4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylic acid methyl ester | 908306-43-4

• 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: 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylic acid methyl ester
• 英文别名: methyl 4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazoline-6-carboxylate
• CAS: 908306-43-4
• 化学式: C₂₃H₁₇ClFN₃O₃
• 分子量: 437.858
• InChiKey: LMKBARZHFHDXNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylic acid methyl ester 在 甲烷磺酸 、 环己氯化镁 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 20.5h， 生成 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-hydroxyethoxyimino)-2-butyn-1-yl)quinazoline
  参考文献：
  名称：

  EP2374801

  摘要：

  公开号：
• 作为产物：
  描述：

  甲醇 、 N-(3-氯-4-((3-氟苄基)氧基)苯基)-6-碘喹唑啉-4-胺盐酸盐 、 一氧化碳 在 bis-triphenylphosphine-palladium(II) chloride 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylic acid methyl ester
  参考文献：
  名称：

  WO2006/90717

  摘要：

  公开号：

文献信息

• PROCESS FOR PRODUCING ALKYNYLKETONE DERIVATIVE
  申请人：Shionogi & Co., Ltd.

  公开号：US20170197943A1

  公开（公告）日：2017-07-13

  The present invention relates to a Sonogashira-Carbonylation reaction using two types of gas, as well as novel crystals which can control a heat of the said reaction and the process of producing the same. In addition, the present invention relates to a ligand (additive) to prevent the deactivation of a palladium catalyst.

  本发明涉及使用两种气体进行Sonogashira-羰基化反应，以及能够控制该反应热量的新型晶体和生产该晶体的过程。此外，本发明还涉及一种配体（添加剂），用于防止钯催化剂的失活。
• PROCESS FOR PRODUCTION OF QUINAZOLINE DERIVATIVE
  申请人：Hagihara Motoyuki

  公开号：US20110257391A1

  公开（公告）日：2011-10-20

  A process for preparing a compound (III) is provided, in which the compound (III) is prepared from a methoxycarbonyl derivative through a methoxyamide derivative. These two reaction steps are continuously carried out and substantially the same as one step. The compound (III) is useful as a synthetic intermediate for preparing a dual tyrosine kinase inhibitor and can be conveniently prepared in high yield according to the present invention.

  提供了一种制备化合物(III)的方法，其中化合物(III)是通过甲氧羰基衍生物经甲氧酰胺衍生物制备的。这两个反应步骤是连续进行的，并且基本上相当于一步。该化合物(III)可用作制备双重酪氨酸激酶抑制剂的合成中间体，并且可以根据本发明方便地高产率地制备。
• Quinazoline Derivatives Having Tyrosine Kinase Inhibitory Activity
  申请人：Kume Masaharu

  公开号：US20090143414A1

  公开（公告）日：2009-06-04

  A compound which inhibits both of EGF receptor tyrosine kinase and HER2 tyrosine kinase is provided. A compound represented by the general formula (I): wherein R X is a group represented by the formula: wherein R 1 is a hydrogen atom, optionally substituted alkyl, etc.; Z is —O—, —N(R 10 )—, etc.; R 10 is a hydrogen atom, alkyl, etc.; R 2 is a hydrogen atom, optionally substituted alkyl, etc.; R 18 is a hydrogen atom, optionally substituted alkyl, etc.; R 19 is optionally substituted alkyl, etc.; W 1 is an optionally substituted non-aromatic nitrogen-containing group; R 17 is a hydrogen atom, optionally substituted alkyl, etc.; R 3 and R 4 are independently a hydrogen atom, optionally substituted alkyl, etc.; X is —O—, —S—, or —N(R 12 )—, etc.; R 12 is a hydrogen atom, alkyl, etc.; and A is phenyl optionally having a substituent, etc., its pharmaceutically acceptable salt, or a solvate thereof.

  提供了一种抑制EGF受体酪氨酸激酶和HER2酪氨酸激酶的化合物。该化合物由通式（I）表示：其中RX是由以下式子表示的基团：其中R1是氢原子，可选取代烷基等；Z是—O—，—N（R10）—等；R10是氢原子，烷基等；R2是氢原子，可选取代烷基等；R18是氢原子，可选取代烷基等；R19是可选取代烷基等；W1是可选取代非芳香族含氮基团；R17是氢原子，可选取代烷基等；R3和R4分别是氢原子，可选取代烷基等；X是—O—，—S—或—N（R12）—等；R12是氢原子，烷基等；A是苯基，可选取代基等，其药物可接受的盐或其溶剂化合物。
• Quinazoline derivatives having tyrosine kinase inhibitory activity
  申请人：Shionogi & Co., Ltd.

