Without any search constraints, Chematica generally identified many of these known solutions (or their very close analogs, differing in insignificant details). The program began to find substantially different pathways especially upon application of restrictive thresholds for the prices/popularities of the starting materials. Figure summarizes 17 routes we found most economically viable and concise (see Supplementary Information for enlarged views). In addition to routes relying on nucleophilic aromatic substitution of dichloroquinoline and reductive amination of aminochloroquinoline, the software was able to avoid these steps, replacing them with methodologies such as A3-coupling (path 15), Cu-cat. coupling between heteroaryl iodide and amine (paths 2 and 3), three-component reaction between amine, aldehyde and halide under Barbier-type conditions (path 14), or alkylation of aromatic amine with alkyl iodide (path 11).