N-ethyl-3,4,5-trimethoxyaniline | 163629-15-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-ethyl-3,4,5-trimethoxyaniline
• CAS: 163629-15-0
• 化学式: C₁₁H₁₇NO₃
• mdl: MFCD11141984
• 分子量: 211.261
• InChiKey: VRIGZMIQTLFNRQ-UHFFFAOYSA-N

物化性质

• 沸点：
  321.7±42.0 °C(Predicted)
• 密度：
  1.070±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  39.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-ethyl-3,4,5-trimethoxyaniline 在 4-二甲氨基吡啶 、 氢溴酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 123.0h， 生成 2,4-diamino-6-[(3',4',5'-trimethoxy-N-ethylanilino)methyl]pyrido[2,3-d]pyrimidine hydrobromide salt
  参考文献：
  名称：

  Synthesis and Dihydrofolate Reductase Inhibitory Activities of 2,4-Diamino-5-deaza and 2,4-Diamino-5,10-dideaza Lipophilic Antifolates

  摘要：

  Two series of nonclassical antifolates (2,4-diamino-5-deaza compounds 2-5 and 5,10-dideaza compounds 6-13) were synthesized as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii (pc) and Toxoplasma gondii (tg) organisms that are responsible for fatal opportunistic infections in AIDS patients. Rat liver (rl) DHFR served as the mammalian reference enzyme to determine selectivity. Syntheses of the target 5-deaza compounds were achieved by initial construction of the pivaloyl-protected 2,4-diamino-6-bromopyrido[2,3-d]-pyrimidine 17 via a cyclocondensation of 2,4,6-triaminopyrimidine with bromomalonaldehyde. Sequential Heck coupling of 17 with styrene followed by ozonolysis afforded the g-formyl derivative 19. Reductive amination of 19 with 3,4,5-trimethoxyaniline afforded the N10-H analog. The NIO-Me and NIO-Et analogs were synthesized by nucleophilic displacement of the 6-bromomethyl derivative 22 (obtained from the g-formyl derivative 19 by reduction and bromination) with the appropriate N-alkylaniline. The trans-5,10-dideaza analogs 6-8 were synthesized via a Heck coupling of the appropriate methoxystyrene with 17, and selective reduction of the resulting 9,10-double bond afforded target compounds 9-11. Further reduction to the tetrahydro derivatives afforded analogs 12 and 13. The 5-deaza NIO-Me 3,4,5-trimethoxy analog 3 maintained the best balance of potency and selectivity against both tgDHFR and pcDHFR. Compared to trimethoprim, compound 3 was only slightly less selective but was 300-fold more potent against tgDHFR. The 5,10-dideaza analogs were generally less potent and selective than the 5-deaza compounds.

  DOI：

  10.1021/jm9606913
• 作为产物：
  描述：

  3,4,5-三甲氧基苯胺 、 乙腈 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 22.0h， 以100%的产率得到N-ethyl-3,4,5-trimethoxyaniline
  参考文献：
  名称：

  在氢化条件下使用腈对胺进行 选择性N-烷基化：仲胺和叔胺的便捷合成†

  摘要：

  发现腈是在催化氢化条件下用于胺的选择性N-烷基化的高效烷基化试剂。对于芳族伯胺，相应的仲胺是在以下条件下有选择地获得的：钯/ C催化的氢化条件。尽管使用电子贫乏的芳族胺或庞大的腈显示出对还原烷基化反应的较低反应性，但添加NH 4 OAc增强了反应活性，从而以优异的产率获得了芳族仲胺。在相同的反应条件下，芳族硝基化合物代替芳族伯胺可以通过多胺反应直接转化为仲胺，该反应涉及硝基的一锅加氢和胺的还原烷基化。脂族胺在以下条件下有效地转化为相应的叔胺钯/ C催化的条件， 铑/ C是用于脂族伯胺的N-单烷基化而不会过度烷基化成叔胺的高效催化剂。此外，铑/ C催化的脂肪族伯胺的N-单烷基化反应及其他钯所得仲脂族胺的/ C催化烷基化可以选择性地制备具有三个不同烷基的脂族叔胺。根据机理研究，似乎可以合理地得出以下结论：在反应的第一步中，在胺发生亲核攻击之前，腈被还原为醛亚胺。

  DOI：

  10.1039/c1ob06303k

文献信息

• Synthesis, Skeletal Rearrangement, and Biological Activities of Spirooxindoles: Exploration of a Stepwise<i>C</i>-Piancatelli Rearrangement
  作者：Li Huang、Xiaoyu Zhang、Jing Li、Ke Ding、Xuehui Li、Wenxu Zheng、Biaolin Yin

  DOI：10.1002/ejoc.201301238

  日期：2014.1

  spiro[thieno-oxindoles] were rearranged under acidic conditions into thieno[2,3-c]quinolin-4-ones, involving an interesting dienone–phenol-like mechanism. The transformation of 2-furylcarbinols into spiro[pentenone-oxindoles] seems to be the first stepwise C-Piancatelli rearrangement. The spirooxindole products were biologically evaluated, and some of them showed promising cytotoxic activities against DU145 and

