EP1899327A1 - 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) - Google Patents

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)

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Withdrawn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
German (de)
English (en)
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/fr
Withdrawn legal-status Critical Current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)

Abstract

Procedé amelioré destiné 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).
EP06780522A 2005-06-30 2006-06-26 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) Withdrawn EP1899327A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN833CH2005 2005-06-30
PCT/IN2006/000213 WO2007013096A1 (fr) 2005-06-30 2006-06-26 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)

Publications (1)

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

Family

ID=37683030

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06780522A Withdrawn EP1899327A1 (fr) 2005-06-30 2006-06-26 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)

Country Status (2)

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

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2590687C (fr) 2004-12-14 2013-09-10 Dr. Reddy's Laboratories Ltd. Procede de preparation de voriconazole
WO2007132354A2 (fr) * 2006-02-01 2007-11-22 Medichem, S.A. Procédé de préparation de voriconazole, nouvelle forme polymorphe d'un produit intermédiaire de ce composé et utilisations dudit composé
KR100889937B1 (ko) * 2007-08-06 2009-03-20 한미약품 주식회사 보리코나졸의 제조방법
WO2009053993A2 (fr) * 2007-10-22 2009-04-30 Lee Pharma Limited Procédé pour la préparation d'un nouveau sel d'oxalate de voriconazole de forme 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 (fr) 2010-03-10 2011-09-15 Synthron B.V. Procédé de préparation de 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
WO2007013096A8 (fr) 2007-03-29
WO2007013096A1 (fr) 2007-02-01

Similar Documents

Publication Publication Date Title
JP2959846B2 (ja) 治療において有用なトリアゾール誘導体
EP2077996B1 (fr) PROCEDE DE PURIFICATION DE MONTELUKAST ET SES SELS D'AMINES& xA;
NO971218L (no) Tetrahydrofuran-antifungale midler
HU189143B (en) Process for preparing 2-/2,4-difluoro-phenyl/-1,3-bis/1h-1,2,4-triazol-1-yl/-propan-2-ol derivatives
WO2009084029A2 (fr) Procédé amélioré de préparation du (2r,3s)-2-(2,4-difluorophényl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl)-butan-2-ol
WO2007013096A1 (fr) 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)
FR2542315A1 (fr) Nouveaux composes azoliques, leur preparation et leur utilisation comme antifongiques et fongicides
WO2010095145A1 (fr) Procédé de préparation de voriconazole
KR100347639B1 (ko) 디페닐 트리아졸 유도체 화합물, 이의 제조방법 및 이를 포함하는 약제학적 조성물
DK166622B1 (da) Analogifremgangsmaade til fremstilling af triazolforbindelser eller farmaceutisk acceptable salte deraf og lacton-forbindelser til anvendelse som mellemprodukter ved fremgangsmaaden
WO2015150947A1 (fr) Procédé de préparation de l'isavuconazole et de ses intermédiaires
KR870000356B1 (ko) 트리아졸 유도체의 제조 방법
EP2678333B1 (fr) Procédé amélioré de préparation du voriconazole et de ses intermédiaires
CA1287059C (fr) Derives ditriazole presentant une activite antifongique
KR880002275B1 (ko) 트리아졸 유도체의 제조방법
US20100029945A1 (en) Process for the purification of Montelukast
WO2025232344A1 (fr) Composé azolol contenant de l'éthynyle et son utilisation
RU2276152C1 (ru) R-(-)-1-[2-(7-ХЛОРБЕНЗО[b]ТИОФЕН-3-ИЛМЕТОКСИ)-2-(2,4-ДИХЛОРФЕНИЛ)ЭТИЛ]-1H-ИМИДАЗОЛ И ЕГО СОЛИ, СПОСОБ ИХ ПОЛУЧЕНИЯ, КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ ПРОТИВОГРИБКОВЫМ ДЕЙСТВИЕМ
BG65699B1 (bg) Метод за синтез на познато тетразолово производно
WO2009053993A2 (fr) Procédé pour la préparation d'un nouveau sel d'oxalate de voriconazole de forme c
JP5553911B2 (ja) 新規中間体を使用したボリコナゾールの製造方法
WO2011045807A2 (fr) Nouveau procédé pour fabriquer du (2r,3s)-2-(2,4-difluorophényl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl)butan-2-ol
JPS6346075B2 (fr)
JP2022515696A (ja) エフィナコナゾールの調製方法
Baji et al. Synthesis, antifungal activity and structure-activity relationships of 2-(alkyl or aryl)-2-(alkyl or polyazol-1-ylmethyl)-4-(polyazol-1-ylmethyl)-1, 3-dioxolanes

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20071231

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

DAX Request for extension of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20100222

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20131001