ethyl 6-[(5-chloro-2-hydroxyphenyl)hydroxymethyl]-2-pyridinecarboxylate | 1180553-44-9

• 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: ethyl 6-[(5-chloro-2-hydroxyphenyl)hydroxymethyl]-2-pyridinecarboxylate
• 英文别名: Ethyl 6-[(5-chloro-2-hydroxyphenyl)-hydroxymethyl]pyridine-2-carboxylate
• CAS: 1180553-44-9
• 化学式: C₁₅H₁₄ClNO₄
• 分子量: 307.733
• InChiKey: MBPUALJXFWVHCX-UHFFFAOYSA-N

物化性质

• 沸点：
  490.9±33.0 °C(Predicted)
• 密度：
  1.367±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  79.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 6-[(5-chloro-2-hydroxyphenyl)hydroxymethyl]-2-pyridinecarboxylate 在 palladium 10% on activated carbon 、 硫酸 、 氢气 、 zinc dibromide 作用下， 以 乙酸乙酯 为溶剂， 65.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 以82%的产率得到ethyl 6-((5-chloro-2-hydroxyphenyl)methyl)-2-pyridinecarboxylate
  参考文献：
  名称：

  Development and Scope of the Phenolic Aldol Reaction of 2-Formylpyridines

  摘要：

  研究表明，2-甲酰基吡啶是镁促进酚醛反应的合适亲电体。研究人员开发了特别温和的反应条件，并对反应范围进行了简要考察。该工艺可通过随后的还原直接获得一系列官能化的 2-羟基苯基-2-吡啶基甲醇和 2-羟基苯基-2-吡啶基甲烷。

  DOI：

  10.1055/s-0029-1217325
• 作为产物：
  描述：

  2,6-吡啶二羧酸二乙酯 在 sodium tetrahydroborate 、 乙基溴化镁 、 三氧化硫吡啶 、 二甲基亚砜 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 甲基叔丁基醚 为溶剂， 反应 2.0h， 生成 ethyl 6-[(5-chloro-2-hydroxyphenyl)hydroxymethyl]-2-pyridinecarboxylate
  参考文献：
  名称：

  Selection and Development of the Manufacturing Route for EP₁ Antagonist GSK269984B

  摘要：

  A potential manufacturing route for the EP1 antagonist GSK269984B was developed. Four synthetic approaches were examined, and a successful realisation of each is presented. The rationale supporting selection of the preferred route is discussed. This route utilised a phenolic aldol reaction as the key step and relied on selective hydrogenolysis to reduce an intermediate diarylmethanol. Further optimisation of the selected route is presented, delivering GSK269984B in three stages and 46% overall yield from readily available starting materials.

  DOI：

  10.1021/op100072y

文献信息

• Development and Scope of the Phenolic Aldol Reaction of 2-Formylpyridines
  作者：Matthew Whiting、Mark Wilkinson、Kathy Harwood

  DOI：10.1055/s-0029-1217325

  日期：——

  2-Formylpyridines have been shown to be suitable electrophiles for the magnesium-promoted phenolic aldol reaction. Exceptionally mild reaction conditions have been developed and a brief survey of the reaction scope has been conducted. This process gives straightforward access to a range of functionalised 2-hydroxy­phenyl-2-pyridylmethanols and 2-hydroxyphenyl-2-pyridylmethanes via their subsequent reduction.

  研究表明，2-甲酰基吡啶是镁促进酚醛反应的合适亲电体。研究人员开发了特别温和的反应条件，并对反应范围进行了简要考察。该工艺可通过随后的还原直接获得一系列官能化的 2-羟基苯基-2-吡啶基甲醇和 2-羟基苯基-2-吡啶基甲烷。
• Selection and Development of the Manufacturing Route for EP₁ Antagonist GSK269984B
  作者：Matthew Whiting、Kathy Harwood、Frank Hossner、Peter G. Turner、Mark C. Wilkinson

  DOI：10.1021/op100072y

  日期：2010.7.16

  A potential manufacturing route for the EP1 antagonist GSK269984B was developed. Four synthetic approaches were examined, and a successful realisation of each is presented. The rationale supporting selection of the preferred route is discussed. This route utilised a phenolic aldol reaction as the key step and relied on selective hydrogenolysis to reduce an intermediate diarylmethanol. Further optimisation of the selected route is presented, delivering GSK269984B in three stages and 46% overall yield from readily available starting materials.
• Development of an in vivo active, dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere
  作者：Jason D. Downey、Sam A. Saleh、Thomas M. Bridges、Ryan D. Morrison、J. Scott Daniels、Craig W. Lindsley、Richard M. Breyer

  DOI：10.1016/j.bmcl.2012.11.046

  日期：2013.1

  Recent preclinical studies demonstrate a role for the prostaglandin E-2 (PGE(2)) subtype 1 (EP1) receptor in mediating, at least in part, the pathophysiology of hypertension and diabetes mellitus. A series of amide and N-acylsulfonamide analogs of a previously described picolinic acid-based human EP1 receptor antagonist (7) were prepared. Each analog had improved selectivity at the mouse EP1 receptor over the mouse thromboxane receptor (TP). A subset of analogs gained affinity for the mouse PGE2 subtype 3 (EP3) receptor, another potential therapeutic target. One analog (17) possessed equal selectivity for EP1 and EP3, displayed a sufficient in vivo residence time in mice, and lacked the potential for acyl glucuronide formation common to compound 7. Treatment of mice with 17 significantly attenuated the vasopressor activity resulting from an acute infusion of EP1 and EP3 receptor agonists. Compound 17 represents a potentially novel therapeutic in the treatment of hypertension and diabetes mellitus. (c) 2012 Elsevier Ltd. All rights reserved.