(±)-bis(Boc)-5-bromo-3-(1-(2,6-dichloro-3-fluoropheny)ethoxy)pyridin-2-amine | 1331786-33-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (±)-bis(Boc)-5-bromo-3-(1-(2,6-dichloro-3-fluoropheny)ethoxy)pyridin-2-amine
• 英文别名: Tetr-butyl-N-{5-bromo-3-[2, 6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-YL-N-[(tert-butoxy)carbonyl]carbamate；tert-butyl N-[5-bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
• CAS: 1331786-33-4
• 化学式: C₂₃H₂₆BrCl₂FN₂O₅
• 分子量: 580.278
• InChiKey: ODVAQMSMMKGMLV-UHFFFAOYSA-N

物化性质

• 沸点：
  566.5±60.0 °C(Predicted)
• 密度：
  1.429±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (±)-bis(Boc)-5-bromo-3-(1-(2,6-dichloro-3-fluoropheny)ethoxy)pyridin-2-amine 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 potassium acetate 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 41.0h， 生成 3-(1-(2,6-二氯-3-氟苯基)乙氧基)-5-(1-(哌啶-4-基)-1H-吡唑-4-基)吡啶-2-胺
  参考文献：
  名称：

  Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal–Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK)

  摘要：

  Because of the critical roles of aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncology targets for therapeutic intervention. The cocrystal structure of 3 (PHA-665752), bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved with 3. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group of 3 via a more direct vector and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.

  DOI：

  10.1021/jm2007613
• 作为产物：
  描述：

  3-(1-(2,6-二氯-3-氟苯基)乙氧基)吡啶-2-胺 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 18.17h， 生成 (±)-bis(Boc)-5-bromo-3-(1-(2,6-dichloro-3-fluoropheny)ethoxy)pyridin-2-amine
  参考文献：
  名称：

  [EN] SPIROCYCLIC MOLECULES AS PROTEIN KINASE INHIBITORS
  [FR] MOLÉCULES SPIROCYCLIQUES CONVENANT COMME INHIBITEURS DE PROTÉINES KINASES

  摘要：

  本发明涉及式I的螺环化合物，即螺环化合物(1H-吡唑-4-基)-3-(1-(2,6-二氯-3-氟苯基)乙氧基)吡啶-2-胺，具有蛋白激酶抑制活性，并且合成和使用这类化合物的方法。优选化合物是c-Met和/或ALK抑制剂，用于治疗异常细胞生长，如癌症。

  公开号：

  WO2013013308A1

文献信息

• [EN] SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS CYCLIQUES SUBSTITUÉS ET PROCÉDÉS D'UTILISATION
  申请人：XI NING

  公开号：WO2013138210A1

  公开（公告）日：2013-09-19

  The present invention provides novel substituted cyclic compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明提供了新颖的取代环化合物，药用可接受的盐及其制剂，用于调节蛋白酪氨酸激酶活性，并调节细胞活动，如增殖、分化、凋亡、迁移和侵袭。该发明还提供了包括这些化合物的药用可接受的组合物，以及在治疗哺乳动物，特别是人类的增生性疾病中使用这些组合物的方法。
• Crizotinib Preparation Method
  申请人：ZHEJIANG JIUZHOU PHARMACEUTICAL CO., LTD.

  公开号：US20150307476A1

  公开（公告）日：2015-10-29

  The present invention relates to the technical field of medicine and organic synthesis, particularly to a method for preparing crizotinib. The method comprises the compound of formula b and the compound of formula e undergoing Suzuki coupling reaction to produce the compound of formula a which then was subjected to deprotection to afford (±) crizotinib.

  本发明涉及医药和有机合成技术领域，特别是一种制备克唑替尼的方法。该方法包括通过式b化合物和式e化合物进行铃木偶联反应，生成式a化合物，然后对其进行去保护以得到(±)克唑替尼。
• [EN] PYRAZOLE-SUBSTITUTED AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS<br/>[FR] COMPOSES AMINOHETEROARYLE A SUBSTITUTION PYRAZOLE SERVANT D'INHIBITEURS DE PROTEINE KINASE
  申请人：PFIZER

  公开号：WO2006021881A2

  公开（公告）日：2006-03-02

  Compounds of formula (1) are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了化学式（1）的化合物，以及它们的合成和使用方法。优选的化合物是c-Met蛋白激酶的有效抑制剂，并可用于治疗异常细胞生长障碍，如癌症。
• Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20060128724A1

  公开（公告）日：2006-06-15

  Compounds of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了化学式1的化合物，以及它们的合成和使用方法。首选的化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长障碍，例如癌症方面非常有用。
• Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US07858643B2

  公开（公告）日：2010-12-28

  Enantiomerically pure compound of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了化学式为1的对映纯化合物，以及它们的合成和使用方法。优选的化合物是c-Met蛋白激酶的强效抑制剂，可用于治疗异常细胞生长紊乱，如癌症。