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

Recently, baricitinib has attracted interest for its potential role as a therapeutic agent in the treatment of COVID-19, creating a need to develop a synthetic route to its deuterium-labelled analogue for use as a mass spectrum internal standard, since the isotopologue is typically somewhat costly. This paper presents a new synthetic route to [2H5]baricitinib from [2H5]ethanesulfonyl chloride. Since the preparation and isolation of [2H5]ethanesulfonyl chloride form a major challenge, these comprise a large focus of the overall work. 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 four 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 - March 25, 2022 Category: Biochemistry Authors: Ross D. Jansen ‐van Vuuren, Rahul Vohra Tags: PRACTITIONER PROTOCOL ‐ SYNTHESIS Source Type: research