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WO2025152131A1 - PROCÉDÉ DE PRÉPARATION D'UN COMPOSÉ β-LACTAME MONOCYCLIQUE - Google Patents

PROCÉDÉ DE PRÉPARATION D'UN COMPOSÉ β-LACTAME MONOCYCLIQUE

Info

Publication number
WO2025152131A1
WO2025152131A1 PCT/CN2024/073149 CN2024073149W WO2025152131A1 WO 2025152131 A1 WO2025152131 A1 WO 2025152131A1 CN 2024073149 W CN2024073149 W CN 2024073149W WO 2025152131 A1 WO2025152131 A1 WO 2025152131A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
reaction
preparation
formula
hydrogen peroxide
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.)
Pending
Application number
PCT/CN2024/073149
Other languages
English (en)
Chinese (zh)
Inventor
谢宗欢
李前勇
刘源
徐庭华
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.)
Zhejiang Raybow Pharmaceutical Co Ltd
Original Assignee
Zhejiang Raybow Pharmaceutical Co 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 Zhejiang Raybow Pharmaceutical Co Ltd filed Critical Zhejiang Raybow Pharmaceutical Co Ltd
Publication of WO2025152131A1 publication Critical patent/WO2025152131A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/18—Preparation of carboxylic acid esters by conversion of a group containing nitrogen into an ester group
    • C07C67/20—Preparation of carboxylic acid esters by conversion of a group containing nitrogen into an ester group from amides or lactams
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members

Definitions

  • the invention belongs to the field of pharmaceutical chemical industry, and specifically relates to a method for preparing a monocyclic beta-lactam compound.
  • ⁇ -lactam antibiotics play an important role in clinical practice due to their broad spectrum, strong efficacy and high safety.
  • monocyclic ⁇ -lactams are simpler in structure than penicillins and cephalosporins, and their chemical properties are more stable than other non-classical ⁇ -lactam antibiotics. Therefore, the research and development of this type of drugs is one of the hot topics in the field of drug research.
  • the molecular structure of monocyclic ⁇ -lactam antibiotics contains a compound with a partial structure of azetidine-2-one, which is an important component of monocyclic ⁇ -lactam antibiotics.
  • the method has unsatisfactory selectivity in the case of small steric hindrance, and will produce other optical isomers, facing the problems of difficulty in separation and low yield.
  • the technical solution provided by the present invention is:
  • the present invention provides a monocyclic ⁇ -lactam compound of formula VII, the structural formula of which is as follows:
  • the present invention provides an intermediate compound of formula VI, the structural formula of which is as follows:
  • the present invention provides an intermediate compound of formula V, the structural formula of which is as follows:
  • the present invention provides a method for preparing a monocyclic ⁇ -lactam compound of formula VII, which is prepared by subjecting a compound of formula VI to an oxidative removal reaction.
  • the reagent for the oxidation removal reaction can be CAN, DDQ or Oxone; preferably, it is cerium ammonium nitrate (CAN).
  • the molar ratio of compound VI to the oxidizing agent in the oxidation removal reaction can be in the range of 1:(2-8).
  • the solvent for the oxidative removal reaction may be an organic solvent or an inorganic solvent; preferably, it is an aqueous solution of acetonitrile.
  • the oxidative removal agent of the oxidative removal reaction can be hydrogen peroxide/lithium hydroxide, hydrogen peroxide/sodium hydroxide, hydrogen peroxide/potassium hydroxide, hydrogen peroxide/cesium hydroxide, hydrogen peroxide/potassium carbonate or hydrogen peroxide/cesium carbonate; preferably hydrogen peroxide/lithium hydroxide.
  • the compound of formula III is prepared by reacting the compound of formula II with 2,6-difluorobenzaldehyde via aldol condensation reaction.
  • the compound of formula II is prepared by condensing a compound of formula I with an oxazolidinone compound.
  • the molar ratio of compound I, oxazolidinone compound and condensation reagent can be in the range of 1:(0.5-2):(2-5).
  • Embodiment 2 is a diagrammatic representation of Embodiment 1:

