7-[(phenoxyacetyl)-amino]-3-hydroxy-3-cephem-4-carboxylic acid, (4-nitrophenyl)methylester

• 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-[(phenoxyacetyl)-amino]-3-hydroxy-3-cephem-4-carboxylic acid, (4-nitrophenyl)methylester
• 英文别名: 4'-nitrobenzyl 7-phenoxyacetamido 3-hydroxy-3-cephem-4-carboxylate；(4-nitrophenyl)methyl (6S)-3-hydroxy-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• 化学式: C₂₂H₁₉N₃O₈S
• 分子量: 485.474
• InChiKey: MSJBRVIZZHKNPL-ZYZRXSCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  176
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  亚磷酸三苯酯 、 7-[(phenoxyacetyl)-amino]-3-hydroxy-3-cephem-4-carboxylic acid, (4-nitrophenyl)methylester 在 吡啶 、 溴 作用下， 以 甲醇 、 ice-water 、 二氯甲烷 、 水 为溶剂， 生成 p-nitrobenzyl 7β-phenoxyacetylamino-3-bromo-3-cephem-4-carboxylate
  参考文献：
  名称：

  Halogenating reagents

  摘要：

  新型卤代试剂源自三芳基膦酸酯和氯或溴。它们可用于将7-酰胺基-3-羟基-3-头孢烷化合物转化为7-酰胺基-3-卤代-3-头孢烷和相应的C-7亚胺卤代头孢烷衍生物。

  公开号：

  US04230644A1

文献信息

• Processes for preparation of beta-lactam compounds
  申请人：ELI LILLY AND COMPANY

  公开号：EP0014567A1

  公开（公告）日：1980-08-20

  Kinetically controlled triaryl phosphite halogen compounds of the formula wherein X is Cl or Br, and Z is hydrogen, halo, C1-C4 alkyl or C1-C4 alkoxy, are used to effect a) halogenation of a C-6 or C-7 acylamine penicillin or cephalosporin, b) halogenation of a 3-hydroxy-3-cephem, c) one step halogenation of a C-7 acylamine-3-hydroxy- cephem d) reduction of a cephalosporin sulfoxide e) one step reduction/halogenation of a 3-hydroxy cephalosporin sulfoxide f) one step reduction/halogenation of a C-7 acylamine cephalosporin sulfoxide g) one step reduction/halogenation of a C-7 acylamino-3-hydroxy cephalosporin sulfoxide.

  动力学控制的三芳基亚磷酸酯卤素化合物的化学式为 其中 X 是 Cl 或 Br，Z 是氢、卤素、C1-C4 烷基或 C1-C4 烷氧基，用于实现 a) C-6 或 C-7 氨基酰青霉素或头孢菌素的卤化、 b) 卤化 3-羟基-3-头孢菌素、 c) C-7 乙酰氨基-3-羟基-头孢的一步卤化反应 d) 还原头孢菌素亚砜 e) 一步还原/卤化 3-羟基头孢菌素亚砜 f) C-7 乙酰氨基头孢菌素亚砜的一步还原/卤化反应 g) C-7 乙酰氨基-3-羟基头孢菌素亚砜的一步还原/卤化反应。
• Halogenating compounds and a process for their production
  申请人：ELI LILLY AND COMPANY

  公开号：EP0015079A1

  公开（公告）日：1980-09-03

  A halogenating compound is described of the general formula which is the kinetically controlled product of the reaction of equivalent amounts of a triaryl phosphite of the formula and chlorine or bromine in a substantially anhydrous inert organic solvent wherein in the above formulas Z is hydrogen, halo, C1-C4 alkyl or C1-C4 alkoxy, and X is Cl or Br.

  描述了一种通式为 是等量的式三芳基亚磷酸酯与氯或溴在基本无水的惰性有机溶剂中反应的动力学控制产物。 和氯或溴在基本无水的惰性有机溶剂中反应的产物，其中上述式子中 Z 为氢、卤素、C1-C4 烷基或 C1-C4 烷氧基，X 为 Cl 或 Br。
• Process for the stabilization of halogenating compound and stabilized halogenating compositions
  申请人：ELI LILLY AND COMPANY

  公开号：EP0015080A1

  公开（公告）日：1980-09-03

  There is described a process for the stabilization of compounds of the general formula wherein X is Cl or Br and Z is hydrogen, halo, C1-C4 alkyl or C1-C. alkoxy, which compounds are the kinetically controlled products of the reaction of equivalent amounts of a triaryl phosphite of the formula and chlorine or bromine in a substantially anhydrous inert organic solvent, which comprises mixing the halogenating compounds in an inert organic solvent with a stabilizing amount of a tertiary amine base or a complexing agent selected from a Lewis acid-metal halide, phosphorous pentachloride or bromine; with the limitation that when X is Cl the complexing agent is not bromine.

