(1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridine-3-yl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridine-3-yl)methanone
• 英文别名: (1,4-diazepan-1-yl)-(6-(4-fluorophenoxy)pyridin-3-yl)methanone；(1,4-Diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone；1,4-diazepan-1-yl-[6-(4-fluorophenoxy)pyridin-3-yl]methanone
• 化学式: C₁₇H₁₈FN₃O₂
• 分子量: 315.347
• InChiKey: DJBQOVQBHHGGBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridine-3-yl)methanone 、 环丁酮 在 三乙酰氧基硼氢化钠 、 水 、 potassium carbonate 作用下， 以 乙酸乙酯 为溶剂， 反应 4.25h， 以90%的产率得到(4-cyclobutyl-1,4-diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone
  参考文献：
  名称：

  SUBSTITUTED PYRIDYL AMIDE COMPOUNDS AS MODULATORS OF THE HISTAMINE H3 RECEPTOR

  摘要：

  某些替代吡啶酰胺化合物是组胺H3受体调节剂，可用于治疗组胺H3受体介导的疾病。

  公开号：

  US20070281923A1
• 作为产物：
  描述：

  6-氯烟酸乙酯 在 正己基锂 、 caesium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridine-3-yl)methanone
  参考文献：
  名称：

  First, Second, and Third Generation Scalable Syntheses of Two Potent H₃ Antagonists

  摘要：

  Our teams have recently completed scale-up campaigns for two structurally similar H-3 receptor antagonists. The first and second generation processes were developed for the synthesis of 107 and 125 g batches of (4-cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone center dot HCl (1 center dot HCl). A third generation process was utilized for production of 104 g of 3-((5-(4-cyclobutyl-1,4-diazepane-1-carbonyl)pyridin-2-yl)oxy)benzonitrile center dot HCl (2 center dot HCl). The evolution from first to second generation process was driven by a desire to minimize cost of goods through employment of symmetrical homopiperazine rather than a more expensive monoprotected variant. Project demands for a late stage intermediate that could provide 1 or 2 led to additional route scouting and the ultimate determination of a third scalable synthesis for these types of molecules. The use of a lithium alkoxide for Lewis base catalysis of an ester to amide transformation represents a key improvement for the third generation synthesis.

  DOI：

  10.1021/op200005e

文献信息

• SUBSTITUTED PYRIDYL AMIDE COMPOUNDS AS MODULATORS OF THE HISTAMINE H3 RECEPTOR
  申请人：Keith John M.

  公开号：US20070281923A1

  公开（公告）日：2007-12-06

  Certain substituted pyridyl amide compounds are histamine H 3 receptor modulators useful in the treatment of histamine H 3 receptor-mediated diseases.

  某些替代吡啶酰胺化合物是组胺H3受体调节剂，可用于治疗组胺H3受体介导的疾病。
• Substituted pyridyl amide compounds as modulators of the histamine H3 receptor
  申请人：Janssen Pharmaceutica NV

  公开号：US07777031B2

  公开（公告）日：2010-08-17

  Processes are disclosed for making certain compounds of Formula (II): or their pharmaceutically active salts, that are histamine H3 receptor modulators useful in the treatment of histamine H3 receptor-mediated diseases. In one embodiment, the process comprises reacting a compound of formula (7-1): with a compound of formula (B3): in the presence of at least one equivalent of a first base, in a first organic solvent, to give a compound of Formula (II).

  揭示了制备公式（II）的某些化合物或其药物活性盐的工艺，这些化合物是组胺H3受体调节剂，可用于治疗组胺H3受体介导的疾病。在一种实施方式中，该工艺包括在第一有机溶剂中，在至少一个第一碱当量的存在下，将公式（7-1）的化合物与公式（B3）的化合物反应，以得到公式（II）的化合物。
• Pre-clinical characterization of aryloxypyridine amides as histamine H3 receptor antagonists: Identification of candidates for clinical development
  作者：Michael A. Letavic、Leah Aluisio、John R. Atack、Pascal Bonaventure、Nicholas I. Carruthers、Christine Dugovic、Anita Everson、Mark A. Feinstein、Ian C. Fraser、Kenway Hoey、Xiaohui Jiang、John M. Keith、Tatiana Koudriakova、Perry Leung、Brian Lord、Timothy W. Lovenberg、Kiev S. Ly、Kirsten L. Morton、S. Timothy Motley、Diane Nepomuceno、Michele Rizzolio、Raymond Rynberg、Kia Sepassi、Jonathan Shelton

  DOI：10.1016/j.bmcl.2010.05.041

  日期：2010.7

  The pre-clinical characterization of novel aryloxypyridine amides that are histamine H-3 receptor antagonists is described. These compounds are high affinity histamine H-3 ligands that penetrate the CNS and occupy the histamine H-3 receptor in rat brain. Several compounds were extensively pro. led pre-clinically leading to the identification of two compounds suitable for nomination as development candidates. (C) 2010 Elsevier Ltd. All rights reserved.
• US7777031B2
  申请人：——

  公开号：US7777031B2

  公开（公告）日：2010-08-17
• US8637520B2
  申请人：——

  公开号：US8637520B2

  公开（公告）日：2014-01-28