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WO2009053993A2 - Procédé pour la préparation d'un nouveau sel d'oxalate de voriconazole de forme c - Google Patents

Procédé pour la préparation d'un nouveau sel d'oxalate de voriconazole de forme c Download PDF

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Publication number
WO2009053993A2
WO2009053993A2 PCT/IN2007/000562 IN2007000562W WO2009053993A2 WO 2009053993 A2 WO2009053993 A2 WO 2009053993A2 IN 2007000562 W IN2007000562 W IN 2007000562W WO 2009053993 A2 WO2009053993 A2 WO 2009053993A2
Authority
WO
WIPO (PCT)
Prior art keywords
voriconazole
preparation
oxalate salt
crystalline form
oxalate
Prior art date
Application number
PCT/IN2007/000562
Other languages
English (en)
Other versions
WO2009053993A3 (fr
Inventor
Venkat Reddy Alla
Jaganmohan G
Aruna Kumari Sirigiri
Raghu Mithra Alla
Sreenivasa Reddy Bodapati
Original Assignee
Lee Pharma Limited
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 Lee Pharma Limited filed Critical Lee Pharma Limited
Publication of WO2009053993A2 publication Critical patent/WO2009053993A2/fr
Publication of WO2009053993A3 publication Critical patent/WO2009053993A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • Voriconazole has the chemical name (2R, 3S)-2-(2,4-difluorophenyl)-3- (5-fluoiOpyrimidin-4-yl)-l-(lH-l,2,4-triazol-yl)-butan-2-ol represented as Formula (I)
  • Voriconazole exhibits excellent antifungal activity against a wide range of yeasts and filamentous fungi as demonstrated by in vitro and in vivo infection models.
  • Voriconazole has excellent activity in vitro against Aspergillus species, shows efficacy in vivo models of aspergillosis and has demonstrated efficacy in both acute and chronic aspergillosis, with few observed side effects.
  • this drug promises to become an important new agent in the treatment of invasive infections due to Aspergillus and other life- threatening fungal infections.
  • the process includes the reaction of 1 -(2,4-difluoro phenyl)-2- (lH-l,2,4-triazol-l-yl) ethanone with di iso propyl amide and in tetra hydro furan medium to yield 3-(4-chloro-5-fluoro pyrimidin-6-yl)-2- (2,4-difluoro phenyl)-l- (lH-l,2,4-triazol-l-yl) butan-2-ol.
  • WO 2006/065726 Discloses the process for the preparation of crystalline form A and B as well as its amorphous form of Voriconazole.
  • (2R,3S/2S, 3R)-3- (4-chloro-5- fluoro pyrimidin-6-yl) -2(2,4- difluoro phenyl -1- (lH-l,2,4-triazol-l- yl)butan-2- ol on reduction with Raney nickel in presence of methanol and Sodium acetate it gives corresponding derivative which on resolution with ⁇ R(-) -10- camphor sulfonic acid in presence of Acetone and Methanol gives corresponding camphor sulfonate salt which on hydrolysis with Aqueous Sodium carbonate in presence of Methylene dichloride solvent and isolated in Iso propanol resulted the formation of crystalline form B.
  • the same patent also describes the crystalline form B by isolation from acetone and water mixture, acetonitrile, methanol
  • WO 9706160 Discloses the preparation of triazoles by organometalic addition. This invention relates to process for the preparation of Voriconazole acid addition salts like Hydrochloride, Hydro bromide, Hydro iodide, sulfate, Nitrate, methane sulfonate , Para toluene sulfonate ,Benzene sulfonate, Camphor sulfonate and 3-Bromo camphor sulfonate.
  • Voriconazole acid addition salts like Hydrochloride, Hydro bromide, Hydro iodide, sulfate, Nitrate, methane sulfonate , Para toluene sulfonate ,Benzene sulfonate, Camphor sulfonate and 3-Bromo camphor sulfonate.
  • the present invention relates to processes for the preparation of Voriconazole and its polymorph.
  • the invention also relates to novel crystalline form C of Voriconazole.
  • the process for preparation of Voriconazole oxalate salt of form C comprises the steps: a) Suspending Voriconazole crystalline form B in suitable solvent, b) Addition of an acid at a suitable temperature, c) Cooling the reaction mass and isolation of the solid, d) Drying the solid.
  • the invention provides a process for the preparation of Voriconazole and its novel salts and its different polymorphic form comprising steps of: Step (1) :
  • Voriconazole camphor sulfonate in a mixture of solvent, such as water and Dichloro methane and in the presence of base such as Sodium hydroxide, layers are separated and extracted with Dichloro methane solvent. Solvent is removed by distillation under reduced pressure at below 40 0 C. The obtained crude Voriconazole is crystallized from Iso propyl ether to get pure Voriconazole crystalline form B.
  • solvent such as water and Dichloro methane
  • base such as Sodium hydroxide
  • the crystalline form B of Voriconazole is characterized by its XRD pattern in accordance with that shown in Fig (1). The most characteristic peaks are located at about 6.9, 12.6, 13.8, 14.8, 15.9, 16.5, 17.4, 19.8, 21.2, 22.5, 23.3, 26.1 & 27.8 ⁇ 0.2 degrees two theta
  • the crystalline form B of Voriconazole is also characterized by its DSC curve having an endotherm at about 132° C that shown in fig (2)
  • the crystalline form B is also characterized by an infrared spectrum in accordance with that show in fig (3) Step (3):
  • Oxalic acid Involves the conversion of Voriconazole crystalline form B to its pharmaceutically acceptable salts such as oxalate in to its novel polymorph form C
  • Voriconazole oxalate is characterized by its XRD pattern as shown in fig (4). The most characterized peaks are located at about
  • the crystalline form C of Voriconazole oxalate is also characterized by DSC fig (5) curve having an endotherm at about 152° C.
  • Voriconazole oxalate crystalline form C 25 gm of Voriconazole crystalline form B and 250 ml of Toluene was taken in to a round bottom flask. 8.7 gm of Oxalic acid was dissolved 50 ml of DM Water was added to the reaction mass and maintained for 2-3 hrs at 25 -30° C. The obtained solid was filtered and wash with 25 ml of Toluene. The material was dried at 60 -65° C for about 10 hr to yield title compound as a Voriconazole crystalline form C.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention a pour objet le procédé d'obtention d'une nouvelle forme polymorphique du voriconazole. Le voriconozole a pour nom chimique le (2R, 3S)-2-(2,4-difluorophényle)-3-(5-fluoropyrimidin-4-yle)-1-(1H-1,2-4- triazol-yle)-butan-2-ol représenté par la Formule (1).
PCT/IN2007/000562 2007-10-22 2007-12-03 Procédé pour la préparation d'un nouveau sel d'oxalate de voriconazole de forme c WO2009053993A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2382CH2007 2007-10-22
IN2382/CHE/2007 2007-10-22

