N-(1-(S)-Ethoxycarbonylbutyl)-L-alanine

• 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: N-(1-(S)-Ethoxycarbonylbutyl)-L-alanine
• 英文别名: N-[1-(S)-ethoxycarbonyl-butyl]-(S)-alanine；N-(1-S-carboethoxybutyl)-S-alanine；N-[(S)-1-ethoxycarbonyl-1-butyl]-(S)-alanine；N-[(S)-Ethoxycarbonyl-1-Butyl]-(S)-Alanine；(2S)-2-[(1-ethoxy-1-oxopentan-2-yl)amino]propanoic acid
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: AUVAVXHAOCLQBF-JAMMHHFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(1-(S)-Ethoxycarbonylbutyl)-L-alanine 、 (2S,3aS,7aS)-八氢吲哚-2-羧酸 在 N,N'-羰基二咪唑 作用下， 以 乙腈 为溶剂， 反应 8.0h， 生成 培哚普利
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF THE L-ARGININE SALT OF PERINDOPRIL

  摘要：

  制备式(I)化合物的过程：

  公开号：

  US20130178635A1
• 作为产物：
  描述：

  L-丙氨酸 、 2-氧代戊酸乙酯 在 钯 盐酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 生成 N-(1-(S)-Ethoxycarbonylbutyl)-L-alanine
  参考文献：
  名称：

  Method for synthesis of n-[(s)]-1-carboxybutyl]-(s)-alanine esters and use in synthesis of perindopril

  摘要：

  一种用于工业合成公式（I）化合物的立体选择性过程：其中R代表线性或支链（C1-C6）烷基。应用于普利度洛及其药学上可接受的盐的合成。

  公开号：

  US20030109743A1

文献信息

• [EN] PROCESS FOR PREPARATION OF PERINDOPRIL AND SALTS THEREOF<br/>[FR] PROCEDE DE PREPARATION DE PERINDOPRIL ET DE SELS DE CELUI-CI
  申请人：LUPIN LTD

  公开号：WO2004075889A1

  公开（公告）日：2004-09-10

  A process for preparation of perindopril of formula (II) and salts thereof which is simple, safe, convenient and cost-effective. The process involves reaction of compound of formula (I), wherein X is chlorine or bromine with compound of formula (VII) wherein A signifies that the six-membered ring of the bicyclic system is either saturated or unsaturated, followed by catalytic hydrogenation to give the perindopril of formula (II).

  一种制备分子式为（II）的贝那普利及其盐的方法，该方法简单、安全、方便且具有成本效益。该过程涉及将具有分子式（I）的化合物（其中X为氯或溴）与具有分子式（VII）的化合物（其中A表示双环系统的六元环是饱和的或不饱和的）发生反应，然后进行催化氢化以得到分子式为（II）的贝那普利。
• PHARMACEUTICAL INTERMEDIATES IN THE SYNTHESIS OF ACE-INHIBITORS AND THE USE THEREOF
  申请人：Porcs-Makkay Marta

  公开号：US20100286404A1

  公开（公告）日：2010-11-11

  The compounds of the general Formula (I), wherein R 1 is aryl or alkyl; R 2 represents alkyl; R 3 represents alkyl or aralkyl, are valuable pharmaceutical intermediates, which can be prepared by reacting a compound of the general Formula (IV) (wherein the definitions of R 1 and R 2 are as above), with at least 2 molar equivalents of the compound of the general Formula (VI) (wherein X represents halogen or tertiary butyloxycarbonyloxy group and R 3 is as defined above). The known compounds of the general Formula (II) (wherein R 1 and R 2 are as defined above) are prepared by reacting the compounds of the general Formula (I) with thionyl chloride. The compounds of the general Formula (I) are new intermediates useful in the synthesis of pharmaceutically active ingredients, particularly in the preparation of ACE-inhibitors, e.g. enalapril, perindopril or ramipril.

  通式（I）化合物中，R1为芳基或烷基；R2代表烷基；R3代表烷基或芳基烷基，是有价值的制药中间体。这些中间体可以通过将通式（IV）化合物（其中R1和R2的定义如上所述）与至少2摩尔当量的通式（VI）化合物（其中X代表卤素或叔丁氧羰氧基，R3如上所定义）反应而制备。通式（II）化合物（其中R1和R2如上所定义）是通过将通式（I）化合物与氯化硫酰反应制备而成。通式（I）化合物是在药物活性成分的合成中有用的新中间体，特别是在ACE抑制剂（例如依那普利、贝那普利或雷米普利）的制备中。
• Process for preparation of perindopril and salts thereof
  申请人：Datta Debashish

