[go: up one dir, main page]

WO2004009591A1 - Procede de preparation de risperidone antipsychotique - Google Patents

Procede de preparation de risperidone antipsychotique Download PDF

Info

Publication number
WO2004009591A1
WO2004009591A1 PCT/IN2003/000207 IN0300207W WO2004009591A1 WO 2004009591 A1 WO2004009591 A1 WO 2004009591A1 IN 0300207 W IN0300207 W IN 0300207W WO 2004009591 A1 WO2004009591 A1 WO 2004009591A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
risperidone
methyl
oxime
pyrido
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/IN2003/000207
Other languages
English (en)
Inventor
Sivakumaran Meenakshisunderam
Shankar Rama
Pandit Chetan
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.)
Aurobindo Pharma Ltd
Original Assignee
Aurobindo Pharma Ltd
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 Aurobindo Pharma Ltd filed Critical Aurobindo Pharma Ltd
Priority to AU2003237597A priority Critical patent/AU2003237597A1/en
Publication of WO2004009591A1 publication Critical patent/WO2004009591A1/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

  • Risperidone (Compound I) is an antipsychotic agent belonging to 3-piperidinyl-l-,2- benzisoxazole derivative reported by Janssen Pharmaceutica in US Patent 4,804,663.
  • COMPOUND I The benzisoxazole intermediate (Compound V) required in this route of risperidone synthesis has been prepared in US Patent 4,804,663 and US Patent 5,134,147 by cyclization of 4-(2,4- difluorobenzoyl)piperidine oxime (Compound III) in aqueous sodium hydroxide solution.
  • This approach of preparing risperidone involves number of chemical steps and results in an overall yield of 40%.
  • the aim of the present invention is to provide a method to obtain highly pure risperidone in high yield.
  • the instant invention relates to an industrially advantageous, economic and efficient method for the preparation of highly pure risperidone.
  • the process comprises reacting 4-(2,4-difluorobenzoyl)piperidine oxime hydrochloride (Compound III) with 3-(2-chlbroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[l,2-a] pyrimidin-4-one monochloride (Compound II) in a solvent such as acetonitrile, methyl isobutyl ketone, NN-Dimethylformamide using potassium carbonate or sodium carbonate base in presence of catalytic amount of potassium iodide to obtain an intermediate oxime (Compound IV) that cyclizes in situ to produce risperidone.
  • the product thus produced is crystallized from ethyl acetate to obtain highly pure risperidone in 81% yield.

Landscapes

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

Abstract

L'invention porte sur un procédé de préparation de risperidone antipsychotique (Formule I); qui consiste à faire réagir 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido-[1,2-a]pyrimidin-4-one (Formule II); avec 4-(2,4-difluorobenzoyl)piperidine oxime (Formule III); afin de former de l'oxime (Formule IV); et comprend la cyclisation in situ d'oxime (Formule IV) afin de former du risperidone (Formule I) dans un solvant choisi dans le groupe acétonitrile,N, N dimetylformamide et méthyle isobutyle cétone.
PCT/IN2003/000207 2002-07-22 2003-06-02 Procede de preparation de risperidone antipsychotique Ceased WO2004009591A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003237597A AU2003237597A1 (en) 2002-07-22 2003-06-02 A process for the preparation of antipsychotic risperidone

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN545/MAS/2002 2002-07-22
IN545CH2002 2002-07-22

Publications (1)

Publication Number Publication Date
WO2004009591A1 true WO2004009591A1 (fr) 2004-01-29

Family

ID=30471464

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2003/000207 Ceased WO2004009591A1 (fr) 2002-07-22 2003-06-02 Procede de preparation de risperidone antipsychotique

Country Status (1)

Country Link
WO (1) WO2004009591A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005030772A1 (fr) * 2003-09-26 2005-04-07 Jubilant Organosys Ltd. Procede de preparation de risperidone
WO2009077551A1 (fr) * 2007-12-18 2009-06-25 Janssen Pharmaceutica Nv Procédé de préparation de la rispéridone

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4804663A (en) * 1985-03-27 1989-02-14 Janssen Pharmaceutica N.V. 3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
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
US5134147A (en) * 1989-11-07 1992-07-28 Adir Et Compagnie 1,2-benzisoxazole compounds
ES2050069A1 (es) * 1992-07-10 1994-05-01 Vita Invest Sa Procedimiento para la obtencion de 3-(2-(4-(6-fluoro-1,2-benzisoxazol-3-il)piperidino)etil)-2-metil-6,7,8,9-tetrahidro-4h-pirido(1,2-a) pirimidin-4-ona.
WO1995014691A1 (fr) * 1993-11-23 1995-06-01 Janssen Pharmaceutica N.V. NOUVEAUX DERIVES DU 9-HYDROXY-PYRIDO[1,2-a]PYRIMIDINE-4-ONE ETHER
WO2003042212A1 (fr) * 2001-11-13 2003-05-22 EGIS Gyógyszergyár Rt. Procede ameliore de preparation de 3-{2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2-methyl-4h-pyrido[1,2-a]pyrimidin-4-one

