about the imidazopyridine–carbonyl bond. The less hindered Z -rotamer is the most abundant conformer (85:15 Z / E at 233 K) and the free energy of activation of the interconversion is 13.2 kcal mol −1 . The rotamer ratio and the interconversion barrier are similar in other solvents, such as CD 3 OD and CDCl 3 .