3-(((1-METHYL-1H-TETRAZOL-5-YL)THIO)METHYL)-7-(2-FORMYLOXY-2-PHENYLACETAMIDO)-3-CEPHEM-4-CARBOXYLIC ACID

• 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: 3-(((1-METHYL-1H-TETRAZOL-5-YL)THIO)METHYL)-7-(2-FORMYLOXY-2-PHENYLACETAMIDO)-3-CEPHEM-4-CARBOXYLIC ACID
• 英文别名: 7-(D-2-formyloxy-2-phenylacetamido)-3-(1-methyl-1H-tetrazol-5-yl-thiomethyl)-3-cephem-4-carboxylic acid；7-(D-2-formyloxy-2-phenylacetamido)-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid；(6R)-7-[(2-formyloxy-2-phenylacetyl)amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• 化学式: C₁₉H₁₈N₆O₆S₂
• 分子量: 490.521
• InChiKey: RRJHESVQVSRQEX-MKTAYPAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  207
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (6R)-3-acetoxymethyl-7t-((Ξ)-2-formyloxy-2-phenyl-acetylamino)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 、 1-甲基-5-巯基-1H-四氮唑 以 四氯化碳 、 1,2-二氯乙烷 为溶剂， 生成 3-(((1-METHYL-1H-TETRAZOL-5-YL)THIO)METHYL)-7-(2-FORMYLOXY-2-PHENYLACETAMIDO)-3-CEPHEM-4-CARBOXYLIC ACID
  参考文献：
  名称：

  Cephalosporin displacement reaction

  摘要：

  本发明涉及一种在有机溶剂和基本无水条件下，通过硫亲核试剂取代头孢菌酸中的乙酰氧基的过程。

  公开号：

  US04144391A1

文献信息

• Process for the preparation of cephalosporin derivatives
  申请人：Korea Advanced of Institute of Science and Technology

  公开号：US04835267A1

  公开（公告）日：1989-05-30

  The present invention relates to an improved process for producing cephalosporin derivatives of formula (I), the 3-position of which being substituted by acetoxymethyl or tetrazolylthiomethyl and the 7-acyl group of which being substituted by D-mandelic acid derivatives, which comprises simultaneously reacting the compound of formula (III) with the compound of formula (IV) in the presence of a compound of formula (II) and anamine in high yield, ##STR1## wherein, R.sup.1 is hydrogen or ##STR2## R.sup.2 is methyl, ethyl, propyl or phenyl, X is ##STR3##

  本发明涉及一种改进的方法，用于生产公式（I）的头孢菌素衍生物，其3位被乙酰氧甲基或四唑基硫甲基取代，7-酰基被D-苯甘酸衍生物取代，其中同时在高产率下通过在化合物公式（III）和化合物公式（IV）的存在下，与化合物公式（II）和胺一起反应，得到以下产物：##STR1## 其中，R.sup.1是氢或##STR2##，R.sup.2是甲基、乙基、丙基或苯基，X是##STR3##。
• Crystalline form of sodium O-formylcefamandole
  申请人：Eli Lilly and Company

  公开号：US04006138A1

  公开（公告）日：1977-02-01

  The cephalosporin antibiotic, sodium 7-(D-.alpha.-formyloxy-.alpha.-phenylacetamido)-3-(1-methyl-1H-tetrazol-5- ylthiomethyl)-3-cephem-4-carboxylate, is provided in a stable, non-solvated anhydrate crystalline form designated as the gamma crystalline form.

  头孢菌素抗生素，即7-（D-.alpha.-甲氧基-.alpha.-苯乙酰胺基）-3-（1-甲基-1H-四唑-5-基硫甲基）-3-头孢烯-4-羧酸钠，以稳定的非溶剂无水晶体形式提供，称为伽玛晶体形式。
• Production of sodium cephamandole derivatives
  申请人：ELI LILLY AND COMPANY

  公开号：EP0007689A1

  公开（公告）日：1980-02-06

  A process for preparing the methanolate crystalline form of sodium cefamandole which comprisesthe step of mixing at a temperature between about 20°C. and about 30°C. a suspension of sodium O-formylcefamandole in methyl alcohol having a ratio of about one gram of sodium 0-formylcefamandole for between about 2.5 ml. and about 3.5 ml. of methyl alcohol, said suspension containing between about 1.5 percent and about 3 percent by volume of water, with a concentrated solution of sodium hydroxide in methyl alcohol in an amount corresponding to about 1 ml. of said concentrated solution per gram of sodium O-formylcefamandole in said suspension. The crystalline sodium cefamandole methanolate can be separated from the suspension and converted to sodium cefamandole anhydrate for pharmaceutical use.

  一种制备头孢孟多钠甲醇溶液结晶形式的工艺，包括以下步骤：在约 20°C 至约 30°C 的温度下，将 O-甲酰基头孢孟多钠在甲醇中的悬浮液与 0-甲酰基头孢孟多钠在约 2.5 毫升至约 3.5 毫升甲醇中的混合比例为约 1 克 0-甲酰基头孢孟多钠。所述悬浮液含有约1.5%至约3%体积的水，以及氢氧化钠在甲醇中的浓溶液，其用量相当于所述悬浮液中每克O-甲酰头孢孟多钠含有约1毫升所述浓溶液。结晶的头孢孟多甲醇钠可以从悬浮液中分离出来，并转化为头孢孟多钠水合物用于制药。
• A method for the preparation of the sodium salt of O-formyl cefamandole
  申请人：TECHNOLOGITSCHEN KOMBINAT SA PROMISCHLENA MIKROBIOLOGIA

  公开号：EP0432297A1

  公开（公告）日：1991-06-19

  This invention refers to a method for the preparation of the broad spectrum antibiotic, sodium cefamandole naph­thate. The object is to provide a technological method warranting a high yield, high purity and stability of the product. The method comprises the following stages: silylation of the initial product 7-amino-3-(1-methyl-1H-­tetrazol-5-yl-thiomethyl)-3-cephem-4-carboxylic acid, acylation and then desilylation. In the method of this invention the desilylation is accompanied by the removal of the solvent. The obtained product is further dissolved in ethylacetate, decolourized, the solvent is removed and the obtained oily product is dissolved in dry methylene chlor­ide, crystallized, separated and dissolved in a non-aqueous medium of two organic solvents and precipitated as sodium salt with sodium acetate or sodium-2-ethylhexanoate.

  本发明涉及一种制备广谱抗生素头孢孟多萘酸钠的方法。 其目的是提供一种技术方法，保证产品的高产率、高纯度和稳定性。 该方法包括以下几个阶段： 初始产物 7-氨基-3-(1-甲基-1H-四唑-5-基硫甲基)-3-头孢-4-羧酸的硅烷化、酰化，然后脱硅。在本发明的方法中，脱硅过程伴随着去除溶剂。得到的产物进一步溶解在乙酸乙酯中，脱溶剂，除去溶剂，得到的油状产物溶解在干二氯甲烷中，结晶，分离，溶解在两种有机溶剂的非水介质中，用乙酸钠或 2-乙基己酸钠沉淀为钠盐。
• US4006138A
  申请人：——

  公开号：US4006138A

  公开（公告）日：1977-02-01