EP1899327A1 - Verbessertes verfahren zur herstellung von 2r, 3s-2-(2,4-difluorphenyl)-3-(5-fluorpyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl)butan-2-ol (voriconazol) - Google Patents

Verbessertes verfahren zur herstellung von 2r, 3s-2-(2,4-difluorphenyl)-3-(5-fluorpyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl)butan-2-ol (voriconazol)

Info

Publication number
EP1899327A1
EP1899327A1 EP06780522A EP06780522A EP1899327A1 EP 1899327 A1 EP1899327 A1 EP 1899327A1 EP 06780522 A EP06780522 A EP 06780522A EP 06780522 A EP06780522 A EP 06780522A EP 1899327 A1 EP1899327 A1 EP 1899327A1
Authority
EP
European Patent Office
Prior art keywords
formula
compound
triazol
fluoropyrimidin
difluorophenyl
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.)
Withdrawn
Application number
EP06780522A
Other languages
English (en)
French (fr)
Inventor
Manne Satyanarayana Reddy
Chakilam Nagaraju
Achampeta Kodanda Ramprasad
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.)
MSN Laboratories Pvt Ltd
Original Assignee
MSN Laboratories Pvt 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 MSN Laboratories Pvt Ltd filed Critical MSN Laboratories Pvt Ltd
Publication of EP1899327A1 publication Critical patent/EP1899327A1/de
Withdrawn legal-status Critical Current

Links

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

  • the present invention relates to a improved process for the preparation of 2R, 3S-2-(2,4- Difluorophenyl)-3-(5- fluoropyrimidin-4-yl)-l -(1H-I, 2,4- triazol-1-yl) butan-2-ol It may 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.
  • Viroconazole 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.
  • US 5,567,817 patent discloses relates to 2-aryl 3-(3-halo ⁇ yridin-4-yl or 5- halopyridin-4-yl)-l-(lH-l,2,4 triazol-l-yl)alkane-2ol derivatives which are useful in the treatment of fungal infections in animals,including human beings.
  • the US 5567817 discloses process for the preparation comprises of reacting 4- chloro-6-ethyl-5-fluoropyrimidine with l-(2,4-difluorophenyl)-2-(lH- 1 ,2,4- triazol-l-yl)ethanone in presence of Lithium diisopropy amine in Tetrahydrofuron as a solvent to get 2-(2,4-difluoro ⁇ henyl)-3-(4-chloro-5-fluoropyrimidin-4-yl)-l- (lH-l,2,4triazol-l-yl)butan-2-ol the compound, which is further dehaloginated with 5% palladium charcol to give a Racemic Voriconazole and then resolution with camphorsufonic acid in presence of methanol medium and subsequently converted to free base with alkaline medium to give (-) Isomer of Voriconazole of Formula ( I )
  • Voriconazole compound of formula ( I ) which is useful in the treat ment of antistal hence it is important to have alternate process which is cost effective and commercially viable for preparing the compound of Formula ( I ). Therefore the main objective of the present invention is to prepare Voriconzole in improved method, which is cost effective, commercially viable and easily scalable.
  • the Voriconazole is prepared in the present invention, in an improved process that is cost effective and the Voriconazole obtained in this process is suitable for pharmaceutical formulations
  • the present invention provides an improved process for the preparation of Voriconazole and its pharmaceutically acceptable salts
  • the improved process of the present invention comprises, the condensation of 4-chloro-6-ethyl-5- ffluoropyrimidine with 1 -(2,4-difluorophenyl)-2-( IH- 1 ,2,4-triazol- 1 -yl)ethanone in presence of Lithium diisopropylamine as a base and n-Heptane as a solvent mixture with tetrahydrofuron to get the resulting compound 2-(2,4- difluorophenyl)-3 -(4-chloro-5-fluoropyrimidin-4-y I)- 1 -( 1 H- 1 ,2,4triazol- 1 - yl)butan-2-ol as solid.
  • the present invention relates to an improved process for the preparation of 2R, 3S-2-(2,4- difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-l -(1H-I, 2,4- triazol-1-yl) butan-2-ol (commonly known as Voriconazole)
  • the process of the present invention is schematically represented as follows.
  • Voriconazole obtained in the present improved process is free flowing and non- solvated solid; hence it is well suited for pharmaceutical formulations,
  • the process of the present invention is cost effective and getting a more yields, eco- friendly and well suited for scale up.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP06780522A 2005-06-30 2006-06-26 Verbessertes verfahren zur herstellung von 2r, 3s-2-(2,4-difluorphenyl)-3-(5-fluorpyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl)butan-2-ol (voriconazol) Withdrawn EP1899327A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN833CH2005 2005-06-30
PCT/IN2006/000213 WO2007013096A1 (en) 2005-06-30 2006-06-26 Improved process for the preparation of 2r, 3s-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl) butan-2-ol (voriconazole)

Publications (1)

Publication Number Publication Date
EP1899327A1 true EP1899327A1 (de) 2008-03-19

Family

ID=37683030

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06780522A Withdrawn EP1899327A1 (de) 2005-06-30 2006-06-26 Verbessertes verfahren zur herstellung von 2r, 3s-2-(2,4-difluorphenyl)-3-(5-fluorpyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl)butan-2-ol (voriconazol)

Country Status (2)

Country Link
EP (1) EP1899327A1 (de)
WO (1) WO2007013096A1 (de)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2590687C (en) * 2004-12-14 2013-09-10 Dr. Reddy's Laboratories Ltd. Process for preparing voriconazole
US8143397B2 (en) 2006-02-01 2012-03-27 Medichem S.A. Process for preparing voriconazole, new polymorphic form of intermediate thereof, and uses thereof
KR100889937B1 (ko) * 2007-08-06 2009-03-20 한미약품 주식회사 보리코나졸의 제조방법
WO2009053993A2 (en) * 2007-10-22 2009-04-30 Lee Pharma Limited Process for preparation of novel salt of voriconazole oxalate form-c
US20110312977A1 (en) * 2009-02-17 2011-12-22 Glenmark Generics Limited Process for the preparation of voriconazole
KR101109215B1 (ko) 2009-06-17 2012-01-30 보령제약 주식회사 보리코나졸의 신규 중간체 및 이를 이용한 보리코나졸의 제조방법
KR100971371B1 (ko) 2010-02-04 2010-07-20 동국제약 주식회사 신규한 중간체를 이용한 보리코나졸의 제조방법
WO2011110198A1 (en) 2010-03-10 2011-09-15 Synthron B.V. A process for making voriconazole
CN106432198B (zh) * 2016-09-08 2022-10-21 浙江华海药业股份有限公司 一种制备伏立康唑拆分中间体的方法
CN111172231B (zh) * 2019-12-27 2023-11-07 丽珠集团丽珠制药厂 一种伏立康唑微生物限度检查方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007013096A1 *

Also Published As

Publication number Publication date
WO2007013096A1 (en) 2007-02-01
WO2007013096A8 (en) 2007-03-29

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