2-chloromethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylic acid ethyl ester | 153394-50-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-chloromethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylic acid ethyl ester
• 英文别名: ethyl 2-chloromethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylate；2-chloromethyl-6,7-dimethoxy-4-(3,4-dimethoxyphenyl)quinoline-3-carboxylic acid ethyl ester；ethyl 2-chloromethyl-6,7-dimethoxy-4-(3,4-dimethoxyphenyl)quinoline-3-carboxylate；ethyl 2-(chloromethyl)-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylate
• CAS: 153394-50-4
• 化学式: C₂₃H₂₄ClNO₆
• 分子量: 445.9
• InChiKey: UZZYPTSLUYJTOW-UHFFFAOYSA-N

物化性质

• 熔点：
  142-143 °C
• 沸点：
  558.3±50.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-chloromethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylic acid ethyl ester 在 盐酸 、 sodium bromide 、 sodium nitrite 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Process development of a disease-modifying antirheumatic drug, TAK-603, based on optimization of Friedel–Crafts reaction and selective substitution of a triazole ring

  摘要：

  A practical method for the preparation of TAK-603, an antirheumatic drug, has been developed. As a result of optimizing the Friedel-Crafts reaction in the presence of SnCl4/POCl3, 2-aminobenzophenone skeleton, the key intermediate of TAK-603, was formed with Pod yield. The selective substitution reaction of 1,2,4-triazole was accomplished using 4-amino-1,2,4-triazole and deamination. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.02.021
• 作为产物：
  描述：

  3,4-二甲氧基苯胺 在 盐酸 、 sodium hydroxide 、 四氯化锡 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 异丁醇 、 水 为溶剂， 反应 18.0h， 生成 2-chloromethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Process development of a disease-modifying antirheumatic drug, TAK-603, based on optimization of Friedel–Crafts reaction and selective substitution of a triazole ring

  摘要：

  A practical method for the preparation of TAK-603, an antirheumatic drug, has been developed. As a result of optimizing the Friedel-Crafts reaction in the presence of SnCl4/POCl3, 2-aminobenzophenone skeleton, the key intermediate of TAK-603, was formed with Pod yield. The selective substitution reaction of 1,2,4-triazole was accomplished using 4-amino-1,2,4-triazole and deamination. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.02.021

文献信息

• Quinoline or quinazoline derivatives, their production and use
  申请人：Takeda Chemical Industries

  公开号：US05436247A1

  公开（公告）日：1995-07-25

  A compound represented by the general formula: ##STR1## wherein Y represents a nitrogen atom or C--G (G represents a carboxyl group which may be esterified); ring R is a nitrogen-containing unsaturated heterocyclic group which may be substituted or unsubstituted; each of rings A and B may have a substituent; n represents an integer from 1 to 4; k represents the integer 0 or 1, or a salt thereof, which serves well as an anti-inflammatory agent, particularly a therapeutic agent for arthritis.

  一种由通式表示的化合物：##STR1## 其中Y代表一个氮原子或C--G（G代表一个可能酯化的羧基）；环R是一个含氮的不饱和杂环基团，可以被取代或未取代；环A和环B中的每一个都可以有一个取代基；n代表一个从1到4的整数；k代表整数0或1，或其盐，可作为一种抗炎药物，特别是治疗关节炎的药物。
• Pharmaceutical composition containing quinoline or quinazoline
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05719157A1

  公开（公告）日：1998-02-17

  The present invention provides a pharmaceutical composition for inhibiting bone resorption or for preventing or treating osteoporosis which comprises a quinoline or quinazoine derivative as an active ingredient.

  本发明提供了一种用于抑制骨吸收或预防/治疗骨质疏松症的药物组合物，其包含喹啉或喹啉衍生物作为活性成分。
• Syntheses of metabolites of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylate (TAK-603)
  作者：Masahiro Mizuno、Makoto Yamashita、Yasuhiro Sawai、Koji Nakamoto、Mitsutaka Goto

  DOI：10.1016/j.tet.2006.06.110

  日期：2006.9

  Convenient and efficient syntheses of ethyl 4-(3-hydroxy-4-methoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylate (1d) and 10-(3,4-dimethoxyphenyl)-7,8-dimethoxy-2H-pyridazino[4,5-b]quinolin-1-one (1e), metabolites of TAK-603 (1), have been achieved. Use of the methanesulfonyl as a protective group of the phenolic hydroxy for Friedel–Crafts reaction enabled a new simpler synthetic

  方便有效地合成4-（3-羟基-4-甲氧基苯基）-6,7-二甲氧基-2-（1,2,4-三唑-1-基甲基）喹啉-3-羧酸乙酯（1d）和10-已经获得了TAK-603（1）的代谢物（3,4-二甲氧基苯基）-7,8-二甲氧基-2 H-吡啶并[4,5 - b ]喹啉-1-酮（1e）。使用甲磺酰基作为酚羟基的保护基团用于Friedel-Crafts反应，可实现一种新的更简单的1d高产合成路线。使用Kröhnke反应将氯甲基衍生物（23）转化为甲酰基衍生物（32），然后用肼环化，形成新化合物1e。
• Processes for production of quinoline or quinazoline derivatives and
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05698699A1

  公开（公告）日：1997-12-16

  Processes for production of quinoline or quinazoline derivatives and intermediates therefor ##STR1## A process for producing a compound of formula (2) of value as antiinflammatory agents, which comprises reacting a compound of formula (3) or a salt thereof with 4-amino-1,2,4-triazole to give a compound of formula (1) or a salt thereof and deaminating the same, and an intermediate compound (1). In the above formulas, Y represents N or C-G in which G represents carboxyl which may be esterified or amidated, acyl, hydroxyalkyl which may be protected, or halogen; ring A and ring B each may be substituted; k is equal to 0 or 1; X represents a leaving group.

  制备喹啉或喹唑啉衍生物及其中间体的工艺 本发明提供了一种制备式（2）化合物的工艺，该化合物具有抗炎作用。该工艺包括将式（3）化合物或其盐与4-氨基-1,2,4-三唑反应，得到式（1）化合物或其盐并脱氨化，以及中间体化合物（1）。在上述式子中，Y代表N或C-G，其中G代表羧基，可以酯化或酰胺化，酰基，可以被保护的羟基烷基或卤素；环A和环B可以被取代；k等于0或1；X代表一个离去基团。
• Pharmaceutical composition containing quinoline and quinazoline
  申请人：Takeda Chemical

  公开号：US05948782A1

  公开（公告）日：1999-09-07

  There is disclosed an anti-inflammatory agent comprising a compound of the formula (I): ##STR1## The quinoline compounds included in the compound (I) are novel and there is also disclosed processes for producing them.

  本发明公开了一种包括式(I)的化合物的抗炎剂：##STR1## 包括在化合物(I)中的喹啉类化合物是新颖的，同时还公开了制备它们的方法。