2) Determination of tolerated functional groups. This is aided by the functional group tolerance study and LSF scope. The major limitations in this respect are presence of amines, alkynes, thioureas, and residual DMSO. The DMSO sensitivity is important to consider in medicinal chemistry applications, as intermediates are often stored as DMSO solutions and residual solvent can be present after evaporation. 3) Steric effects on the substrate should be examined in order to determine selectivity and/or productivity. Based on the observed results, the reaction proceeds on the less sterically hindered ortho position when two suitable reaction sites are available. Meta substitution with sterically demanding substituents blocks 1,2,3-substitution. Substituents on the directing group and in the ortho position of the system to be functionalized can negatively affect the reaction outcome by twisting the directing group out of plane. 4) Reaction solvent is chosen based on desired application. While DCE showed best overall performance, substitution by EtOAc and CPME is possible if the use of a greener solvent is desired. The use of NMP is ideal for applications in miniaturization, as well as for applications with polar drug-like molecules displaying low solubility in DCE.