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4804663A (en) * 1985-03-27 1989-02-14 Janssen Pharmaceutica N.V. 3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
US5134147A (en) * 1989-11-07 1992-07-28 Adir Et Compagnie 1,2-benzisoxazole compounds
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
ES2050069A1 (es) * 1992-07-10 1994-05-01 Vita Invest Sa Procedimiento para la obtencion de 3-(2-(4-(6-fluoro-1,2-benzisoxazol-3-il)piperidino)etil)-2-metil-6,7,8,9-tetrahidro-4h-pirido(1,2-a) pirimidin-4-ona.
WO1995014691A1 (fr) * 1993-11-23 1995-06-01 Janssen Pharmaceutica N.V. NOUVEAUX DERIVES DU 9-HYDROXY-PYRIDO[1,2-a]PYRIMIDINE-4-ONE ETHER
WO2003042212A1 (fr) * 2001-11-13 2003-05-22 EGIS Gyógyszergyár Rt. Procede ameliore de preparation de 3-{2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2-methyl-4h-pyrido[1,2-a]pyrimidin-4-one

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"RISPERIDONE", DRUGS OF THE FUTURE, BARCELONA, ES, vol. 13, no. 12, 1 December 1988 (1988-12-01), pages 1052 - 1055, XP002046839, ISSN: 0377-8282 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005030772A1 (fr) * 2003-09-26 2005-04-07 Jubilant Organosys Ltd. Procede de preparation de risperidone
WO2009077551A1 (fr) * 2007-12-18 2009-06-25 Janssen Pharmaceutica Nv Procédé de préparation de la rispéridone

Similar Documents

Publication Publication Date Title
CA1163994A (fr) Derives de la 3-(1-piperidinylalkyl)-4h-pyrido ¬1,2-a|-pyrimidin-4-one
EP0086422B1 (fr) Pyrazolo (4,3-c)pyridines à activité pharmacologique
WO2007120592A1 (fr) Sel antagoniste de cgrp
PH12015501494B1 (en) Method for producing substituted 5-fluoro-1h-pyrazolopyrimidines
HU222247B1 (hu) 1- és 2-helyzetben szubsztituált 1H-imidazo[4,5-c]kinolin-4-amin-származékok előállításában alkalmazható 1H-imidazo[4,5-c]kinolin-5N-oxid-származékok
KR20090079189A (ko) Ｃｍｈｔｐ 및 이의 중간체의 합성 방법
AU2007238894A1 (en) Process for the preparation of pyridine heterocycle CGRP antagonist intermediate
EP2300467A2 (fr) Nouveaux procédés améliorés de préparation de la palipéridone
US8940749B2 (en) Preparation of 3-[2-[4-((6-fluoro-1, 2-benzisoxazol-3-yl)-l-piperidinyl)-6, 7, 8, 9-tetrahydor-9-hydroxy-2-methyl-4H-pyrido[ 1, 2-A]-pyrimidin-4-one(paliperidone) and paliperidone palmitate
EP2202234A1 (fr) Purification de la palipéridone
WO2004009591A1 (fr) Procede de preparation de risperidone antipsychotique
EP2007764B1 (fr) Procédé de préparation d'un antagoniste cgrp
EP2007731B1 (fr) Procédé de préparation d'un intermédiaire d'antagoniste du peptide cgrp de caprolactame
EP1461338B1 (fr) Procede ameliore de preparation de 3-(2-(4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1-piperidinyl)ethyl)-6,7,8,9-tetrahydro-2-methyl-4h-pyrid-(1, 2-a)-pyrimidin-4-one
EP2321311B1 (fr) Synthèse de palipéridone
NZ570482A (en) Process for preparing 1-halo-2,7-naphthyridinyl derivatives
US20120259116A1 (en) Novel Process for the Preparation of Paliperidone
AU2003219010A1 (en) Process for preparing 3-(2-(4-(6-fluorobenzo(d) isoxazol-3-yl)-piperidin-1yl)-ethyl)-2-methyl-6,7,8,9-tetrahydro-4h-pyrido-(1,2-a) pyrimidin-4-one
CA2540360A1 (fr) Procede de preparation de risperidone
KR100457496B1 (ko) 3-[2-[4-(6-플루오로-1,2-벤즈이속사졸-3-일)-1-피페리디닐]에틸]-6,7,8,9-테드라하이드로-2-메틸-4Ｈ-피리도[1,2-ａ]피리미딘-4-온의 제조방법 및 이를 위한 중간체
NO174670B (no) Analogifremgangsmaate for fremstilling av terapeutisk aktive 1H-pyrido-(4,3-b)indol-1-on-derivater
WO2002024696A1 (fr) Procede de production de derive heterocyclique fondu tricyclique
HK1009647A1 (en) Process for the preparation of lactam derivatives

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP