To demonstrate the applicability of our methodology, we scaled up the reaction using 1a, 1d, and 1c as model substrates. With industrial applications in mind, we selected to run this reaction under solvent-free conditions affording 67% isolated yield (Figure .a.). Moreover, as the costs of large scale columns are prohibitive, we opted to recrystallize the product, which is facilitated by the solvent-free conditions in this reaction set-up. Next, we aimed to apply this methodology in late-stage functionalization to create a specific structural core found in a wide variety of biological active molecules. Namely, we constructed in a single step the amidine core of a glibenclamide-derivative, which is a very commonly prescribed diabetes medication. The ketone and amine components were commercially available, and we synthesized the required sulfonyl azide in three steps (See SI section 3.8 for details). We then submitted the three components to our standard reaction conditions to afford the desired product 7 in 52% isolated yield (Figure .b.). In summary, we have developed a novel methodology for the synthesis of sulfonyl amidines from readily available starting materials in a metal-free one-pot reaction. These reaction conditions afford a broad substrate scope and functional group tolerance. Studies focused on intercepting reaction intermediates and submitting them to our reaction conditions provide insights on the reaction mechanism, which are further supported by Hammett analysis and multivariate linear regression models. Moreover, this mechanistic analysis led to the discovery of a highly regioselective amidination of aliphatic ketones. The one-step, multicomponent synthesis of a bioactive glibenclamide derivative demonstrated the efficacy of this methodology in drug development.