ZINC database compounds were filtered and clustered exactly as described previously by Coupry and Pogány, 2022, 71 resulting in 1.113B structures distributed across 16.7M clusters. From these, all primary amines, thioureas, thio compounds, terminal alkenes, isocyanates, Michael acceptors and halogens except fluorides, were removed in order to assure the compatibility of the product structures with the limitations of the Buchwald-Hartwig and Suzuki-Miyaura reactions, reducing the set to 872M. One structure was randomly selected from each cluster, which gave 15.6M compounds. ZINC compounds decorated with unprotected functionalities were duplicated for each transformation type, and the copies protected with randomly sampled protective groups of alcohols, carboxylic acids and secondary cyclic aliphatic amines (Table ). The resulting SMILES were checked against the reaction SMARTS for C-N Buchwald-Hartwig and sp 2 -sp 2 , sp 2 -sp 3 Suzuki coupling, and when possible, the ZINC structures were cut using RDKit to afford all the appropriate reactant structures. The employed disconnection SMARTS patterns are shown in Table Molecules failing the final check, were removed.