Efficient Syntheses of Dual Radioisotope-Labelled PF-00217830,a D 2 -Partial Agonist for the Treatment of Schizophrenia Disorder

PF-00217830 is a D₂-partial agonist developed for the treatment of schizophrenia. The dual ¹⁴C/¹⁴C and ¹⁴C/³H-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 ¹⁴C/¹⁴C- and dual ¹⁴C/³H-labelled PF-00217830. [¹⁴C]PF-00217830-L labelled at the naphthalene ring was prepared in three steps starting with [¹⁴C]naphthalene, while [³H]PF-00217830-R was synthesised by Pd-catalysed tritium de-bromination of brominated PF-00217830 in a single radiosynthetic step. The dual [¹⁴C/³H]PF-00217830 was made by mixing 1:10 radioactivity ratio of [¹⁴C]PF-00217830-L and [³H]PF-00217830-R. The chemistry for [¹⁴C]PF-00217830-R labelled at the pyridine ring was also described.