4-[2-(甲基-2-吡啶基氨基)乙氧基]苯甲醛 | 122321-03-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 4-[2-(甲基-2-吡啶基氨基)乙氧基]苯甲醛
• 中文别名: 4-[2-[N-甲基-N-(2-吡啶基)氨基]-乙氧基]苯甲醛；4-[2-(甲基-2-吡啶氨基)乙氧基]苯甲醛
• 英文名称: 4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzaldehyde
• 英文别名: 4-[2-[N-methyl-N-(2-pyridyl)]amino]ethoxybenzaldehyde；4-[2-[N-methyl-N-(pyridin-2-yl)amino]ethoxy]benzaldehyde；4-(2-(Methyl(pyridin-2-yl)amino)ethoxy)benzaldehyde；4-[2-[methyl(pyridin-2-yl)amino]ethoxy]benzaldehyde
• CAS: 122321-03-3
• 化学式: C₁₅H₁₆N₂O₂
• 分子量: 256.304
• InChiKey: FRMKJZNBTRONBV-UHFFFAOYSA-N

物化性质

• 沸点：
  440.9±30.0 °C(Predicted)
• 密度：
  1.179±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 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：

  4-[2-(甲基-2-吡啶基氨基)乙氧基]苯甲醛 在 哌啶 、 碘 、 magnesium 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 5.0h， 生成 罗格列酮
  参考文献：
  名称：

  An alternative synthetic route for an antidiabetic drug, rosiglitazone

  摘要：

  A convenient and scalable four-step novel route has been developed for the synthesis of rosiglitazone (8), an antidiabetic drug. This multistep route requires 4-fluoro benzaldehyde (4), 2,4-thiazolidinedione (6) and 2-chloro pyridine (1) as key reactants and gives overall better yield of rosiglitazone. In addition, some steps have been accelerated, which leads to an overall time saving of 10 h. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.020
• 作为产物：
  描述：

  2-氟吡啶 在 polymer-supported chromic acid 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 生成 4-[2-(甲基-2-吡啶基氨基)乙氧基]苯甲醛
  参考文献：
  名称：

  Polymer-assisted solution phase synthesis of the antihyperglycemic agent Rosiglitazone (Avandia™)

  摘要：

  具有商业重要性的抗高血糖药物罗格列酮1（商品名：Avandia™），已通过多步骤、聚合物辅助的溶液相合成法（PASP）以高纯度制备，过程中无需对任何中间体进行传统的色谱纯化。

  DOI：

  10.1039/b307549d

文献信息

• Oxime derivatives for the treatment of dyslipidemia and hypercholesteremia
  申请人：——

  公开号：US20030083357A1

  公开（公告）日：2003-05-01

  The present invention relates to compounds of Formula (I) which may be useful in the treatment of diseases, such as, metabolic disorders, dyslipidemia and/or hyperchloesterolemia: 1

  本发明涉及Formula (I)的化合物，可能在治疗疾病，如代谢紊乱、血脂异常和/或高胆固醇血症方面有用：
• Process for the Preparation of Intermediates of Rosiglitazone, Rosiglitazone and New Polymorphic Forms Thereof
  申请人：Lopez Ernesto Duran

  公开号：US20090234128A1

  公开（公告）日：2009-09-17

  The invention relates to a polymorphic form of 5-(4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene)-2,4-thiazolidinedione (Formula (I)): to a process for its preparation and to the use of such compound for preparing rosiglitazone in the form of a free base or a salt thereof. The invention also relates to a polymorphic form of rosiglitazone in the form of a free base, to a process for its preparation and to the use of such polymorph for preparing a salt of rosiglitazone. The invention also relates to a process of preparing a polymorphic form of a rosiglitazone salt.

