N-[1-[[[6-甲氧基-4-[[5-[(甲基氨基)羰基]-2-萘基]氧基]-7-喹啉基]氧基]甲基]环丙基]氨基甲酸苄酯 | 1058137-21-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: N-[1-[[[6-甲氧基-4-[[5-[(甲基氨基)羰基]-2-萘基]氧基]-7-喹啉基]氧基]甲基]环丙基]氨基甲酸苄酯
• 英文名称: benzyl 1-((6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)methyl)cyclo-propylcarbamate
• 英文别名: benzyl 1-[(6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)methyl]cyclopropylcarbamate；benzyl N-[1-[[6-methoxy-4-[5-(methylcarbamoyl)naphthalen-2-yl]oxyquinolin-7-yl]oxymethyl]cyclopropyl]carbamate
• CAS: 1058137-21-5
• 化学式: C₃₄H₃₁N₃O₆
• 分子量: 577.637
• InChiKey: AWDOLDSJAALBNQ-UHFFFAOYSA-N

物化性质

• 沸点：
  822.1±65.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[1-[[[6-甲氧基-4-[[5-[(甲基氨基)羰基]-2-萘基]氧基]-7-喹啉基]氧基]甲基]环丙基]氨基甲酸苄酯 在 钯 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 6-[[7-[(1-氨基环丙基)甲氧基]-6-甲氧基-4-喹啉基]氧基]-N-甲基-1-萘甲酰胺
  参考文献：
  名称：

  Spiro substituted compounds as angiogenesis inhibitors

  摘要：

  本发明涉及公式I的螺环（四碳）取代化合物，其制备方法，含有它们作为活性成分的制药组合物，用于治疗与血管生成有关的疾病状态的方法，例如与蛋白酪氨酸激酶相关的癌症，以及它们作为药物用于在温血动物，如人类中产生抑制酪氨酸激酶减少效果的制剂。

  公开号：

  US08163923B2
• 作为产物：
  描述：

  6-羟基-N-甲基-1-萘羧酰胺 、 (1-(((4-chloro-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropyl)carbamic acid benzyl ester 在 6-羟基-N-甲基-1-萘羧酰胺 作用下， 以66的产率得到N-[1-[[[6-甲氧基-4-[[5-[(甲基氨基)羰基]-2-萘基]氧基]-7-喹啉基]氧基]甲基]环丙基]氨基甲酸苄酯
  参考文献：
  名称：

  Process for the preparation of 6-(7-((1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide and synthetic intermediates thereof

  摘要：

  本发明涉及一种制备化合物6-(7-4(1-氨基环丙基)甲氧基)-6-甲氧基喹啉-4-氧基)-N-甲基-1-萘酰胺（I）及其药学上可接受的盐的高产率和纯度的方法。该方法相较于先前描述的方法具有各种优点，特别是避免了酰基叠氮中间体及其Curtius重排的使用。还描述了用于制备化合物（I）的新型中间体。

  公开号：

  US08642767B2

文献信息

• [EN] PROCESS FOR PREPARING THE ANTI-TUMOR AGENT 6-(7-((1-AMINOCYCLOPROPYL) METHOXY)-6-METHOXYQUINOLIN-4-YLOXY)-N-METHYL-1-NAPHTHAMIDE AND ITS CRYSTALLINE<br/>[FR] PROCÉDÉ POUR L'ÉLABORATION D'UN AGENT ANTITUMORAL, LA 6-(7-((1-AMINO-CYCLO-PROPYL)-MÉTHOXY)-6- MÉTHOXYQUINOLIN-4-YLOXY)-N-MÉTHYL-1-NAPHTHAMIDE,ET DE SA FORME CRISTALLINE
  申请人：ADVENCHEN PHARMACEUTICALS LLC

  公开号：WO2014113616A1

  公开（公告）日：2014-07-24

  The present invention relates a new process to synthesize 6-(7-((l-aminocyclo-propyl)- methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl- l -naphthamide (AL3810) by deprotection of substituted benzyl 1 -((6-methoxy-4-(5-(methylcarbamoyl)naphthalen-2-yloxy)quinolin-7-yloxy)- methyl)cyc-lopropylcarbamate (Formula I) under a diluted or weak acidic condition. A stable crystalline form of 6-(7-((l-aminocyclo-propyl)-methoxy)-6-methoxyquinolin-4-yloxy)-N- methyl- 1 -naphthamide has also been prepared.

