3-((tert-butylamino)methyl)-4-chloroaniline | 1138471-45-0

• 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: 3-((tert-butylamino)methyl)-4-chloroaniline
• 英文别名: 3-(tert-butylamino-methyl)-4-chloro-phenylamine；3-[(Tert-butylamino)methyl]-4-chloroaniline
• CAS: 1138471-45-0
• 化学式: C₁₁H₁₇ClN₂
• 分子量: 212.722
• InChiKey: BJKRMXICBIWYOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,7-二氯喹啉 、 3-((tert-butylamino)methyl)-4-chloroaniline 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 生成 [3-(tert-butylaminomethyl)-4-chlorophenyl](7-chloroquinolin-4-yl)amine
  参考文献：
  名称：

  Synthesis, Antimalarial Activity, and Preclinical Pharmacology of a Novel Series of 4′-Fluoro and 4′-Chloro Analogues of Amodiaquine. Identification of a Suitable “Back-Up” Compound for N-tert-Butyl Isoquine

  摘要：

  On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline arnodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed ADME studies and in vitro and in vivo toxicological assessment. 4'-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as a candidate for further development studies based on potent activity versus chloroquine-sensitive and resistant parasites,, moderate to excellent oral bioavailability, low toxicity in in vitro studies, and an acceptable safety profile.

  DOI：

  10.1021/jm8012757
• 作为产物：
  描述：

  tert-butyl-(2-chloro-5 nitro-benzyl)-amine 在 盐酸 、 tin 、 水 作用下， 反应 1.5h， 以77%的产率得到3-((tert-butylamino)methyl)-4-chloroaniline
  参考文献：
  名称：

  Synthesis, Antimalarial Activity, and Preclinical Pharmacology of a Novel Series of 4′-Fluoro and 4′-Chloro Analogues of Amodiaquine. Identification of a Suitable “Back-Up” Compound for N-tert-Butyl Isoquine

  摘要：

  On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline arnodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed ADME studies and in vitro and in vivo toxicological assessment. 4'-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as a candidate for further development studies based on potent activity versus chloroquine-sensitive and resistant parasites,, moderate to excellent oral bioavailability, low toxicity in in vitro studies, and an acceptable safety profile.

  DOI：

  10.1021/jm8012757

文献信息

• Advancing <i>Meta</i>-Selective C–H Amination through Non-Covalent Interactions
  作者：Qianqian Lv、Zongxing Hu、Yousong Zhang、Zhihan Zhang、Honghui Lei

  DOI：10.1021/jacs.3c09904

  日期：2024.1.24

  Regioselective C–H amination of simple arenes is highly desirable, but accessing meta-sites of ubiquitous arenes has proven challenging due to the lack of both electronic and spatial preference. This study demonstrates the successful use of various privileged nitrogen-containing functionalities found in pharmaceutical compounds to direct meta-C–H amination of arenes, overcoming the long-standing requirement

  简单芳烃的区域选择性 C-H 胺化是非常理想的，但由于缺乏电子和空间偏好，访问普遍存在的芳烃的元位点已被证明具有挑战性。这项研究证明了成功地利用药物化合物中发现的各种独特的含氮官能团来指导芳烃的间-C-H胺化，克服了长期以来对冗余导向基团的要求。通过发现前所未有的有机引发剂和非共价相互作用的战略利用，在精确区域化学控制的官能团调节方面取得了显着进展。该方案已成功应用于药物分子的简洁合成和后期衍生化，否则这是很难实现的。