7-[α-(2-Aminothiazol-4-yl)-α-(Z)-methoxyiminoacetamido]-3-[(1-methyl-1-pyrrolidinio) methyl]-3-cephem-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 7-[α-(2-Aminothiazol-4-yl)-α-(Z)-methoxyiminoacetamido]-3-[(1-methyl-1-pyrrolidinio) methyl]-3-cephem-4-carboxylate
• 英文别名: 7-[2-(2-aminothiazol-4-yl)-2-(Z)methoxyiminoacetamido]-3-[(1-methyl-1-pyrrolidinio)methyl]ceph-3-em-4-carboxylate；(6S)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(1-methylpyrrolidin-1-ium-1-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• 化学式: C₁₉H₂₄N₆O₅S₂
• 分子量: 480.569
• InChiKey: HVFLCNVBZFFHBT-LIALDOLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  204
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (6R,7R)-7-amino-3-[(1-methyl-1-pyrrolidinio)methyl]ceph-3-em-4-carboxylate monohydriodide 、 4-甲基-2-戊酮 在 sodium hydroxide 、 硫酸 、 1-羟基苯并三唑 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 7-[α-(2-Aminothiazol-4-yl)-α-(Z)-methoxyiminoacetamido]-3-[(1-methyl-1-pyrrolidinio) methyl]-3-cephem-4-carboxylate
  参考文献：
  名称：

  Cephalosporin intermediates

  摘要：

  公式为##STR1##的稳定的、结晶的头孢菌素中间体，其中X为HI或HCl，Nu和Nu.sup..sym.是通过硫原子或环氮原子连接的某些含氮杂环，分别基本上不含.DELTA..sup.2异构体；上述化合物的制备过程和中间体；以及广谱头孢菌素抗生素的制备过程。

  公开号：

  US04714760A1

文献信息

• [EN] PROCESS FOR PREPARING PURE CEPHALOSPORINE INTERMEDIATES<br/>[FR] PROCEDE DE PREPARATION D'INTERMEDIAIRES DE CEPHALOSPORINE PURES
  申请人：HETERO DRUGS LTD

  公开号：WO2006008749A1

  公开（公告）日：2006-01-26

  The present invention relates to a process for preparing key intermediates for cephalosporin antibiotics substantially free of undesired delta A2 isomer. Thus, 7-aminocephalosporanic acid (7-ACA) is silylated with hexamethyldisilazane in cyclohexane at reflux temperature. (6R,7R)-3-[(Acetyloxy)methyl]-7-(trimethylsilyl)aminoceph-3-em-4-oic acid obtained is reacted with the mixture of N-methylpyrrolidine and trimethylsilyliodide in cyclohexane, desilylated with isopropyl alcohol and treated with hydrochloric acid to obtain [6R-(6a,7b)]-1-[[7-Amino-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium inner salt hydrochloride. [6R-(6a,7b)]-1-[[7-Amino-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium inner salt hydrochloride is N-acylated with syn-2-(2-aminothiazol-4-yl)-2-methoxyimino acetic acid 2-benzothiazolyl thioester (MAEM) followed by treatment with hydrochloric acid to give cefepime dihydrochloride monohydrate.

  本发明涉及一种制备头孢菌素抗生素的关键中间体的方法，该方法基本上不含不需要的δA2异构体。因此，7-氨基头孢菌酸（7-ACA）在环己烷中与六甲基二硅氮烷在回流温度下硅化。得到的（6R,7R）-3-[(乙酰氧)甲基]-7-(三甲基硅基)氨基头孢-3-烯-4-酸与N-甲基吡咯烷和三甲基硅碘酸酯的混合物在环己烷中反应，用异丙醇脱硅，然后用盐酸处理，得到[6R-(6a,7b)]-1-[[7-氨基-2-羧基-8-氧代-5-硫代-1-氮杂双环[4.2.0]辛-2-烯-3-基]甲基]-1-甲基吡咯烷内盐盐酸盐。[6R-(6a,7b)]-1-[[7-氨基-2-羧基-8-氧代-5-硫代-1-氮杂双环[4.2.0]辛-2-烯-3-基]甲基]-1-甲基吡咯烷内盐盐酸盐与syn-2-(2-氨基噻唑-4-基)-2-甲氧基亚氨基乙酸2-苯并噻唑基硫酯（MAEM）N-酰化，然后用盐酸处理，得到头孢哌酮二盐酸盐一水合物。
• Novel intermediates for synthesis of cephalosporins and process for preparation of such intermediates
  申请人：Datta Debashish

