(3R)-8-hydroxy-7-(3-hydroxy-3-phenylpropyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide | 856449-27-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: (3R)-8-hydroxy-7-(3-hydroxy-3-phenylpropyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide
• 英文别名: 8-hydroxy-7-((R)-3-hydroxy-3-phenylpropyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide；(3R)-8-hydroxy-7-(3-hydroxy-3-phenyl-propyl)-2,3-dimethyl-imidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide；8-Hydroxy-7-[(3R)-3-hydroxy-3-phenyl-propyl]-2,3-dimethyl-imidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide；8-hydroxy-7-[(3R)-3-hydroxy-3-phenylpropyl]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
• CAS: 856449-27-9
• 化学式: C₂₁H₂₅N₃O₃
• 分子量: 367.448
• InChiKey: ZTLQIHQKRFRFGN-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R)-8-hydroxy-7-(3-hydroxy-3-phenylpropyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 1.33h， 以58%的产率得到(9S)-2,3-dimethyl-9-phenyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide
  参考文献：
  名称：

  7H-8,9-二氢吡喃并[2,3-c]咪唑并[1,2-a]吡啶类化合物的合成和评价。

  摘要：

  鉴定出具有优异的理化和药理特性的7H-8,9-二氢吡喃并[2,3-c]咪唑并[1,2-a]吡啶，它们可作为钾竞争性酸阻滞剂（P-CABs）的进一步开发。按照合成途径制备标题化合物，所述合成途径依赖于克莱森重排/交叉复分解反应或前手性酮的（不对称）还原。研究了取代基R3，R6和Ar的特性对目标化合物的生物学活性和理化性质的影响。与母体系统（R6 = H）相反，其中R6代表羧酰胺残基的化合物通常显示出更高的体内活性和有利的pKa / log D值。尽管R3的变化可用于获得具有改良的碱性和亲脂性的目标化合物，但仅对于R3 =甲基，观察到了对H + / K + -ATPase的强抑制作用和有效的体内活性。允许对芳基进行小的修饰，例如氢取代氟原子或甲基。（9S）-对映异构体负责胃酸分泌抑制作用，而（9R）-对映异构体实际上是无活性的。

  DOI：

  10.1021/jm7010063
• 作为产物：
  描述：

  8-hydroxy-2,3-dimethyl-7-(3-oxo-3-phenylpropyl)imidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide 在 RuCI₂[(S)-BINAP][(S)-DAIPEN] potassium tert-butylate 、 氢气 作用下， 以 异丙醇 为溶剂， 20.0 ℃ 、4.0 MPa 条件下， 反应 24.75h， 以92%的产率得到(3R)-8-hydroxy-7-(3-hydroxy-3-phenylpropyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxylic acid dimethylamide
  参考文献：
  名称：

  [EN] TRICYCLIC IMIDAZOPYRIDINES FOR USE AS GASTRIC SECRETION INHIBITORS
  [FR] IMIDAZOPYRIDINES TRICYCLIQUES UTILISEES COMME INHIBITEURS DE SECRETION GASTRIQUE

  摘要：

  这项发明提供了化合物的公式（1），其中取代基和符号如描述中所定义。这些化合物抑制胃酸的分泌。

  公开号：

  WO2005058325A1

文献信息

• Tricyclic imidzopyridines for use as gastric secretion inhibitors
  申请人：Palmer Andreas

  公开号：US20070066674A1

  公开（公告）日：2007-03-22

  The invention provides compounds of the formula 1, in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.

  该发明提供了式1的化合物，其中取代基和符号如描述中所定义。这些化合物可抑制胃酸分泌。
• Intermediates for the preparation of tricyclic dihydropyrano-imidazo-pyridines derivatives
  申请人：Altana Pharma AG

  公开号：US07326784B2

  公开（公告）日：2008-02-05

  The invention relates to compounds of the formula 1, in which R1, R2, R3, Arom and PG have the meanings as indicated in the description. These compounds are valuable intermediates for the preparation of pharmaceutically active compounds.

  本发明涉及公式1的化合物，其中R1、R2、R3、Arom和PG的含义如说明书中所示。这些化合物是制备具有药理活性化合物的有价值的中间体。
• Preparation of tricyclic imidazopyridines by asymmetric ketone hydrogenation in the presence of RuCl2[(S)-Xyl-P-Phos][(S)-DAIPEN]
  作者：Andreas Marc Palmer、Antonio Zanotti-Gerosa、Hans Nedden

  DOI：10.1016/j.tetasy.2008.05.013

  日期：2008.6

  The novel complex RuCl2[(S)-Xyl-P-Phos][(S)-DAIPEN] was identified as a highly active catalyst for the asymmetric reduction of a variety of prochiral ketones possessing an imidazo[1,2-a]pyridine scaffold. The corresponding alcohols were obtained in excellent enantiomeric purities (>96% ee) and served as valuable intermediates for the synthesis of pharmacologically active 7H-8,9-dihydropyrano[2,3-c]imidazo[ 1,2-alpyridines. The complexity of these multi-functional substrates required the development of specific reaction conditions. Whereas the reduction with RuCl2[PP][NN] catalysts (Noyori catalysts) has never been reported to occur under aqueous conditions, in the present case, the use of aqueous isopropanol or tert-butanol was not only tolerated, but also turned out to be beneficial, especially when the reduction was conducted at high substrate to catalyst (S/C) ratios. (C) 2008 Elsevier Ltd. All rights reserved.
• WO2007/141253
  申请人：——

  公开号：——

  公开（公告）日：——
• Preparation of tricyclic imidazopyridines by asymmetric ketone hydrogenation in the presence of ruthenium phosphino-oxazoline catalyst
  作者：Andreas M. Palmer、Ulrike Nettekoven

  DOI：10.1016/j.tetasy.2007.10.013

  日期：2007.10

  The asymmetric hydrogenation of the prochiral heterocyclic ketone 2 and its O-protected analogues 9 to 11 in the presence of the ruthenium POX catalyst RuCl2(PPh3)(Ph2P-Fc-oxa(i)Pr) was studied. The reactivity of the substrate and the enantioselectivity of the reduction depended on the nature of the protecting group. The best results were achieved with the thexyldimethylsilyl protecting group: The corresponding alcohol 13 was obtained in 86% yield and 88% ee and constitutes a valuable intermediate for the synthesis of the potassium-competitive acid blocker BYK 311319 1. (c) 2007 Elsevier Ltd. All rights reserved.