(6R,7R)-7-[[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;dihydrochloride

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (6R,7R)-7-[[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;dihydrochloride
• 化学式: C19H26Cl2N6O5S2
• 分子量: 553.5
• InChiKey: XQQAUWFZBOTKFQ-OJYPLKCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.52
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  201
• 氢给体数：
  4
• 氢受体数：
  11

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。
• [EN] PROCESS FOR PREPARATION OF CEFEPIME DIHYDROCHLORIDE MONOHYDRATE<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE DICHLORHYDRATE DE CÉFÉPIME MONOHYDRATÉ
  申请人：NECTAR LIFESCIENCES LTD

  公开号：WO2011121389A1

  公开（公告）日：2011-10-06

  A process for preparation of cefepime dihydrochloride monohydrate is provided. The process comprises condensing 7-amino-3-[(l -methyl- 1 -pyrrolidino)methyl]-3-cephem-4-carboxylate monohydrochloride dihydrate and 2-mercaptobenzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate in the presence of a base in an alcohol solvent.

  提供一种制备头孢匹罗啉二盐酸盐一水合物的方法。该方法包括在醇溶剂中，在碱的存在下，将7-氨基-3-[(l-甲基-1-吡咯啉基)甲基]-3-头孢-4-羧酸单盐酸盐二水合物和2-巯基苯并噻唑基-(Z)-2-(2-氨基噻唑-4-基)-2-甲氧基亚胺乙酸酯进行缩合。
• Processes for the preparations of cefepime
  申请人：Sandoz AG

  公开号：EP2218723A2

  公开（公告）日：2010-08-18

  The invention relates to new processes for the preparation of 1-[[(6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)methoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methyl-pyrrolidinium dihydrochloride hydrate (cefepime dihydrochloride monohydrate).

  本发明涉及制备头孢吡肟二盐酸盐一水合物（cefepime dihydrochloride monohydrate）的新工艺。
• Process for preparing pure cephalosporine intermediates
  申请人：Parthasaradhi Reddy Bandi

  公开号：US20070111980A1

  公开（公告）日：2007-05-17

  The present invention relates to a process for preparing key intermediates for cephalosporin antibiotics substantially free of undesired Δ 2 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 trimethylsilyl iodide in cyclohexane, desilylated with isopropyl alcohol and treated with hydrochloric acid to obtain [6R-(6α,7β)]-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-(6α,7β)]-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关键中间体的方法，该方法基本上不含不需要的Δ2异构体。因此，将7-氨基头孢烷酸（7-ACA）在环己烷中回流温度下与六甲基二硅氮烷硅化，得到（6R，7R）-3-[(乙酰氧)甲基]-7-(三甲基硅基)氨基头孢-3-烯-4-酸，然后将其与N-甲基吡咯烷和三甲基硅基碘混合物在环己烷中反应，用异丙醇去除硅基，再用盐酸处理，得到[6R-(6α,7β)]-1-[[7-氨基-2-羧基-8-氧代-5-硫-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。然后，用syn-2-(2-氨基噻唑-4-基)-2-甲氧基亚硝基乙酸2-苯并噻唑基硫酯（MAEM）对[6R-(6α,7β)]-1-[[7-氨基-2-羧基-8-氧代-5-硫-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进行N-酰化，然后用盐酸处理，得到头孢哌酮二盐酸盐一水合物。
• 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。