L-八氢吲哚-2-羧酸苄酯对甲苯磺酸盐 | 94062-52-9

• 物质功能分类: 化学试剂 - 有机试剂
• 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
• 中文名称: L-八氢吲哚-2-羧酸苄酯对甲苯磺酸盐
• 中文别名: 培多普利中间体；八氢吲哚-2-羧酸苄酯对甲苯磺酸盐；2S-(2alpha,3alpha,beta,7alpha,beta-八氢-1h-吲哚-2-羧酸苯甲酯
• 英文名称: (2S,3aS,7aS)-2-<(benzyloxy)carbonyl>perhydroindole tosylate
• 英文别名: (2S,3aS,7aS)-octahydro-1H-indole-2-carboxylic acid phenylmethyl ester 4-methylbenzenesulfonate；para-toluene sulfonate of benzyl ester of (2S, 3aS, 7aS)-octahydroindole-2-carboxylic acid；(2S,3aS,7aS)-octahydroindole-2-carboxylic acid benzyl ester para-toluene-sulphonate；(2S,3aS,7aS)-octahydro-indole-2-carboxylic acid benzyl ester p-toluenesulfonate；(2S,3aS,7aS)-octahydro-indole-2-carboxylic acid benzyl ester para-toluene sulfonate；octahydro-1H-indole-2-carboxylic acid benzyl ester p-toluenesulfonic acid salt；benzyl (2S,3aS,7aS)-perhydroindole-2-carboxylate para-toluenesulphonate；benzyl (2S,3aS,7aS)-2,3,3a,4,5,6,7,7a-octahydro-1H-indole-2-carboxylate;4-methylbenzenesulfonic acid
• CAS: 94062-52-9
• 化学式: C₇H₈O₃S*C₁₆H₂₁NO₂
• 分子量: 431.553
• InChiKey: PTLASYHTXGUCJU-WDTSGDEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.89
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  L-八氢吲哚-2-羧酸苄酯对甲苯磺酸盐 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、294.18 kPa 条件下， 反应 38.0h， 生成 (2S,3aS,7aS)-1-glycinyl>-2-carboxyperhydroindole tert-butylamine salt
  参考文献：
  名称：

  Configuration and preferential solid-state conformations of perindoprilat (S-9780). Comparison with the crystal structures of other ACE inhibitors and conclusions related to structure-activity relationships

  摘要：

  The conformation of perindoprilat, an antihypertensive drug, is studied in the solid state by X-ray analysis. The resolution of its structure reveals important analogies between its observed conformation and that of several ACE inhibitors of the same family. This comparison points out a constant relative orientation of the functional groups, regardless of the molecular environment. This angular constancy appears to us as not being accidental and is a good argument for the spatial design of the ACE binding site. Although ACE is a carboxydipeptidase, the binding site may not contain two but one unique hydrophobic pocket receiving the C-terminal end of the inhibitors.

  DOI：

  10.1021/jm00106a030
• 作为产物：
  描述：

  (S)-吲哚啉-2-羧酸 在 palladium on activated charcoal 氢气 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 50.0 ℃ 、4.9 MPa 条件下， 反应 22.0h， 生成 L-八氢吲哚-2-羧酸苄酯对甲苯磺酸盐
  参考文献：
  名称：

  Configuration and preferential solid-state conformations of perindoprilat (S-9780). Comparison with the crystal structures of other ACE inhibitors and conclusions related to structure-activity relationships

  摘要：

  The conformation of perindoprilat, an antihypertensive drug, is studied in the solid state by X-ray analysis. The resolution of its structure reveals important analogies between its observed conformation and that of several ACE inhibitors of the same family. This comparison points out a constant relative orientation of the functional groups, regardless of the molecular environment. This angular constancy appears to us as not being accidental and is a good argument for the spatial design of the ACE binding site. Although ACE is a carboxydipeptidase, the binding site may not contain two but one unique hydrophobic pocket receiving the C-terminal end of the inhibitors.

  DOI：

  10.1021/jm00106a030

文献信息

• [EN] AN IMPROVED PROCESS FOR PREPARATION OF PERINDOPRIL INTERMEDIATE<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION D'UN INTERMÉDIAIRE DE PÉRINDOPRIL
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2014057404A1

  公开（公告）日：2014-04-17

  The present invention relates to an improved process for the preparation of (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-lH-indole-2-carboxylic acid benzyl ester( the compound of formula II) comprising reacting (2S,3aS,7aS)-octahydro-1H-indole-2-carboxylic acid phenylmethyl ester 4-methylbenzenesulfonate (the compound of formula III) with N-[(S)-ethoxycarbonyl-1-butyl]-(S)-alanine (the compound of formula IV), using 1-hydroxybenzotriazole (HOBT), dicyclohexylcarbodiimide (DCC) and triethylamine in the presence of toluene as a solvent at a temperature of 5°C to 40°C.

