2-amino-4-trifluoromethyl-5-pyridineboronic acid | 1045861-32-2

• 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: 2-amino-4-trifluoromethyl-5-pyridineboronic acid
• 英文别名: (6-Amino-4-(trifluoromethyl)pyridin-3-yl)boronic acid；[6-amino-4-(trifluoromethyl)pyridin-3-yl]boronic acid
• CAS: 1045861-32-2
• 化学式: C₆H₆BF₃N₂O₂
• 分子量: 205.932
• InChiKey: BFGHJUHRLUFXHE-UHFFFAOYSA-N

物化性质

• 沸点：
  391.8±52.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.64
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  79.4
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  2-amino-4-trifluoromethyl-5-pyridineboronic acid 、 3-(6-bromo-4-chloroquinolin-3-yl)acrylate 、 间氨基三氟甲苯 在 盐酸 、 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 水 、 异丙醇 为溶剂， 反应 0.42h， 生成 9-(6-amino-4-(trifluoromethyl)pyridin-3-yl)-1-(3(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one
  参考文献：
  名称：

  1,9取代的苯并[ h ] [1,6]萘啶-2（1 H）-酮的高效合成及其对恶性疟原虫的杀细胞活性的评价

  摘要：

  为合成苯并[ h ] [1,6]萘啶-2（1 H），开发了一种新颖的三组分，两步，一锅亲核芳香取代（S N Ar）-分子内环化-Suzuki偶联反应。-一个（Torins）。在新的有效收敛的合成路线的基础上，合成了都灵类似物的文库。使用生长抑制测定法评估这些化合物对无性寄生虫的抗疟活性，并使用生存力测定法评估配子细胞。

  DOI：

  10.1021/acscombsci.7b00119
• 作为产物：
  描述：

  5-溴-4-(三氟甲基)吡啶-2-胺 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 联硼酸频那醇酯 、 水 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 acetontrile 为溶剂， 反应 8.0h， 生成 2-amino-4-trifluoromethyl-5-pyridineboronic acid
  参考文献：
  名称：

  Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer

  摘要：

  Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocydic pyrirnidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrirnidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.

  DOI：

  10.1021/ml200156t

文献信息

• Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer
  作者：Matthew T. Burger、Sabina Pecchi、Allan Wagman、Zhi-Jie Ni、Mark Knapp、Thomas Hendrickson、Gordana Atallah、Keith Pfister、Yanchen Zhang、Sarah Bartulis、Kelly Frazier、Simon Ng、Aaron Smith、Joelle Verhagen、Joshua Haznedar、Kay Huh、Ed Iwanowicz、Xiaohua Xin、Daniel Menezes、Hanne Merritt、Isabelle Lee、Marion Wiesmann、Susan Kaufman、Kenneth Crawford、Michael Chin、Dirksen Bussiere、Kevin Shoemaker、Isabel Zaror、Sauveur-Michel Maira、Charles F. Voliva

  DOI：10.1021/ml200156t

  日期：2011.10.13

  Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocydic pyrirnidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrirnidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.
• Efficient Synthesis of 1,9-Substituted Benzo[<i>h</i>][1,6]naphthyridin-2(1<i>H</i>)-ones and Evaluation of their <i>Plasmodium falciparum</i> Gametocytocidal Activities
  作者：Hao Li、Wei Sun、Xiuli Huang、Xiao Lu、Paresma R. Patel、Myunghoon Kim、Meghan J. Orr、Richard M. Fisher、Takeshi Q Tanaka、John C. McKew、Anton Simeonov、Philip E. Sanderson、Wei Zheng、Kim C. Williamson、Wenwei Huang

  DOI：10.1021/acscombsci.7b00119

  日期：2017.12.11

  A novel three-component, two-step, one-pot nucleophilic aromatic substitution (SNAr)–intramolecular cyclization–Suzuki coupling reaction was developed for the synthesis of benzo[h][1,6]naphthyridin-2(1H)-ones (Torins). On the basis of the new efficiently convergent synthetic route, a library of Torin analogs was synthesized. The antimalarial activities of these compounds were evaluated against asexual

  为合成苯并[ h ] [1,6]萘啶-2（1 H），开发了一种新颖的三组分，两步，一锅亲核芳香取代（S N Ar）-分子内环化-Suzuki偶联反应。-一个（Torins）。在新的有效收敛的合成路线的基础上，合成了都灵类似物的文库。使用生长抑制测定法评估这些化合物对无性寄生虫的抗疟活性，并使用生存力测定法评估配子细胞。