A One-Pot Asymmetric Synthesis of a <i>N</i>‑Acylated 4,5-Dihydropyrazole, A Key Intermediate of Thrombin Inhibitor AZD8165

A short, chromatography-free, and scalable synthetic route to thrombin inhibitor <b>1</b>, the active metabolite of the propionic ester prodrug <b>AZD8165</b>, has been developed. The key synthetic step involved cycloaddition of TMS–diazomethane and ethyl acrylate to give an intermediate racemic dihydropyrazole which was reacted with enantiomerically pure 4-fluoro mandelic acid chloride in a one-pot dynamic kinetic resolution (DKR) process