The split into tranche 1 and tranche 2 of the LEF expansion was retained from the previous publication and used in our analysis. Typically, models were trained on the LEF4000 and then used to predict tranche 2. Tranche 1 was occasionally used to augment the training set and expose models to a part of the chemical space that the expansion to the LEF5500 had explored. Of the approximately 300 CF2 containing molecules in the LEF5500 all that had not been part of the LEF4000 before the expansion were added to tranche 2 to perform time-split experiments on these motifs as well. We maintained the split of Enamine data into the FDS-1000 and the FFL-d6 as a train/test split and all overlapping molecules were added to the FDS-1000, the training set.