ethyl 4-(benzhydrylamino)benzoate

• 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: ethyl 4-(benzhydrylamino)benzoate
• 英文别名: Ethyl 4-(benzhydrylamino)benzoate
• 化学式: C₂₂H₂₁NO₂
• 分子量: 331.414
• InChiKey: LDRVHQFPMSUUBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-(benzhydrylamino)benzoate 在 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 8.0h， 以88%的产率得到4-(benzhydrylamino)benzoic acid
  参考文献：
  名称：

  8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells

  摘要：

  Ras converting enzyme 1 (Rce1) is an endoprotease that catalyzes processing of the C-terminus of Ras protein by removing -aaX from the CaaX motif. The activity of Rce1 is crucial for proper localization of Ras to the plasma membrane where it functions. Ras is responsible for transmitting signals related to cell proliferation, cell cycle progression, and apoptosis. The disregulation of these pathways due to constitutively active oncogenic Ras can ultimately lead to cancer. Ras, its effectors and regulators, and the enzymes that are involved in its maturation process are all targets for anti-cancer therapeutics. Key enzymes required for Ras maturation and localization are the farnesyltransferase (FTase), Rce1, and isoprenylcysteine carboxyl methyltransferase (ICMT). Among these proteins, the physiological role of Rce1 in regulating Ras and other CaaX proteins has not been fully explored. Small-molecule inhibitors of Rce1 could be useful as chemical biology tools to understand further the downstream impact of Rce1 on Ras function and serve as potential leads for cancer therapeutics. Structure-activity relationship (SAR) analysis of a previously reported Rce1 inhibitor, NSC1011, has been performed to generate a new library of Rce1 inhibitors. The new inhibitors caused a reduction in Rce1 in vitro activity, exhibited low cell toxicity, and induced mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells giving rise to a phenotype similar to that observed with siRNA knockdowns of Rce1 expression. Several of the new inhibitors were more effective at mislocalizing K-Ras compared to a potent farnesyltransferase inhibitor (FTI), which is significant because of the preponderance of K-Ras mutations in cancer. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.043
• 作为产物：
  描述：

  ethyl 4-((diphenylmethylene)amino)benzoate 在 (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以74%的产率得到ethyl 4-(benzhydrylamino)benzoate
  参考文献：
  名称：

  分批和连续流动的二丙胺的光催化和化学选择性转移加氢

  摘要：

  描述了用于间歇和连续流动的亚胺化学选择性转移氢化的可见光光催化方法。该反应利用Et 3 N作为氢源和单电子供体，从而能够选择性还原衍生自含有其他可还原官能团（包括腈，卤化物，酯和酮）的二芳基酮亚胺的亚胺。Et 3 N的双重作用已通过荧光猝灭测量，瞬态吸收光谱和氘标记研究得到了证实。连续流处理有助于直接扩大反应规模。

  DOI：

  10.1021/acs.orglett.7b03565

文献信息

• Gold(III)/Sodium Diphenylphosphinobenzene-3-sulfonate (TPPMS) Catalyzed Dehydrative N-Benzylation of Electron-Deficient Anilines in Water
  作者：Hidemasa Hikawa、Mika Matsumoto、Sayoko Tawara、Shoko Kikkawa、Isao Azumaya

  DOI：10.1055/s-0037-1611519

  日期：2019.7

  tolerates aerobic conditions. A Hammett study in the reaction of para-substituted benzhydryl alcohols shows negative σ values, indicating a build-up of cationic charge during the rate-determining sp3 C–O bond-cleavage step. The inverse kinetic solvent isotope effect (KSIE = 0.6) is consistent with a specific acid catalysis mechanism. This simple protocol can be performed under mild conditions in an atom-economic

  抽象的 已经开发出一种用于缺电子的苯胺在水中的脱水N-苄基化的策略。金（III）/二苯基膦基苯-3-磺酸钠（TPPMS）催化剂作为路易斯酸非常有效，可活化醇并耐受有氧条件。Hammett在对位取代的苯甲醇的反应中的研究显示出负σ值，表明在速率确定sp 3 C–O键断裂步骤期间阳离子电荷的积累。逆动力学溶剂同位素效应（KSIE = 0.6）与特定的酸催化机理一致。这种简单的方案可以在原子经济过程中的温和条件下进行，而无需碱或其他添加剂，从而提供了电子不足的N-苄基苯胺具有中等至优异的收率，并且水是唯一的副产物。 已经开发出一种用于缺电子的苯胺在水中的脱水N-苄基化的策略。金（III）/二苯基膦基苯-3-磺酸钠（TPPMS）催化剂作为路易斯酸非常有效，可活化醇并耐受有氧条件。Hammett在对位取代的苯甲醇的反应中的研究显示出负σ值，表明在速率确定sp 3 C–O键断裂步骤期间阳离子电荷的积累。逆动力学溶剂同位素效应（KSIE
• Photocatalytic and Chemoselective Transfer Hydrogenation of Diarylimines in Batch and Continuous Flow
  作者：Dean J. van As、Timothy U. Connell、Martin Brzozowski、Andrew D. Scully、Anastasios Polyzos

