Fig. 2: Overview of Minisci-type reactions and screening plate.
A General reaction scheme of a Minisci-type alkylation reaction. An alkyl substituent obtained from a radical generator, e.g., through decarboxylation of the carboxylic acid, is introduced to an electron-deficient heterocycle, often a pyridine. Depending on the development scope and applied technology, a variety of oxidants, catalysts, additives and solvents are used. B Schematic overview of the Minisci-type reaction reported by Sutherland et al.16, including the equivalents of the components. C Reaction screening plate used in this study. This setup allows to assess the coupling performance of a molecule of interest with 23 different alkyl carboxylic acids (a–w) that are relevant to medicinal chemistry applications. This configuration enables the evaluation of how well a molecule of interest couples with 23 distinct alkyl carboxylic acids (labeled as a–w), which are pertinent to medicinal chemistry applications. Condition B4 served as a reference reaction, ensuring consistent performance under the applied conditions. On all screening plates, B4 comprised starting material 1 and carboxylic acid e, providing a quality control mechanism for the generated data. If B4 had not yielded the expected outcome, the entire plate would have been reprocessed. The reaction conditions were adjusted to allow miniaturized parallel reaction screening on a nanomolar scale (0.5 μmol). Boc tert-Butyloxycarbonyl, DMSO dimethylsulfoxide.
