4,6-Dichloro-8-fluoroquinazoline | 1566199-66-3

• 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: 4,6-Dichloro-8-fluoroquinazoline
• CAS: 1566199-66-3
• 化学式: C₈H₃Cl₂FN₂
• 分子量: 217.03
• InChiKey: BVBYNWPRFHMXTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,6-Dichloro-8-fluoroquinazoline 在 bis(2,2,6,6-tetramethylpiperidinyl)zinc, lithium chloride, magnesium chloride complex 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 14.92h， 生成 tert-butyl 4-(6-chloro-8-fluoro-7-(2-fluoro-6-methoxyphenyl)quinazolin-4-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  [EN] METHODS FOR PREPARATION OF QUINAZOLINE DERIVATIVES
  [FR] PROCÉDÉS DE PRÉPARATION DE DÉRIVÉS DE QUINAZOLÉINE

  摘要：

  提供制备具有以下结构（I）的化合物的方法：（结构式（I））或其药学上可接受的盐，立体异构体或互变异构体，其中R1，R2a，R2b，R3a，R3b，R4a，R4b和R4c如本文所定义。同时也提供了相关的化合物和制备方法。

  公开号：

  WO2017100546A1
• 作为产物：
  描述：

  6-氯-8-氟喹唑啉-4(3H)-酮 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以60%的产率得到4,6-Dichloro-8-fluoroquinazoline
  参考文献：
  名称：

  [EN] METHODS FOR PREPARATION OF QUINAZOLINE DERIVATIVES
  [FR] PROCÉDÉS DE PRÉPARATION DE DÉRIVÉS DE QUINAZOLÉINE

  摘要：

  提供制备具有以下结构（I）的化合物的方法：（结构式（I））或其药学上可接受的盐，立体异构体或互变异构体，其中R1，R2a，R2b，R3a，R3b，R4a，R4b和R4c如本文所定义。同时也提供了相关的化合物和制备方法。

  公开号：

  WO2017100546A1

文献信息

• Substituted quinazoline compounds and methods of use thereof
  申请人：Araxes Pharma LLC

  公开号：US10246424B2

  公开（公告）日：2019-04-02

  Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have one of the following structures (I), (II) or (III): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, B, G1, G2, L1, L2, m1, m2, n, x, y, X and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

  本研究提供了具有抑制 G12C 突变 KRAS 蛋白活性的化合物。这些化合物具有以下结构之一 (I)、(II) 或 (III)： 或其药学上可接受的盐、立体异构体或原药，其中 R1、R2a、R2b、R2c、R3a、R3b、R4a、R4b、R5a、R5b、R6、A、B、G1、G2、L1、L2、m1、m2、n、x、y、X 和 E 如本文所定义。还提供了与制备和使用此类化合物相关的方法、包含此类化合物的药物组合物以及调节G12C突变型KRAS蛋白活性以治疗疾病（如癌症）的方法。
• SUBSTITUTED QUINAZOLINE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Araxes Pharma LLC

  公开号：US20160297774A1

  公开（公告）日：2016-10-13

  Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have one of the following structures (I), (II) or (III): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R 1 , R 2a , R 2b , R 2c , R 3a , R 3b , R 4a , R 4b , R 5a , R 5b , R 6 , A, B, G 1 , G 2 , L 1 , L 2 , m 1 , m 2 , n, x, y, X and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
• METHODS FOR PREPARATION OF QUINAZOLINE DERIVATIVES
  申请人：Araxes Pharma LLC

  公开号：US20170190672A1

  公开（公告）日：2017-07-06

  Methods for preparing compounds having the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 4a , R 4b and R 4c , are as defined herein are provided. Related compounds and methods for making the same are also provided.
• US9988357B2
  申请人：——

  公开号：US9988357B2

  公开（公告）日：2018-06-05
• [EN] SUBSTITUTED QUINAZOLINE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS QUINAZOLINE SUBSTITUÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ARAXES PHARMA LLC

  公开号：WO2016164675A1

  公开（公告）日：2016-10-13

  Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have one of the following structures (I), (II) or (III): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, B, G1, G2, L1, L2, m1, m2, n, x, y, X and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.