Copyright (c) 2013 AJC
This work is licensed under a Creative Commons Attribution 4.0 International License.
Isolation and Characterization of Process Related Substances of an Antipsychotic Drug: Iloperidone
Corresponding Author(s) : Ravendra Babu Kilaru
Asian Journal of Chemistry,
Vol. 25 No. 10 (2013): Vol 25 Issue 10
Abstract
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), 1,1'-[4,4'-(propane-1,3- diylbis(oxy))bis(3-methoxy-4,1-phenylene)]diethanone (10), 1-[3-(4-acetyl-2-methoxyphenoxy)-propyl]-4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine-1-oxide (11) and in final other two impurities 1-(4-hydroxy-3-methoxyphenyl)-ethanone (2) and 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (5). The present work describes the formation, synthesis and characterization of these impurities.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- H.O. Kalkman, D. Feuerbach, E. Lötscher and P. Schoeffter, Life Sci., 73, 1151 (2003).
- L.J. Scott, CNS Drugs, 23, 867 (2009).
- J.T. Strupczewski, K.J. Bordeau, Y. Chiang, E.J. Glamkowski, P.G. Conway, R. Corbett, H.B. Hartman, M.R. Szewczak, C.A. Wilmot and G.C. Helsley, J. Med. Chem., 38, 1119 (1995).
- V. Miklos, WO Patent 031497 (2010).
- J.T. Strupczewski, EP Patent 0402644 (1990).
- J.A. Dodge, M.G. Stocksdale, K.J. Fahey and C.D. Jones, J. Org. Chem., 60, 739 (1995).
- J.T. Strupczewski, EP Patent 0542136 (1992).
- International Conference on Harmonization guidelines Q3A (R) Impurities in New Drug Substances February, this guideline provides guidance for registration application on the content and qualification of impurities in new drug substances produced by the chemical synthesis (2002).
- International Conference on Harmonization guidelines Q3B (R) Impurities in New Drug Substances February, Guidance for registration or marketing application on the content and qualification of impurities in new drug product (2002).
References
H.O. Kalkman, D. Feuerbach, E. Lötscher and P. Schoeffter, Life Sci., 73, 1151 (2003).
L.J. Scott, CNS Drugs, 23, 867 (2009).
J.T. Strupczewski, K.J. Bordeau, Y. Chiang, E.J. Glamkowski, P.G. Conway, R. Corbett, H.B. Hartman, M.R. Szewczak, C.A. Wilmot and G.C. Helsley, J. Med. Chem., 38, 1119 (1995).
V. Miklos, WO Patent 031497 (2010).
J.T. Strupczewski, EP Patent 0402644 (1990).
J.A. Dodge, M.G. Stocksdale, K.J. Fahey and C.D. Jones, J. Org. Chem., 60, 739 (1995).
J.T. Strupczewski, EP Patent 0542136 (1992).
International Conference on Harmonization guidelines Q3A (R) Impurities in New Drug Substances February, this guideline provides guidance for registration application on the content and qualification of impurities in new drug substances produced by the chemical synthesis (2002).
International Conference on Harmonization guidelines Q3B (R) Impurities in New Drug Substances February, Guidance for registration or marketing application on the content and qualification of impurities in new drug product (2002).