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To make a detailed characterization of the mechanism of inhibition and selectivity of a novel fatty acid amide hydrolase inhibitor PF-622, 3 tritium isotopomers were prepared. [ H]PF-622a labeled at the piperazine ring B and [ H]PF-622b labeled at both the ring B and phenyl ring A were synthesized via catalytic H(hydrogen)-T(tritium) exchange, utilizing 1 equiv and excess of Crabtree's catalyst, respectively. The preparation of [ H]PF-622c labeled only at the phenyl ring A was achieved via tritiodebromination of the bromide precursor, using Pd(PPh ) as a catalyst. The observations from these tritiation reactions might open a new perspective in the labeling for the targets having a similar moiety.

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. [14C]PD0198961 was prepared from [14C]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 [14C]cyanide as a key radiolabeling step was investigated. The deuterium‐labeling was accomplished in a different reaction sequence from the 14C labeling. This convergent process introduced stable isotope labeling via cis‐2,6‐dimethyl[2H5]piperidine, which was synthesized by catalytic hydrogenation of 2,6‐dimethylpyridine with deuterium gas. Copyright © 2009 John Wiley & Sons, Ltd.

CP‐I is a potent subtype‐selective GABAA receptor partial agonist. Owing to its significant metabolic cleavage at C8 observed in preliminary biotransformation studies with non‐radiolabeled CP‐I, the syntheses of CP‐I labeled at the right or left hand side with 14C or labeled with 3H at the right hand side were required. The two compounds labeled with 14C at the left or right hand side were synthesized in 2 and 5 radio‐synthetic steps using [14C]2‐chloroacetyl chloride and [14C]NaCN as starting radiolabeled materials, respectively. CP‐I was labeled with tritium at the right hand side by a tritium de‐halogenation method. Batches of radiolabeled CP‐I were mixed to give dual‐radioisotope‐labeled CP‐I. An efficient approach to [14C]fluoropyridinyl imidazole was developed, and a short synthesis of iodo‐substituted fluoropyridinyl imidazole was also achieved. The details of these syntheses are discussed. Copyright © 2011 John Wiley & Sons, Ltd.