Synthesis of [2H5]baricitinib via [2H5]ethanesulfonyl chloride

Baricitinib, typically applied as a treatment for rheumatoid arthritis, has recently attracted the attention of clinicians and researchers as a potential treatment for COVID-19. Naturally, there has been a need for the preparation of the isotope-labelled analogue of baricitinib to probe the pharmacokinetics of baricitinib in this new role. As such, we have developed a simple synthetic route to deuterated [2H5]baricitinib, facilitating its formation over 4 steps and in a 29% overall yield based on starting [2H5]ethanethiol (19% if we start with [2H5]bromoethane instead). A critical component of the overall process involves the synthesis of [2H5]ethanesulfonyl chloride and we describe in detail the two routes that were explored to optimize this step.
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: PRACTITIONER PROTOCOL ‐ SYNTHESIS Source Type: research