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WO2006034965A1 - Procede de purification de la ziprasidone - Google Patents

Procede de purification de la ziprasidone Download PDF

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Publication number
WO2006034965A1
WO2006034965A1 PCT/EP2005/054589 EP2005054589W WO2006034965A1 WO 2006034965 A1 WO2006034965 A1 WO 2006034965A1 EP 2005054589 W EP2005054589 W EP 2005054589W WO 2006034965 A1 WO2006034965 A1 WO 2006034965A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
acid
process according
ziprasidone
maleate
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/EP2005/054589
Other languages
English (en)
Inventor
Carme Burgarolas Montero
Jordi BOSCH ILLADÓ
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.)
Medichem SA
Original Assignee
Medichem SA
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 Medichem SA filed Critical Medichem SA
Publication of WO2006034965A1 publication Critical patent/WO2006034965A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Definitions

  • This invention relates to the purification of ziprasidone base using the maleic acid or acetic acid addition salt thereof.
  • the ziprasidone free base i.e. 5- [2- [4- (1, 2-benzisothiazol-3-yl) -1-piperazinyl] ethyl] - 6-chloro-l, 3-dihydro-2H-indol-2-one
  • solvents e.g. to filter off insoluble contaminants, to recrystallize, or to decolorize.
  • ziprasidone base is very insoluble in common solvents. This is demonstrated e.g.
  • the object of the present invention is to obtain a derivative of ziprasidone base that is more soluble than ziprasidone base, thereby reducing the need for large volumes of solvents and/or high temperatures .
  • the inventors solved this objective by providing the maleic acid or acetic acid addition salt of ziprasidone base, ziprasidone maleate or acetate.
  • Ziprasidone maleate or acetate is readily dissolvable, and the solution can be treated with a decolouring agent and/ or filtered at room temperature to obtain a solution of purified ziprasidone maleate or acetate of improved quality, i.e. without insoluble components / less coloured.
  • the invention relates to a process for the purification of 5- [2- [4- (1, 2-benzisothiazol-3-yl) -1- piperazinyl] ethyl] -6-chloro-l, 3-dihydro-2H-indol-2-one of the formula (I)
  • R is CH or
  • the acid addition salt according to the above formula (II) is separated from insoluble components of the composition, preferably by filtration.
  • the acid addition salt according to the above formula (II) can be further treated with a decolorizing agent, preferably at least one selected from alumina, activated alumina, silica and charcoal.
  • a decolorizing agent preferably at least one selected from alumina, activated alumina, silica and charcoal.
  • the acid addition salt according to the above formula (II) can be reacted with an acid, preferably selected from hydrochloric acid, hydrobromic acid and methanesulphonic acid, most preferably hydrochloric acid in order to obtain an acid addition salt of the compound according to the following formula (III) :
  • Rl is halogen or CH3SO3
  • the acid addition salt according to the above formula (III) can be further purified by using at least one organic solvent, preferably selected from isopropanol, tetrahydrofuran, n-butanol and butan-2-one.
  • the present invention further provides for the use of an acid addition salt of formula (II) in a process according to any one of the embodiments described above.
  • ziprasidone relates to the free base of ziprasidone (i.e. 5- [2- [4- (1,2-benzisothiazol-3-yl) -1-piperazinyl]ethyl] -6-chloro- 1, 3-dihydro-2H-indol-2-one) , unless stated otherwise.
  • the free base of ziprasidone can be used in the current invention irrespective of the process used for its production.
  • the maleate or acetate acid addition salt according to formula (II) can be treated with any conventional decolorizing agent.
  • conventional decolorizing agents include, but are not limited to, alumina, activated alumina, silica and charcoal.
  • the solution of the acid addition salt according to formula (II) can be treated with hydrochloric acid or with hydrogen chloride or with a solution of hydrogen chloride in order to precipitate ziprasidone hydrochloride.
  • addition salt according to formula II can be treated with a base in order to precipitate ziprasidone base, which is then converted to the corresponding acid addition salt according to formula
  • Suitable bases comprise sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate sodium bicarbonate, potassium bicarbonate and ammonium hydroxide.
  • the test is carried out in a Kromasil C8 column of 5 ⁇ m and 250x4.6mm.
  • the chromatograph is equipped with a UV detector set at 229 nm and the flow rate is 1.0 ml per minute at room temperature
  • the samples are prepared by dissolving the appropriate amount of sample to obtain 0.5 mg per ml of a mixture of acetonitrile / trifluoroacetic acid 19.6:0.4 v/v and 20 ⁇ l are injected.
  • a wet mixture of zipradisone and inorganic salts is obtained, that is further washed with acetonitrile.
  • the resulting wet mixture of ziprasidone and inorganic salts is stirred with 675 ml of water at reflux temperature for 1 h to remove inorganic salts.
  • the suspension is cooled to room temperature, stirred for 30 minutes and filtered.
  • the solid is washed with water, and 140 g of wet solid (corresponding to 87 g of dry material) are obtained.
  • the wet solid is stirred again with water at reflux temperature for 1 h to remove residual inorganic salts.
  • the suspension is cooled to room temperature, stirred for 30 minutes and filtered.
  • the solid is washed with water, and 170 g of wet solid (corresponding to 81 g of dry- material) are obtained.
  • HPLC analysis reveals a purity of 97.8%.
  • the solid obtained is ziprasidone base having a purity of 99.4% by HPLC and the global yield from the starting compounds is 51% (molar yield) .
  • Potentiometric titration with HClO 4 100.03%
  • the ziprasidone base obtained can be converted to its hydrochloride, or alternatively can be purified to improve its quality attributes like colour and absence of insoluble matter according to the following process.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur la purification de ziprasidone. L'invention concerne un procédé qui permet de purifier une 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-pipérazinyl]éthyl]-6-chloro-1,3-dihydro-2H-indol-2-one de la formule (I) à partir d'une composition renfermant ledit composé, composé que l'on met à réagir avec de l'acide maléique ou de l'acide acétique afin d'obtenir un sel d'addition acide de la formule (II) suivante, dans laquelle R représente la formule (IV) ou la formule (V).
PCT/EP2005/054589 2004-09-29 2005-09-15 Procede de purification de la ziprasidone Ceased WO2006034965A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP200402316 2004-09-29
ES200402316A ES2250001B1 (es) 2004-09-29 2004-09-29 Proceso para la purificacion de ziprasidona.

