N-benzyl-3,5-difluoro-N-methylaniline

• 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: N-benzyl-3,5-difluoro-N-methylaniline
• 英文别名: N-Benzyl-3,5-difluoro-N-methylaniline
• 化学式: C₁₄H₁₃F₂N
• 分子量: 233.261
• InChiKey: QNAUIJSJASCBDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-benzyl-3,5-difluoro-N-methylaniline 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 正丁基锂 、 ammonium acetate 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 14.5h， 生成 N'-<1-(4-N-benzyl-N-methylamino-2,6-difluorophenyl)-2-propyl>-N,N-dibenzylglycinamide
  参考文献：
  名称：

  Prodrugs of neuron-selective monoamine oxidase inhibitors: amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes

  摘要：

  Six amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes and their parent amines were synthezised and tested for their potency and selectivity in inhibiting monoamine oxidase (MAO) in vitro and in vivo. The amino acid derivatives were 300-1000 times less potent than the parent amines in inhibiting the MAO-A activity in a rat brain mitochondrial preparation in vitro. All compounds, except the (R)-valinamide derivative (22), were potent inhibitors of MAO in the rat brain in vivo and were, like the parent amines markedly more potent within the monoaminergic neurons than in other neurons. The glycinamide derivative 7 showed the largest difference between intra- and extra-neuronal inhibition in serotonergic neurons. The time course of the inhibitory effect of 7 in vivo showed that it is a reversible inhibitor with a long duration. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80047-6
• 作为产物：
  描述：

  3,5-二氟苯甲酸 在 ammonium hydroxide 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 氯化亚砜 、 溴 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 N-benzyl-3,5-difluoro-N-methylaniline
  参考文献：
  名称：

  Prodrugs of neuron-selective monoamine oxidase inhibitors: amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes

  摘要：

  Six amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes and their parent amines were synthezised and tested for their potency and selectivity in inhibiting monoamine oxidase (MAO) in vitro and in vivo. The amino acid derivatives were 300-1000 times less potent than the parent amines in inhibiting the MAO-A activity in a rat brain mitochondrial preparation in vitro. All compounds, except the (R)-valinamide derivative (22), were potent inhibitors of MAO in the rat brain in vivo and were, like the parent amines markedly more potent within the monoaminergic neurons than in other neurons. The glycinamide derivative 7 showed the largest difference between intra- and extra-neuronal inhibition in serotonergic neurons. The time course of the inhibitory effect of 7 in vivo showed that it is a reversible inhibitor with a long duration. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80047-6

文献信息

• Mechanism and Scope of Base-Controlled Catalyst-Free N-Arylation of Amines with Unactivated Fluorobenzenes
  作者：Christian Borch Jacobsen、Morten Meldal、Frederik Diness

  DOI：10.1002/chem.201604098

  日期：2017.1.18

  of amines has been developed. Mechanistic studies have revealed that the ability of the base to facilitate the desired amination without promoting unwanted side reactions is the guiding factor. By employing lithium bis(trimethylsilyl)amide as a base the resultant deprotonated amines readily react with a range of unactivated fluorobenzene derivatives. This new arylation method is utilized for the simple

  已经开发了一种用于胺类的无过渡金属N芳基化的通用方法。机理研究表明，碱促进所需胺化而不促进不希望的副反应的能力是指导因素。通过使用双（三甲基甲硅烷基）酰胺锂作为碱，所得的去质子化的胺容易与一系列未活化的氟苯衍生物反应。这种新的芳基化方法用于抗抑郁药伏替西汀的简单两步合成。
• [EN] ARYLATION OF ALIPHATIC AMINES<br/>[FR] ARYLATION D'AMINES ALIPHATIQUES
  申请人：AAA CHEMISTRY APS

  公开号：WO2017137047A1

  公开（公告）日：2017-08-17

  The invention relates to a method for arylation of amines, such as aliphatic amines by reaction of aryl-halogens, e.g. chloro- or fluorobenzene derivatives without strongly electron withdrawing substituents in the presence of a strong base.

  这项发明涉及一种方法，用于通过芳基卤代烃（例如氯苯或氟苯衍生物）与强碱在场的情况下对胺进行芳基化，例如脂肪族胺。
• ARYLATION OF ALIPHATIC AMINES
  申请人：AAA Chemistry ApS

  公开号：EP3414216A1

  公开（公告）日：2018-12-19
• Prodrugs of neuron-selective monoamine oxidase inhibitors: amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes
  作者：Lennart Florvall、Ingrid Fagervall、Lars-Gunnar Larsson、Svante B Ross

  DOI：10.1016/s0223-5234(99)80047-6

  日期：1999.2

  Six amino acid derivatives of 1-(4-aminophenyl)-2-aminopropanes and their parent amines were synthezised and tested for their potency and selectivity in inhibiting monoamine oxidase (MAO) in vitro and in vivo. The amino acid derivatives were 300-1000 times less potent than the parent amines in inhibiting the MAO-A activity in a rat brain mitochondrial preparation in vitro. All compounds, except the (R)-valinamide derivative (22), were potent inhibitors of MAO in the rat brain in vivo and were, like the parent amines markedly more potent within the monoaminergic neurons than in other neurons. The glycinamide derivative 7 showed the largest difference between intra- and extra-neuronal inhibition in serotonergic neurons. The time course of the inhibitory effect of 7 in vivo showed that it is a reversible inhibitor with a long duration. (C) Elsevier, Paris.