Isolation and Characterization of Process Related Substances of an Antipsychotic Drug: Iloperidone

摘要

Seven unknown recurring impurities were isolated during the synthesis of Iloperidone process. All six impurities were subsequently synthesized and characterized by FTIR, MS and NMR spectral data. The structures of impurities were confirmed as 1 -[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (4), 1-[4-(3-hydroxypropoxy)-3-methoxy phenyl]ethanone (7), 1-[4-(3-bromopropoxy)-3-methoxyphenyl] ethanone (9), 14'-[4,4'-(propane-13-diylbis(oxy))bis(3-memoxy-4,1-phenylene)]diethanone (10), 1-[3-(4-acetyl-2-methoxyphenoxy)-propyl]-4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine-l-oxide (11) and in final other two impurities 1-(4-hydroxy-3-methoxyphenyl)-ethanpne (2) and 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (5). The present work describes the formation, synthesis and characterization of these impurities.