The syntheses and in vitro biotransformation studies of [14C]apixaban, a highly potent, selective, efficacious and orally bioavailable inhibitor of blood coagulation Factor Xa

Apixaban is a potent inhibitor of blood coagulation Factor Xa in the late stages of development. [C-14] apixaban was synthesized with the 14C label in the two different lactam ring systems within the molecule for various in vitro and in vivo metabolism studies. A nine-step synthesis of [C-14] apixaban, 10, with the label in the central lactam ring was completed in 14% overall yield. A second synthesis of [C-14] apixaban, 14, with the C-14 label in the outer lactam ring was completed in three steps in a 14% overall yield. No significant differences were observed between the metabolite profiles of 10 and 14, [C-14] apixaban, from both rat and human hepatocyte or microsomal incubations.