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WO2016058467A1 - Procédé de préparation de phosphate de tédizolide - Google Patents

Procédé de préparation de phosphate de tédizolide Download PDF

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Publication number
WO2016058467A1
WO2016058467A1 PCT/CN2015/089734 CN2015089734W WO2016058467A1 WO 2016058467 A1 WO2016058467 A1 WO 2016058467A1 CN 2015089734 W CN2015089734 W CN 2015089734W WO 2016058467 A1 WO2016058467 A1 WO 2016058467A1
Authority
WO
WIPO (PCT)
Prior art keywords
phosphate
compound
preparing
pyridine
methyltetrazol
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.)
Ceased
Application number
PCT/CN2015/089734
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English (en)
Chinese (zh)
Inventor
许学农
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.)
ZHEREN PHARMACEUTICAL NANJING Co Ltd
Suzhou Miracpharma Technology Co Ltd
Original Assignee
ZHEREN PHARMACEUTICAL NANJING Co Ltd
Suzhou Miracpharma Technology 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 ZHEREN PHARMACEUTICAL NANJING Co Ltd, Suzhou Miracpharma Technology Co Ltd filed Critical ZHEREN PHARMACEUTICAL NANJING Co Ltd
Publication of WO2016058467A1 publication Critical patent/WO2016058467A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

Definitions

  • the invention belongs to the technical field of organic synthesis route design and preparation technology of raw materials and intermediates, and particularly relates to a preparation method of a novel oxazolidinone antibiotic phosphotidazole.
  • Tedizolid phosphate is an oxazolidinone antibiotic developed by Cubist Pharmaceuticals. Tedizolid phosphate was approved by the US FDA in June 2014 and is marketed under the trade name Sivextro. This drug is the first second-generation oxazolidinone antibiotic to be approved by the FDA. Compared with the first-generation product linezolid, Sivextro has 2-8 times higher inhibitory activity against some bacteria, and the safety is also somewhat Improved. Since the compound Tedizolid does not yet have a standard Chinese translation, the applicant hereby transliterates it as "tedizamide.”
  • Tedizolid phosphate is ⁇ (5R)-3-[3-fluoro-4-[6-(2-methyl-2H-tetrazole-5-yl)pyridine-3- Phenyl]-2-oxazol-5-yl ⁇ methanol phosphate (I), the structural formula is:
  • 2-(2-methyltetrazol-5-yl)-5-bromopyridine (Intermediate A) is an azide via 2-cyano-5-bromopyridine
  • the reaction produces a tetrazolyl derivative, and the methylation reagent such as methyl iodide or dimethyl sulfate is used to methylate the tetrazole ring to obtain 2-(2-methyltetrazole-5- a mixture of 5-bromopyridine (intermediate A) and 2-(1-methyltetrazol-5-yl)-5-bromopyridine (by-product), which is isolated by column chromatography or recrystallization.
  • the methylation reagent such as methyl iodide or dimethyl sulfate
  • the intermediate B or B' is an organotin reagent or an organoboron reagent prepared by R-3-(3-fluoro-4-iodophenyl)-2-oxo-5-oxazolidinemethanol, which is passed through The Stille or Suzuki coupling reaction allows coupling to Intermediate A.
  • the existing preparation methods have weaknesses such as long preparation steps, difficult to obtain raw materials, and high cost; the preparation and use of organotin reagents have high requirements on equipment and environment, and there are hidden dangers of environmental pollution. Further, the simultaneous presence of fluorine and iodine of the halogen in the intermediate B or B' structure lowers the selectivity in the formation of the organometallic reagent, increases the side reaction, and makes it difficult to effectively control the product quality.
  • the object of the present invention is to provide a preparation method of teridinamine phosphate which is easy to obtain raw materials, simple in process, economical and environmentally friendly, and suitable for industrialization, in view of the defects in the prior art.
  • the present invention adopts the following main technical solutions: a preparation method of teridinamine phosphate (I),
  • the preparation step comprises the steps of: coupling a compound of the formula II with a compound of the formula III to form teridinamine (I).
  • R is hydrogen, methyl, ethyl, propyl, isopropyl, phenyl or pinacol
  • the corresponding compound of formula II is 2-(2-methyltetrazol-5-yl).
  • Pyridine-5-boric acid dimethyl 2-(2-methyltetrazol-5-yl)pyridine-5-borate, 2-(2-methyltetrazol-5-yl)pyridine-5-borate Ethyl ester, 2-(2-methyltetrazol-5-yl)pyridine-5-borate dipropyl ester, 2-(2-methyltetrazol-5-yl)pyridine-5-borate diisopropyl ester, 2-(2-methyltetrazol-5-yl)pyridine-5-boronic acid diphenyl ester or 2-(2-methyltetrazol-5-yl)pyridine-5-boronic acid pinamate.
  • the halogen X in the compound of the formula III is bromine or iodine, and the corresponding compound of the formula III is, in turn, R-3-(3-fluoro-4-bromo-phenyl)-2-oxo-5-oxazolidinylalkylmethanol Phosphate or R-3-(3-fluoro-4-iodo-phenyl)-2-oxo-5-oxazole alkyl methanol phosphate.
  • the molar ratio of the compound of the formula II to the compound of formula III in the coupling reaction is from 1:0.5 to 1.5, preferably from 1:0.9 to 1.1.
  • the catalyst for the coupling reaction is palladium chloride, palladium acetate, bis(dibenzylideneacetone)palladium, tetrakis(triphenylphosphine)palladium, [1,1'-bis(diphenylphosphino)ferrocene Palladium dichloride, bis(tricyclohexylphosphine)palladium dichloride or bis(triphenylphosphine)palladium dichloride, preferably tetrakis(triphenylphosphine)palladium or [1,1'-bis(diphenyl) Phosphine) ferrocene] palladium dichloride.
  • the base promoter of the coupling reaction is potassium carbonate, sodium carbonate, barium carbonate, barium fluoride, potassium acetate or potassium phosphate, preferably barium carbonate or potassium phosphate.
  • the solvent for the coupling reaction is acetonitrile, 1,4-dioxane, toluene, xylene, N,N-dimethylformamide, N,N-dimethylacetamide or dimethyl sulfoxide, preferably 1,4-dioxane or toluene.
  • the temperature of the coupling reaction is from 50 to 150 ° C, preferably from 80 to 130 ° C.
  • the preparation method of the teridinamine phosphate (I) according to the invention has the characteristics of easy availability of raw materials, simple process and environmental protection economy, thereby facilitating the industrial production of the raw material drug and promoting its economic technology. development of.
  • Embodiment 1 is a diagrammatic representation of Embodiment 1:
  • Embodiment 2 is a diagrammatic representation of Embodiment 1:
  • Embodiment 3 is a diagrammatic representation of Embodiment 3