  DOI：10.1021/acs.orglett.7b03565

  日期：2018.2.16

  imines in batch and continuous flow is described. The reaction utilizes Et3N as both hydrogen source and single-electron donor, enabling the selective reduction of imines derived from diarylketimines containing other reducible functional groups including nitriles, halides, esters, and ketones. The dual role of Et3N was confirmed by fluorescence quenching measurements, transient absorption spectroscopy,

  描述了用于间歇和连续流动的亚胺化学选择性转移氢化的可见光光催化方法。该反应利用Et 3 N作为氢源和单电子供体，从而能够选择性还原衍生自含有其他可还原官能团（包括腈，卤化物，酯和酮）的二芳基酮亚胺的亚胺。Et 3 N的双重作用已通过荧光猝灭测量，瞬态吸收光谱和氘标记研究得到了证实。连续流处理有助于直接扩大反应规模。
• Correction to Photocatalytic and Chemoselective Transfer Hydrogenation of Diarylimines in Batch and Continuous Flow
  作者：Dean J. van As、Timothy U. Connell、Martin Brzozowski、Andrew D. Scully、Anastasios Polyzos

  DOI：10.1021/acs.orglett.8b02023

  日期：2018.7.20
• 8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells
  作者：Idrees Mohammed、Shahienaz E. Hampton、Louise Ashall、Emily R. Hildebrandt、Robert A. Kutlik、Surya P. Manandhar、Brandon J. Floyd、Haley E. Smith、Jonathan K. Dozier、Mark D. Distefano、Walter K. Schmidt、Timothy M. Dore

  DOI：10.1016/j.bmc.2015.11.043

  日期：2016.1

  Ras converting enzyme 1 (Rce1) is an endoprotease that catalyzes processing of the C-terminus of Ras protein by removing -aaX from the CaaX motif. The activity of Rce1 is crucial for proper localization of Ras to the plasma membrane where it functions. Ras is responsible for transmitting signals related to cell proliferation, cell cycle progression, and apoptosis. The disregulation of these pathways due to constitutively active oncogenic Ras can ultimately lead to cancer. Ras, its effectors and regulators, and the enzymes that are involved in its maturation process are all targets for anti-cancer therapeutics. Key enzymes required for Ras maturation and localization are the farnesyltransferase (FTase), Rce1, and isoprenylcysteine carboxyl methyltransferase (ICMT). Among these proteins, the physiological role of Rce1 in regulating Ras and other CaaX proteins has not been fully explored. Small-molecule inhibitors of Rce1 could be useful as chemical biology tools to understand further the downstream impact of Rce1 on Ras function and serve as potential leads for cancer therapeutics. Structure-activity relationship (SAR) analysis of a previously reported Rce1 inhibitor, NSC1011, has been performed to generate a new library of Rce1 inhibitors. The new inhibitors caused a reduction in Rce1 in vitro activity, exhibited low cell toxicity, and induced mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells giving rise to a phenotype similar to that observed with siRNA knockdowns of Rce1 expression. Several of the new inhibitors were more effective at mislocalizing K-Ras compared to a potent farnesyltransferase inhibitor (FTI), which is significant because of the preponderance of K-Ras mutations in cancer. (C) 2015 Elsevier Ltd. All rights reserved.
• A Chemoselective and Scalable Transfer Hydrogenation of Aryl Imines by Rapid Continuous Flow Photoredox Catalysis
  作者：Rowan L. Pilkington、Nikolai P. Rossouw、Dean J. Van As、Anastasios Polyzos

  DOI：10.2533/chimia.2019.823

  日期：——

  accessed through precise control of reaction and irradiation time by continuous flow visible light photoredox catalysis. The method enables the mild and efficient transfer hydrogenation of diaryl imines in the presence of sensitive functionality including halides, ester, ketone, and cyano groups. The flow protocol is efficient, rapid (>98% conversion within 9 min) and readily scaled to deliver multigram

  在竞争性可还原基团存在下，二芳基亚胺的化学选择性还原是通过连续流可见光光氧化还原催化精确控制反应和照射时间来实现的。该方法能够在卤化物、酯、酮和氰基等敏感官能团存在下对二芳基亚胺进行温和有效的转移氢化。该流程方案高效、快速（9 分钟内转化率>98%），并且易于扩展以提供数克数量的高纯度胺产品。