3-[5-(4-cyclobutyl[1,4]diazepane-1-carbonyl)pyridin-2-yloxy]benzonitrile | 959740-40-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-[5-(4-cyclobutyl[1,4]diazepane-1-carbonyl)pyridin-2-yloxy]benzonitrile
• 英文别名: 3-[5-(4-Cyclobutyl-[1,4]diazepane-1-carbonyl)-pyridin-2-yloxy]-benzonitrile；3-[5-(4-cyclobutyl-[1,4]-diazepan-1-carbonyl)-pyridin-2-yloxy]-benzonitrile；3-(5-(4-Cyclobutyl-1,4-diazepane-1-carbonyl)pyridin-2-yloxy)benzonitrile；3-[5-(4-cyclobutyl-1,4-diazepane-1-carbonyl)pyridin-2-yl]oxybenzonitrile
• CAS: 959740-40-0
• 化学式: C₂₂H₂₄N₄O₂
• 分子量: 376.458
• InChiKey: WWZNPNMHGHEVNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  69.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[5-(4-cyclobutyl[1,4]diazepane-1-carbonyl)pyridin-2-yloxy]benzonitrile 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 2.0h， 以104.2 g的产率得到3-[5-(4-cyclobutyl[1,4]diazepane-1-carbonyl)pyridin-2-yloxy]benzonitrile hydrochloride
  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
• 作为产物：
  描述：

  高哌嗪 在 potassium carbonate 、 caesium carbonate 作用下， 以 2-甲基-2-丁醇 、 1,1-二氯乙烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 42.5h， 生成 3-[5-(4-cyclobutyl[1,4]diazepane-1-carbonyl)pyridin-2-yloxy]benzonitrile
  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。
• PROCESS FOR THE PREPARATION OF HISTAMINE H3 RECEPTOR MODULATORS
  申请人：Broggini Diego

  公开号：US20120029189A1

  公开（公告）日：2012-02-02

  The present invention is directed to novel processes for the preparation of histamine H3 receptor modulators, in the treatment of for example, cognitive disorders, sleep disorders and/or psychiatric disorders.

  本发明涉及一种新型的组织胺H3受体调节剂制备方法，用于治疗认知障碍、睡眠障碍和/或精神障碍。
• Process for the preparation of histamine H3 receptor modulators
  申请人：Broggini Diego

  公开号：US08748596B2

  公开（公告）日：2014-06-10

  The present invention is directed to novel processes for the preparation of histamine H3 receptor modulators, in the treatment of for example, cognitive disorders, sleep disorders and/or psychiatric disorders.

  本发明涉及一种新型组织胺H3受体调节剂的制备方法，用于治疗认知障碍、睡眠障碍和/或精神障碍等疾病。
• 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.
• [EN] PROCESS FOR THE PREPARATION OF HISTAMINE H3 RECEPTOR MODULATORS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE MODULATEURS DES RÉCEPTEURS D'HISTAMINE H3
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010107897A3

  公开（公告）日：2011-04-14