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

L'invention concerne un procédé de préparation de phosphate de tédizolide (I) et l'étape de préparation associée consiste à produire du phosphate de tédizolide (I) au moyen d'une réaction de couplage d'un composé de formule II et d'un composé de formule III. Le procédé de préparation utilise des matières premières facilement disponibles et un procédé simple, est économique et respectueux de l'environnement, et est approprié pour une production industrielle.
PCT/CN2015/089734 2014-10-17 2015-09-16 Procédé de préparation de phosphate de tédizolide Ceased WO2016058467A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201410553205.2A CN104327119A (zh) 2014-10-17 2014-10-17 磷酸泰地唑胺的制备方法
CN201410553205.2 2014-10-17

Publications (1)

Publication Number Publication Date
WO2016058467A1 true WO2016058467A1 (fr) 2016-04-21

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PCT/CN2015/089734 Ceased WO2016058467A1 (fr) 2014-10-17 2015-09-16 Procédé de préparation de phosphate de tédizolide

Country Status (2)

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CN (1) CN104327119A (fr)
WO (1) WO2016058467A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112500433A (zh) * 2020-12-23 2021-03-16 桂林南药股份有限公司 一种磷酸特地唑胺的制备方法
CN113563679A (zh) * 2021-08-31 2021-10-29 戴科元 一种阻燃抗菌pvc材料及其制备方法
CN113979835A (zh) * 2021-11-14 2022-01-28 重庆医科大学 一种帕唑帕尼三聚体杂质中间体的合成方法
US11555033B2 (en) 2020-06-18 2023-01-17 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof

