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WO2009077551A1 - Procédé de préparation de la rispéridone - Google Patents

Procédé de préparation de la rispéridone Download PDF

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Publication number
WO2009077551A1
WO2009077551A1 PCT/EP2008/067691 EP2008067691W WO2009077551A1 WO 2009077551 A1 WO2009077551 A1 WO 2009077551A1 EP 2008067691 W EP2008067691 W EP 2008067691W WO 2009077551 A1 WO2009077551 A1 WO 2009077551A1
Authority
WO
WIPO (PCT)
Prior art keywords
risperidone
temperature
formula
water
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2008/067691
Other languages
English (en)
Inventor
Ronny Vanierschot
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Janssen Pharmaceutica NV
Original Assignee
Janssen Pharmaceutica NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Janssen Pharmaceutica NV filed Critical Janssen Pharmaceutica NV
Publication of WO2009077551A1 publication Critical patent/WO2009077551A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention concerns an improved process of preparing risperidone (I).
  • Risperidone (I) may be prepared by a variety of processes.
  • EP-0, 196, 132 discloses the preparation of risperidone (I) byN-alkylation of a piperidine intermediate of formula (II) with an alkylating agent of formula (III).
  • risperidone (I) is prepared by an intramolecular aromatic substitution reaction of a compound of formula (IV) in the presence of a base in a solvent mixture of toluene and water.
  • This strained aminal compound (V) was hard to purify and isolate as a solid. Presumably the compound (V) hydrolysed to an aldehyde (VI) which could decompose into a variety of other contaminants.
  • the invention is therefore concerned with a process for preparing risperidone of formula (I) -A-
  • the reaction can conveniently be conducted in stainless steel or enamel or glass- lined equipment provided that the oxygen concentration is constantly maintained above 0.1 %.
  • the remainder of the atmosphere may be either argon or nitrogen or any mixture thereof.
  • the oxygen concentration is preferably from 1 % to 8 %.
  • the conversion reaction of compound (IV) is preferably conducted at a temperature above 80 0 C for 4 to 5 hours.
  • Suitable bases in the reaction are alkali metal hydroxides, preferably potassium hydroxide (KOH).
  • the process comprises the steps of a) charging a reaction vessel with toluene and KOH; b) adding water to the suspension obtained in a) while keeping the temperature between 30 and 40 °C; c) adjusting the concentration of oxygen in the atmosphere of the reaction vessel to between 1 and 8 %; d) adding an intermediate of formula (IV) while keeping the temperature above 30 0 C; e) heating the reaction mixture to a temperature above 80 0 C for 4 to 5 hours; f) diluting the reaction mixture with water at a temperature of 80 0 C; g) separating the water phase; h) extracting the organic layer three times with water at a temperature of 80 0 C; i) cooling the organic layer to a temperature between 0 and 10 0 C while stirring for
  • Risperidone (I) prepared according to the above process does not contain the contaminant product (V) and thus is useful for the preparation of drug product such as risperi- done long acting injection.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

La présente invention concerne un procédé perfectionné de préparation de la rispéridone (I).
PCT/EP2008/067691 2007-12-18 2008-12-17 Procédé de préparation de la rispéridone Ceased WO2009077551A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP2007064137 2007-12-18
EPPCT/EP2007/064137 2007-12-18

Publications (1)

Publication Number Publication Date
WO2009077551A1 true WO2009077551A1 (fr) 2009-06-25

Family

ID=39495548

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/067691 Ceased WO2009077551A1 (fr) 2007-12-18 2008-12-17 Procédé de préparation de la rispéridone

Country Status (1)

Country Link
WO (1) WO2009077551A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102206210A (zh) * 2011-04-01 2011-10-05 常州市第四制药厂有限公司 一种6-氟-3-(4-哌啶基)-1，2-苯并异噁唑盐酸盐的生产方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2006888A6 (es) * 1988-04-08 1989-05-16 Janssen Pharmaceutica Nv Nuevo procedimiento para preparar 3-piperidinil-1, 2-benzoisoxazoles.
EP0453042A1 (fr) * 1990-04-19 1991-10-23 Janssen Pharmaceutica N.V. 4H-pyrido-(1,2-a)pyrimidin-4-ones substituées sur les positiones 2 et 9
WO2004009591A1 (fr) * 2002-07-22 2004-01-29 Aurobindo Pharma Ltd. Procede de preparation de risperidone antipsychotique
US20040097523A1 (en) * 2002-11-13 2004-05-20 Pavel Slanina Process for making risperidone and intermediates therefor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2006888A6 (es) * 1988-04-08 1989-05-16 Janssen Pharmaceutica Nv Nuevo procedimiento para preparar 3-piperidinil-1, 2-benzoisoxazoles.
EP0453042A1 (fr) * 1990-04-19 1991-10-23 Janssen Pharmaceutica N.V. 4H-pyrido-(1,2-a)pyrimidin-4-ones substituées sur les positiones 2 et 9
WO2004009591A1 (fr) * 2002-07-22 2004-01-29 Aurobindo Pharma Ltd. Procede de preparation de risperidone antipsychotique
US20040097523A1 (en) * 2002-11-13 2004-05-20 Pavel Slanina Process for making risperidone and intermediates therefor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TOMAR R S ET AL: "Identification and characterization of major degradation products of risperidone in bulk drug and pharmaceutical dosage forms", JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, NEW YORK, NY, US, vol. 36, no. 1, 21 September 2004 (2004-09-21), pages 231 - 235, XP004553458, ISSN: 0731-7085 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102206210A (zh) * 2011-04-01 2011-10-05 常州市第四制药厂有限公司 一种6-氟-3-(4-哌啶基)-1，2-苯并异噁唑盐酸盐的生产方法
CN102206210B (zh) * 2011-04-01 2014-07-02 常州市第四制药厂有限公司 一种6-氟-3-(4-哌啶基)-1，2-苯并异噁唑盐酸盐的生产方法

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