Synthesis of anti-CMV RPR111423 labeled with carbon-14, deuterium and tritium

RPR111423, 2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-l-carboxamide (CAS Registry Number: 186829-19-6) is a potent, orally active anti-CMV compound under investigation as a potential therapeutic agent for the treatment of cytomegalovirus infections. It is a very potent inhibitor of CMV replication in vitro (IC50 in the range of 0.3 to 3 ng/ml). It is 50 to 90,000 times more active than the reference drugs (ganciclovir, cidofovir, foscarnet). C-14, H-3 and H-2 -labeled RPR111423 were required for ADME, protein binding and mass spectometric assay. This paper will present the synthesis of the [C-14], [H-3], and [H-2] of RPR111423 in Scheme 1, 2, and 3.