  本发明描述了一种通式化合物的稳定化工艺，其中 X 为 Cl 或 Br，Z 为氢、卤素、C1-C4 烷基或 C1-C. 烷氧基。 其中 X 是 Cl 或 Br，Z 是氢、卤素、C1-C4 烷基或 C1-C.烷氧基，该化合物是等量的式三芳基亚磷酸酯与氯或溴在基本无水的惰性有机溶剂中反应的动力学控制产物。 和氯或溴在基本无水的惰性有机溶剂中的反应，其中包括在惰性有机溶剂中将卤化化合物与稳定量的叔胺碱或选自路易斯酸-金属卤化物、五氯化磷或溴的络合剂混合；但当 X 为 Cl 时，络合剂不是溴。
• Thiazolinoazetidinone compounds useful as intermediates for preparing cephalosporins and a process for their preparation
  申请人：ELI LILLY AND COMPANY

  公开号：EP0019387A1

  公开（公告）日：1980-11-26

  Thiazolinoazetidinone compounds are described which are useful as intermediates in the preparation of cephalosporins. They have the general formula wherein R is hydrogen, methoxy, C1-C2 alkoxycarbonyl, C1-C8 alkyl, C1-C8 alkyl monosubstituted with protected hydroxy, Cl-C3 alkoxy or cyano, C2-C8 alkenyl, C2-C8 alkenyl monosubstituted with protected hydroxy, C1-C3 alkoxy or cyano, C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted with protected hydroxy, C1-C3 alkoxy or cyano, OR R' is hydrogen, protected hydroxy, chloro, bromo, C1-C3 alkyl, C1-C3 alkoxy, nitro or cyano; Y is oxygen or a carbon-carbon bond; R3 is protected hydroxy, C1-C4 alkyl or protected amino; m is 0-2; n is 0-2; R1 is a carboxylic acid protecting group; provided that the 1- and 5-position C-H bonds in the resulting thiazolinoazetidinone are in the a-position. These compounds are prepared by an allylic chlorination process in which a chlorine atom is inserted on the saturated methyl group of a 3-methyl-2- but-3-enoate group attached to the thiazolinoazetidinone ring.

  所述噻唑氮杂环丁酮化合物可用作制备头孢菌素的中间体。它们的通式为 其中 R 是氢 甲氧基 C1-C2烷氧基羰基 C1-C8 烷基 被保护羟基、Cl-C3 烷氧基或氰基单取代的 C1-C8 烷基、 C2-C8 烯基 C1-C8烷基、C1-C8烷基与受保护羟基、Cl-C3 烷氧基或氰基的单取代基 C1-C3 烷氧基或氰基的单取代基、 C3-C8 环烷基、 被保护羟基、C1-C3 烷氧基或氰基取代的 C3-C8 环烷基、 或 R' 是氢、受保护羟基、氯、溴、C1-C3 烷基、C1-C3 烷氧基、硝基或氰基； Y 是氧或碳-碳键； R3 是受保护的羟基、C1-C4 烷基或受保护的氨基； m 为 0-2； n 为 0-2； R1 是羧酸保护基；条件是所得噻唑嗪二酮中的 1 位和 5 位 C-H 键位于 a 位。 这些化合物是通过烯丙基氯化工艺制备的，在该工艺中，一个氯原子被插入连接到噻唑嗪酮环上的 3-甲基-2-丁-3-烯酸酯基团的饱和甲基上。
• Process for preparing enamine derivatives, compounds so produced and process for preparing a 3-hydroxy-cephalosporin
  申请人：Lilly Industries Limited

  公开号：EP0019401A1

  公开（公告）日：1980-11-26

  There is described a process for preparing an enamine of formula (IX): where R2 is a carboxylic acid protecting group and R3 is the residue of a carboxylic acid derived acyl group and where R5 and R6 are the same or different C1-4 alkyl or C7-10 aralkyl groups; or taken together with the adjacent nitrogen atom form a heterocyclic ring containing from 4 to 8 carbon atoms and optionally a further heteroatom selected from oxygen and nitrogen; by reacting a compound of formula (XII) : with an amine of formula HNR5R6, the reactant of formula (XII) being prepared by reaction of an appropriate enol derivative with a phosphorus reagent. The enamines of formula (IX) are useful in the preparation of 3-hydroxycephalosporins.

  本发明描述了一种制备式(IX)烯胺的工艺： 其中 R2 是羧酸保护基，R3 是羧酸衍生酰基的残基，R5 和 R6 是相同或不同的 C1-4 烷基或 C7-10 芳烷基；或与相邻的氮原子一起形成含有 4 至 8 个碳原子和任选地另一个选自氧和氮的杂原子的杂环；通过使式 (XII) ： 与式 HNR5R6 的胺反应，式 (XII) 的反应物通过适当的烯醇衍生物与磷试剂反应制备。式（IX）的烯胺可用于制备 3-羟基头孢菌素。