  本发明涉及一种新的合成过程，通过在稀释或弱酸性条件下去保护取代苄基1-((6-甲氧基-4-(5-(甲基氨甲酰)萘-2-氧基)喹啉-7-氧基)-甲基)环丙基氨基甲酸酯（化学式I），合成6-(7-((1-氨基环丙基)-甲氧基)-6-甲氧基喹啉-4-氧基)-N-甲基-1-萘酰胺（AL3810）通过脱保护。同时还制备了6-(7-((1-氨基环丙基)-甲氧基)-6-甲氧基喹啉-4-氧基)-N-甲基-1-萘酰胺的稳定晶型。
• [EN] A PROCESS FOR THE PREPARATION OF 6-(7-((1-AMINOCYCLOPROPYL)METHOXY)-6-METHOXYQUINOLIN-4-YLOXY)-N-METHYL-1-NAPHTHAMIDE AND SYNTHETIC INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 6-(7-((L-AMINOCYCLOPROPYL)MÉTHOXY)-6-MÉTHOXYQUINOLIN-4-YLOXY)-N-MÉTHYL-1-NAPHTHAMIDE ET DE SES INTERMÉDIAIRES DE SYNTHÈSE
  申请人：EOS ETHICAL ONCOLOGY SCIENCE SPA IN ABBREVIATED FORM EOS SPA

  公开号：WO2010105761A1

  公开（公告）日：2010-09-23

  A process for the preparation in high yields and purity of the compound 6-(7-((l-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl- 1 -naphthamide of formula (I) and of the pharmaceutically acceptable salts thereof is described. The process has various advantages over those previously described, in particular it avoids the use of acyl azide intermediates and their Curtius rearrangement. Novel intermediates useful for the preparation of compound (I) are also described.

  描述了一种用于高产率和纯度制备化合物6-(7-((1-氨基环丙基)甲氧基)-6-甲氧基喹啉-4-氧基)-N-甲基-1-萘酰胺（式(I)）及其药用可接受盐的方法。该方法相对于先前描述的方法具有各种优点，特别是避免了使用酰基叠氮中间体及其Curtius重排。还描述了用于制备化合物(I)的新型中间体。
• Spiro Substituted Compounds As Angiogenesis Inhibitors
  申请人：Chen Guoqing Paul

  公开号：US20080227812A1

  公开（公告）日：2008-09-18

  The present invention relates to spiro (tetracarbon) substituted compound of Formula I, processes for their preparation, pharmaceutical compositions containing them as active ingredient, methods for the treatment of disease states associated with angiogenesis, such as cancers associated with protein tyrosine kinases, to their use as medicaments for use in the production of inhibition of tyrosine kinases reducing effects in warm-blooded animals such as humans.

  本发明涉及Formula I的螺环（四碳）取代化合物，以及其制备方法、含有其作为活性成分的药物组合物、用于治疗与血管生成相关的疾病状态的方法，如与蛋白酪氨酸激酶相关的癌症，以及它们作为药物在生产中用于减少温血动物（如人类）中酪氨酸激酶抑制效果的用途。
• SPIRO SUBSTITUTED COMPOUNDS AS ANGIOGENESIS INHIBITORS
  申请人：CHEN Guoqing Paul

  公开号：US20120165371A1

  公开（公告）日：2012-06-28

  The present invention relates to spiro (tetracarbon) substituted compound of Formula I, processes for their preparation, pharmaceutical compositions containing them as active ingredient, methods for the treatment of disease states associated with angiogenesis, such as cancers associated with protein tyrosine kinases, to their use as medicaments for use in the production of inhibition of tyrosine kinases reducing effects in warm-blooded animals such as humans.

  本发明涉及一种式子I的螺环（四羰基）取代化合物，其制备方法，含有其作为活性成分的制药组合物，用于治疗与血管生成相关的疾病状态的方法，例如与蛋白酪氨酸激酶相关的癌症，以及它们作为药物用于在温血动物（如人类）中产生抑制酪氨酸激酶的减少效果。
• PROCESS FOR THE PREPARATION OF 6-(7-((1-AMINOCYCLOPROPYL)METHOXY)-6-METHOXYQUINOLIN-4-YLOXY)-N-METHYL-1-NAPHTHAMIDE AND SYNTHETIC INTERMEDIATES THEREOF
  申请人：Spinelli Silvano

  公开号：US20120010415A1

  公开（公告）日：2012-01-12

  A process for the preparation in high yields and purity of the compound 6-(7-4(1-aminocyclopropyl)methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide of formula (I) and of the pharmaceutically acceptable salts thereof is described. The process has various advantages over those previously described, in particular it avoids the use of acyl azide intermediates and their Curtius rearrangement. Novel intermediates useful for the preparation of compound (I) are also described.

  本发明描述了一种制备化合物6-(7-4(1-氨基环丙基)甲氧基)-6-甲氧基喹啉-4-氧基)-N-甲基-1-萘酰胺（I）及其药学上可接受的盐的高产率和高纯度的方法。该方法相对于以前描述的方法具有各种优点，特别是避免了使用酰基叠氮中间体及其Curtius重排反应。还描述了用于制备化合物（I）的新型中间体。