WO2012027951A1 - Intermédiaire utilisé pour la préparation du médicament imipénème, son procédé de préparation et son utilisation - Google Patents

Intermédiaire utilisé pour la préparation du médicament imipénème, son procédé de préparation et son utilisation Download PDF

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Publication number
WO2012027951A1
WO2012027951A1 PCT/CN2011/001365 CN2011001365W WO2012027951A1 WO 2012027951 A1 WO2012027951 A1 WO 2012027951A1 CN 2011001365 W CN2011001365 W CN 2011001365W WO 2012027951 A1 WO2012027951 A1 WO 2012027951A1
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WO
WIPO (PCT)
Prior art keywords
group
formula
compound
aryl
reaction
Prior art date
Application number
PCT/CN2011/001365
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English (en)
Chinese (zh)
Inventor
张工
张艳丽
Original Assignee
上海巴迪生物医药科技有限公司
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 上海巴迪生物医药科技有限公司 filed Critical 上海巴迪生物医药科技有限公司
Publication of WO2012027951A1 publication Critical patent/WO2012027951A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/51—Y being a hydrogen or a carbon atom
    • 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

Definitions

  • the asymmetric hydrogenation reaction is relatively simple, but the preparation of the terminal olefinic compound is relatively difficult.
  • Aldol condensation aldol condensation
  • Reformatsky Revelsky reaction
  • most Aldd condensation reactions rely on compounds having a particular cyclic structural auxiliary group such as 2-oxazolidinone, such as 1,3 -oxazole-2. -thione, 1,3-thiazole-2-thione, as described in U.S. Patent Nos. 4,791,207, 5,104,984, and European Patent Publication No. EP 197432.
  • reaction route is as follows -
  • R 2 S0 2 C1 is a sulfonyl chloride compound
  • R 2 is an aryl group, a fluorenyl group or an aryl fluorenyl group, and the aryl group, fluorenyl group or aryl fluorenyl group may further have a substituent.
  • R 1 represents a d-C 3 lower hydrocarbon group, a nitro group, a halogenated group or the like which is optionally substituted at a position.
  • R 2 preferably includes phenyl, tolyl, chlorophenyl, nitrophenyl, benzyl or methyl.
  • R 1 is a lower hydrocarbon group of ⁇ , including, for example, methyl, trifluoromethyl, trichloromethyl, ethyl, n-propyl, isopropyl, etc.; when R 1 is a halogen group, Including fluorine atoms, chlorine atoms, and bromine atoms And iodine atoms and the like.
  • the basic condition may be lithium hydroxide, sodium hydroxide or the like, but a mild alkaline hydrolysis condition such as lithium hydroxide/hydrogen peroxide is preferred; the amount of the base is equivalent to the formula (V of 2.0) 4.0 equivalent; The reaction temperature is selected from -10 to 25 ° C, and the reaction time is from 4.0 to 8.0 h.
  • Example 2 The procedure was the same as in Example 1 and Example 2 except that 4-chlorobenzenesulfonyl chloride 13.5 g (0.1 mol) and R-1-m-toluethylamine 22.1 g (0.105 mol) were used to give a white powder. 34.6 g (yield 78.2%) 2-bromo-N-(4-chlorophenylsulfonyl)-N-((R)-1-m-toluethylethyl)propanamide.
  • the mixture was allowed to stand for stratification, and the aqueous phase was collected; the organic phase was suction filtered, and the reaction flask, the separatory funnel and the filter residue were separately washed with a 1% NaOH solution, and the filtrate was layered to obtain an aqueous layer, and the aqueous layer was combined.
  • the aqueous phase was transferred to a reaction flask, 60 ml of ethyl acetate was added, and the temperature was lowered to 0 to 5 ° C, stirred, and 4N hydrochloric acid brine was added dropwise to a pH of 2 to 3.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un intermédiaire utilisé pour la préparation du médicament imipénème, son procédé de préparation et son utilisation. Ledit intermédiaire est illustré par la structure de formule (I), dans laquelle R1 représente un groupe alkyle inférieur en C1 à C3, nitryle, un atome d'halogène ou d'hydrogène substitué en n'importe quelle position; R2 représente un groupe aryle, alkyle ou arylalkyle; ledit groupe aryle, alkyle ou arylalkyle contient ou ne contient pas de groupe substituant. L'intermédiaire est préparé par réaction d'aniline avec du chlorure de sulfuryle, et ensuite réaction du produit avec du bromure de 2-bromo-propionyle en présence de base organique. L'intermédiaire peut être utilisé dans la synthèse des carbapénèmes, c'est-à-dire, l'intermédiaire clé de la béta-méthylazétidin-2-one (4BMA) d'imipénème. Le procédé présente les avantages d'un procédé simple, de matières premières peu onéreuses faciles à obtenir, de coût bas, de recyclage du précurseur après sa récupération, de stéréo-sélectivité et de rendement élevés.
PCT/CN2011/001365 2010-09-02 2011-08-16 Intermédiaire utilisé pour la préparation du médicament imipénème, son procédé de préparation et son utilisation WO2012027951A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201010272764.8 2010-09-02
CN 201010272764 CN101973915B (zh) 2010-09-02 2010-09-02 一种合成培南类药物的中间体及其制备方法和应用

Publications (1)

Publication Number Publication Date
WO2012027951A1 true WO2012027951A1 (fr) 2012-03-08

Family

ID=43573833

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2011/001365 WO2012027951A1 (fr) 2010-09-02 2011-08-16 Intermédiaire utilisé pour la préparation du médicament imipénème, son procédé de préparation et son utilisation

Country Status (2)

Country Link
CN (1) CN101973915B (fr)
WO (1) WO2012027951A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101973915B (zh) * 2010-09-02 2013-06-26 上海巴迪生物医药科技有限公司 一种合成培南类药物的中间体及其制备方法和应用
CN102491992A (zh) * 2011-11-24 2012-06-13 山东润泽制药有限公司 一种碳青霉烯类抗生素关键中间体4-bma的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6340751B1 (en) * 1998-07-24 2002-01-22 Takasago International Corporation Process for the preparation of 4-substituted azetidinone derivatives
WO2005033120A1 (fr) * 2003-10-02 2005-04-14 Takasago International Corporation Procede pour produire un derive de capbapenem
CN101973915A (zh) * 2010-09-02 2011-02-16 上海巴迪生物医药科技有限公司 一种合成培南类药物的中间体及其制备方法和应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6340751B1 (en) * 1998-07-24 2002-01-22 Takasago International Corporation Process for the preparation of 4-substituted azetidinone derivatives
WO2005033120A1 (fr) * 2003-10-02 2005-04-14 Takasago International Corporation Procede pour produire un derive de capbapenem
CN101973915A (zh) * 2010-09-02 2011-02-16 上海巴迪生物医药科技有限公司 一种合成培南类药物的中间体及其制备方法和应用

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Publication number Publication date
CN101973915B (zh) 2013-06-26
CN101973915A (zh) 2011-02-16

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