Amines and carboxylic acids are abundant chemical feedstocks that are nearly exclusively united via the amide coupling. The disproportionate use of the amide coupling leaves a large section of unexplored reaction space between two of the most common chemical building blocks. Herein we conduct a thorough exploration of amine–acid reaction space via systematic enumeration of reactions involving a simple amine–carboxylic acid pair. This approach to chemical space exploration investigates the coarse and fine modulation of physicochemical properties and molecular shapes. While the invention of reaction methods becomes increasingly automated bringing conceptual reactions into reality, our map will provide an entirely new axis of chemical space exploration for rational property design.