Protein-ligand crystallography is widely used to drive advanced stages of drug optimization or to generate starting points for medicinal chemistry by fragment soaking. However, recent progress in protein crystallography could allow for a more integrated role of protein crystallography into the early drug discovery cycle. Here we demonstrate for the first time the interplay of high throughput synthesis and high throughput crystallography. For this we describe a practical multicomponent reaction approach to high diversity acrylamides and esters from diverse building blocks. Surprisingly, in the majority of acrylamides precipitation during the reaction was observed, making library synthesis on a mmol scale and a 96-well format particularly comfortable. The synthesis is also suitable for a high throughput nanoscale format in a highly automated fashion. Moreover, we exemplified the synthesis on a multigram scale featuring good yield and simple work-up. High throughput crystallography of our libraires yielded potent covalent inhibitors of the main protease of the COVID-19 causing agent SARS-CoV-2 in a time efficient manner. Our results demonstrate, that the marriage of in situ HT synthesis of (covalent) libraires and HT crystallography has the potential to accelerate hit finding and to provide meaningful strategies for medicinal chemistry projects.