|Inventors||Manne Satyanarayana Reddy, Muppa Kishore Kumar, Srinivasan Thirumalai Rajan,Durgadas Shyla Prasad,|
|Original Assignee||Msn Laboratories Limited|
- The EP patent 457559 uses alkali metal hydride like sodium hydride in the preparation of duloxetine, which is commercially not recommended.
- Duloxetine hydrochloride prepared as per the prior art process having high level of impurities like DU-I and R-isomer of duloxetine hydrochloride.
- The U.S. Pat. No. 5,362,886 describes the process for the preparation of (+) Duloxetine hydrochloride by isolating the (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2 thienyl)propanamine as phosphoric acid salt leads to one more step and preparation of hydrochloride salt of Duloxetine using aqueous hydrochloric acid and ethyl acetate as a solvent leads to degradation of the obtained compound as shown below.
- Before Purification: MR: 113-115° C.; SOR: (+) 31° (C=1; Methanol) Corresponding derivative of R-isomer by Chiral HPLC: 7.0%
- After Purification: MR: 121-124° C.; SOR: (+) 33° (C=1; Methanol) Corresponding derivative of R-isomer by Chiral HPLC: Nil
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US5023269||27 Mar 1990||11 Jun 1991||Eli Lilly And Company||3-aryloxy-3-substituted propanamines|
|US5362886||12 Oct 1993||8 Nov 1994||Eli Lilly And Company||Asymmetric synthesis|
|US5491243||18 Jul 1994||13 Feb 1996||Eli Lilly And Company||Intermediate useful for the asymmetric synthesis of duloxetine|
|US20050197503||16 Feb 2005||8 Sep 2005||Boehringer Ingelheim International Gmbh||Process for the preparation of N-alkyl-N-methyl-3-hydroxy-3-(2-thienyl)-propylamines|
|US20080015363 *||21 Feb 2007||17 Jan 2008||Santiago Ini||Process for the preparation of (S)-(-)-N,N-dimethyl-3-(2-thienyl)-3-hydroxypropananine, a duloxetine intermediate|
|EP0273658B1||18 Dec 1987||31 Oct 1990||Eli Lilly And Company||3-aryloxy-3-substituted propanamines|
|EP0457559A2||15 May 1991||21 Nov 1991||Eli Lilly And Company||Chiral synthesis of 1-aryl-3-aminopropan-1-ols|
|EP0650965B1||7 Oct 1994||7 Feb 2001||Eli Lilly And Company||Asymmetric synthesis of (S)-(+)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine an intermediate in the preparation of duloxetine|
|WO2006099433A1||14 Mar 2006||21 Sep 2006||Teva Pharmaceutical Industries Ltd.||Pure duloxetine hydrochloride|
|1||*||English translation of Gao et al. (Chinese Journal of New Drugs, vol. 14, No. 1, pp. 74-76). Translated by Schreiber Translations, Inc in Mar. 2012.|
|2||*||Gao et al. (Chinese Journal of New Drugs, vol. 14, No. 1, pp. 74-76).|
|3||*||Gao et al. (Chinese Journal of New Drugs, vol. 14, No. 1, pp. 74-76, 2005).|
|4||Luo, G., et al. "An Improved Synthesis Method of Antidepressant Drug Duloxetine Hydrochloride. Yaouxue J." (2006), 30(4), 181-184, Columbus Ohio, USA: Chemical Abstracts vol. 146, Jun. 21, 2006, the abstract No. 592369.|
|5||PCT Written Opinion of the International Searching Authority from PCT/IN2007/000003, Dated: Mar. 3, 2008.|