as activated acid, it already encapsulates acid information, making the amine + acid + intermediate descriptors redundant. Consequently, the more precise amine + intermediate descriptors yield better results by avoiding redundant information and focusing on the critical reaction components. To ensure data consistency, we performed 5-fold cross-validation on the randomly split test datasets, as detailed in Section 3.9 of the SI. However, due to constraints with our dataset, this validation approach could not be applied to test sets with partial or full substrate novelty, which were split only once, but only the random split test dataset.