diethyl ((4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazoline-6-ylcarbamoyl)methyl)phosphonate

• 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: diethyl ((4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazoline-6-ylcarbamoyl)methyl)phosphonate
• 英文别名: Diethyl (2-((4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)amino)-2-oxoethyl)phosphonate；N-[4-(3-chloro-4-fluoroanilino)-7-(oxolan-3-yloxy)quinazolin-6-yl]-2-diethoxyphosphorylacetamide
• 化学式: C₂₄H₂₇ClFN₄O₆P
• 分子量: 552.927
• InChiKey: FNGRCLBEXKFSST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  二甲氨基乙醛缩二乙醇 、 diethyl ((4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazoline-6-ylcarbamoyl)methyl)phosphonate 在 盐酸 、 lithium chloride 、 potassium hydroxide 作用下， 以 水 为溶剂， 反应 10.3h， 以78%的产率得到阿法替尼
  参考文献：
  名称：

  [EN] CRYSTALLINE FORMS OF AFATINIB DI-MALEATE
  [FR] FORMES CRISTALLINES DE DI-MALÉATE D'AFATINIB

  摘要：

  本申请描述了阿法替尼二雄酸盐的晶体形式及其制备方法。本发明还包括这些阿法替尼二雄酸盐晶体形式的药物组合物，其制备方法和用于治疗需要的患者的使用方法。本发明还描述了制备阿法替尼游离碱和阿法替尼的盐，除阿法替尼二雄酸盐外，以及它们的固体形式。

  公开号：

  WO2013052157A1

文献信息

• Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
  申请人：Himmelsbach Frank

  公开号：US20050107358A1

  公开（公告）日：2005-05-19

  The present invention relates to bicyclic heterocycles of general formula wherein R a , R b , R c , R d , R e and X are defined as in claim 1, the tautomers, the stereoisomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids, which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases and benign prostatic hyperplasia (BPH), diseases of the lungs and respiratory tract, and the preparation thereof.

  本发明涉及一般式的双环杂环化合物 其中 R a ，R b ，R c ，R d ，R e 和X的定义如权利要求书中所述， 其互变异构体、立体异构体、它们的混合物及其盐，特别是其与无机或有机酸形成的生理上可接受的盐，具有有价值的药理特性，特别是对酪氨酸激酶介导的信号传导具有抑制作用，其用于治疗疾病，特别是肿瘤性疾病和良性前列腺增生（BPH），肺部和呼吸道疾病，以及其制备。
• Process for preparing aminocrotonylamino-substituted quinazoline derivatives
  申请人：SCHROEDER Juergen

  公开号：US20110207929A1

  公开（公告）日：2011-08-25

  The invention relates to an improved process for preparing aminocrotonylamino-substituted quinazoline derivatives of general formula (I) wherein the groups R a , R b , R c and R d have the meanings given in the claims, as well as sulphonyl derivatives of formula and the use thereof as synthesis components for preparing quinazolines of formula (I). The quinazoline derivatives of formula (I) are inhibitors of signal transduction mediated by tyrosinekinases and by the Epidermal Growth Factor-Receptor (EGF-R) and are therefore particularly suitable for the treatment of tumoral diseases.

  本发明涉及一种改进的制备氨基丙烯酰氨基取代喹噁啉衍生物的方法，其一般式为（I），其中Ra、Rb、Rc和Rd基团具有权利要求中给出的含义，以及公式的磺酰衍生物，以及它们作为合成喹噁啉的组分的用途。公式（I）的喹噁啉衍生物是酪氨酸激酶介导的信号转导和表皮生长因子受体（EGF-R）介导的信号转导的抑制剂，因此特别适用于治疗肿瘤疾病。
• PROCESS FOR PREPARING AMINOCROTONYLAMINO-SUBSTITUTED QUINAZOLINE DERIVATIVES
  申请人：Schroeder Juergen

  公开号：US20090306378A1

  公开（公告）日：2009-12-10

  The invention relates to an improved process for preparing aminocrotonylamino-substituted quinazoline derivatives of general formula (I) wherein the groups R a , R b , R c and R d have the meanings given in the claims, as well as sulphonyl derivatives of formula (XIII) and the use thereof as synthesis components for preparing quinazolines of formula (I). The quinazoline derivatives of formula (I) are inhibitors of signal transduction mediated by tyrosinekinases and by the Epidermal Growth Factor-Receptor (EGF-R) and are therefore particularly suitable for the treatment of tumoral diseases.

  本发明涉及一种改进的制备氨基丙烯酰基氨基取代的喹嗪衍生物的方法，其通式为(I)，其中Ra、Rb、Rc和Rd基团的含义如权利要求中所述，以及式(XIII)的磺酰衍生物及其作为合成组分制备式(I)喹嗪的用途。式(I)的喹嗪衍生物是酪氨酸激酶介导的信号转导和表皮生长因子受体(EGF-R)的抑制剂，因此特别适用于治疗肿瘤性疾病。
• Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof
  申请人：Himmelsbach Frank

  公开号：US20050159436A1

  公开（公告）日：2005-07-21

  The present invention relates to bicyclic heterocycles of general formula wherein R a , R b , R c , A, B, C, D, E and X are defined as in claim 1, the tautomers, the stereoisomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases, as well as benign prostatic hyperplasia (BPH), diseases of the lungs and respiratory tract, and the preparation thereof.

  本发明涉及一般式为的双环杂环化合物， 其中Ra，Rb，Rc，A，B，C，D，E和X如权利要求1所定义，其互变异构体、立体异构体、混合物及其与无机或有机酸形成的生理上可接受的盐，具有有价值的药理学特性，特别是对酪氨酸激酶介导的信号转导具有抑制作用，其用于治疗疾病，特别是肿瘤性疾病、良性前列腺增生（BPH）、肺和呼吸道疾病，以及其制备方法。
• BICYCLIC HETEROCYCLES, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS, THEIR USE AND PROCESSES FOR THE PREPARATION THEREOF
  申请人：Himmelsbach Frank

  公开号：US20080103161A1

  公开（公告）日：2008-05-01

  The present invention relates to bicyclic heterocycles of general formula wherein R a , R b , R c , A, B, C, D, E and X are defined as in claim 1 , the tautomers, the stereoisomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases, as well as benign prostatic hyperplasia (BPH), diseases of the lungs and respiratory tract, and the preparation thereof.

  本发明涉及一般式为的双环杂环化合物 其中Ra，Rb，Rc，A，B，C，D，E和X如权利要求1中所定义，其互变异构体，立体异构体，混合物和盐，特别是其与无机或有机酸的生理上可接受的盐，具有有价值的药理特性，特别是对由酪氨酸激酶介导的信号转导具有抑制作用，其用于治疗疾病，特别是肿瘤性疾病，以及良性前列腺增生症（BPH），肺和呼吸道疾病，以及其制备方法。