Respiratory diseases such as asthma and chronic obstructive pulmonary disorder (COPD) are highly prevalent and affect millions of people all over the world. Several research programs are still in progress, and these days, clarified that β2-adrenergic receptor agonists exhibit modest biological activity. Chiral β-amino-α-hydroxy quinolinone moiety is one of the platforms for the most common β2 adrenergic receptor agonists, including Carmoterol, Indacaterol, and Abediterol. The modification of the quinolinone derivatives led to the synthesis of several highly biologically active derivatives, including GSK961081, a combination of a β2-adrenergic receptor and a muscarinic receptor antagonist. In order to continue creating new drug candidates, the efficient and scalable synthetic method of versatile intermediate such as (R)-5 becomes essential. Whereas the majority of reported synthetic methods enabled the preparation of the corresponding bioactive compounds in high yield, these methods experienced a stoichiometric explosive reagent and/or concomitant byproducts, and consequently, there is still a room for the improvement to safely prepare the useful intermediate (R)-5 with excellent purity. We herein wish to report an alternative synthetic route of (R)-5 using Ms-DENEB®, a novel ruthenium catalyst developed by Takasago International Corporation. Our new approach is advantageous in its preparation of (R)-5 with excellent purity in safe, ecofriendly and robust aspect.

Process development for β2 adrenergic receptor agonist moiety via ruthenium-catalyzed asymmetric reduction

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.