(1R,5S,6S)-2-[(1-(4-fluorobenzyl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylic acid | 878534-37-3

• 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: (1R,5S,6S)-2-[(1-(4-fluorobenzyl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylic acid
• 英文别名: (4R,5S,6S)-3-[1-[(4-fluorophenyl)methyl]azetidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
• CAS: 878534-37-3
• 化学式: C₂₀H₂₃FN₂O₄S
• 分子量: 406.478
• InChiKey: DONWOGZLKWECRU-HOJOPBEUSA-N

物化性质

• 沸点：
  588.3±50.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,5S,6S)-2-[(1-(4-fluorobenzyl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylic acid 、 特戊酸碘甲酯 在 potassium carbonate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以72%的产率得到pivaloyloxymethyl (1R,5S,6S)-2-[(1-(4-fluorobenzyl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate
  参考文献：
  名称：

  [EN] 2-ARYLMETHYLAZETIDINE-CARBAPENEM-3-CARBOXYLIC ACID ESTER DERIVATIVE OR ITS SALT, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  [FR] DÉRIVÉ D' ESTER D'ACIDE 2-ARYLMÉTHYLAZETIDINE-CARBAPENEM-3-CARBOXYLIQUE OU SELS DE CE DÉRIVÉ, PROCESSUS DE PRÉPARATION DE CE COMPOSÉ ET COMPOSITION PHARMACEUTIQUE LE COMPRENANT

  摘要：

  公开号：

  WO2009066917A3
• 作为产物：
  描述：

  potassium (1R,5S,6S)-2-(1-(4-fluorobenzyl)-azetidine-3-yl-thio)-6-[(1R)-1-hydroxylethyl]-1-methylcarbapen-2-em-3-carboxylate 在 水 、 溶剂黄146 作用下， 以95%的产率得到(1R,5S,6S)-2-[(1-(4-fluorobenzyl)azetidin-3-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylic acid
  参考文献：
  名称：

  [EN] 2-ARYLMETHYLAZETIDINE-CARBAPENEM-3-CARBOXYLIC ACID ESTER DERIVATIVE OR ITS SALT, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  [FR] DÉRIVÉ D' ESTER D'ACIDE 2-ARYLMÉTHYLAZETIDINE-CARBAPENEM-3-CARBOXYLIQUE OU SELS DE CE DÉRIVÉ, PROCESSUS DE PRÉPARATION DE CE COMPOSÉ ET COMPOSITION PHARMACEUTIQUE LE COMPRENANT

  摘要：

  公开号：

  WO2009066917A3

文献信息

• ACID ADDITION SALTS OF SYNTHETIC INTERMEDIATES FOR CARBAPENEM ANTIBIOTICS AND PROCESSES FOR PREPARING THE SAME
  申请人：Kim Chang-Seob

  公开号：US20100274003A1

  公开（公告）日：2010-10-28

  The present invention provides a process for preparing an acid addition salt of a synthetic intermediate for carbapenem antibiotics and a novel acid addition salt of a synthetic intermediate for carbapenem antibiotics obtained from the process. The present invention also provides a process for preparing a carbapenem antibiotic using the acid addition salt. According to the process of the present invention, an acid addition salt of a synthetic intermediate for carbapenem antibiotics can be prepared in a high yield and high purity, without conducting column chromatography. Thus, the process of the present invention can be applied to mass production with an industrial scale. Furthermore, since the acid addition salts have solid forms, they are easy to handle and keep in a manufacturing site.

  本发明提供了一种用于制备碳青霉烯抗生素的合成中间体的酸性加成盐的方法，以及通过该方法获得的新的碳青霉烯抗生素合成中间体的酸性加成盐。本发明还提供了一种使用该酸性加成盐制备碳青霉烯抗生素的方法。根据本发明的过程，可以在不进行柱色谱的情况下，以高收率和高度纯净地制备碳青霉烯抗生素的合成中间体的酸性加成盐。因此，本发明的过程适用于工业规模的大规模生产。而且，由于酸性加成盐具有固态形式，因此在制造现场易于处理和保存。
• 2-ARYLMETHYLAZETIDINE-CARBAPENEM-3-CARBOXYLIC ACID ESTER DERIVATIVE OR ITS SALT, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：Choi Young-Ro

  公开号：US20110118229A1

  公开（公告）日：2011-05-19

  The present invention provides a 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivatives or their pharmaceutically acceptable salts show high oral absorption rate, and thus can be orally administered. The active metabolites thereof have a broad spectrum of antibacterial activities against Gram-positive and Gram-negative bacteria and excellent antibacterial activities against methicillin-resistant Staphylococcus aurus (MRSA) and quinolone-resistant strains (QRS). In particular, the acid addition salts of the 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivatives are obtained in crystalline forms having excellent stability.

  本发明提供了2-芳基甲基氮杂环戊烯-碳青霉烯-3-羧酸酯衍生物或其药学上可接受的盐，其制备方法以及包含其的制药组合物。2-芳基甲基氮杂环戊烯-碳青霉烯-3-羧酸酯衍生物或其药学上可接受的盐具有高口服吸收率，因此可以口服给药。其活性代谢物对革兰氏阳性和革兰氏阴性细菌具有广谱的抗菌活性，并且对甲氧西林耐药金黄色葡萄球菌（MRSA）和喹诺酮耐药菌株（QRS）具有优异的抗菌活性。特别是，2-芳基甲基氮杂环戊烯-碳青霉烯-3-羧酸酯衍生物的酸加成盐以晶体形式获得，具有优异的稳定性。
• [EN] 2-ARYLMETHYLAZETIDINE-CARBAPENEM-3-CARBOXYLIC ACID ESTER DERIVATIVE OR ITS SALT, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME<br/>[FR] DÉRIVÉ D' ESTER D'ACIDE 2-ARYLMÉTHYLAZETIDINE-CARBAPENEM-3-CARBOXYLIQUE OU SELS DE CE DÉRIVÉ, PROCESSUS DE PRÉPARATION DE CE COMPOSÉ ET COMPOSITION PHARMACEUTIQUE LE COMPRENANT
  申请人：KUKJE PHARM IND CO LTD

  公开号：WO2009066917A3

  公开（公告）日：2009-07-30