4-(6-chloro-2,3-methylenedioxyanilino)-5,7-difluoroquinazoline | 893428-69-8

• 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-chloro-2,3-methylenedioxyanilino)-5,7-difluoroquinazoline
• 英文别名: N-(5-Chlorobenzo[d][1,3]dioxol-4-yl)-5,7-difluoroquinazolin-4-amine；N-(5-chloro-1,3-benzodioxol-4-yl)-5,7-difluoroquinazolin-4-amine
• CAS: 893428-69-8
• 化学式: C₁₅H₈ClF₂N₃O₂
• 分子量: 335.697
• InChiKey: IRRFUONCARFPDN-UHFFFAOYSA-N

物化性质

• 沸点：
  414.9±45.0 °C(Predicted)
• 密度：
  1.617±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  四氢吡喃-4-醇 、 4-(6-chloro-2,3-methylenedioxyanilino)-5,7-difluoroquinazoline 在 sodium tert-pentoxide 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 5.0h， 以80%的产率得到N-(5-氯苯并[d][1,3]二氧代l-4-基)-7-氟-5-((四氢-2H-吡喃-4-基)氧基)喹唑啉-4-胺
  参考文献：
  名称：

  A Simplified Process for the Manufacture of AZD0530, a Potent SRC Kinase Inhibitor

  摘要：

  An efficient process for the manufacture of AZD0530 1, a potent SRC kinase inhibitor, has been developed. The key transformation, reaction of monofluoroanilide 7 with alcohol 8, was much simplified between manufacturing campaigns. The development of a robust, efficient, and scalable process for this transformation drew on both a practical and theoretical understanding of the process and is described herein

  DOI：

  10.1021/op200079g
• 作为产物：
  描述：

  5,7-二氟-3,4-二氢喹唑啉-4-酮 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 苯甲醚 为溶剂， 反应 5.5h， 生成 4-(6-chloro-2,3-methylenedioxyanilino)-5,7-difluoroquinazoline
  参考文献：
  名称：

  A Simplified Process for the Manufacture of AZD0530, a Potent SRC Kinase Inhibitor

  摘要：

  An efficient process for the manufacture of AZD0530 1, a potent SRC kinase inhibitor, has been developed. The key transformation, reaction of monofluoroanilide 7 with alcohol 8, was much simplified between manufacturing campaigns. The development of a robust, efficient, and scalable process for this transformation drew on both a practical and theoretical understanding of the process and is described herein

  DOI：

  10.1021/op200079g

文献信息

• Chemical Process
  申请人：Ford James Gair

  公开号：US20090099196A1

  公开（公告）日：2009-04-16

  The present invention relates to chemical processes useful in the manufacture of the compound 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline (the active entity within AZD0530), to intermediates useful in the manufacture of that compound and to processes for the manufacture of those intermediates. The invention also relates to particular crystalline forms of that compound such as a difumarate salt and a trihydrate and to pharmaceutical compositions containing such crystalline forms.

  本发明涉及用于制造化合物4-(6-氯-2,3-亚甲二氧基苯胺基)-7-[2-(4-甲基哌嗪-1-基)乙氧基]-5-四氢吡喃-4-氧基喹唑啉（AZD0530中的活性物质）的化学过程，用于制造该化合物的中间体以及制造这些中间体的过程。本发明还涉及该化合物的特定晶体形式，例如双富马酸盐和三水合物，以及含有这种晶体形式的药物组合物。
• Crystalline forms of 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline
  申请人：AstraZeneca AB

  公开号：US08304417B2

  公开（公告）日：2012-11-06

  The present invention relates to chemical processes useful in the manufacture of the compound 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline (the active entity within AZD0530), to intermediates useful in the manufacture of that compound and to processes for the manufacture of those intermediates. The invention also relates to particular crystalline forms of that compound such as a difumarate salt and a trihydrate and to pharmaceutical compositions containing such crystalline forms.

  本发明涉及化学过程，用于制造化合物4-(6-氯-2,3-亚甲二氧基苯胺基)-7-[2-(4-甲基哌嗪-1-基)乙氧基]-5-四氢吡喃-4-氧基喹唑啉（AZD0530中的活性成分），以及制造该化合物的中间体和制造这些中间体的过程。本发明还涉及该化合物的特定晶型，例如双富马酸盐和三水合物，以及含有这种晶型的药物组合物。
• [EN] CHEMICAL PROCESS<br/>[FR] PROCEDE CHIMIQUE
  申请人：ASTRAZENECA AB

  公开号：WO2006064217A3

  公开（公告）日：2006-12-21
• PROCESS FOR THE PREPARATION OF 4-(6-CHLORO-2,3-METHYLENEDIOXYANILINO)-7-[2-(4-METHYLPIPERAZIN-1-YL)ETHOXY]-5-TETRAHYDROPYRAN-4-YLOXYQUINAZOLINE,THEIR INTERMEDIATES AND CRYSTALLINE SALTS THEREOF
  申请人：AstraZeneca AB

  公开号：EP1871769A2

  公开（公告）日：2008-01-02
• CRYSTALLINE FORMS OF THE COMPOUND 4-(6-CHLORO-2,3-METHYLENEDIOXYANILINO)-7-[2-(4-METHYLPIPERAZIN-1-YL)ETHOXY]-5-TETRAHYDROPYRAN-4-YLOXYQUINAZOLINE.
  申请人：AstraZeneca AB

  公开号：EP1871769B1

  公开（公告）日：2017-02-22