(6-chloropyridin-3-yl)[1,4]diazepan-1-yl-methanone | 1240566-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (6-chloropyridin-3-yl)[1,4]diazepan-1-yl-methanone
• 英文别名: (6-chloropyridin-3-yl)-[1,4]-diazepan-1-yl-methanone；1-[(6-Chloropyridin-3-yl)carbonyl]-1,4-diazepane；(6-chloropyridin-3-yl)-(1,4-diazepan-1-yl)methanone
• CAS: 1240566-92-0
• 化学式: C₁₁H₁₄ClN₃O
• mdl: MFCD16811417
• 分子量: 239.705
• InChiKey: JQGDMBZKNOVOPM-UHFFFAOYSA-N

物化性质

• 沸点：
  422.2±45.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6-chloropyridin-3-yl)[1,4]diazepan-1-yl-methanone 在 caesium carbonate 作用下， 以 1,1-二氯乙烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 35.0h， 生成 (4-cyclobutyl-1,4-diazepan-1-yl)[6-(4-fluorophenoxy)pyridin-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
• 作为产物：
  描述：

  高哌嗪 、 6-氯烟酸乙酯 在 正己基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 18.7h， 以69%的产率得到(6-chloropyridin-3-yl)[1,4]diazepan-1-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

• 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。
• [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
• Org. Process Res. Dev. 2011, 15, 638-648
  作者：

  DOI：——

  日期：——
• US20140343279A1
  申请人：——

  公开号：——

  公开（公告）日：——