Efficient syntheses of dual radioisotope-labelled PF-00217830, a D 2 -partial agonist for the treatment of schizophrenia disorder

PF-00217830 is a D-2-partial agonist developed for the treatment of schizophrenia. The dual C-14/C-14 and C-14/H-3-labelled PF-00217830 were required for animal and human absorption, distribution, metabolism and elimination (ADME) studies. This report describes the development of the syntheses of dual C-14/C-14- and dual C-14/H-3-labelled PF-00217830. [C-14]PF-00217830-L labelled at the naphthalene ring was prepared in three steps starting with [C-14] naphthalene, while [H-3]PF-00217830-R was synthesised by Pd-catalysed tritium de-bromination of brominated PF-00217830 in a single radiosynthetic step. The dual [C-14/H-3]PF-00217830 was made by mixing 1:10 radioactivity ratio of [C-14] PF-00217830-L and [H-3]PF-00217830-R. The chemistry for [C-14] PF-00217830-R labelled at the pyridine ring was also described.