Innovation in synthetic organic chemistry is of fundamental importance to the improvement of the drug discovery process. While the field has seen tremendous developments over the past century, recent advances in synthetic methods, chemoinformatics, and increasing applicability of automation and miniaturization in synthesis have the potential to further transform and improve modern drug discovery. Two particular technological and synthetic approaches stand at the forefront of our interest and focus in this work: high-throughput experimentation (HTE), and C-H functionalization. HTE techniques attracted significant interest from the pharmaceutical industry, and are now increasingly utilized in the drug discovery process. From the methodology development perspective the advantages are clear: access to more high-quality and well-rounded results with decreased material and time cost associated. Adding to this is the importance large, high quality datasets for the generation of predictive reactivity models. At the same time, reaction miniaturization allows for more sustainable chemistry by means of decreased material consumption, including reagents, solvents, and especially high-value advanced intermediates and catalysts. Finally, technologies such as automated liquid and solid dispensing allow chemists to avoid repetitive non-intellectual tasks, while providing high reproducibility and evading the risk for human error in setting up large arrays. Given the abundance of C-H bonds in drugs and their building blocks, C-H functionalizations are among the most desirable transformations in drug discovery. Of particular interest are late-stage functionalizations (LSF), where the controlled chemoselective transformation of desired C-H bonds in complex drug-like molecules has the potential to greatly aid the hit-to-lead and lead-optimization processes. Bypassing the need for time, material and labor intensive de novo synthesis of analogues would greatly aid structure-activity relation (SAR) studies, or even the generation of new candidate drugs. In terms of desirable transformations, the introduction of small functional groups like -CH3, -CF3, -NH2, -OH and -F are of highest priority, and would be widely used in the industry. Further motivating the development of new amination methodologies, a recent analysis of X-ray structural data identified N-H hydrogen bond donors on aromatic and aliphatic amines as the most common polar functional groups involved in fragment-protein binding (For examples of anilines see Figure , a). Directed C-H activations offer a means of introducing amine moieties in the vicinity of Lewis basic groups commonly present in drug-like molecules with high regioselectivity. Over the past decade a number of methodologies for C(sp 2 ) -H to C-N bond transformation have been developed, utilizing among others Co, Rh, Ir and Ru 25-28 catalysts. However, applicability for LSF in a drug discovery context remains challenging. We identified several factors which limit the utility of reported C-H aminations in this respect. Firstly, the inaccessibility of free amines. The majority of reported directed C-H to C-N bond forming reactions, while introducing protected amines in form of amides and sulfonamides, do not include deprotection protocols. Although the introduction of larger substituents can be of utility for fragment-based drug discovery, applications to LSF are of limited use if the free amines cannot be obtained under mild-enough conditions to tolerate a large array of reactive and/or sensitive functional groups present in drug-like molecules. Secondly, the limited functional group tolerance. A common shortcoming of the reported procedures is a lack of compatibility with polar functional groups commonly present in drug-like molecules, such as heterocycles, alcohols, amines, carboxylic acids or amides (practical examples in Figure ). The third limitation is closely related to this, and it is the lack of reporting of unsuccessful transformations and limited number of reports on applicability to complex substrates. This situation would be largely mitigated by full disclosure of the investigated substrate scope. Aside from this, two distinct approaches have been recently developed to improve the predictability of chemical methods in a more systematic fashion; the intermolecular robustness screening approach developed by the Glorius group, and the chemistry informer library approach by Krska and coworkers. The intermolecular robustness screening approach evaluates the compatibility of additives bearing a wide variety of functional groups with the transformation of a single substrate. In the informer library approach, the compatibility of a methodology with a large number of complex substrates bearing structural features relevant to pharmaceuticals is evaluated. While the former has been previously used for reported C-H activation methodologies, the latter has so far only been applied to more well established crosscoupling reactions. Herein we report the development of an iridium-catalyzed directed ortho-C-H amination applicable to a large number of directing groups (DGs) with outstanding functional group tolerance and regioselectivity. The use of [Cp*Ir(H2O)3]SO4 catalyst allows for regioselective functionalization governed by DGs inherently present in building blocks, drugs and natural products, without the need for additional ligands. An empirical predictive model based on a DG informer library, functional group tolerance studies and LSF informer library serves to guide potential users in predicting reaction applicability for complex substrates. The obtained Moz-protected amines can be deprotected under three distinct conditions, further increasing the utility of the amination protocol to complex molecules.