Having established the workflow, we sought to additionally validate the workflow using two molecules of synthetic interest: P300, a delta opioid agonist precursor (42-43) (Fig. ), and P301, an indoline precursor (44-46) (Fig. ). P300 can be accessed through the coupling of an unhindered aryl-bromide with a highly nucleophilic primary amine. This combination is predicted to yield above 20%, with a confidence level of 66% (equivalent to ~12 out of 18 ligands expected to yield the predicted results). The experimental outcomes demonstrated an alignment with the predictions, with precisely 12 out of the 18 tested ligands yielding the anticipated results surpassing 20%. Upon examining the top-performing ligands from the two nearest neighbors, we found that all six suggested ligands (L26, L28, L30, L33, L35, and L36, indicated by the asterisk symbol in Fig. ) yielded the anticipated results, with L36 being the topperformer for P300. This underscores the effectiveness of the workflow and highlights the feasibility of streamlining synthetic efforts to the targeted selection of only six recommended ligands based on the two nearest neighbors in chemical space.