Publications (2)

Publication Number Publication Date
WO2009053993A2 true WO2009053993A2 (fr) 2009-04-30
WO2009053993A3 WO2009053993A3 (fr) 2009-09-24

Family

ID=40580200

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2007/000562 WO2009053993A2 (fr) 2007-10-22 2007-12-03 Procédé pour la préparation d'un nouveau sel d'oxalate de voriconazole de forme c

Country Status (1)

Country Link
WO (1) WO2009053993A2 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2788344A4 (fr) * 2011-12-06 2015-06-24 Basf Se Système cristallin à plusieurs composants de voriconazole avec de l'acide fumarique
CN108276387A (zh) * 2018-01-24 2018-07-13 成都倍特药业有限公司 一种伏立康唑的纯化方法
WO2021229359A3 (fr) * 2020-05-12 2022-01-06 Cellix Bio Private Limited Procédé de préparation de sels de composés de triazole
US20220340551A1 (en) * 2016-11-28 2022-10-27 Cellix Bio Private Limited Compositions and methods for the treatment of fungal infections

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0402491D0 (en) * 2004-02-04 2004-03-10 Pfizer Ltd Medicaments
EP1828170A4 (fr) * 2004-12-14 2009-11-11 Reddys Lab Ltd Dr Procede de preparation de voriconazole
EP1899327A1 (fr) * 2005-06-30 2008-03-19 MSN Laboratories Limited Procede ameliore destine a la preparation de 2r, 3s-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl) butan-2-ol (voriconazole)
CN1847243A (zh) * 2005-07-08 2006-10-18 北京博尔达生物技术开发有限公司 一种新的伏立康唑可溶性盐的制备方法及其制剂

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2788344A4 (fr) * 2011-12-06 2015-06-24 Basf Se Système cristallin à plusieurs composants de voriconazole avec de l'acide fumarique
US20220340551A1 (en) * 2016-11-28 2022-10-27 Cellix Bio Private Limited Compositions and methods for the treatment of fungal infections
CN108276387A (zh) * 2018-01-24 2018-07-13 成都倍特药业有限公司 一种伏立康唑的纯化方法
WO2021229359A3 (fr) * 2020-05-12 2022-01-06 Cellix Bio Private Limited Procédé de préparation de sels de composés de triazole

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Publication number Publication date
WO2009053993A3 (fr) 2009-09-24

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