(1S,2S)-1-(4-氯-3-甲氧基苯基)-N-(2,2-二甲氧基乙基)-N-甲基-1,2,3,4-四氢萘-2-胺 | 168965-34-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: (1S,2S)-1-(4-氯-3-甲氧基苯基)-N-(2,2-二甲氧基乙基)-N-甲基-1,2,3,4-四氢萘-2-胺
• 英文名称: (+)-trans-(1S,2S)-1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-1,2,3,4-tetrahydro-N-methyl-2-naphthalenamine
• 英文别名: (+)-trans-1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-1,2,3,4-tetrahydro-N-methyl-2-naphthalenamine；(1S,2S)-1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-2-amine
• CAS: 168965-34-2
• 化学式: C₂₂H₂₈ClNO₃
• 分子量: 389.922
• InChiKey: LEIMDLVAMAFLQF-UGKGYDQZSA-N

物化性质

• 沸点：
  492.7±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2S)-1-(4-氯-3-甲氧基苯基)-N-(2,2-二甲氧基乙基)-N-甲基-1,2,3,4-四氢萘-2-胺 在 甲烷磺酸 、 硼烷-叔丁基胺 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 以70%的产率得到trans-(-)-(6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-12-methoxy-5H-benzonaphth<2,1-b>azepine
  参考文献：
  名称：

  Catalytic enantioselective synthesis of the dopamine D1 antagonist ecopipam

  摘要：

  A concise asymmetric synthesis of the potent dopamine D1 antagonist, ecopipam, has been accomplished in six steps with 33% overall yield via catalytic enantioselective aziridination and subsequent one-pot Friedel-Crafts cyclization of an in situ generated tethered aziridine with high diastereo- and enantioselectivities. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.01.017
• 作为产物：
  描述：

  4-chloro-3-methoxyphenylmethyl(triphenyl)phosphonium bromide 在 正丁基锂 、 4-甲氧基苯硫酚 、 potassium fluoride on basic alumina 、 copper(II) bis(trifluoromethanesulfonate) 、 sodium hydride 、 (S,S)-2,2'-异亚丙基双(4-苯基-2-恶唑啉) 、 potassium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， 反应 39.0h， 生成 (1S,2S)-1-(4-氯-3-甲氧基苯基)-N-(2,2-二甲氧基乙基)-N-甲基-1,2,3,4-四氢萘-2-胺
  参考文献：
  名称：

  Catalytic enantioselective synthesis of the dopamine D1 antagonist ecopipam

  摘要：

  A concise asymmetric synthesis of the potent dopamine D1 antagonist, ecopipam, has been accomplished in six steps with 33% overall yield via catalytic enantioselective aziridination and subsequent one-pot Friedel-Crafts cyclization of an in situ generated tethered aziridine with high diastereo- and enantioselectivities. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.01.017

文献信息

• Reaction of aziridinium ions with organometallic reagents: optimization of the key step of ecopipam synthesis
  作者：David R Andrews、Vilas H Dahanukar、Jeffrey M Eckert、Dinesh Gala、Brian S Lucas、Doris P Schumacher、Ilia A Zavialov

  DOI：10.1016/s0040-4039(02)01337-0

  日期：2002.8

  Formation, stability and reactivity of aziridinium ions 3 towards organometallic reagents was explored and optimized for the efficient preparation of key drug intermediate 5c.

  为有效制备关键药物中间体5c，探索并优化了氮丙啶鎓离子3对有机金属试剂的形成，稳定性和反应性。
• Draper, Richard W.; Hou, Donald, Organic Process Research and Development, 1998, vol. 2, # 3, p. 186 - 193
  作者：Draper, Richard W.、Hou, Donald

  DOI：——

  日期：——
• Novel Stereoselective Syntheses of the Fused Benzazepine Dopamine D₁ Antagonist (6a<i>S</i>,13b<i>R</i>)-11-Chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5<i>H</i>- benzo[<i>d</i>]naphth[2,1-<i>b</i>]azepin-12-ol (Sch 39166):  1. Aziridinium Salt Based Syntheses
  作者：Richard W. Draper、Donald Hou、Radha Iyer、Gary M. Lee、Jimmy T. Liang、Janet L. Mas、Wanda Tormos、Eugene J. Vater、Frank Günter、Ingrid Mergelsberg、Dominik Scherer

  DOI：10.1021/op970121s

  日期：1998.5.1

  Several novel enantioselective syntheses of the dopamine D-1 antagonist (6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7- methyl-5H-benzo[d]naphth[2,1-b]azepin-12-ol (2) are described in which the key intermediate was 1-(2,2 dimethoxyethyl)-1-methyl-1a,2,3,7b-tetrahydro-1H-naphth[1,2-b] aziridinium salt (20), The latter species was prepared either from 1-(2,2-dimethoxyethyl)-1a,2,3,7b-tetrahydro-]H-naphth[1,2-b]- azirine (18) by methylation or from the tertiary amino alcohols 1-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro-2 -naphthalenol (23) or 2-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro -1-naphthalenol (24) by tosylation and in situ ring closure. Regioselective trapping of 20 with Grignard reagent (4-chloro-3-methoxyphenyl)magnesium bromide (10) then afforded the transamine 1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-1,2,3,4 -tetrahydro-N-methyl-2-naphth-alenamine (22), which was cyclized to give 11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-12-methoxy-5H-benzo [d]- naphth[2,1-b]azepine (9), a known precursor of 2, Several enantioselective syntheses, including a Jacobsen epoxidation route, a de novo synthesis from L-homophenylalanine, and a classical salt resolution sequence, were developed for the preparation of the key intermediates in chiral form.
• Org. Process Res. Dev. 1998, 2, 186-193
  作者：

  DOI：——

  日期：——
• Tetrahedron: Asymmetry 2012, 23, 151-156
  作者：

  DOI：——

  日期：——