Efficient syntheses of isotopically labeled PD0198961, a novel synthetic coagulation factor Xa inhibitor

✍ Scribed by Yinsheng Zhang

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: French
• Weight: 140 KB
• Volume: 52
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1595

✦ Synopsis

Abstract

PD0198961 was investigated as a potent and selective inhibitor of coagulation factor Xa for the treatment of thrombotic disorders. Radioactive and stable isotope‐labeled PD0198961 were synthesized for absorption, distribution, metabolism and elimination studies of the compound in animals and for use as mass spectral internal standards in support of bioanalytical assays, respectively. [^14^C]PD0198961 was prepared from [^14^C]CuCN in four radiosynthetic steps in an overall yield of 48% with a radiochemical purity of >99%. The cyanation reaction of an aromatic bromide with inorganic [^14^C]cyanide as a key radiolabeling step was investigated. The deuterium‐labeling was accomplished in a different reaction sequence from the ^14^C labeling. This convergent process introduced stable isotope labeling via cis‐2,6‐dimethyl[^2^H~5~]piperidine, which was synthesized by catalytic hydrogenation of 2,6‐dimethylpyridine with deuterium gas. Copyright © 2009 John Wiley & Sons, Ltd.