N-(2,2-dimethoxyethyl)-3-fluorobenzylamine

• 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-(2,2-dimethoxyethyl)-3-fluorobenzylamine
• 英文别名: N-[(3-fluorophenyl)methyl]-2,2-dimethoxyethanamine
• 化学式: C₁₁H₁₆FNO₂
• mdl: MFCD12148392
• 分子量: 213.252
• InChiKey: JGQUJDPTYSSMCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2,2-dimethoxyethyl)-3-fluorobenzylamine 在 四氯化钛 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 7-fluoro-2-tosyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  通过TiCl4介导的环化和Et3SiH还原合成四氢异喹啉

  摘要：

  摘要报道了一种通用且有效的伸缩反应序列，用于合成四氢异喹啉（THIQs），该序列使用TiCl4促进苄氨基缩醛衍生物的环化反应，并使用Et3SiH还原中间体4-羟基-THIQ。此方法是对经典Pomeranz-Fritsch和相关反应的补充，因为它可以耐受吸电子取代基并允许使用8位取代的THIQ。

  DOI：

  10.1016/j.cclet.2019.09.023
• 作为产物：
  描述：

  N-<(3-fluorophenyl)methylene>-2,2-dimethoxyethanamine 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 N-(2,2-dimethoxyethyl)-3-fluorobenzylamine
  参考文献：
  名称：

  Multisubstrate inhibitors of dopamine .beta.-hydroxylase. 2. Structure-activity relationships at the phenethylamine binding site

  摘要：

  1-Aralkylimidazole-2-thiones have been shown to be potent multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1). In the present study, a series of 1-benzylimidazole-2-thiones was prepared to explore the effects of substitution in the benzyl ring on the inhibition of DBH. A detailed structure-activity relationship for in vitro activity was discovered and this was shown by a modified Hansch analysis to correlate (r = 0.91) with four key structural features of the benzyl ring: the presence of a hydroxyl at the 4-position, molar refractivity at the 3-, 4-, and 5-positions, inductive effects of the substituents at the 3-, 4-, and 5-positions, and pi-electron density. The affinity (Kis) of eight substituted inhibitors for DBH was shown to correlate (r = 0.75) with the affinity (KD) of comparably substituted tyramines for the ternary DBH-oxygen-tyramine complex. This correlate is used to support the hypothesis that binding of inhibitor to DBH occurs in a fashion that mimics the binding of tyramine substrates. The most potent inhibitors were selected for study in vivo in the spontaneously hypertensive rat model of hypertension. The changes in vascular dopamine and norepinephrine levels that resulted from oral administration of the inhibitors corresponded to the observed reduction in mean arterial blood pressure. A divergence between in vitro potency and in vivo efficacy upon oral dosing was noted and is suggested to result from an in vivo metabolic conjugation of the phenolic group of inhibitor.

  DOI：

  10.1021/jm00386a008

文献信息

• Self-modulated highly chemoselective direct-reductive-amination (DRA) of benzaldehydes straightforward to N-monosubstituted benzylamine hydrochlorides
  作者：Lixin Xing、Chuanjie Cheng、Rui Zhu、Boyang Zhang、Xinyan Wang、Yuefei Hu

  DOI：10.1016/j.tet.2008.09.072

  日期：2008.12

  All unprecedented efficient and chemoselective DRA of benzaldehydes and primary amines was developed to directly yield N-monosubstituted benzylamine hydrochlorides as single products in practically quantitative yields. The method was characterized by simply adding a few milliliters of CHCl3 in the conventional Pd-C catalytic hydrogenation system at atmospheric pressure and room temperature. A self-modulated system and a four-stage cyclic pathway were proposed. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis of tetrahydroisoquinolines through TiCl4-mediated cyclization and Et3SiH reduction
  作者：Zeyu Shi、Qiong Xiao、Dali Yin

  DOI：10.1016/j.cclet.2019.09.023

  日期：2020.3

  Abstract A versatile and efficient telescoped reaction sequence for the synthesis of tetrahydroisoquinolines (THIQs) is reported that uses TiCl4 to promote cyclization of a benzylaminoacetal derivative and Et3SiH for reduction of the intermediate 4-hydroxy-THIQ. This method is complimentary to the classical Pomeranz-Fritsch and related reactions since it tolerates electron-withdrawing substituents

  摘要报道了一种通用且有效的伸缩反应序列，用于合成四氢异喹啉（THIQs），该序列使用TiCl4促进苄氨基缩醛衍生物的环化反应，并使用Et3SiH还原中间体4-羟基-THIQ。此方法是对经典Pomeranz-Fritsch和相关反应的补充，因为它可以耐受吸电子取代基并允许使用8位取代的THIQ。
• Multisubstrate inhibitors of dopamine .beta.-hydroxylase. 2. Structure-activity relationships at the phenethylamine binding site
  作者：Lawrence I. Kruse、Carl Kaiser、Walter E. DeWolf、James S. Frazee、Stephen T. Ross、Joyce Wawro、Merrie Wise、Kathryn E. Flaim、John L. Sawyer

  DOI：10.1021/jm00386a008

  日期：1987.3

  1-Aralkylimidazole-2-thiones have been shown to be potent multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1). In the present study, a series of 1-benzylimidazole-2-thiones was prepared to explore the effects of substitution in the benzyl ring on the inhibition of DBH. A detailed structure-activity relationship for in vitro activity was discovered and this was shown by a modified Hansch analysis to correlate (r = 0.91) with four key structural features of the benzyl ring: the presence of a hydroxyl at the 4-position, molar refractivity at the 3-, 4-, and 5-positions, inductive effects of the substituents at the 3-, 4-, and 5-positions, and pi-electron density. The affinity (Kis) of eight substituted inhibitors for DBH was shown to correlate (r = 0.75) with the affinity (KD) of comparably substituted tyramines for the ternary DBH-oxygen-tyramine complex. This correlate is used to support the hypothesis that binding of inhibitor to DBH occurs in a fashion that mimics the binding of tyramine substrates. The most potent inhibitors were selected for study in vivo in the spontaneously hypertensive rat model of hypertension. The changes in vascular dopamine and norepinephrine levels that resulted from oral administration of the inhibitors corresponded to the observed reduction in mean arterial blood pressure. A divergence between in vitro potency and in vivo efficacy upon oral dosing was noted and is suggested to result from an in vivo metabolic conjugation of the phenolic group of inhibitor.