Preparation of tritium-labeled PF-622, a novel fatty acid amide hydrolase inhibitor.

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.