WO2019077627A1 - Procédé de fabrication de posaconazole - Google Patents

Procédé de fabrication de posaconazole Download PDF

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Publication number
WO2019077627A1
WO2019077627A1 PCT/IN2018/050664 IN2018050664W WO2019077627A1 WO 2019077627 A1 WO2019077627 A1 WO 2019077627A1 IN 2018050664 W IN2018050664 W IN 2018050664W WO 2019077627 A1 WO2019077627 A1 WO 2019077627A1
Authority
WO
WIPO (PCT)
Prior art keywords
difluorophenyl
lit
benzyloxy
tetrahydrofuran
methyl
Prior art date
Application number
PCT/IN2018/050664
Other languages
English (en)
Inventor
Venkateswara Rao Nandepu
Venkata krishna Reddy BIJJULA
Satyanarayana Bathina
Original Assignee
Metrochem Api 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 Metrochem Api Pvt Ltd. filed Critical Metrochem Api Pvt Ltd.
Publication of WO2019077627A1 publication Critical patent/WO2019077627A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • a further objective of the present invention to provide a commercially viable process for the production of Posaconazole by reacting the intermediate compounds of formula A and B.
  • the O-Sulphonyloxy derivative (B-7) is selected from the group consisting of (2S)- 2-(Benzyloxy)-l-ethylpropyl-4-chlorobenzene sulfonate (example-8); (2S)-2- (Benzyloxy)-l-ethylpropyl-4-nitrobenzene sulfonate(example-lO); and 2- (Benzyloxy)-l-ethylpropyl-4-methylbenzene sulfonate.
  • Toluene (10 lit) was added to the flask along with 4-(2,4-Difluoro phenyl)-4- oxobutanoic acid (1 kg) and Methyl Triphenyl phosphonium bromide (2.2 kg) at room temperature under Nitrogen media.
  • the reaction mass was cooled to 10-15°C.
  • Sodium t-but oxide (1.12 kg) was added and heated to 60-65°C and maintained for 5 hrs. Then it was cooled to 10°C. After the addition of water (10 lit), temperature was raised to 30°C. Toluene layer and aqueous layer were separated. Aqueous layer was washed with Dichloromethane (5 lit) and stirred for 15 min.
  • Tetrahydrofuran (5 lit) and Sodium borohydride (0.32 kg) were added to the flask and stirred for 30 min at room temperature.
  • Lithium bromide (0.8 kg) was added and stirred for overnight at room temperature and cooled to 0-5°C.
  • (4S)-3- ⁇ [(5R)- 5-(2,4-Difluorophenyl)-5-(iodomethyl)tetrahydrofuran-3-yl]carbonyl ⁇ -4-phenyl- l,3-oxazolidin-2-one (1 kg) and Tetrahydrofuran (5 lit) were slowly added to the reaction mixture and stirred for 30 min at same temperature under Nitrogen media. Chilled water (6.6 lit) was slowly added.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne un procédé amélioré pour la fabrication de Posaconazole, un agent antifongique appartenant à la catégorie de composé de triazole tétrahydrofurane substitué. La présente invention concerne en outre la préparation de formule A et de formule B, des intermédiaires clés dans la préparation de Posaconazole. L'invention concerne également de nouveaux intermédiaires qui sont utiles dans la synthèse de Posaconazole.
PCT/IN2018/050664 2017-10-16 2018-10-16 Procédé de fabrication de posaconazole WO2019077627A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201741036698 2017-10-16
IN201741036698 2017-10-16

Publications (1)

Publication Number Publication Date
WO2019077627A1 true WO2019077627A1 (fr) 2019-04-25

Family

ID=66173606

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2018/050664 WO2019077627A1 (fr) 2017-10-16 2018-10-16 Procédé de fabrication de posaconazole

Country Status (1)

Country Link
WO (1) WO2019077627A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109956885A (zh) * 2019-04-29 2019-07-02 江苏万年长药业有限公司 一种泊沙康唑中间体的制备方法
CN110862355A (zh) * 2019-12-03 2020-03-06 济南大学 一种艾氟康唑中间体的合成方法
CN113666915A (zh) * 2021-08-27 2021-11-19 江苏海洋大学 一种泊沙康唑中间体的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013124280A1 (fr) * 2012-02-20 2013-08-29 Lek Pharmaceuticals D.D. Synthèse d'acide 2-(3,4-difluorophenyl)cyclopropanecarboxylique
US20140343285A1 (en) * 2011-09-19 2014-11-20 Msn Laboratories Limited Process for the Preparation of Triazole Antifungal Drug, Its Intermediates and Polymorphs Thereof
US20160237066A1 (en) * 2013-10-22 2016-08-18 Msn Laboratories Private Limited Improved process for the preparation of ((3s,5r)-5-((1h-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl-4-methylbenzenesulfonate

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140343285A1 (en) * 2011-09-19 2014-11-20 Msn Laboratories Limited Process for the Preparation of Triazole Antifungal Drug, Its Intermediates and Polymorphs Thereof
WO2013124280A1 (fr) * 2012-02-20 2013-08-29 Lek Pharmaceuticals D.D. Synthèse d'acide 2-(3,4-difluorophenyl)cyclopropanecarboxylique
US20160237066A1 (en) * 2013-10-22 2016-08-18 Msn Laboratories Private Limited Improved process for the preparation of ((3s,5r)-5-((1h-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl-4-methylbenzenesulfonate

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109956885A (zh) * 2019-04-29 2019-07-02 江苏万年长药业有限公司 一种泊沙康唑中间体的制备方法
CN110862355A (zh) * 2019-12-03 2020-03-06 济南大学 一种艾氟康唑中间体的合成方法
CN113666915A (zh) * 2021-08-27 2021-11-19 江苏海洋大学 一种泊沙康唑中间体的制备方法
CN113666915B (zh) * 2021-08-27 2022-08-16 江苏海洋大学 一种泊沙康唑中间体的制备方法

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