N-[(2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-N-valeroyl-(L)-valine benzyl ester | 137864-44-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-[(2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-N-valeroyl-(L)-valine benzyl ester
• 英文别名: N-[(2'-(1-triphenylmethyltetrazol-5-yl)biphenyl-4-yl)methyl]-N-valeroyl-(L)-valine benzyl ester；benzyl N-pentanoyl-N-[{2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl]-1,1'-biphenyl-4-yl}methyl]-L-valinate；N-(1-oxopentyl)-N-[[2'-(1-trityl-1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine benzyl ester；N-[(2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-N-valeryl-(L)-valine benzyl ester；trityl benzyl valsartan；benzyl (2S)-3-methyl-2-[pentanoyl-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoate
• CAS: 137864-44-9
• 化学式: C₅₀H₄₉N₅O₃
• 分子量: 767.971
• InChiKey: GZPZPZBRCUIQNZ-MFERNQICSA-N

物化性质

• 沸点：
  895.6±75.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.1
• 重原子数：
  58
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  90.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-N-valeroyl-(L)-valine benzyl ester 在 钯 异丙醇 、 水 、 氢氧化钾 、 甲苯 、 乙酸乙酯 、 raw product 、 环己烷 作用下， 以 甲醇 为溶剂， 反应 26.0h， 以yielded 250 g (67%) of valsartan的产率得到缬沙坦
  参考文献：
  名称：

  Method of preparation of N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-y1) [1,1'-biphenyl]-4-y1]methyl]-L-valine (valsartan)

  摘要：

  从起始的4-溴甲基-2'-（1-三苯甲基四唑-5-基）联苯开始，通过与L-缬氨酸苄酯反应得到式7的N-[(2'-(1-三苯甲基四唑-5-基)联苯-4-基)甲基]-(L)-缬氨酸苄酯，然后通过与戊酰氯反应并去除保护基将其转化为式I的缬沙坦。该方法包括使用盐酸将在第一阶段得到的式7的N-[(2'-(1-三苯甲基四唑-5-基)联苯-4-基)甲基]-(L)-缬氨酸苄酯转化为式III的N-[(2'-(1-三苯甲基四唑-5-基)联苯-4-基)甲基]-(L)-缬氨酸苄酯盐酸盐，可选择性地重结晶。

  公开号：

  US20090192318A1
• 作为产物：
  描述：

  N-(三苯基甲基)-5-(4'-溴甲基联苯-2-基)四氮唑 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 1.0h， 生成 N-[(2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-N-valeroyl-(L)-valine benzyl ester
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF ANGIOTENSIN II ANTAGONISTS AND INTERMEDIATES THEREOF

  摘要：

  本发明涉及一种改进的制备肾素受体拮抗剂及其中间体的方法。特别是本发明涉及一种改进的制备Formula 1中N-(1-oxopentyl)-N-[[2′-(1H-噻唑-5-基)[1,1′-联苯]-4-基]甲基]-L-缬氨酸的方法，通过Formula-4.H3PO3的亚磷酸盐，最好是Formula-4′.H3PO3的亚磷酸盐。

