α,α-dimethyl-1,3-benzodioxole-5-propanamine | 76310-64-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: α,α-dimethyl-1,3-benzodioxole-5-propanamine
• 英文别名: 4-(benzo[d][1,3]dioxol-5-yl)-2-methylbutan-2-amine；4-(1,3-Dioxaindan-5-yl)-2-methylbutan-2-amine；4-(1,3-benzodioxol-5-yl)-2-methylbutan-2-amine
• CAS: 76310-64-0
• 化学式: C₁₂H₁₇NO₂
• 分子量: 207.272
• InChiKey: QFJBSFSZMMREMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(2-溴-乙酰基)-2-羟基-苯甲酸甲酯 、 α,α-dimethyl-1,3-benzodioxole-5-propanamine 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Salicylamide derivatives related to medroxalol with .alpha.- and .beta.-adrenergic antagonist and antihypertensive activity

  摘要：

  Analogues of medroxalol (1) were prepared in which the carboxamide function, the phenolic hydroxy group, and the aralkylamine side chain were modified. N-alkyl-substituted amide analogues of 1 showed diminishing beta-blocking activity with increasing steric bulk of the alkyl group. This allowed the conclusion that deactivation of the phenolic hydroxy group of 1 by the carbonyl group of the amide function is responsible for the beta-adrenergic antagonistic properties of 1. This conclusion was strengthened by the finding that the phenolic O-methyl analogue 5-[2-[[3-(1,3-benzodioxol-5-yl)-1-methylpropyl]amino]-1hydroxyethyl]-2-methoxybenzamide (13) was found to have enhanced beta-adrenergic blocking activity. The finding that 13 also had decreased alpha-blocking activity compared to 1 indicated that the phenolic hydroxy group of 1 enhances alpha-adrenergic antagonism. The finding that 1 and 13 showed such a large difference in relative alpha- to beta-blocking potency while exhibiting approximately equal antihypertensive activity in spontaneously hypertensive rats was surprising. In indicated that pharmacologic properties other than alpha- and beta-adrenergic blockade may contribute to the antihypertensive activity of medroxalol. One of the analogues in which the aralkylamine side chain of 1 was replaced by a fragment of a known alpha-adrenergic receptor blocker, 2-hydroxy-5-[1-hydroxy-2-[4-(2-methylphenyl)-1-piperazinyl]ethyl]benzamide (22), showed an interesting pharmacologic profile of potential therapeutic usefulness.

  DOI：

  10.1021/jm00135a017
• 作为产物：
  描述：

  胡椒基丙酮 在 sodium hydroxide 、 硫酸 、 溶剂黄146 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 67.0h， 生成 α,α-dimethyl-1,3-benzodioxole-5-propanamine
  参考文献：
  名称：

  Salicylamide derivatives related to medroxalol with .alpha.- and .beta.-adrenergic antagonist and antihypertensive activity

  摘要：

  Analogues of medroxalol (1) were prepared in which the carboxamide function, the phenolic hydroxy group, and the aralkylamine side chain were modified. N-alkyl-substituted amide analogues of 1 showed diminishing beta-blocking activity with increasing steric bulk of the alkyl group. This allowed the conclusion that deactivation of the phenolic hydroxy group of 1 by the carbonyl group of the amide function is responsible for the beta-adrenergic antagonistic properties of 1. This conclusion was strengthened by the finding that the phenolic O-methyl analogue 5-[2-[[3-(1,3-benzodioxol-5-yl)-1-methylpropyl]amino]-1hydroxyethyl]-2-methoxybenzamide (13) was found to have enhanced beta-adrenergic blocking activity. The finding that 13 also had decreased alpha-blocking activity compared to 1 indicated that the phenolic hydroxy group of 1 enhances alpha-adrenergic antagonism. The finding that 1 and 13 showed such a large difference in relative alpha- to beta-blocking potency while exhibiting approximately equal antihypertensive activity in spontaneously hypertensive rats was surprising. In indicated that pharmacologic properties other than alpha- and beta-adrenergic blockade may contribute to the antihypertensive activity of medroxalol. One of the analogues in which the aralkylamine side chain of 1 was replaced by a fragment of a known alpha-adrenergic receptor blocker, 2-hydroxy-5-[1-hydroxy-2-[4-(2-methylphenyl)-1-piperazinyl]ethyl]benzamide (22), showed an interesting pharmacologic profile of potential therapeutic usefulness.

