The activation energy for the reaction of pyridinebased ester 1a with the different amines 2a, 2b and 2c is 21.0 kJ/mol, 29.1 kJ/mol, and 24.6 kJ/mol, respectively. This reactivity follows a trend for amine nucleophiles: primary > cyclic secondary > acyclic secondary (2a > 2c > 2b). The same order of reactivity was also observed for carbocyclic ester 1b. Activation energies of 26.7 kJ/mol, 34.0 kJ/mol, and 31.9 kJ/mol were fitted for its reaction with 2a, 2b and 2c, respectively. Although the reactivity order of cyclic vs acyclic secondary amines follows known nucleophilicity scales, the primary amine would be expected to be less reactive. This implies that other factors, such as steric effects or hydrogen bonding capabilities, have an increased influence in this reaction. The electron-deficient nature of heterocyclic ester 1a significantly enhances the reaction rate compared to carbocyclic ester 1b. The increased reactivity was reflected in the lower activation energies for 1a in reactions with all three different amines. This is in agreement with the reported large positive Hammett substituent constant for a 3-pyridyl substituent (σ = +0.55). A slightly lower activation energy of 26.7 kJ/mol was obtained for 1b compared to 1e (29.6 kJ/mol) in the reaction with 2a, quantifying the difference in reactivity between aromatic and aliphatic esters. By means of comparing the influence of the alkoxy group on ester reactivity, the methyl moiety (1b) has a lower activation energy than ethyl (1c), which is lower than the sterically bulky isopropyl group (1d). Although this trend would be expected (methyl > ethyl > isopropyl), we have quantified the relationship between these esters. Interestingly, this study has also demonstrated that the reactivity of both the amine and ester partners are of key importance to achieving successful reaction, which is not immediately intuitive, when considering the mechanism proceeding via a TBD N-acyl intermediate.