6-amino-5-bromopyridine 2-carboxylic acid | 1221629-04-4

• 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-amino-5-bromopyridine 2-carboxylic acid
• 英文别名: 6-Amino-5-bromopicolinic acid；6-amino-5-bromopyridine-2-carboxylic acid
• CAS: 1221629-04-4
• 化学式: C₆H₅BrN₂O₂
• mdl: MFCD08062949
• 分子量: 217.022
• InChiKey: SXKGMTDVECHQRI-UHFFFAOYSA-N

物化性质

• 沸点：
  380.6±42.0 °C(Predicted)
• 密度：
  1.909±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  2,3,5-三氯苯硼酸 、 6-amino-5-bromopyridine 2-carboxylic acid 在 potassium fluoride 、 tris-(dibenzylideneacetone)dipalladium(0) 、 tetrafluoroboric acid 、 三叔丁基膦 作用下， 以 四氢呋喃 为溶剂， 以80%的产率得到6-amino-5-(2,3,5-trichlorophenyl)-pyridine-2-carboxylic acid
  参考文献：
  名称：

  Discovery and Optimization of Selective Na_v1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain

  摘要：

  Voltage-gated sodium channels, in particular Na(v)1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we described the optimization of Na(v)1.8 modulator series to deliver subtype selective, state, and use-dependent chemical matter that is efficacious in preclinical models of neuropathic and inflammatory pain.

  DOI：

  10.1021/acsmedchemlett.5b00059
• 作为产物：
  描述：

  N-(3-bromo-6-methylpyridin-2-yl)acetamide 在 potassium dihydrogenphosphate 、 sodium permanganate 、 硫酸 作用下， 以 甲醇 、 水 为溶剂， 生成 6-amino-5-bromopyridine 2-carboxylic acid
  参考文献：
  名称：

  Discovery and Optimization of Selective Na_v1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain

  摘要：

  Voltage-gated sodium channels, in particular Na(v)1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we described the optimization of Na(v)1.8 modulator series to deliver subtype selective, state, and use-dependent chemical matter that is efficacious in preclinical models of neuropathic and inflammatory pain.

  DOI：

  10.1021/acsmedchemlett.5b00059

文献信息

• Optimisation of Permanganate Oxidation and Suzuki−Miyaura Coupling Steps in the Synthesis of a Na_v1.8 Sodium Channel Modulator
  作者：M. Jonathan Fray、Adam T. Gillmore、Melanie S. Glossop、David J. McManus、Ian B. Moses、Céline F.B. Praquin、Keith A. Reeves、Lisa R. Thompson

  DOI：10.1021/op900092h

  日期：2010.1.15

  The development is described (if a viable kilo-scale synthesis of the Na(v)1.8 sodium channel modulator, N-methyl-6-amino5-(2,3,5-trichlorophenyl)pyridine-2-carboxamide (PF-1247324) in five steps, starting from 6-amino-5-bromo-2-picoline, in 33% overall yield. Two key steps required significant optimisation to improve yield and reproducibility. Oxidation or 6-acetamido-5-bromo-2-methylpyridine by permanganate to give the corresponding carboxylic acid derivative was improved by adding potassium dihydrogen phosphate, which moderated the reaction mixture pH and doubled the yield. The potassium fluoride-promoted Suzuki-Miyaura coupling between 2,4,5-trichlorophenylboronic acid and methyl 6-amino-5-bromopyridine-2-carboxylate, catalysed by tri(tert-butyl)phosphinepalladium (0), proceeded reliably to completion at room temperature in high yield when water was added. Anhydrous reaction mixtures reacted much more slowly, and 'wet' mixtures led to significant proto-deboronation in the absence of sufficient active catalyst. In the final step, amidation of the ester with methylamine gave PF-1247324.
• Discovery and Optimization of Selective Na_v1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain
  作者：Sharan K. Bagal、Peter J. Bungay、Stephen M. Denton、Karl R. Gibson、Melanie S. Glossop、Tanya L. Hay、Mark I. Kemp、Charlotte A. L. Lane、Mark L. Lewis、Graham N. Maw、William A. Million、C. Elizabeth Payne、Cedric Poinsard、David J. Rawson、Blanda L. Stammen、Edward B. Stevens、Lisa R. Thompson

  DOI：10.1021/acsmedchemlett.5b00059

  日期：2015.6.11

  Voltage-gated sodium channels, in particular Na(v)1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we described the optimization of Na(v)1.8 modulator series to deliver subtype selective, state, and use-dependent chemical matter that is efficacious in preclinical models of neuropathic and inflammatory pain.