  公开号：US08202879B2

  公开（公告）日：2012-06-19

  A compound which inhibits both of EGF receptor tyrosine kinase and HER2 tyrosine kinase is provided. A compound represented by the general formula (I): wherein RX is a group represented by the formula: wherein R1 is a hydrogen atom, optionally substituted alkyl, etc.; Z is —O—, —N(R10)—, etc.; R10 is a hydrogen atom, alkyl, etc.; R2 is a hydrogen atom, optionally substituted alkyl, etc.; R18 is a hydrogen atom, optionally substituted alkyl, etc.; R19 is optionally substituted alkyl, etc.; W1 is an optionally substituted non-aromatic nitrogen-containing group; R17 is a hydrogen atom, optionally substituted alkyl, etc.; R3 and R4 are independently a hydrogen atom, optionally substituted alkyl, etc.; X is —O—, —S—, or —N(R12)—, etc.; R12 is a hydrogen atom, alkyl, etc.; and A is phenyl optionally having a substituent, etc., its pharmaceutically acceptable salt, or a solvate thereof.

  提供了一种抑制EGF受体酪氨酸激酶和HER2酪氨酸激酶的化合物。该化合物由下式表示： 其中，RX是由以下式表示的基团： 其中，R1是氢原子，可选择地被取代的烷基等；Z是-O-，-N（R10）-等；R10是氢原子，烷基等；R2是氢原子，可选择地被取代的烷基等；R18是氢原子，可选择地被取代的烷基等；R19是可选择地被取代的烷基等；W1是可选择地被取代的非芳香氮含有基团；R17是氢原子，可选择地被取代的烷基等；R3和R4分别是氢原子，可选择地被取代的烷基等；X是-O-，-S-或-N（R12）-等；R12是氢原子，烷基等；A是苯环，可选择地具有取代基等，其制药上可接受的盐或其溶剂。
• QUINAZOLINE DERIVATIVES HAVING TYROSINE KINASE INHIBITORY ACTIVITY
  申请人：KUME Masaharu

  公开号：US20120123114A1

  公开（公告）日：2012-05-17

  A compound which inhibits both of EGF receptor tyrosine kinase and HER2 tyrosine kinase is provided. A compound represented by the general formula (I): wherein R X is a group represented by the formula: wherein R 1 is a hydrogen atom, optionally substituted alkyl, etc.; Z is —O—, —N(R 10 )—, etc.; R 10 is a hydrogen atom, alkyl, etc.; R 2 is a hydrogen atom, optionally substituted alkyl, etc.; R 18 is a hydrogen atom, optionally substituted alkyl, etc.; R 19 is optionally substituted alkyl, etc.; W 1 is an optionally substituted non-aromatic nitrogen-containing group; R 17 is a hydrogen atom, optionally substituted alkyl, etc.; R 3 and R 4 are independently a hydrogen atom, optionally substituted alkyl, etc.; X is —O—, —S—, or —N(R 12 )—, etc.; R 12 is a hydrogen atom, alkyl, etc.; and A is phenyl optionally having a substituent, etc., its pharmaceutically acceptable salt, or a solvate thereof.

  提供了一种同时抑制EGF受体酪氨酸激酶和HER2酪氨酸激酶的化合物。该化合物的普遍式表示为（I）：其中，RX是由以下式表示的基团：其中，R1是氢原子，可选地取代的烷基等；Z为—O—，—N(R10)—等；R10为氢原子，烷基等；R2为氢原子，可选地取代的烷基等；R18为氢原子，可选地取代的烷基等；R19为可选地取代的烷基等；W1为可选地取代的非芳香族含氮基团；R17为氢原子，可选地取代的烷基等；R3和R4分别为氢原子，可选地取代的烷基等；X为—O—，—S—或—N(R12)—等；R12为氢原子，烷基等；A为苯基，可选地具有取代基等，其药学上可接受的盐或其溶剂化物。