  本发明涉及一种改进的制备过程，用于制备(2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl]辛氢-1H-吲哚-2-羧酸苄酯（化合物式 II），包括将(2S,3aS,7aS)-辛氢-1H-吲哚-2-羧酸苄酯-4-甲基苯磺酸盐（化合物式 III）与N-[(S)-乙氧羰基-1-丁基]-(S)-丙氨酸（化合物式 IV）反应，使用1-羟基苯并三唑（HOBT）、二环己基碳酰亚胺（DCC）和三乙胺，在甲苯存在下，温度为5°C至40°C。
• Process for the synthesis of perindopril and pharmaceutically acceptable salts thereof.
  申请人：Dubuffet Thierry

  公开号：US20070093663A1

  公开（公告）日：2007-04-26

  Process for the industrial synthesis of perindopril of formula (I): and pharmaceutically acceptable salts thereof.

  工业合成perindopril的过程，其化学式为(I)，以及其药用可接受的盐。
• Novel method for synthesissing (2s,3as,7as)-perhydroindole-2-carboxylic acid and the esters thereof and the use thereof for perindopril synthesis
  申请人：Dubuffet Thierry

  公开号：US20060167273A1

  公开（公告）日：2006-07-27

  Process for the synthesis of compounds of formula (I): wherein R represents hydrogen or a protecting group. Application in the synthesis of perindopril and pharmaceutically acceptable salts thereof.

  合成化合物的公式(I)的过程：其中R代表氢或保护基团。在贝利地普利及其药用盐的合成中的应用。
• [EN] NOVEL METHOD FOR PREPARATION OF CRYSTALLINE PERINDOPRIL ERBUMINE<br/>[FR] NOUVELLE METHODE DE PREPARATION DE PERINDOPRIL ERBUMINE CRISTALLINE
  申请人：LUPIN LTD

  公开号：WO2005037788A1

  公开（公告）日：2005-04-28

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

  一种制备结晶盐酸培哌普利的方法，其化学式为(II)，表现出X射线（粉末）衍射图谱，类似于所示图中的图谱。该方法包括将化学式(I)的培哌普利溶液在从N,N-二甲基甲酰胺或低碳链脂肪醛和酮的二甲基缩醛中选择的溶剂中与叔丁胺反应，并通过加热反应混合物至沸腾，热过滤，逐渐冷却至20°C至30°C，进一步冷却至0°C至15°C 30分钟至1小时，最后过滤和干燥晶体来结晶盐酸培哌普利。
• Process for making (2S, 3aS, 7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl) butyl] amino]-1-oxopropyl] octahydro-1H-indole-2-carboxylic acid
  申请人：Kumar Ashok

  公开号：US20060178422A1

  公开（公告）日：2006-08-10

  The present invention discloses a process for the synthesis and isolation of (2S, 3aS, 7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)butyl]amino]-1-oxopropyl] octahydro-1H-indole-2-carboxylic acid and its tert-butylamine salt, by condensing (2S, 3aS, 7aS)-octahydroindole-2-carboxylic acid benzyl ester and N[(S)1-carboxybutyl]-(S)-alanine ethyl ester in nonreactive solvents in turn avoiding the formation of impurity viz. N-acetyl (2S,3aS,7aS)-octahydroindole-2-carboxylic acid benzyl ester (Formula V). The de-protection of benzyl ester group is optimized and then isolation of the product from aqueous layer by extraction using an organic solvent, which eliminates the need of lyophilization. The process of the present invention yields perindopril erbumnine salt of Formula 1B free of contaminants derivable from dicyclohexylcarbodiimide and impurities originated by the use of ethyl acetate.

  本发明揭示了一种合成和分离(2S, 3aS, 7aS)-1-[(2S)-2-[[(1S)-1-(乙氧羰基)丁基]氨基]-1-氧代丙基]辛烷基-1H-吲哚-2-羧酸及其叔丁基胺盐的方法，通过在非反应性溶剂中依次将(2S, 3aS, 7aS)-辛烷基-1H-吲哚-2-羧酸苄酯和N[(S)1-羧基丁基]-(S)-丙氨酸乙酯缩合，避免形成杂质，即N-乙酰(2S,3aS,7aS)-辛烷基-1H-吲哚-2-羧酸苄酯（式V）。苄酯基的去保护经过优化，然后通过有机溶剂的萃取从水层中分离产物，从而消除了冷冻干燥的需要。本发明的方法使得得到的盐酸贝利普利酯盐（Formula 1B）不含有由二环己基碳酰胺和乙酸乙酯使用产生的杂质。