  本发明涉及5-(4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苯基亚甲基)-2,4-噻唑烷二酮(Formula (I))的多形形式，其制备方法以及使用该化合物制备自由基或其盐的罗格列酮。本发明还涉及罗格列酮的自由基的多形形式，其制备方法以及使用该多形形式制备罗格列酮的盐。本发明还涉及制备罗格列酮盐的多形形式的方法。
• [EN] SYNTHESIS OF ANTIDIABETIC ROSIGLITAZONE DERIVATIVES<br/>[FR] SYNTHESE DE DERIVES DE ROSIGLITAZONE CONTRE LE DIABETE
  申请人：CIPLA LTD

  公开号：WO2005105794A1

  公开（公告）日：2005-11-10

  A process of preparing rosiglitazone, or a pharmaceutically acceptable salt thereof, which process employs an intermediate metabisulphite complex of 4-[2-(N-methyl-N-(2-pyridyl)amino) ethoxy] benzaldehyde, which metabisulphite complex is represented by following formula (III); where X represents an alkali metal. The present invention further provides rosiglitazone, or a pharmaceutically acceptable salt thereof, prepared by the above process.

  一种制备罗格列酮或其药用可接受盐的过程，该过程利用4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苯甲醛的亚硫酸盐复合物作为中间体，该亚硫酸盐复合物由以下式（III）表示；其中X代表碱金属。本发明还提供了通过上述过程制备的罗格列酮或其药用可接受盐。
• [EN] PROCESS FOR THE PREPARATION OF ROSIGLITAZONE<br/>[FR] PROCEDE DE PREPARATION DE ROSIGLITAZONE
  申请人：MEDICHEM SA

  公开号：WO2005108394A1

  公开（公告）日：2005-11-17

  The present invention relates to a process for the preparation of 5-4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl-2,4-thiazolidinedione of formula (I) (Rosiglitazone), which comprises the reaction of 5-4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxyl]benzylidene-2,4-thiazolidinedione of formula (II), with a 1,4-dihydropyridine of general formula (III).

  这项发明涉及一种制备5-4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苯甲基-2,4-噻唑烷二酮的方法，该方法包括将式(I)的5-4-[2-(N-甲基-N-(2-吡啶基)氨基)乙氧基]苯甲基-2,4-噻唑烷二酮与一般式(III)的1,4-二氢吡啶反应。
• Synthetic optimization of rosiglitazone and related intermediates for industrial purposes
  作者：Ge Meng、Meilin Zheng、Mengshu Dong、Yang Gao、Aqun Zheng、Zhenyu Li、Ruizhi Hu

  DOI：10.1007/s11164-015-2132-0

  日期：2016.3

  As an important newly Food and Drug Administration (FDA)-approved drug for treating diabetes, rosiglitazone (1) has received much attention from researchers in many areas. To search for an economical and convenient synthesis method for 1, we explored the reaction conditions and workup of a scalable five-step synthetic route by an orthogonal method to determine the best condition for each reaction step. The starting materials are commercially available, including 2-chloropyridine (2), N-methylethanolamine (3), 4-fluorobenzaldehyde (4a) or 4-hydroxybenzaldehyde (4b), and 1,3-thiazolidine-2,4-dione (5). The five sequential reaction steps are cyclization, alkylation, etherification, condensation, and reduction, having optimal yield of 90, 99, 59, 75, and 91 %, respectively. The best overall yield to synthesize rosiglitazone based on compound 2 was 40 %, being suitable for industrial purposes, using water as a green solvent and avoiding column chromatography during the last three reaction steps.

  作为一种重要的、新近获得美国食品药品监督管理局(FDA)批准的糖尿病治疗药物，罗格列酮(1)受到了众多领域研究人员的广泛关注。为寻找一种经济便捷的合成罗格列酮的方法，我们采用正交方法探究了五步可扩展合成路线的反应条件和后处理工艺，以确定每一步反应的最佳条件。起始原料均为市售品，包括2-氯吡啶(2)、N-甲基乙醇胺(3)、4-氟苯甲醛(4a)或4-羟基苯甲醛(4b)以及1,3-噻唑烷-2,4-二酮(5)。该五步连续反应分别为环化、烷基化、醚化、缩合和还原，其最佳产率分别为90%、99%、59%、75%和91%。基于化合物2合成罗格列酮的最佳整体产率为40%，适合工业化生产，以水为绿色溶剂，在最后三步反应中避免使用柱层析。