头孢丙烯杂质7 | 111900-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: 头孢丙烯杂质7
• 英文名称: (6R,7R)-7-[2-amino-2-(4-hydroxyphenyl)acetamido]-3-[(Z)-propenyl]-3-cephem-4-carboxylic acid monohydrate
• 英文别名: Cefzil；(6R,7R)-7-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(E)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;hydrate
• CAS: 111900-24-4
• 化学式: C₁₈H₁₉N₃O₅S*H₂O
• 分子量: 407.447
• InChiKey: ALYUMNAHLSSTOU-CIRGZYLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.12
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  159
• 氢给体数：
  5
• 氢受体数：
  8

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：有限的信息表明，头孢丙烯在乳汁中产生的水平较低，预计不会对哺乳婴儿造成不良影响。偶尔有报道称，使用头孢菌素会破坏婴儿的胃肠道菌群，导致腹泻或鹅口疮，但这些影响尚未得到充分评估。头孢丙烯在哺乳期母亲中是可以接受的。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Limited information indicates that cefprozil produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with cephalosporins, but these effects have not been adequately evaluated. Cefprozil is acceptable in nursing mothers. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为产物：
  描述：

  头孢丙烯(E)-异构体 在 水 、 乙酸乙酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 头孢丙烯杂质7
  参考文献：
  名称：

  Process for preparation of 7-[α-amino (4-hydroxyphenyl) acetamido]-3-substituted-3-cephem-4-carboxylic acid

  摘要：

  一种制备高纯度、基本无杂质的7-[D-α-氨基-α-(4-羟基苯基)乙酰氨基]-3-(1-丙烯-1-基)-3-头孢烯-4-羧酸，即式(I)的方法，包括选择试剂的加入顺序和温度，制备混合酸酐，并将其与保护的7-APCA缩合；随后进行水解、分离和纯化，得到单水合物形式的式(I)的头孢唑酯。

  公开号：

  US07427692B2

文献信息

• Process for preparation of 7-[alpha-amino (4-hydroxyphenyl) acetamido]-3-substituted-3-cephem-4-carboxylic acid
  申请人：Tyagi Dutt Om

  公开号：US20050113570A1

  公开（公告）日：2005-05-26

  A process for preparation of 7-[D-α-amino-α-(4-hydroxyphenyl)acetamido]-3-(1-propen-1-yl)-3-cephem-4-carboxylic acid viz. Cefprozil of formula (I) igh purity, substantially free of impurities, which comprises preparation of mixed acid anhydride by selecting the sequence and temperature of addition of the reagents and its subsequent condensation with a protected 7-APCA; followed by hydrolysis, isolation and purification to give Cefprozil of formula (I) in the form of a monohydrate.

  一种制备高纯度、基本无杂质的7-[D-α-氨基-α-(4-羟基苯基)乙酰氨基]-3-(1-丙烯-1-基)-3-头孢烯-4-羧酸，即化学式(I)的方法，包括通过选择试剂的加入顺序和温度制备混合酸酐，并将其与保护的7-APCA缩合；随后进行水解、分离和纯化，以得到一水合物形式的化学式(I)的头孢唑酯。
• Process for preparation of 7-[a-amino (4-hydroxyphenyl) acetamido]-3-substituted-3-cephem-4-carboxylic acid
  申请人：Tyagi Dutt Om

  公开号：US20060149096A1

  公开（公告）日：2006-07-06

  A process for preparation of 7-[D-α-amino-α-(4-hydroxyphenyl)acetamido]-3-(1-propen-1-yl)-3-cepham-4-carboxylic acid viz. Cefprozil of formula (I) igh purity, substantially free of impurities, which comprises preparation of mixed acid anhydride by selecting the sequence and temperature of addition of the reagents and its subsequent condensation with a protected 7-APCA; followed by hydrolysis, isolation and purification to give Cefprozil of formula (I) in the form of a monohydrate.

  一种制备高纯度、基本无杂质的7-[D-α-氨基-α-(4-羟基苯基)乙酰氨基]-3-(1-丙烯-1-基)-3-头孢-4-羧酸（式(I)）的方法，包括通过选择试剂的加入顺序和温度制备混合酸酐，然后与保护的7-APCA缩合；随后进行水解、分离和纯化，得到一水合物形式的式(I)的Cefprozil。
• Process for preparation of 7-[α-Amino (4-hydroxyphenyl) acetamido]-3-substituted-3-cephem-4-carboxylic acid
  申请人：Lupin Ltd.

