The syntheses and in vitro biotransformation studies of [ 14 C]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. [ 14 C]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 [ 14 C]apixaban, 10 , with the label in the central lactam ring was completed in 14% overall yield. A second synthesis of [ 14 C]apixaban, 14 , with the 14C 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 , [ 14 C]apixaban, from both rat and human hepatocyte or microsomal incubations. Copyright © 2011 John Wiley & Sons, Ltd.