  在我们先前研究的基础上，研究了2-呋喃基甲醇转化为螺呋喃吲哚的范围，以及螺[呋喃-羟吲哚]和螺[噻吩-羟吲哚]的骨架重排。螺[呋喃-羟吲哚]通过涉及4π-电子系统的旋转电环化的机制热重排成螺[戊烯酮-羟吲哚]。计算电环化步骤的自由能以解释立体化学结果。相比之下，spiro[thieno-oxindoles] 在酸性条件下重排为 thieno[2,3-c] quinolin-4-ones，涉及有趣的二烯酮-苯酚样机制。2-呋喃基甲醇转化为螺[戊烯酮-羟吲哚] 似乎是第一个逐步的 C-Piancatelli 重排。对螺环吲哚产品进行了生物学评价，
• [EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS D'HISTONE DEACETYLASE
  申请人：METHYLGENE INC

  公开号：WO2005030704A1

  公开（公告）日：2005-04-07

  The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  这项发明涉及抑制组蛋白去乙酰化酶。该发明提供了抑制组蛋白去乙酰化酶酶活性的化合物和方法。该发明还提供了治疗细胞增殖性疾病和症状的组合物和方法。
• Reductive and Catalytic Monoalkylation of Primary Amines Using Nitriles as an Alkylating Reagent
  作者：Hironao Sajiki、Takashi Ikawa、Kosaku Hirota

  DOI：10.1021/ol047871o

  日期：2004.12.1

  and catalytic mono-N-alkylation method of both aromatic and aliphatic amines using nitriles as an alkylating agent with Pd/C or Rh/C as a catalyst is described. This method is particularly attractive to provide an environmentally benign and applicable alkylation method of amines without using toxic and corrosive alkylating agents such as alkyl halides and carbonyl compounds.

  [反应：参见正文]描述了使用腈作为烷基化剂，以Pd / C或Rh / C为催化剂的芳香族和脂肪族胺的选择性催化单N-烷基化方法。该方法对于提供一种环境友好的胺的烷基化方法而不使用有毒和腐蚀性的烷基化剂（例如卤代烷和羰基化合物）特别有吸引力。
• Direct <i>N‐</i> Alkylation/Fluoroalkylation of Amines Using Carboxylic Acids via Transition‐Metal‐Free Catalysis
  作者：Chunlei Lu、Zetian Qiu、Maojie Xuan、Yan Huang、Yongjia Lou、Yiling Zhu、Hao Shen、Bo‐Lin Lin

  DOI：10.1002/adsc.202000679

  日期：2020.10.6

  scalable protocol of direct N‐mono/di‐alkyl/fluoroalkylation of primary/secondary amines has been constructed with various carboxylic acids as coupling agents under the catalysis of a simple air‐tolerant inorganic salt, K3PO4. Advantageous features include 100 examples, 10 drugs and drug‐like amines, fluorinated complex tertiary amines, gram‐scale synthesis and isotope‐labelling amine, thus demonstrating

  在简单的耐空气无机盐K 3 PO 4的催化下，已使用各种羧酸作为偶联剂构建了伯/仲胺直接N-单/二烷基/氟烷基化的可扩展方案。有利的特征包括100种实例，10种药物和类药物胺，氟化复杂的叔胺，克级合成和同位素标记胺，因此证明了该方法在工业上的潜在适用性。与减少酰胺中间体所需的传统反应性金属氢化物或硼氢化物相比，反应性较小的氢化硅的参与可能有助于显着的官能团相容性。
• 6-Substituted 2,4-Diamino-5-methylpyrido[2,3-d]pyrimidines as Inhibitors of Dihydrofolate Reductases from Pneumocystis carinii and Toxoplasma gondii and as Antitumor Agents
  作者：Aleem Gangjee、Anil Vasudevan、Sherry F. Queener、Roy L. Kisliuk

  DOI：10.1021/jm00010a022

  日期：1995.5

  analogues, increasing the size of the N-10 substituent from a methyl group to larger groups resulted in a decrease in selectivity and potency for both P. carinii and T. gondii DHFR. For the dimethoxy-substituted analogues, N-10 methylation in general decreased potency but increased selectivity for T. gondii DHFR. In an attempt to improve the cell penetration of these analogues, the N-10 naphthyl-substituted

  报道了15个6-取代的2，4-二氨基-5-甲基吡啶并[2，3-d]-嘧啶的合成和生物活性。通过修改我们先前报道的程序，可以提高产率合成这些化合物。具体地，合成了在N-10位具有H和CH 3的二甲氧基苯基取代的化合物和具有N-10个乙基，异丙基和炔丙基基团的三甲氧基苯基取代的化合物。这些化合物被评估为卡氏肺孢子虫，弓形虫和大鼠肝脏的二氢叶酸还原酶（DHFR）抑制剂，所选的类似物被评估为弓形虫和培养物中肿瘤细胞生长的抑制剂。与曲美曲塞相比，所有化合物都显示出对弓形虫DHFR的选择性增加（相对于大鼠肝脏DHFR）。通常，对于三甲氧基取代的类似物，将N-10取代基的大小从甲基增加到较大的基团会导致卡氏疟原虫和刚地弓形虫DHFR的选择性和效能降低。对于二甲氧基取代的类似物，N-10甲基化通常会降低效力，但会增加弓形虫DHFR的选择性。为了提高这些类似物的细胞渗透性，还合成了N-10萘基取代的类似物。