Premium
Synthesis of 3 H‐ and 14 C‐labelled CP‐88,059: A potent atypical antipsychotic agent
Author(s) -
Howard Harry R.,
Shenk Kevin D.,
Smolarek Teresa A.,
Marx Michael H.,
Windels James H.,
Roth Robert W.
Publication year - 1994
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580340203
Subject(s) - chemistry , medicinal chemistry , bicyclic molecule , acylation , stereochemistry , moiety , catalysis , organic chemistry
The syntheses of 3 H‐ and 14 C‐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 D 2 /5‐HT 2 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/BaSO 4 catalysis, provided 3 H‐CP‐88,059 ( 5c ). Incorporation of 14 C into the ethylene portion of the molecule was achieved via the Friedel‐Crafts acylation of 6‐chlorooxindole with [2‐ 14 C]‐chloroacetyl chloride, followed by triethylsilane reduction of the aryl carbonyl and coupling with N‐(1,2‐benzisothiazol‐3‐yl)piperazine in refluxing aqueous Na 2 CO 3 .