Figure compiles possible outcomes of the predictions made by RegioSQM. Firstly, compounds 3, 4, 6, 11, and 12 are examples where only a single position is proposed at 1 kcal/mol leading to correct predictions (this applies to ca. 400 compounds in the dataset). Similarly there are ca. 40 cases including 5 with two proposed sites at 1 kcal/mol and where the corresponding bis-halogenated products were obtained. The incorrect prediction for 7 may reflect sterical hindrance due to tert-butyl-diphenylsilyl group or be a consequence of deprotonation of indazole under the somewhat unusual basic reaction conditions (KO t Bu/N-chlorosuccinimide (NCS)). The corresponding tert-butyl-dimethylsilyl analog 8 illustrates that the 3-position of this ring system is also a reactive site. Furthermore, chlorination and nitration of 6-hydroxy-indazole occur at the 7-position in agreement with the predictions. Steric effects may also explain the experimental data for 9 and 10. Conversely, it is difficult to rationalize the regioselectivity for 13 although a directing effect of the primary alcohol cannot be ruled out. Imidazole 12 is to react with NCS at the 4-position in agreement with the predictions. However, bromination of the same substrate with Br 2 has been reported to occur at the 2-postions of the imidazole ring. RegioSQM is also applicable to Molander's potassium trifluoroborates as illustrated for 14. Broad functional group compatibility (Figure ) is important when considering the potential of using halogen substituents not only as chemical handles for further derivatization but also as orthogonal protective groups in complex molecule synthesis. With the ability to predict the regiochemical outcome of EAS chemistry chemists could focus on synthesis of key scaffolds from which substituents could be installed as late as possible, for example in the context of exploring Structure-Activity-Relationships (SAR) or to support large scale preparation of one of more analogs from a common late-stage intermediate.