Synthesis of 3H- and 14C-labelled CP-88,059: A potent atypical antipsychotic agent

Article abstract of DOI:10.1002/jlcr.2580340203

The syntheses of ³H- and ¹⁴C-labelled CP-88,059 [i.e., 5-(2-(4-(1,2-benzisothiazol-3-yl)piperazinyl)ethyl)-6-chloro-1, 3-dihydro-2H-indol-2-one] are described. CP-88,059 (5b) is a combined D₂/5-HT₂ antagonist currently undergoing clinical evaluation as an antipsychotic agent with reduced potential for induction of EPS in schizophrenic patients. Displacement of bromine from the 7-position of the benzisothiazole moiety, by reductive dehydrogenation with tritium gas and Pd/BaSO₄ catalysis, provided ³H-CP-88,059 (5c). Incorporation of ¹⁴C into the ethylene portion of the molecule was achieved via the Friedel-Crafts acylation of 6-chlorooxindole with [2-¹⁴C]-chloroacetyl chloride, followed by triethylsilane reduction of the aryl carbonyl and coupling with N-(1,2-benzisothiazol-3-yl)piperazine in refluxing aqueous Na₂CO₃.