Synthesis of stable isotope labeled anacetrapib, its major metabolites and [14C]anacetrapib

Cholesteryl ester transfer protein inhibitors are an important class of compounds designed to treat hypocholesterolemia and prevent cardiovascular disease. Anacetrapib (MK‐0859) is currently in phase III trials for the treatment of elevated cholesterol levels and prevention of cardiovascular disease. In order to further support the development of anacetrapib, we prepared [M + 6]MK‐0859, which was required in support of an absolute bioavailability study of the active pharmaceutical ingredient (API). Additional support included the synthesis of an internal standard [M + 13] and three stable isotope labeled metabolites, which were used to analyze clinical samples, and [14C]MK‐0859 to support drug metabolism studies. A labeling strategy for the preparation of [M + 6], [M + 13], and [14C]anacetrapib is described. The preparation of stable isotope labelled metabolites of anacetrapib is also described.