  公开号：US20060276659A1

  公开（公告）日：2006-12-07

  A process for preparation of perindopril of formula (II) and salts thereof which is simple, safe convenient and cost-effective. The process involves reaction of compound of formula (I), wherein X is chlorine or bromine with compound of formula (VII) wherein A signifies that the six-membered ring of the bicyclic system is either saturated or unsaturated to give compound of formula (VIII), wherein A is as defined above, followed by catalytic hydrogenation of the compound of formula (VIII) thus obtained to give the perindopril of formula (II). The above process for the manufacture of perindopril would specifically avoid the use of harmful chemicals like phosgene or costly coupling agents like dicyclohexylcarbodiimide and 1-hydroxybenxotriazole usually used for such manufacture. The process would also not require any intervention of a catalyst and does not require any alkaline or acidic reaction conditions. Importantly, the process provides for manufacture of perindopril with high stereoselectively giving perindopril (II) having (S)-configuration in all the five chiral centres of the molecule, conforming to pharmacoepeial specifications. The invention also relates to a method for preparation of the compound of formula (I) and also to a method for preparation of N-[(S)- 1 -carbethoxybutyl]-(S)-alanine of formula (III) used in the process.

  一种制备公式（II）的普利度洛及其盐的方法，该方法简单、安全、方便、经济。该方法涉及公式（I）化合物（其中X为氯或溴）与公式（VII）化合物反应（其中A表示双环系统的六元环饱和或不饱和），以得到公式（VIII）化合物（其中A如上所定义），随后对所得的公式（VIII）化合物进行催化氢化，以得到公式（II）的普利度洛。上述制备普利度洛的方法将特别避免使用有害化学品如光气或昂贵的偶联剂如二环己基碳二亚胺和1-羟基苯并三唑通常用于此类制造。该方法也不需要催化剂的干预，也不需要碱性或酸性反应条件。重要的是，该方法提供了高立体选择性的普利度洛制造，使得分子的所有五个手性中心都具有（S）-构型，符合药典规格。本发明还涉及公式（I）化合物的制备方法，以及在该过程中使用的公式（III）N-[(S)-1-羧乙氧基丁基] -（S）-丙氨酸的制备方法。
• Novel method for preparation of crystalline perindopril erbumine
  申请人：Singh Pal Girij

  公开号：US20070149604A1

  公开（公告）日：2007-06-28

  A process for preparation of crystalline perindopril erbumine of formula (II) which exhibits the X-ray (powder) diffraction pattern like that shown in FIG. 2 The process comprises reacting a solution of perindopril of formula (I), in a solvent selected from N,N-dimethylformamide, dimethyl acetals of lower aliphatic aldehydes, dimethyl ketals of lower aliphatic ketones and 1,2-dialkoxyethane with tertiary butylamine and crystallization of the erbumine salt thus obtained by heating the reaction mixture to reflux, filtering hot, cooling gradually to 20° C. to 30° C., and further cooling to 0° C. to 15° C. for 30 minutes to 1 hour and finally filtering off and drying the crystals.

  一种制备式（II）晶体型的依普利酸厄贝林的方法，其展现出类似于图2所示的X射线（粉末）衍射图谱。该方法包括在从N,N-二甲基甲酰胺、低级脂肪醛的二甲基缩醛、低级脂肪酮的二甲基缩酮和1,2-二烷氧基乙烷中选择的溶剂中反应式（I）的依普利酸溶液，与叔丁胺反应，并通过将反应混合物加热至回流，过滤热，逐渐冷却至20°C至30°C，然后进一步冷却至0°C至15°C，保持30分钟至1小时，最后过滤并干燥晶体来结晶得到厄贝林盐。
• Process for the preparation of high purity perindopril
  申请人：Simig Guyla

  公开号：US20070197821A1

  公开（公告）日：2007-08-23

  The invention relates to 1-2(S)-[1(S)-(ethoxycarbonyl)butylamino]propionyl}-(3aS,7aS)octahydroindol-2(S)-carboxylic acid of the Formula I and the t-butylamine salt of the Formula I′ thereof free of contaminations derivable from dicyclohexyl carbodiimide, and a process for the preparation thereof. The invention also relates to new intermediates of the general Formula III (wherein R stands for lower alkyl or aryl lower alkyl). The compound of the Formula I—perindopril—is a known ACE inhibitor.

  本发明涉及公式I的1-2(S)-[1(S)-(ethoxycarbonyl)butylamino]propionyl}-(3aS,7aS)八氢吲哚-2(S)-羧酸及其不含二环己基氨基甲酸酯污染物的t-丁基胺盐的制备方法。本发明还涉及一般公式III的新中间体（其中R代表低碳基或芳基低碳基）。公式I化合物perindopril是一种已知的ACE抑制剂。