4-ethyl-N,N-diisopropylbenzamide

• 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: 4-ethyl-N,N-diisopropylbenzamide
• 英文别名: 4-ethyl-N,N-di(propan-2-yl)benzamide
• 化学式: C₁₅H₂₃NO
• 分子量: 233.354
• InChiKey: YTFWQRLGPJGPTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-ethyl-N,N-diisopropylbenzamide 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 4.5h， 生成 (E)-N,N-diisopropyl-4-<2-(1,2-dihydro-1-methyl-2-oxopyridine-5-yl)-1-methylethenyl>benzamide
  参考文献：
  名称：

  Novel 5α-reductase inhibitors. Synthesis and structure-activity studies of 5-substituted 1-methyl-2-pyridones and 1-methyl-2-piperidones

  摘要：

  In search for nonsteroidal inhibitors of 5 alpha-reductase for the treatment of benign prostatic hyperplasia (BPH) and possibly prostate cancer, substrate mimicks were synthesized comprising of a 1-methyl-2-pyridone (2, 4-16) or 1-methyl-2-piperidone (1, 3, 17-22) moiety (mimicking steroidal ring A) and a diisopropyl (1, 2, (E)-5-(E)-7, (Z)-5-(Z)-7, 11-13, 17-19) or a tert-butyl (3, 4, (E)-8-(E)-10, (Z)-8(Z)-10, 14-16, 20-22) benzamide (mimicking steroidal ring D). The bridge connecting the 5 and 4 positions of the rings consisted of amide (CONH: 1-4), ethenyl (CH=CH, CCH3=CH, CH=CH3: (E)-5-(E)-10, (Z)-5(Z)-10) or ethylene groups (CH2CH2, CHCH3CH2, CH2CHCH3: 11-22). The amides 1-4 were obtained by amidation of the carboxylic acid chlorides with the 4-amino-N-substituted benzamides. The ethenyl compounds (E)-5(E)-10 and (Z)-5-(Z)-10 were synthesized by Wittig reaction of the carbonyl compounds and the corresponding triphenylphosphonium salts and subsequent separation of the stereoisomers. Depending on the time of reaction, catalytic hydrogenation of the ethenyl isomers (E)-5-(E)-10 led to the pyridone-substituted ethylene compounds 11-16 as well as to the piperidone-substituted ethylene compounds 17-22. The 5 alpha-reductase inhibitory properties were determined using rat ventral prostate, as well as human BPH and prostate cancer as source, 1 beta,2 beta-[H-3]testosterone as substrate and a HPLC procedure for the separation of dihydrotestosterone (DHT). Tested at a concentration of 100 mu M, the inhibition values of 1-22 ranged from 0-99%. Significant differences were observed between rat and human enzyme. The most active compound was N,N-diisopropyl-4-[2-(1-methyl-2-oxo-piperidine-5-yl)ethylene]benzamide 17 (IC50: 13 mu M).

  DOI：

  10.1016/0223-5234(94)90104-x
• 作为产物：
  描述：

  对乙基苯甲酸 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 4-ethyl-N,N-diisopropylbenzamide
  参考文献：
  名称：

  通过两个 C-H 键的自由基介导的分子内偶联轻松合成异吲哚啉酮

  摘要：

  开发了一种通过自由基介导的 N,N-二异丙基苯甲酰胺的两个 C-H 键分子内偶联来构建 3,3-二甲基异吲哚啉酮的无金属方法。反应可以以中等到高产率进行，并具有出色的化学选择性。提出了通过烷基C-H键氧化裂解形成烷基自由基和通过分子内均裂芳族取代形成内酰胺环的反应顺序。

  DOI：

  10.1055/a-2043-4862

文献信息

• Iron‐Catalyzed C( <i>sp</i> ² )−C( <i>sp</i> ³ ) Cross‐Coupling of Chlorobenzamides with Alkyl Grignard Reagents: Development of Catalyst System, Synthetic Scope, and Application
  作者：Elwira Bisz、Michal Szostak

  DOI：10.1002/adsc.201800849

  日期：2019.1.11

  preparation of alkylated amide‐derivatives by cross‐coupling chemistry using sustainable protocols is challenging due to sensitivity of the amide functional group to reaction conditions. Herein, we report the synthesis of alkyl‐substituted amides by iron‐catalyzed C(sp2)−C(sp3) cross‐coupling of Grignard reagents with aryl chlorides. The products of these reactions are broadly used in the synthesis of pharmaceuticals

  由于酰胺官能团对反应条件的敏感性，使用可持续方案通过交叉偶联化学方法直接制备烷基化酰胺衍生物具有挑战性。本文中，我们报道了铁催化的C（sp 2）-C（sp 3）合成烷基取代的酰胺的过程。）格氏试剂与芳基氯的交叉偶联。这些反应的产物广泛用于合成药物，农用化学品和其他具有生物活性的分子。此外，酰胺被用作通用中间体，可以参与有价值的酮和胺的合成，从而提供了广泛的合成兴趣基序。该反应的特点是具有良好的底物范围，可以耐受各种酰胺取代，包括空间大体积的，敏感的和易于修饰的酰胺。该反应可与具有β氢的具有挑战性的有机金属相容，并且可在非常温和，操作简单的条件下进行。催化剂体系的优化证明了O配位配体对交叉偶联的有益作用。发现该反应在较小的空间受阻位置对单取代具有完全的化学选择性。机理研究确定了反应的顺序，并深入了解了酰胺在控制烷基化单选择性中的作用。该协议提供了使用可持续的交叉耦合条件高效便捷地获得烷基酰胺结构基块的可能性。
• Dynemicin A Derivatives as Potential Cancer Chemotherapeutics by Mutasynthesis
  作者：Paramita Pal、Jamie R. Alley、Douglas R. Cohen、Craig A. Townsend