  公开号：

  US20140316142A1

文献信息

• Acyl compounds
  申请人：Ciba-Geigy Corp

  公开号：US05399578A1

  公开（公告）日：1995-03-21

  Compounds of the formula ##STR1## in which R.sub.1 is an aliphatic hydrocarbon radical which is unsubstituted or substituted by halogen or hydroxyl, or a cycloaliphatic or araliphatic hydrocarbon radical; X.sub.1 is CO, SO.sub.2, or --O--C(.dbd.O)-- with the carbon atom of the carbonyl group being attached to the nitrogen atom shown in formula I; X.sub.2 is a divalent aliphatic hydrocarbon radical which is unsubstituted or substituted by hydroxyl, carboxyl, amino, guanidino or a cycloaliphatic or aromatic radical, or is a divalent cycloaliphatic hydrocarbon radical, it being possible for a carbon atom of the aliphatic hydrocarbon radical to be additionally bridged by a divalent aliphatic hydrocarbon radical; R.sub.2 is carboxyl which, if desired, is esterified or amidated, substituted or unsubstituted amino, formyl which, if desired, is acetalized, 1H-tetrazol-5-yl, pyridyl, hydroxyl which, if desired, is etherified, S(O).sub.m --R where m is 0, 1 or 2 and R is hydrogen or an aliphatic hydrocarbon radical, alkanoyl, unsubstituted or N-substituted sulfamoyl or PO.sub.n H.sub.2 where n is 2 or 3; X.sub.3 is a divalent aliphatic hydrocarbon; R.sub.3 is carboxyl, 5-tetrazolyl, SO.sub.3 H, PO.sub.2 H.sub.2, PO.sub.3 H.sub.2 or haloalkylsulfamoyl; and the rings A and B independently of one another are substituted or unsubstituted; in free form or in salt form, can be prepared in a manner known per se and can be used, for example, as medicament active ingredients.

  式为##STR1##的化合物，其中R.sub.1是未取代或取代为卤素或羟基的脂肪烃基，或者是环脂烃或芳基脂肪烃基；X.sub.1是CO、SO.sub.2或--O--C(.dbd.O)--，其中羰基的碳原子连接到式I中显示的氮原子；X.sub.2是未取代或取代为羟基、羧基、氨基、胍基或环脂烃或芳香基的二价脂肪烃基，或者是二价环脂烃脂肪烃基，脂肪烃基的碳原子还可以通过另一个二价脂肪烃基进行桥接；R.sub.2是羧基，如果需要，可以酯化或酰胺化，取代或未取代的氨基，甲酰基，如果需要，可以缩醛化，1H-四唑-5-基，吡啶基，羟基，如果需要，可以醚化，S(O).sub.m --R，其中m为0、1或2，R为氢或脂肪烃基，烷酰基，未取代或N-取代的磺酰胺基或PO.sub.n H.sub.2，其中n为2或3；X.sub.3是二价脂肪烃基；R.sub.3是羧基，5-四唑基，SO.sub.3 H，PO.sub.2 H.sub.2，PO.sub.3 H.sub.2或卤代烷基磺酰胺基；环A和B彼此独立地被取代或未取代；以自由形式或盐形式，可以按已知方法制备，并可用作药物活性成分。
• [EN] A METHOD OF PREPARATION OF N-(1-OXOPENTYL)-N-[[2'-(1H-TETRAZOL-5-y1) [1,1'-BIPHENYL] -4-y1]METHYL]-L-VALINE (VALSARTAN)<br/>[FR] PROCEDE DE PREPARATION DE N-(1-OXOPENTYL)-N-[[2'-(1H-TETRAZOL-5-Y1)[1,1'-BIPHENYL]-4-Y1]METHYL]-L-VALINE (VALSARTAN)
  申请人：ZENTIVA AS

  公开号：WO2004101534A1

  公开（公告）日：2004-11-25

  From the starting 4-bromomethyl-2'-(1-triphenylmethyltetrazol-5-yl)biphenyl, N-[(2'­(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester of formula 7 is obtained via a reaction with L-valine benzyl ester, and is converted to valsartan of formula I via a reaction with valeryl chloride and removing of protective groups. The method consists in converting, with hydrochloric acid, N-[(2'-(l-triphenylmethyl-tetrazol-5-yl)biphenyl-4­yl)methyl]-(L)-valine benzyl ester of formula 7, obtained in the first stage, to N-[(2'-(1-­triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester hydrochloride of formula III, which is optionally re-crystallized.

