(3-methoxy[1,5]naphthyridin-4-yl)methyl bromide | 893566-34-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (3-methoxy[1,5]naphthyridin-4-yl)methyl bromide
• 英文别名: 4-(Bromomethyl)-3-methoxy-1,5-naphthyridine
• CAS: 893566-34-2
• 化学式: C₁₀H₉BrN₂O
• 分子量: 253.098
• InChiKey: RISCCLMZGVPXIY-UHFFFAOYSA-N

物化性质

• 沸点：
  367.0±37.0 °C(Predicted)
• 密度：
  1.548±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-methoxy[1,5]naphthyridin-4-yl)methyl bromide 在 potassium acetate 、 甲醇 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以63%的产率得到(3-甲氧基-1,5-萘啶-4-基)甲醇
  参考文献：
  名称：

  Process Development of a Novel Azetidinyl Ketolide Antibiotic

  摘要：

  Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.

  DOI：

  10.1021/op300064b
• 作为产物：
  描述：

  5-甲氧基-4-甲基吡啶-3-胺盐酸盐 在 ferrous(II) sulfate heptahydrate 、 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 sodium 3-nitrobenzene sulfonate 、 硼酸 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 水 为溶剂， 反应 6.0h， 生成 (3-methoxy[1,5]naphthyridin-4-yl)methyl bromide
  参考文献：
  名称：

  Process Development of a Novel Azetidinyl Ketolide Antibiotic

  摘要：

  Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.

  DOI：

  10.1021/op300064b

文献信息

• Macrolides
  申请人：Chupak S. Louis

  公开号：US20060135447A1

  公开（公告）日：2006-06-22

  Macrolide compounds per se, as shown below and defined herein, and their use, e.g., as antibacterial and antiprotozoal agents in animals, including humans: Also disclosed are methods of preparing the compounds, intermediates, and pharmaceutical compositions thereof, and methods of treating or preventing disease by administering the compounds to subjects in need. This abstract is only an excerpt and is not limiting of the invention.

  本发明涉及以下Macrolide化合物及其定义，以及它们在动物中，包括人类中作为抗菌和抗原虫剂的用途：还公开了制备这些化合物、中间体和药物组成物的方法，以及通过将这些化合物用于需要的主体治疗或预防疾病的方法。此摘要仅为摘录，不限制本发明。
• Discovery of Azetidinyl Ketolides for the Treatment of Susceptible and Multidrug Resistant Community-Acquired Respiratory Tract Infections
  作者：Thomas V. Magee、Sharon L. Ripp、Bryan Li、Richard A. Buzon、Lou Chupak、Thomas J. Dougherty、Steven M. Finegan、Dennis Girard、Anne E. Hagen、Michael J. Falcone、Kathleen A. Farley、Karl Granskog、Joel R. Hardink、Michael D. Huband、Barbara J. Kamicker、Takushi Kaneko、Michael J. Knickerbocker、Jennifer L. Liras、Andrea Marra、Ivy Medina、Thuy-Trinh Nguyen、Mark C. Noe、R. Scott Obach、John P. O’Donnell、Joseph B. Penzien、Usa Datta Reilly、John R. Schafer、Yue Shen、Gregory G. Stone、Timothy J. Strelevitz、Jianmin Sun、Amelia Tait-Kamradt、Alfin D. N. Vaz、David A. Whipple、Daniel W. Widlicka、Donn G. Wishka、Joanna P. Wolkowski、Mark E. Flanagan

  DOI：10.1021/jm900729s

  日期：2009.12.10

  Respiratory tract bacterial strains are becoming increasingly resistant to currently marketed macrolide antibiotics. The current alternative telithromycin (1) from the newer ketolide class of macrolides addresses resistance but is hampered by serious safety concerns, hepatotoxicity in particular. We have discovered a novel series of azetidinyl ketolides that focus on mitigation of hepatotoxicity by minimizing hepatic turnover and time-dependent inactivation of CYP3A isoforms in the liver without compromising the potency and efficacy of 1.
• MACROLIDES
  申请人：Pfizer Products Inc.

  公开号：EP1836211B1

  公开（公告）日：2010-03-03
• US7462600B2
  申请人：——

  公开号：US7462600B2

  公开（公告）日：2008-12-09
• Process Development of a Novel Azetidinyl Ketolide Antibiotic
  作者：Bryan Li、Thomas V. Magee、Richard A. Buzon、Daniel W. Widlicka、Dave R. Bill、Thomas Brandt、Xiaoping Cao、Michael Coutant、Haijian Dou、Karl Granskog、Mark E. Flanagan、Cheryl M. Hayward、Bin Li、Fengwei Liu、Wei Liu、Thuy-Trinh Nguyen、Jeffrey W. Raggon、Peter Rose、Joseph Rainville、Usa Datta Reilly、Yue Shen、Jianmin Sun、Glenn E. Wilcox

  DOI：10.1021/op300064b

  日期：2012.5.18

  Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.