(4-cyclobutyl[1,4]diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone hydrochloride

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-cyclobutyl[1,4]diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone hydrochloride
• 英文别名: (4-cyclobutyl-[1,4]-diazepan-1-yl)-[6-(4-fluorophenoxy)-pyridin-3-yl]-methanone hydrochloride；(4-cyclobutyl-[1,4]diazepan-1-yl)-[6-(4-fluoro-phenoxy)-pyridin-3-yl]-methanone hydrochloride；(4-Cyclobutyl-1,4-diazepan-1-yl)-[6-(4-fluorophenoxy)pyridin-3-yl]methanone;hydrochloride
• 化学式: C₂₁H₂₄FN₃O₂*ClH
• 分子量: 405.9
• InChiKey: BTZJMBZRZXELJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.14
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  45.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  高哌嗪 在 盐酸 、 potassium carbonate 、 caesium carbonate 作用下， 以 2-甲基-2-丁醇 、 乙醚 、 1,1-二氯乙烷 、 乙醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 53.5h， 生成 (4-cyclobutyl[1,4]diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-3-yl]methanone 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

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：Janssen Pharmaceutica NV

  公开号：US10323002B2

  公开（公告）日：2019-06-18

  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.

  本发明涉及组胺 H3 受体调节剂的新型制备工艺，用于治疗认知障碍、睡眠障碍和/或精神障碍等疾病。
• [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
• US20140343279A1
  申请人：——

  公开号：US20140343279A1

  公开（公告）日：2014-11-20