Publications (1)

Publication Number Publication Date
WO2006034965A1 true WO2006034965A1 (fr) 2006-04-06

Family

ID=35431425

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/054589 Ceased WO2006034965A1 (fr) 2004-09-29 2005-09-15 Procede de purification de la ziprasidone

Country Status (3)

Country Link
AR (1) AR051032A1 (fr)
ES (1) ES2250001B1 (fr)
WO (1) WO2006034965A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1700857A1 (fr) * 2005-03-07 2006-09-13 Dipharma S.p.A. Ziprasidone exempt des impuretés colorées et un procédé pour sa préparation
WO2006094396A1 (fr) * 2005-03-11 2006-09-14 Apotex Pharmachem Inc. Preparation de sels d'addition acides de ziprasidone et intermediaires de ceux-ci a l'aide de reactions en phase solide-phase gazeuse
WO2008062244A1 (fr) * 2006-11-24 2008-05-29 Richter Gedeon Nyrt. Polymorphes de bromhydrate de 5-{2-[4-(1,2-benzisothiazol-3-yl)-1-pipérazinyl]-éthyl}-6-chloro-1,3-dihydro-2h-indol-2-one et leurs procédés de préparation
WO2011080749A1 (fr) * 2009-12-29 2011-07-07 Hetero Research Foundation Procédé pour la purification de ziprasidone

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0584903A1 (fr) * 1992-08-26 1994-03-02 Pfizer Inc. Procédé de préparation de dérivés aryl pipérazinyl-hétérocycliques
WO2001091756A2 (fr) * 2000-06-02 2001-12-06 Pfizer Products Inc. S-methyl-dihydro-ziprasidone utilise dans le traitement des troubles psychiatriques et oculaires
WO2003070246A1 (fr) * 2002-02-20 2003-08-28 Pfizer Products Inc. Synthese controlee de ziprasidone et ses compositions
WO2004050655A1 (fr) * 2002-12-04 2004-06-17 Dr. Reddy's Laboratories Limited Formes polymorphes de ziprasidone et son chlorhydrate
US20050059680A1 (en) * 2003-06-03 2005-03-17 Anna Balanov Crystalline ziprasidone HCI and processes for preparation thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU730856C (en) * 1996-05-07 2001-11-15 Pfizer Inc. Mesylate trihydrate salt of 5-(2-(4-(1,2-benzisothiazol- 3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihydro-2(1H)- indol-2-one(=ziprasidone),it's preparation and it's use as dopamine D2 antagonist
DE10043659A1 (de) * 2000-09-05 2002-03-14 Merck Patent Gmbh Arylpiperazinderivate
AU2003260942A1 (en) * 2002-05-24 2003-12-12 Sun Pharmaceutical Industries Limited A process for the preparation of oxindole derivatives

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0584903A1 (fr) * 1992-08-26 1994-03-02 Pfizer Inc. Procédé de préparation de dérivés aryl pipérazinyl-hétérocycliques
WO2001091756A2 (fr) * 2000-06-02 2001-12-06 Pfizer Products Inc. S-methyl-dihydro-ziprasidone utilise dans le traitement des troubles psychiatriques et oculaires
WO2003070246A1 (fr) * 2002-02-20 2003-08-28 Pfizer Products Inc. Synthese controlee de ziprasidone et ses compositions
WO2004050655A1 (fr) * 2002-12-04 2004-06-17 Dr. Reddy's Laboratories Limited Formes polymorphes de ziprasidone et son chlorhydrate
US20050059680A1 (en) * 2003-06-03 2005-03-17 Anna Balanov Crystalline ziprasidone HCI and processes for preparation thereof

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1700857A1 (fr) * 2005-03-07 2006-09-13 Dipharma S.p.A. Ziprasidone exempt des impuretés colorées et un procédé pour sa préparation
WO2006094396A1 (fr) * 2005-03-11 2006-09-14 Apotex Pharmachem Inc. Preparation de sels d'addition acides de ziprasidone et intermediaires de ceux-ci a l'aide de reactions en phase solide-phase gazeuse
WO2008062244A1 (fr) * 2006-11-24 2008-05-29 Richter Gedeon Nyrt. Polymorphes de bromhydrate de 5-{2-[4-(1,2-benzisothiazol-3-yl)-1-pipérazinyl]-éthyl}-6-chloro-1,3-dihydro-2h-indol-2-one et leurs procédés de préparation
WO2011080749A1 (fr) * 2009-12-29 2011-07-07 Hetero Research Foundation Procédé pour la purification de ziprasidone

Also Published As

Publication number Publication date
AR051032A1 (es) 2006-12-13
ES2250001A1 (es) 2006-04-01
ES2250001B1 (es) 2007-06-01

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