Syntheses of dual‐radioisotope‐labeled CP‐I, a GABA A receptor partial agonist

CP‐I is a potent subtype‐selective GABA A receptor partial agonist. Owing to its significant metabolic cleavage at C 8 observed in preliminary biotransformation studies with non‐radiolabeled CP‐I, the syntheses of CP‐I labeled at the right or left hand side with 14 C or labeled with 3H at the right hand side were required. The two compounds labeled with 14 C at the left or right hand side were synthesized in 2 and 5 radio‐synthetic steps using [ 14 C]2‐chloroacetyl chloride and [ 14 C]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 [ 14 C]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.