An ultra-large virtual chemical space containing approximately 10 billion compounds was constructed from 180,576 unique building blocks and 56 two-component reactions. The building blocks were obtained from the Enamine BB US Stock catalog in ZINC20, which originally contained 232,739 entries. After standardization and removal of duplicates, a final set of 180,576 unique building blocks was obtained. The 56 two-component reactions were employed from the work of Hartenfeller et al. with minor modifications to the reaction SMARTS strings to ensure compatibility with SpaceLight 49 for similarity searching (see below). The chemical space was precisely defined as the set of all possible compounds that could be generated by combining any two of the 180,576 building blocks using any one of the 56 reactions.