5-(4,6-dimorpholino-2-pyridyl)-4-(trifluoromethyl)pyridin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-(4,6-dimorpholino-2-pyridyl)-4-(trifluoromethyl)pyridin-2-amine
• 英文别名: BKM-120；5-(4,6-Dimorpholin-4-ylpyridin-2-yl)-4-(trifluoromethyl)pyridin-2-amine
• 化学式: C₁₉H₂₂F₃N₅O₂
• 分子量: 409.411
• InChiKey: ISMFMKZKSBGEPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,4,6-三氯吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium phosphate 、 XPhos Pd G2 、 2-(二叔丁基膦)联苯 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 28.0h， 生成 5-(4,6-dimorpholino-2-pyridyl)-4-(trifluoromethyl)pyridin-2-amine
  参考文献：
  名称：

  [EN] NOVEL MANUFACTURING PROCESS FOR TRIAZINE, PYRIMIDINE AND PYRIDINE DERIVATIVES
  [FR] NOUVEAU PROCÉDÉ DE FABRICATION DE DÉRIVÉS DE TRIAZINE, PYRIMIDINE ET PYRIDINE

  摘要：

  该发明涉及一种制造三嗪、嘧啶和吡啶衍生物的方法，其化学式为(I)，其中U、V、W和Z为氮或碳原子，其中至少一个为氮，其他取代基如说明书中所定义，通过将相应的卤代三嗪、嘧啶或吡啶与吡啶基或嘧啶基硼烷进行铂铃偶联反应，其中氨基功能以甲酰胺基进行保护。该发明还涉及适当的中间体和制造这些中间体的方法。此外，该发明还涉及固态纯的5-(4,6-二吗啉基-1,3,5-三嗪-2-基)-4-(三氟甲基)吡啶-2-胺。

  公开号：

  WO2015162084A1

文献信息

• TRIAZINE, PYRIMIDINE AND PYRIDINE ANALOGS AND THEIR USE AS THERAPEUTIC AGENTS AND DIAGNOSTIC PROBES
  申请人：Cmiljanovic Vladimir

  公开号：US20110275762A1

  公开（公告）日：2011-11-10

  The invention relates to novel therapeutic agents and diagnostic probes. The invention also relates to phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor triazine-, pyrimidine- and pyridine-based compoundŝ Formula (I), their stereoisomers, geometric isomers, tautomers, solvates, metabolites, N-oxide derivatives, pharmaceutically acceptable salts, and prodrugs thereof compositions of the new compounds; either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, for treating disorders mediated by lipid kinases. •Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. (Formula I)

  本发明涉及新型治疗剂和诊断探针。本发明还涉及磷脂酰肌醇3-激酶（PI3K）和哺乳动物雷帕霉素靶蛋白酶（mTOR）抑制剂三嗪基、嘧啶基和吡啶基化合物̂公式（I），它们的立体异构体、几何异构体、互变异构体、溶剂化物、代谢物、N-氧化衍生物、药学上可接受的盐以及前药的组合物；新化合物的组合物，可以单独使用或与至少一种额外的治疗剂结合，与药学上可接受的载体；以及使用新化合物的方法，可以单独使用或与至少一种额外的治疗剂结合，用于治疗由脂质激酶介导的疾病。公开了使用公式（I）化合物的方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗这种疾病或相关病理条件。(公式I)
• Manufacturing process for triazine, pyrimidine and pyridine derivatives
  申请人：UNIVERSITAET BASEL

  公开号：US10100031B2

  公开（公告）日：2018-10-16

  The invention relates to a method of manufacturing triazine, pyrimidine and pyridine derivatives of formula (I), wherein U, V, W and Z are nitrogen or carbon atoms, whereby at least one of U, V and W is nitrogen, and the other substituents are defined as in the specification, by condensing a corresponding halo-triazine, pyrimidine or pyridine in a type of Suzuki coupling with a pyridyl- or pyrimidinyl-borane, wherein the amino function is protected as a formamidine. The invention further relates to suitable intermediates and methods of manufacturing of such intermediates. Furthermore the invention relates to pure 5-(4,6-dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine in solid form.

  本发明涉及一种制造式(I)三嗪、嘧啶和吡啶衍生物的方法，其中 U、V、W 和 Z 为氮原子或碳原子，其中 U、V 和 W 中至少有一个为氮原子，其他取代基定义如说明书所述，制造方法是将相应的卤代三嗪、嘧啶或吡啶与吡啶基或嘧啶基硼烷通过一种类型的铃木偶联进行缩合，其中氨基功能作为甲脒受到保护。本发明还涉及合适的中间体和制造这种中间体的方法。此外，本发明还涉及固体形式的纯 5-(4,6-二吗啉基-1,3,5-三嗪-2-基)-4-(三氟甲基)吡啶-2-胺。
• NOVEL MANUFACTURING PROCESS FOR TRIAZINE, PYRIMIDINE AND PYRIDINE DERIVATIVES
  申请人：Universität Basel

  公开号：EP3134388A1

  公开（公告）日：2017-03-01
• US8921361B2
  申请人：——

  公开号：US8921361B2

  公开（公告）日：2014-12-30
• [EN] TRIAZINE, PYRIMIDINE AND PYRIDINE ANALOGS AND THEIR USE AS THERAPEUTIC AGENTS AND DIAGNOSTIC PROBES<br/>[FR] ANALOGUES DE TRIAZINE, PYRIMIDINE ET PYRIDINE ET LEUR UTILISATION EN TANT QU'AGENTS THÉRAPEUTIQUES ET SONDES DE DIAGNOSTIC
  申请人：UNIV BASEL

  公开号：WO2010052569A2

  公开（公告）日：2010-05-14

  The invention relates to novel therapeutic agents and diagnostic probes. The invention also relates to phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor triazine, pyrimidine and pyridine-based compounds of Formula (I), their stereoisomers, geometric isomers, tautomers, solvates, metabolites, N-oxide derivatives, pharmaceutically acceptable salts, and prodrugs thereof compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, for treating disorders mediated by lipid kinases. Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. (Formula I)