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WO2016041505A1 (fr) * 2014-09-17 2016-03-24 正大天晴药业集团股份有限公司 Phosphate de tédizolide, intermédiaire et procédé de préparation correspondants
CN106928214A (zh) * 2014-09-17 2017-07-07 博瑞生物医药（苏州）股份有限公司 一种噁唑烷酮类化合物及其中间体的制备方法
CN104327119A (zh) * 2014-10-17 2015-02-04 苏州明锐医药科技有限公司 磷酸泰地唑胺的制备方法
CN105837634B (zh) * 2015-01-30 2020-09-04 上海创诺制药有限公司 一种泰地唑胺磷酸酯结晶体及其制备方法
CN104592218B (zh) * 2015-02-13 2015-11-04 江苏欧信医药化工有限公司 一种泰地唑胺的合成方法
CN104892592A (zh) * 2015-03-30 2015-09-09 成都惟新医药科技有限公司 一种泰地唑胺的制备方法
CN106146485B (zh) * 2015-04-01 2021-04-30 上海迪赛诺化学制药有限公司 一种制备泰地唑胺的方法及其得到的泰地唑胺结晶体
CN110078764B (zh) * 2015-04-10 2021-10-26 博瑞生物医药（苏州）股份有限公司 一种噁唑烷酮类化合物的制备方法
CN106279282B (zh) * 2015-05-21 2019-08-23 博瑞生物医药（苏州）股份有限公司 一种磷酸特地唑胺的纯化方法
CN106608884A (zh) * 2015-10-27 2017-05-03 博瑞生物医药（苏州）股份有限公司 泰地唑胺合成中间体的晶型
CN106632298B (zh) * 2015-11-03 2021-06-01 上海科胜药物研发有限公司 一种泰地唑胺的制备方法及其中间体
CN105418681A (zh) * 2015-12-15 2016-03-23 南京艾德凯腾生物医药有限责任公司 一种磷酸特地唑胺的制备方法
CN105753904B (zh) * 2016-04-22 2017-12-08 南京济群医药科技股份有限公司 一种磷酸特地唑胺的精制方法
CN107382995A (zh) * 2017-09-01 2017-11-24 杭州新博思生物医药有限公司 一锅法合成泰地唑胺
CN115873026B (zh) * 2022-09-29 2025-12-05 石药集团欧意药业有限公司 特地唑胺中间体及磷酸特地唑胺的制备方法

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WO2009020616A1 (fr) * 2007-08-06 2009-02-12 Micurx Pharmaceuticals, Inc. Orthofluorophényle oxazolidinones antimicrobiennes pour le traitement d'infections bactériennes
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CN104327119A (zh) * 2014-10-17 2015-02-04 苏州明锐医药科技有限公司 磷酸泰地唑胺的制备方法

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WO2006038100A1 (fr) * 2004-10-08 2006-04-13 Ranbaxy Laboratories Limited Derives d'oxazolidinone utilises comme agents antimicrobiens
WO2009020616A1 (fr) * 2007-08-06 2009-02-12 Micurx Pharmaceuticals, Inc. Orthofluorophényle oxazolidinones antimicrobiennes pour le traitement d'infections bactériennes
WO2010042887A2 (fr) * 2008-10-10 2010-04-15 Trius Therapeutics Procédés pour préparer des oxazolidinones et compositions contenant celles-ci
CN104327119A (zh) * 2014-10-17 2015-02-04 苏州明锐医药科技有限公司 磷酸泰地唑胺的制备方法

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11555033B2 (en) 2020-06-18 2023-01-17 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof
US11566023B2 (en) 2020-06-18 2023-01-31 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof
US12116361B2 (en) 2020-06-18 2024-10-15 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof
US12145928B2 (en) 2020-06-18 2024-11-19 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof
CN112500433A (zh) * 2020-12-23 2021-03-16 桂林南药股份有限公司 一种磷酸特地唑胺的制备方法
CN113563679A (zh) * 2021-08-31 2021-10-29 戴科元 一种阻燃抗菌pvc材料及其制备方法
CN113979835A (zh) * 2021-11-14 2022-01-28 重庆医科大学 一种帕唑帕尼三聚体杂质中间体的合成方法
CN113979835B (zh) * 2021-11-14 2023-09-26 重庆医科大学 一种帕唑帕尼三聚体杂质中间体的合成方法

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