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention relève du domaine des produits chimiques pharmaceutiques, et concerne principalement un procédé de préparation d'un composé β-lactame monocyclique. Actuellement, la sélectivité de réaction dans l'état de la technique n'est pas idéale, et certains problèmes persistent tels qu'une difficulté de résolution élevée et un faible rendement. Dans la présente invention, pour construire un centre chiral cible à l'avance, les problèmes selon lesquels un isomère optique est difficile à séparer et a un faible rendement dans des conditions de faible encombrement stérique sont résolus, et une synthèse directionnelle d'une configuration cible permet d'augmenter le taux d'utilisation d'atomes et d'obtenir une production à l'échelle industrielle, réduisant ainsi la pollution environnementale et améliorant la faisabilité commerciale.
PCT/CN2024/073149 2024-01-16 2024-01-19 PROCÉDÉ DE PRÉPARATION D'UN COMPOSÉ β-LACTAME MONOCYCLIQUE Pending WO2025152131A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202410057557.2 2024-01-16
CN202410057557.2A CN120329232A (zh) 2024-01-16 2024-01-16 单环β内酰胺化合物的制备方法

Publications (1)

Publication Number Publication Date
WO2025152131A1 true WO2025152131A1 (fr) 2025-07-24

Family

ID=96353780

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2024/073149 Pending WO2025152131A1 (fr) 2024-01-16 2024-01-19 PROCÉDÉ DE PRÉPARATION D'UN COMPOSÉ β-LACTAME MONOCYCLIQUE

Country Status (2)

Country Link
CN (1) CN120329232A (fr)
WO (1) WO2025152131A1 (fr)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4536334A (en) * 1979-06-28 1985-08-20 Sumitomo Chemical Company, Limited Preparation of β-lactam derivatives
US4751299A (en) * 1983-11-18 1988-06-14 Takeda Chemical Industries, Ltd. Optically active β-lactams and method of their production
JPH03145460A (ja) * 1989-10-27 1991-06-20 Yasuyuki Kita β―ラクタム系化合物の製造法
CN101134739A (zh) * 2006-09-01 2008-03-05 长春吉大天元化学技术股份有限公司 新的β-内酰胺类化合物及其制备方法及其药物用途
WO2008035153A2 (fr) * 2006-08-02 2008-03-27 Orchid Chemicals & Pharmaceuticals Limited Procédé de préparation d'antibiotique bêta-lactame
CN101157647A (zh) * 2007-11-01 2008-04-09 厦门大学 一种合成碳青霉烯类抗生素药物中间体的方法
CN101238098A (zh) * 2005-06-10 2008-08-06 佛罗里达州立大学研究基金有限公司 β-内酰胺的合成
CN113801050A (zh) * 2021-09-27 2021-12-17 山东大学 一种多取代β-内酰胺类化合物及其制备方法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4536334A (en) * 1979-06-28 1985-08-20 Sumitomo Chemical Company, Limited Preparation of β-lactam derivatives
US4751299A (en) * 1983-11-18 1988-06-14 Takeda Chemical Industries, Ltd. Optically active β-lactams and method of their production
JPH03145460A (ja) * 1989-10-27 1991-06-20 Yasuyuki Kita β―ラクタム系化合物の製造法
CN101238098A (zh) * 2005-06-10 2008-08-06 佛罗里达州立大学研究基金有限公司 β-内酰胺的合成
WO2008035153A2 (fr) * 2006-08-02 2008-03-27 Orchid Chemicals & Pharmaceuticals Limited Procédé de préparation d'antibiotique bêta-lactame
CN101134739A (zh) * 2006-09-01 2008-03-05 长春吉大天元化学技术股份有限公司 新的β-内酰胺类化合物及其制备方法及其药物用途
CN101157647A (zh) * 2007-11-01 2008-04-09 厦门大学 一种合成碳青霉烯类抗生素药物中间体的方法
CN113801050A (zh) * 2021-09-27 2021-12-17 山东大学 一种多取代β-内酰胺类化合物及其制备方法

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