6-(2-chloroethoxy)-4-hydroxy-7-methoxyquinazoline | 1188906-91-3

• 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: 6-(2-chloroethoxy)-4-hydroxy-7-methoxyquinazoline
• 英文别名: 6-(2-Chloroethoxy)-4-hydroxy-7-methoxyquinazoline；6-(2-chloroethoxy)-7-methoxy-3H-quinazolin-4-one
• CAS: 1188906-91-3
• 化学式: C₁₁H₁₁ClN₂O₃
• 分子量: 254.673
• InChiKey: RVQFXAVHIQVROL-UHFFFAOYSA-N

物化性质

• 沸点：
  429.9±55.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(2-chloroethoxy)-4-hydroxy-7-methoxyquinazoline 在 三乙胺 、 三氯氧磷 作用下， 以 异丙醇 、 甲苯 为溶剂， 生成 4-(3-chloro-4-fluorophenylamino)-6-(2-chloroethoxy)-7-methoxyquinazoline
  参考文献：
  名称：

  Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors

  摘要：

  We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4] octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.049
• 作为产物：
  描述：

  3-羟基-4-甲氧基苯甲酸甲酯 在 palladium 10% on activated carbon 、 氢气 、 硝酸 、 乙酸酐 、 potassium carbonate 作用下， 以 乙醇 、 溶剂黄146 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-(2-chloroethoxy)-4-hydroxy-7-methoxyquinazoline
  参考文献：
  名称：

  4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors

  摘要：

  Aryl phenyl ureas with a 4-quinazolinoxy substituent at the meta-position of the phenyl ring are potent inhibitors of mutant and wild type BRAF kinase. Compound 7 (1-(5-tert-butylisoxazol-3-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy) phenyl) urea hydrochloride) exhibits good pharmacokinetic properties in rat and mouse and is efficacious in a mouse tumor xenograft model following oral dosing. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.019

文献信息

• Metal-Free C-2-H Alkylation of Quinazolin-4-ones with Alkanes via Cross-Dehydrogenative Coupling
  作者：Shuai Mao、Kaixiu Luo、Lu Wang、Hong-Yi Zhao、Andrea Shergalis、Minhang Xin、Nouri Neamati、Yi Jin、San-Qi Zhang

  DOI：10.1021/acs.orglett.9b00638

  日期：2019.4.5

  A practically useful approach for the cross-dehydrogenative coupling of quinazolin-4-one with simple nonactivated alkanes is reported. The products were smoothly formed under mild reaction conditions, within short reaction time at ambient temperature. The formation of new Csp3-Csp2 bonds occurred at the electron-poor C-2 position of quinazolin-4-one. The approach has the potential to be an important

  报道了一种用于喹唑啉-4-酮与简单的未活化烷烃的交叉脱氢偶联的实用方法。在温和的反应条件下，在环境温度下短的反应时间内，可以平稳地形成产物。新的Csp 3 -Csp 2键的形成发生在喹唑啉-4-one的电子贫乏的C-2位。该方法有可能成为高级合成中间体后期功能化的重要工具，并可能在药物化学中找到许多应用。
• RAF KINASE MODULATOR COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Abraham Sunny

  公开号：US20110118245A1

  公开（公告）日：2011-05-19

  Compounds according to formula (I), compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. Formula (I): or a pharmaceutically acceptable salt, solvate, clathrate of hydrate thereof, wherein X is O or S(O) t ; R a is O or S.

  提供了按照公式(I)的化合物、组合物和方法，用于调节RAF激酶的活性，包括BRAF激酶，并用于治疗、预防或缓解由RAF激酶介导的一种或多种疾病或障碍的症状。公式(I)：或其药学上可接受的盐、溶剂化合物、包合物或水合物，其中X为O或S(O)t；R为O或S。
• RAF kinase modulator compounds and methods of use thereof
  申请人：Ambit Biosciences Corporation

  公开号：US08969587B2

  公开（公告）日：2015-03-03

  Compounds, compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases.

  本发明提供了用于调节RAF激酶活性的化合物、组合物和方法，包括BRAF激酶，并用于治疗、预防或改善由RAF激酶介导的一种或多种疾病或障碍的症状。
• 1-(3-(6,7-DIMETHOXYQUINAZOLIN-4-YLOXY)PHENYL)-3-(5-(1,1,1-TRIFLUORO-2-METHYLPROPAN-2-YL)ISOXAZOL-3-YL)UREA AS RAF KINASE MODULATOR IN THE TREATMENT OF CANCER DISEASES
  申请人：Ambit Biosciences Corporation

  公开号：EP2947072A1

  公开（公告）日：2015-11-25

  Compounds, compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. The compound is 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea, having the structure or a pharmaceutically acceptable salt, solvate, clathrate or hydrate thereof.

  本发明提供了用于调节 RAF 激酶（包括 BRAF 激酶）活性以及治疗、预防或改善由 RAF 激酶介导的疾病或紊乱的一种或多种症状的化合物、组合物和方法。 该化合物为 1-(3-(6,7-二甲氧基喹唑啉-4-氧基)苯基)-3-(5-(1,1,1-三氟-2-甲基丙-2-基)异恶唑-3-基)脲，其结构为 或其药学上可接受的盐、溶液、凝胶或水合物。
• [EN] QUINAZOLINE DERIVATIVES AS RAF KINASE MODULATORS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS QUINAZOLINE UTILES EN TANT QUE DE MODULATEURS DES KINASES RAF ET MÉTHODES D'UTILISATION DE CES DERNIERS
  申请人：AMBIT BIOSCIENCES CORP

  公开号：WO2009117080A8

  公开（公告）日：2010-11-04