2-butyl-4-chloro-1-<<2'-<(triphenylmethyl)tetrazol-5-yl>biphenyl-4-yl>methyl>imidazole-5-carboxaldehyde | 133910-00-6

• 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: 2-butyl-4-chloro-1-<<2'-<(triphenylmethyl)tetrazol-5-yl>biphenyl-4-yl>methyl>imidazole-5-carboxaldehyde
• 英文别名: 2-butyl-5-chloro-3-[2'-(2-trityl-2H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazole-4-carbaldehyde；2-n-Butyl-4-chloro-1-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-imidazole-5-carboxaldehyde；2-n-butyl-4-chloro-1-{[2'-(2-triphenylmethyl-2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]methyl}-1H-imidazole-5-carbaldehyde；2-Butyl-4-chloro-1-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-1H-Imidazole-5-carboxaldehyde; N-Trityl Losartan Carboxaldehyde；2-butyl-5-chloro-3-[[4-[2-(2-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carbaldehyde
• CAS: 133910-00-6
• 化学式: C₄₁H₃₅ClN₆O
• 分子量: 663.221
• InChiKey: QZDHSVQYGMONFS-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于氯仿、二氯甲烷、二甲基甲酰胺、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  49
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  78.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-butyl-4-chloro-1-<<2'-<(triphenylmethyl)tetrazol-5-yl>biphenyl-4-yl>methyl>imidazole-5-carboxaldehyde 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 氯沙坦甲醛
  参考文献：
  名称：

  非肽血管紧张素II受体拮抗剂：发现了一系列N-（联苯基甲基）咪唑类有效的口服活性降压药。

  摘要：

  制备了一系列新的非肽血管紧张素II（AII）受体拮抗剂。这些N-（联苯基-甲基）咪唑，例如2-丁基-1-[[（2'-羧基联苯-4-基）甲基] -4-氯-5-（羟甲基）咪唑，不同于先前报道的N-（苯甲酰氨基苄基）咪唑和相关化合物，因为它们在口服时产生有效的降压作用；较早的系列通常仅在静脉内给药时才有效。已经发现联苯的2'-位的酸性基团是必不可少的。仅邻位取代的酸具有对AII受体的高亲和力和良好的口服降压效能。羧酸基团已被各种酸性等排体取代，并且发现四唑环是最有效的。四唑衍生物DuP 753

  DOI：

  10.1021/jm00112a031
• 作为产物：
  描述：

  cozaar 在 manganese(IV) oxide 、 三甲胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 5.58h， 生成 2-butyl-4-chloro-1-<<2'-<(triphenylmethyl)tetrazol-5-yl>biphenyl-4-yl>methyl>imidazole-5-carboxaldehyde
  参考文献：
  名称：

  Synthesis and evaluation of new designed multiple ligands directed towards both peroxisome proliferator-activated receptor-γ and angiotensin II type 1 receptor

  摘要：

  Because of the complex biological networks, many pathologic disorders fail to be treated with a molecule directed towards a single target. Thus, combination therapies are often necessary, but they have many drawbacks. An alternative consists in building molecules intended to interact with multiple targets, called designed multiple ligands. We followed such a strategy in order to treat metabolic syndrome, by setting up molecules directed towards both type 1 angiotensin II (AT(1)) receptor and peroxisome proliferator-activated receptor-gamma (PPAR-gamma). For this purpose, many molecules were prepared by merging both pharmacophores following three different strategies. Their ability to activate PPAR-gamma and to block AT(1) receptors were evaluated in vitro. This strategy led to the preparation of many new PPAR-gamma activating and AT(1) blocking molecules. Among them, some exhibited both activities, highlighting the convenience of this approach. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.08.082

文献信息

• Process for preparing biphenyltetrazole compounds
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US05310928A1

  公开（公告）日：1994-05-10

  Method for the preparing biphenyltetrazole compounds which are angiotensin II receptor antagonists or which are useful intermediates to prepare angiotensin II receptor antagonists. An illustrative biphenyl tetrazole compound is 2-n-butyl-4-chloro-1-[(2'-(tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-im idazole-5-methanol, potassium salt.

  制备双苯基四唑化合物的方法，这些化合物是血管紧张素II受体拮抗剂，或者是制备血管紧张素II受体拮抗剂的有用中间体。一个示例性的双苯基四唑化合物是2-正丁基-4-氯-1-[(2'-(四唑-5-基)-1,1'-联苯基-4-基)甲基]-1H-咪唑-5-甲醇，钾盐。
• Tetrazolylphenylboronic acid intermediates for the synthesis of AII
  申请人：——

  公开号：US05130439A1

  公开（公告）日：1992-07-14

  Novel tetrazolylphenylboronic acids, methods for their preparation, and their use in the syntheses of angiotensin II receptor antagonists are disclosed.