  从起始的4-溴甲基-2'-(1-三苯基甲基四唑-5-基)联苯，通过与L-缬氨酸苄酯反应，得到公式7的N-[(2'-(1-三苯基甲基-四唑-5-基)联苯基-4-基)甲基]-(L)-缬氨酸苄酯，然后通过与缬酰氯反应并去除保护基将其转化为公式I的缬沙坦。该方法包括将第一阶段获得的公式7的N-[(2'-(1-三苯基甲基-四唑-5-基)联苯基-4-基)甲基]-(L)-缬氨酸苄酯转化为公式III的N-[(2'-(1-三苯基甲基-四唑-5-基)联苯基-4-基)甲基]-(L)-缬氨酸苄酯盐酸盐，随后可选择性地再结晶。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF ANGIOTENSIN II ANTAGONISTS AND INTERMEDIATES THEREOF.<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION D'ANTAGONISTES DE L'ANGIOTENSINE II ET D'INTERMÉDIAIRES DE SYNTHÈSE DE CEUX-CI
  申请人：ALKEM LAB LTD

  公开号：WO2013072924A1

  公开（公告）日：2013-05-23

  The present invention relates to an improved process for the preparation of angiotensin receptor antagonists and intermediates thereof. Particularly the present invention relates to an improved process for the preparation of N-(l-oxopentyl)-N-[[2'-(lH-tetrazoI-5-yl) [1, 1 '-biphenyl]-4-yl] methyl]-L- valine of Formula (1) Formula-1 Formula-4.H3P03 via a phosphite salt of Formula-4.H3P03 preferably a phosphite salt of Formula-4'.H3P03 Ph3C N-[2'-1 -triphenylmethyl-tetra zol-5-yl)biphenyl-4-yl)methyl ]-(L)-Valine Benzyl ester H3P03 salt Formula-4'.H3P03 salt.

  本发明涉及一种改进的制备肾素受体拮抗剂及其中间体的方法。特别是本发明涉及一种改进的制备N-(l-氧代戊基)-N-[[2'-(1H-四氮唑-5-基)[1,1'-联苯]-4-基] 甲基]-L-缬氨酸的方法，其化学式为（1）Formula-1 Formula-4.H3P03，通过一种磷酸酯盐，优选为一种Formula-4.H3P03的磷酸酯盐，Ph3C N-[2'-1-三苯甲基-四氮唑-5-基)联苯-4-基)甲基]-(L)-缬氨酸苄酯H3P03盐Formula-4'.H3P03盐。
• Intermediate Compounds for the Preparation of an Angiotensin II Receptor Antagonist
  申请人：Rafecas Jane Llorenc

  公开号：US20090124577A1

  公开（公告）日：2009-05-14

  It comprises new substituted 4-valinylmethylphenyl boronic acids of formula (II) and their derivatives and also its preparation process. It also comprises a preparation process of Valsartan (I) from such intermediates. The process comprises the reaction of the new 4-valinylmethylphenyl boronic compounds with a (halophenyl)tetrazole compound which proceeds with high yields. The process is particularly advantageous in its practical industrial realization because it avoids the use of azide derivatives and also the use of expensive biphenyl intermediates.

  它包括公式（II）的新取代4-缬氨酸甲基苯硼酸及其衍生物，以及其制备过程。它还包括从这种中间体制备缬沙坦（I）的制备过程。该过程包括将新的4-缬氨酸甲基苯硼化合物与（卤代苯基）四唑化合物反应，反应产率高。该过程在其实际工业实现中特别优越，因为它避免了使用叠氮衍生物和昂贵的联苯中间体。
• Process for Preparing Valsartan
  申请人：Kankan Rajendra Narayanrao

  公开号：US20110105763A1

  公开（公告）日：2011-05-05

  An N-[(2′-(1-triphenyl methyl tetrazole-5-yl)biphenyl]-4-yl]methyl]-L-valine benzyl ester organic salt of formula (IVA) wherein A represents an organic carboxylic acid, a process for its preparation and its use in the synthesis of valsartan or salts thereof.

  一种化学式为(IVA)的有机盐，其化合物为N-[(2′-(1-三苯甲基四唑-5-基)联苯)-4-基]甲基]-L-缬氨酸苄酯，其中A代表有机羧酸，本发明还提供了其制备方法以及在缬沙坦或其盐的合成中的应用。