  公开号：US20060135761A1

  公开（公告）日：2006-06-22

  A novel 4-halo-2-oxyimino-3-oxo butyric acid-N,N-dimethyl formiminium chloride chlorosulfate of formula (I) useful in the preparation of cephalosporin antibiotics wherein X is chlorine or bromine; R is hydrogen, C 1-4 alkyl group, an easily removable hydroxyl protective group, —CH 2 COOR 5 , or —C(CH 3 ) 2 COOR 5 , wherein R 5 is hydrogen or an easily hydrolysable ester group. The compound of formula (I) is prepared by reacting 4-halo-2-oxyimino-3-oxobutyric acid of formula (IV 1 ), wherein X, R and R 5 are as defined above, with N,N-dimethylformiminium chloride chlorosulphate of formula (VII) in an organic solvent at a temperature ranging from −30° C. to −15° C. The cephalosporins that may be prepared from the intermediate include cefdinir, cefditoren pivoxil, cefepime, cefetamet pivoxil, cefixime, cefmenoxime, cefodizime, cefoselis, cefotaxime, cefpirome, cefpodoxime proxetil, cefquinome, ceftazidime, cefteram pivoxil, ceftiofur, ceftizoxime, ceftriaxone and cefuzonam.

  本发明涉及一种化合物，其化学式为（I），该化合物为一种新型的4-卤代-2-氧基亚胺基-3-酮丁酸-N，N-二甲基甲酰亚胺氯磺酸盐，可用于头孢菌素类抗生素的制备。其中，X为氯或溴；R为氢、C1-4烷基、易于去除的羟基保护基、—CH2COOR5或—C(CH3)2COOR5，其中，R5为氢或易水解的酯基。该化合物可通过将化学式为（IV1）的4-卤代-2-氧基亚胺基-3-酮丁酸（其中，X、R和R5如上所述）与化学式为（VII）的N，N-二甲基甲酰亚胺氯磺酸盐在有机溶剂中在温度范围为-30℃至-15℃反应制备而成。从中间体中可以制备头孢菌素，包括头孢地尼、头孢地奈、头孢哌酮、头孢替安、头孢克肟、头孢菌素、头孢哌醇、头孢普罗胺、头孢曲松、头孢他嗪、头孢噻肟、头孢替拉孜和头孢唑南。
• Crystalline dihydrate of a cephalosporin dihydrochloride salt and injectable compositions thereof
  申请人：Bristol-Myers Squibb Company

  公开号：EP0587121A1

  公开（公告）日：1994-03-16

  The present invention relates to a new crystalline dihydrochloride dihydrate salt of the cephalosporin antibiotic, cefepime. In particular, this invention provides a temperature and moisture stable crystalline dihydrochloride dihydrate form of cefepime having enhanced stability and a specific x-ray powder diffraction pattern as described herein. The present invention also provides physical admixtures of the new crystalline dihydrochloride dihydrate salt of cefepime with a pharmaceutically acceptable non-toxic organic or inorganic base. In particular, this invention provides physical admixtures of a temperature and moisture stable crystalline dihydrochloride dihydrate form of cefepime having a specific X-ray powder diffraction pattern as described herein with L(+) arginine.

  本发明涉及头孢菌素类抗生素头孢吡肟的一种新的结晶二盐酸盐二水合物。特别是，本发明提供了一种温度和湿度稳定的头孢吡肟二盐酸盐二水合物结晶形式，具有更高的稳定性和本文所述的特定 X 射线粉末衍射图样。本发明还提供了头孢吡肟的新型结晶二盐酸盐二水合物与药学上可接受的无毒有机或无机碱的物理混合物。特别是，本发明提供了具有本文所述特定 X 射线粉末衍射图样的头孢吡肟二盐酸盐二水合物晶体的温度和湿度稳定型与 L（+）精氨酸的物理混合物。
• A stably storable and readily water soluble composition of cephalosporin for injections
  申请人：MEIJI SEIKA KAISHA LTD.

  公开号：EP0695548A1

  公开（公告）日：1996-02-07

  A stably storable and readily water soluble composition for use in preparing injections and containing Cefditoren, namely a cephalosporin of the formula is now provided, which composition comprises a physical mixture of Cefditoren or a non-toxic salt thereof with a proportion of arginine and/or lysine and/or a non-toxic salt thereof. This new composition of Cefditoren can be stored for long periods of time without discoloration and without undesirable reduction in the antibacterial activity, and the composition can be dissolved completely and quickly in water.

  一种用于配制注射剂并含有头孢地托伦的稳定可贮存且易溶于水的组合物，即一种头孢菌素，其式为 该组合物由头孢妥仑或其无毒盐与一定比例的精氨酸和/或赖氨酸和/或其无毒盐的物理混合物组成。这种新的头孢妥仑组合物可以长期保存，不会变色，抗菌活性也不会降低，而且该组合物可以完全快速地溶解在水中。
• PROCESS FOR PREPARING CEPHALOSPORIN INTERMEDIATES
  申请人：Bristol-Myers Company

  公开号：EP0233271A1

  公开（公告）日：1987-08-26