  揭示了新型四唑基苯硼酸、其制备方法以及其在合成血管紧张素II受体拮抗剂中的应用。
• [EN] A PROCESS FOR PREPARATION OF 2-N-BUTYL -4-CHLORO - 1 - {[2`- (2-TRIPHENYLMETHYL - 2H - TETRAZOLE - 5- YL) - 1, 1' - BIPHENYL-4-YL] METHYL}-LH- IMIDAZOIE-5-METHANOL (INTERMEDIATE OF LOSARTAN)<br/>[FR] PROCEDE DE PREPARATION DU 2-N-BUTYL-4-CHLORO-1-{[2'-(2-TRIPHENYLMETHYL-2H-TETRAZOLE-5-YL)-1,1'-BIPHENYL-4-YL]METHYL}-IH-IMIDAZOLE-5-METHANOL (INTERMEDIAIRE DU LOSARTAN)
  申请人：MATRIX LAB LTD

  公开号：WO2006038223A1

  公开（公告）日：2006-04-13

  The present invention relates to a process for preparation of N-substituted heterocyclic derivative,2-n-Butyl-4-chloro- 1 - [2' -(2-triphenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl -4-yl] methyl} -lH-imidazole-5-methanol, an important intermediate in the synthesis of Losartan and its pharmaceutically acceptable salts using phase transfer catalyst and minimal number of solvents with improved yield.

  本发明涉及一种制备N-取代杂环衍生物，2-正丁基-4-氯-1-[2'-(2-三苯甲基-2H-四唑-5-基)-1,1'-联苯-4-基]甲基}-1H-咪唑-5-甲醇的工艺，该化合物是洛卡特普的合成中的重要中间体，使用相转移催化剂和最少量的溶剂，产率得到改进。
• Process for the preparation of losartan
  申请人：Veera Reddy Arava

  公开号：US20100222597A1

  公开（公告）日：2010-09-02

  The invention relates to a improved process for the preparation of Losartan and its potassium salt, which comprises: (i) reacting bromo OTBN with BCFI in the presence of a base and a phase transfer catalyst to produce a cyano aldehyde; reacting the formed cyano aldehyde with sodium azide in the presence of tributyl tin chloride to produce aldehyde tetrazole; reducing the formed aldehyde tetrazole with sodium borohydride to produce Losartan; and, if desired, converting the formed Losartan to its potassium salt by known method.

  这项发明涉及一种改进的制备洛卡特普及其钾盐的方法，包括：(i) 在碱和相转移催化剂的存在下，将溴代OTBN与BCFI反应以产生氰基醛；将形成的氰基醛与叠氮化钠在三丁基锡氯化物存在下反应以产生醛四唑；用硼氢化钠还原形成的醛四唑以产生洛卡特普；如有需要，通过已知方法将形成的洛卡特普转化为其钾盐。
• A process for the preparation of losartan derivatives by chlorination and reduction of the respective 1H-imidazole-5-carbaldehydes
  申请人：KRKA, D.D., Novo Mesto

  公开号：EP1741711A1

  公开（公告）日：2007-01-10

  The invention provides a process for the preparation of a sartan derivative of formula (I): wherein R = C2-C7 straight or branched alkyl or C3-C9 cycloalkyl, or a pharmaceutically acceptable salt thereof, comprising the steps of chlorinating and reducing, in any order, a compound of formula (III): wherein R is defined as above to form a compound of formula (VI), wherein R is defined as above and then deprotecting said compound of formula (VI) to obtain the sartan derivative of formula (I), and optionally converting said sartan derivative into one of its pharmaceutically acceptable salts. A preferred embodiment of this invention is a process for the preparation of losartan and, particularly, its potassium salt.

  本发明提供了一种制备公式（I）的萨替洛尔衍生物的过程：其中R = C2-C7直链或支链烷基或C3-C9环烷基，或其药学上可接受的盐，包括以下步骤：在任意顺序下进行氯化和还原，以形成公式（VI）的化合物，其中R如上所述，然后去保护该公式（VI）的化合物以获得公式（I）的萨替洛尔衍生物，并可选择将该萨替洛尔衍生物转化为其药学上可接受的盐之一。本发明的一种优选实施方案是制备洛卡新和特别是其钾盐的过程。