6-bromohexano-2',6'-xylidide | 77470-80-5

• 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: 6-bromohexano-2',6'-xylidide
• 英文别名: 6-Bromo-N-(2,6-dimethylphenyl)hexanamide
• CAS: 77470-80-5
• 化学式: C₁₄H₂₀BrNO
• 分子量: 298.223
• InChiKey: RFGFFOJYLRGQBI-UHFFFAOYSA-N

物化性质

• 熔点：
  158.5-159.5 °C
• 沸点：
  404.5±33.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-bromohexano-2',6'-xylidide 在 盐酸 、 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 6-aminohexano-2',6'-xylidide
  参考文献：
  名称：

  New antiarrhythmic agents. 6. Quantitative structure-activity relationships of aminoxylidides

  摘要：

  The synthesis and pharmacological evaluation of primary and tertiary aminoxylidides with the amino group in the 2-7 position of the acyl chain are described. 2,6-Xylidine was acylated with haloacyl halides and converted to the target compounds by direct amination or by the Gabriel procedure. Alternatively, 2,6-xylidine was coupled with keto acids, and the ketoxylidides were converted to the amines by reductive amination. The target compounds were evaluated in mice both for antiarrhythmic efficacy against chloroform-induced tachycardia and for central nervous system toxicity. Experimentally determined values of partition coefficients and pKa values were used for quantitative structure-activity analyses. While the antiarrhythmic activity could be described as a function of log P alone, the CNS toxicity was best described as a function of both log P and pKa. The results suggest that antiarrhythmic potency can be increased by increasing lipophilicity, while the therapeutic index can be improved by increasing the pKa.

  DOI：

  10.1021/jm00139a007
• 作为产物：
  描述：

  5-chloropentano-2',6'-xylidide 在 sodium iodide 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 48.0h， 生成 6-bromohexano-2',6'-xylidide
  参考文献：
  名称：

  New antiarrhythmic agents. 6. Quantitative structure-activity relationships of aminoxylidides

  摘要：

  The synthesis and pharmacological evaluation of primary and tertiary aminoxylidides with the amino group in the 2-7 position of the acyl chain are described. 2,6-Xylidine was acylated with haloacyl halides and converted to the target compounds by direct amination or by the Gabriel procedure. Alternatively, 2,6-xylidine was coupled with keto acids, and the ketoxylidides were converted to the amines by reductive amination. The target compounds were evaluated in mice both for antiarrhythmic efficacy against chloroform-induced tachycardia and for central nervous system toxicity. Experimentally determined values of partition coefficients and pKa values were used for quantitative structure-activity analyses. While the antiarrhythmic activity could be described as a function of log P alone, the CNS toxicity was best described as a function of both log P and pKa. The results suggest that antiarrhythmic potency can be increased by increasing lipophilicity, while the therapeutic index can be improved by increasing the pKa.

  DOI：

  10.1021/jm00139a007

文献信息

• 一种麻醉剂丁哌卡因杂质的合成方法
  申请人：青岛市妇女儿童医院

  公开号：CN108727214B

  公开（公告）日：2021-04-23

  本发明涉及一种麻醉剂丁哌卡因杂质的合成方法，它包括以下步骤：（a）向反应容器中加入6‑溴己酸、二氯甲烷和N,N‑二甲基甲酰胺，在冰盐浴、氮气保护的条件下滴加草酰氯，加毕后在0~25℃进行反应；反应结束后进行浓缩，随后加入甲苯再次浓缩得6‑溴己酰氯粗品；将所述6‑溴己酰氯粗品溶于二氯甲烷，在冰盐浴、氮气保护的条件下滴加二甲苯胺的二氯甲烷溶液，加毕后在5~10℃进行反应；反应结束后直接抽滤、洗涤、干燥得化合物ii；（b）向另一反应容器中加入所述化合物ii、正丁胺、碳酸钾和乙腈，在30~50℃进行反应；反应结束后提纯即可。通过采用6‑溴己酸和草酰氯为原料制备被欧洲药典定入药品质量标准的丁派卡因杂质，该方法工艺简单、反应步骤便捷。
• TENTHOREY, P. A.;BLOCK, A. J.;RONFELD, R. A.;MCMASTER, P. D.;BYRNES, E. W+, J. MED. CHEM., 1981, 24, N 7, 798-806
  作者：TENTHOREY, P. A.、BLOCK, A. J.、RONFELD, R. A.、MCMASTER, P. D.、BYRNES, E. W+

  DOI：——

  日期：——