  DOI：

  10.1021/jm00135a017

文献信息

• Palladium-Catalyzed C(sp³ )−H Arylation of Primary Amines Using a Catalytic Alkyl Acetal to Form a Transient Directing Group
  作者：Sahra St John-Campbell、Alex K. Ou、James A. Bull

  DOI：10.1002/chem.201804515

  日期：2018.12.3

  requires derivatization at nitrogen with a directing group. Transient directing groups (TDGs) permit C−H functionalization in a single operation, without needing these additional steps for directing group installation and removal. Here we report a palladium catalyzed γ‐C−H arylation of amines using catalytic amounts of alkyl acetals as transient activators (e.g. commercially available (2,2‐dimethoxyethoxy)benzene)

  由于胺与过渡金属催化剂的强烈络合，胺的 C−H 官能化是一个突出的挑战，因此通常需要用导向基团在氮上进行衍生化。瞬态定向基团 (TDG) 允许在单个操作中实现 CH 功能化，而不需要这些额外的步骤来安装和移除定向基团。在这里，我们报道了使用催化量的烷基缩醛作为瞬时活化剂（例如市售的（2,2-二甲氧基乙氧基）苯）的钯催化的胺的γ-C-H芳基化。这种简单的添加剂可以使胺与多种芳基碘化物发生芳基化。对新型 TDG 的关键结构特征进行了研究，证明了掩蔽的羰基和醚官能团的重要作用。详细的动力学 (RPKA) 和机制研究确定了所有试剂的顺序，并将环钯化确定为周转限制步骤。最后，报道了一种前所未有的非循环游离胺定向的芳基化产物的ε-环钯化反应。
• Salicylamide derivatives related to medroxalol with .alpha.- and .beta.-adrenergic antagonist and antihypertensive activity
  作者：J. Martin Grisar、George P. Claxton、Thomas M. Bare、Richard C. Dage、Hsien C. Cheng、James K. Woodward

  DOI：10.1021/jm00135a017

  日期：1981.3

  Analogues of medroxalol (1) were prepared in which the carboxamide function, the phenolic hydroxy group, and the aralkylamine side chain were modified. N-alkyl-substituted amide analogues of 1 showed diminishing beta-blocking activity with increasing steric bulk of the alkyl group. This allowed the conclusion that deactivation of the phenolic hydroxy group of 1 by the carbonyl group of the amide function is responsible for the beta-adrenergic antagonistic properties of 1. This conclusion was strengthened by the finding that the phenolic O-methyl analogue 5-[2-[[3-(1,3-benzodioxol-5-yl)-1-methylpropyl]amino]-1hydroxyethyl]-2-methoxybenzamide (13) was found to have enhanced beta-adrenergic blocking activity. The finding that 13 also had decreased alpha-blocking activity compared to 1 indicated that the phenolic hydroxy group of 1 enhances alpha-adrenergic antagonism. The finding that 1 and 13 showed such a large difference in relative alpha- to beta-blocking potency while exhibiting approximately equal antihypertensive activity in spontaneously hypertensive rats was surprising. In indicated that pharmacologic properties other than alpha- and beta-adrenergic blockade may contribute to the antihypertensive activity of medroxalol. One of the analogues in which the aralkylamine side chain of 1 was replaced by a fragment of a known alpha-adrenergic receptor blocker, 2-hydroxy-5-[1-hydroxy-2-[4-(2-methylphenyl)-1-piperazinyl]ethyl]benzamide (22), showed an interesting pharmacologic profile of potential therapeutic usefulness.