Synthesis of [ 2 H 5 ]baricitinib via [ 2 H 5 ]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 [ 2 H 5 ]baricitinib, facilitating its formation over four steps and in a 29% overall yield based on starting [ 2 H 5 ]ethanethiol (19% if we start with [ 2 H 5 ]bromoethane instead). A critical component of the overall process involves the synthesis of [ 2 H 5 ]ethanesulfonyl chloride, and we describe in detail the two routes that were explored to optimize this step.