In medicinal chemistry, the modular synthesis of novel drug candidates can be carried out using building blocks, functionalized chemical reagents typically selected for their drug-like properties. Aromatic and heteroaromatic fragments are typically functionalized by one or multiple halogen atoms, enabling an array of cross-coupling reactions to be performed. Computed carbon-halogen BDE values have been used to predict the relative rates of oxidative addition by a Pd-catalyst, enabling siteselectivities in the Suzuki cross-couplings of polyhalogenated aromatics to be predicted. The general ability to accurately predict C-X BDE values for singly-and multiply-halogenated (hetero)aromatics with ML is thus desirable from the perspective of synthesis planning and reaction prediction. We thus focused on commercially available building block libraries for medicinal chemistry developed by Enamine. We tested our newly developed model (herein model 1) on halogenated compounds from the Enamine database: For this dataset, we found relatively large errors for the weakest bonds (BDE values under 80 kcal mol -1 ). These correspond to dissociation at multiply halogenated carbons, which yield resonancestabilized radicals and hence smaller BDE values (Fig. ).