Potential metabolites of the neuroleptic agent octoclothepin; Synthesis of 8-chloro-2,6-dihydroxy and 8-chloro-3,6-dihydroxy derivatives of 10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepin

Abstract

[2-(4-Chloro-2-methoxyphenylthio)-5-methoxyphenyl]acetic acid (V) and [2-(4-chloro-2-methoxyphenylthio)-4-methoxyphenyl]acetic acid (XVII) were synthesized and cyclized to 8-chloro-2,6-dimethoxy (VII) and 8-chloro-3,6-dimethoxydibenzo[b,f]thiepin-10(11H)-one (XVIII). Two further steps afforded dichlorodimethoxy derivatives XI and XXII which reacted with 1-methylpiperazine and gave the 8-chloro-2,6-dimethoxy (II) and 8-chloro-3,6-dimethoxy derivative of 10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepin (IV). Demethylations with boron tribromide resulted in the title compounds I and III being new potential metabolites of the neuroleptic agent octoclothepin.