  DOI：10.1002/hlca.202300123

  日期：2023.12

  The enediyne antitumor antibiotics have remarkable structures and exhibit potent DNA cleavage properties that have inspired continued interest as cancer therapeutics. Their complex structures and high reactivity, however, pose formidable challenges to their production and development in the clinic. We report here proof-of-concept studies using a mutasynthesis strategy to combine chemical synthesis

  烯二炔抗肿瘤抗生素具有非凡的结构，并表现出强大的 DNA 切割特性，这激发了人们对癌症治疗的持续兴趣。然而，它们复杂的结构和高反应活性对其临床生产和开发提出了巨大的挑战。我们在此报告了概念验证研究，使用变合成策略将化学合成与关键碘蒽-γ-硫内酯中间体的选择性修饰结合起来，用于动力霉素 A 和所有其他已知的蒽醌稠合烯二炔 (AFE) 的生物合成。通过对无法合成这种基本结构单元的突变细菌生产者进行化学互补，我们表明可以制备取代蒽醌基序 A 环的动力霉素衍生物。在没有来自该中间体的天然生产的竞争的情况下，最有效地利用这些外部提供的结构类似物进行前体定向的生物合成成为可能。为了实现这一目标，我们描述了所需的 Δ orf15阻断突变体以及碘蒽结构变体库的一般合成路线。它们的成功掺入为增强 DNA 结合和调节修饰烯二炔的生物还原激活以进行 DNA 切割打开了大门。
• Novel 5α-reductase inhibitors. Synthesis and structure-activity studies of 5-substituted 1-methyl-2-pyridones and 1-methyl-2-piperidones
  作者：R HARTMANN、M REICHERT、S GOHRING

  DOI：10.1016/0223-5234(94)90104-x

  日期：——

  In search for nonsteroidal inhibitors of 5 alpha-reductase for the treatment of benign prostatic hyperplasia (BPH) and possibly prostate cancer, substrate mimicks were synthesized comprising of a 1-methyl-2-pyridone (2, 4-16) or 1-methyl-2-piperidone (1, 3, 17-22) moiety (mimicking steroidal ring A) and a diisopropyl (1, 2, (E)-5-(E)-7, (Z)-5-(Z)-7, 11-13, 17-19) or a tert-butyl (3, 4, (E)-8-(E)-10, (Z)-8(Z)-10, 14-16, 20-22) benzamide (mimicking steroidal ring D). The bridge connecting the 5 and 4 positions of the rings consisted of amide (CONH: 1-4), ethenyl (CH=CH, CCH3=CH, CH=CH3: (E)-5-(E)-10, (Z)-5(Z)-10) or ethylene groups (CH2CH2, CHCH3CH2, CH2CHCH3: 11-22). The amides 1-4 were obtained by amidation of the carboxylic acid chlorides with the 4-amino-N-substituted benzamides. The ethenyl compounds (E)-5(E)-10 and (Z)-5-(Z)-10 were synthesized by Wittig reaction of the carbonyl compounds and the corresponding triphenylphosphonium salts and subsequent separation of the stereoisomers. Depending on the time of reaction, catalytic hydrogenation of the ethenyl isomers (E)-5-(E)-10 led to the pyridone-substituted ethylene compounds 11-16 as well as to the piperidone-substituted ethylene compounds 17-22. The 5 alpha-reductase inhibitory properties were determined using rat ventral prostate, as well as human BPH and prostate cancer as source, 1 beta,2 beta-[H-3]testosterone as substrate and a HPLC procedure for the separation of dihydrotestosterone (DHT). Tested at a concentration of 100 mu M, the inhibition values of 1-22 ranged from 0-99%. Significant differences were observed between rat and human enzyme. The most active compound was N,N-diisopropyl-4-[2-(1-methyl-2-oxo-piperidine-5-yl)ethylene]benzamide 17 (IC50: 13 mu M).
• Facile Synthesis of Isoindolinones via Radical-Mediated Intramolecular Coupling of Two C–H Bonds
  作者：Yingsheng Zhao、Gong Chen、Shuxiong Han、Shuo He、Zhibin Huang

  DOI：10.1055/a-2043-4862

  日期：——

  radical-mediated intramolecular coupling of two C–H bonds of N,N-diisopropyl benzamides was developed. The reactions can proceed in moderate to high yield and with excellent chemoselectivity. A reaction sequence of the formation of an alkyl radical via oxidative cleavage of alkyl C–H bond and the formation of lactam ring via intramolecular homolytic aromatic substitution was proposed.

  开发了一种通过自由基介导的 N,N-二异丙基苯甲酰胺的两个 C-H 键分子内偶联来构建 3,3-二甲基异吲哚啉酮的无金属方法。反应可以以中等到高产率进行，并具有出色的化学选择性。提出了通过烷基C-H键氧化裂解形成烷基自由基和通过分子内均裂芳族取代形成内酰胺环的反应顺序。