Synthesis of Carbon‐13 and Carbon‐14 Labeled BI 690517 (Vicadrostat) and Its O ‐Glucuronide Metabolite BI 689875

Vicadrostat, also known as BI 690517 (1) is a novel, potent, and selective aldosterone synthase CYP11B2 inhibitor being developed in combination with empagliflozin to slow the progression of kidney damage and reduce cardiovascular events in people with chronic kidney diseases (CDK). The stable isotope labeled BI 690517 was obtained in a 12-step synthesis starting from aniline-13C6. The product was isolated with high chemical purity and enantiomeric excess. Carbon-14 labeled BI 690517 was prepared in one radioactive step from a chiral iodo-analog BI 764437 and zinc cyanide-14C. 14C-1 was obtained with a specific activity of 55.6 mCi/mmol (2.05 GBq/mmol), chemical and radiochemical purities higher than 98%, and with enantiomeric excess higher than 99%. Vicadrostat undergoes extensive hepatic glucuronidation to form the O-glucuronide BI 689875 (2). Both carbon-13 and carbon-14 labeled BI 689875 were also synthesized.