  公开号：US07230097B2

  公开（公告）日：2007-06-12

  A process for preparation of 7-[D-α-amino-α-(4-hydroxyphenyl)acetamido]-3-(1-propen-1-yl)-3-cephem-4-carboxylic acid viz. Cefprozil of formula (I) in high purity, substantially free of impurities, which comprises preparation of mixed acid anhydride by selecting the sequence and temperature of addition of the reagents and its subsequent condensation with a protected 7-APCA; followed by hydrolysis, isolation and purification to give Cefprozil of formula (I) in the form of a monohydrate.

  一种制备高纯度、基本无杂质的7-[D-α-氨基-α-(4-羟基苯基)乙酰氨基]-3-(1-丙烯-1-基)-3-头孢烯-4-羧酸，即公式（I）的头孢普罗酯的方法，包括通过选择试剂加入的顺序和温度制备混合酸酐，并将其与保护的7-APCA缩合；随后进行水解、分离和纯化，得到以单水合物形式存在的公式（I）的头孢普罗酯。
• NOVEL PROCESS FOR PREPARATION OF CEFPROZIL INTERMEDIATE
  申请人：PARTHASARADHI REDDY Bandi

  公开号：US20090048460A1

  公开（公告）日：2009-02-19

  The present invention relates to a process for preparing a key intermediate of cefprozil and use of this intermediate in the preparation of cefprozil thereby avoiding impurity-causing self-acylation. [R-(Z)]-[4-hydroxy-α-[(3-methoxy-1-methyl-3-oxo-1-propenyl)amino]] benzeneacetic acid, mono potassium salt is reacted with ethyl chloroformate to obtain mixed anhydride which is then silylated with N,O-bis(trimethylsilyl)acetamide. The silylated compound obtained is reacted with [7-trimethylsilylamino-3-(Z/E-propen-1-yl)-3-cephem-4-carboxylic acid]trimethylsilyl ester and deprotected with aqueous hydrochloric acid to give cefprozil.

  本发明涉及一种制备头孢普罗酯的关键中间体的方法，以及利用该中间体在制备头孢普罗酯过程中避免产生杂质引起的自酰化。首先将[R-(Z)]-[4-羟基-α-[(3-甲氧基-1-甲基-3-酮基-1-丙烯基)氨基]]苯乙酸单钾盐与氯甲酸乙酯反应得到混合酸酐，然后用N，O-双(三甲基硅基)乙酰胺对其进行硅化反应。得到的硅化化合物与[7-三甲基硅氨基-3-(Z/E-丙烯-1-基)-3-头孢烯-4-羧酸]三甲基硅酯发生反应，并用水盐酸去保护，最终得到头孢普罗酯。
• Novel Process For Preparation of Cefprozil Intermediate
  申请人：Parthasaradhi Reddy Bandi

  公开号：US20080281093A1

  公开（公告）日：2008-11-13

  The present invention relates to a process for preparing a key intermediate of cefprozil and use of this intermediate in the preparation of cefprozil thereby avoiding impurity-causing self-acylation. [R-(Z)]-[4-hydroxy-α-[(3-methoxy-1-methyl-3-oxo-1-propenyl)amino]]benzeneacetic acid, mono potassium salt is reacted with ethyl chloroformate to obtain mixed anhydride which is then silylated with N,O-bis(trimethylsilyl)acetamide. The silylated compound obtained is reacted with [7-trimethylsilylamino-3-(Z/E-propen-1-yl)-3-cephem-4-carboxylic acid]trimethylsilyl ester and deprotected with aqueous hydrochloric acid to give cefprozil.

  本发明涉及一种制备头孢普罗酯的关键中间体的方法，以及利用该中间体在制备头孢普罗酯过程中避免自酰化引起的杂质。将[R-(Z)]-[4-羟基-α-[(3-甲氧基-1-甲基-3-氧代-1-丙烯基)氨基]]苯乙酸单钾盐与氯甲酸乙酯反应，得到混合酐，然后用N，O-双(三甲基硅基)乙酰胺硅化。所得到的硅化合物与[7-三甲基硅氨基-3-(Z/E-丙烯基)-3-头孢烯-4-羧酸]三甲基硅酯反应，并用水盐酸脱保护，得到头孢普罗酯。