2,6-dimethyl-3,5-di(methoxycarbonyl)-4-(m-methoxyphenyl)-1,4-dihydropyridine | 43114-34-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,6-dimethyl-3,5-di(methoxycarbonyl)-4-(m-methoxyphenyl)-1,4-dihydropyridine
• 英文别名: Dimethyl 4-(3-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 43114-34-7
• 化学式: C₁₈H₂₁NO₅
• 分子量: 331.368
• InChiKey: UVZJDLNWYRQSSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-dimethyl-3,5-di(methoxycarbonyl)-4-(m-methoxyphenyl)-1,4-dihydropyridine 在 ammonium cerium(IV) nitrate 作用下， 以 水 、 丙酮 为溶剂， 反应 0.17h， 以100%的产率得到3,5-Dimethyl 4-(3-methoxyphenyl)-2,6-dimethyl-3,5-pyridinedicarboxylate
  参考文献：
  名称：

  Rapid, High-Yield Oxidation of Hantzsch-Type 1,4-Dihydropyridines with Ceric Ammonium Nitrate

  摘要：

  使用两个当量的硝酸铈铵，4-芳基-2,6-二甲基-1,4-二氢-3,5-吡啶二羧酸盐（汉茨奇型 1,4-二氢吡啶）可被快速氧化成相应的吡啶衍生物，产量极佳。

  DOI：

  10.1055/s-1990-26982
• 作为产物：
  描述：

  乙酰乙酸甲酯 、 3-甲氧基苯甲醛 在 Zn₄O(2-amino-1,4-benzenedicarboxylate)₃ 、 ammonium acetate 作用下， 以 neat (no solvent) 为溶剂， 反应 5.0h， 以76%的产率得到2,6-dimethyl-3,5-di(methoxycarbonyl)-4-(m-methoxyphenyl)-1,4-dihydropyridine
  参考文献：
  名称：

  Biginelli和Hantzsch偶联的基本等孔纳米多孔金属-有机骨架：IRMOF-3是无溶剂条件下绿色且可回收的多相催化剂†

  摘要：

  IRMOF-3金属-有机骨架（MOF）是适合的绿色催化剂，可通过Biginelli和Hantzsch反应一锅合成二氢嘧啶酮和二氢吡啶衍生物，所需产物在温和的条件下以高收率和短反应时间获得。无溶剂条件。可以将MOF从反应混合物中分离出来并重新使用。

  DOI：

  10.1039/c3ra46709k

文献信息

• N-Alkylated 1,4-Dihydropyridines: New Agents to Overcome Multidrug Resistance.
  作者：Koji OHSUMI、Kazuo OHISHI、Yoshihiro MORINAGA、Ryusuke NAKAGAWA、Yasuyo SUGA、Takaaki SEKIYAMA、Yukio AKIYAMA、Takashi TSUJI、Takashi TSURUO

  DOI：10.1248/cpb.43.818

  日期：——

  New N-alkylated 1, 4-dihydropyridine derivatives were synthesized and their ability to overcome multidrug resistance was examined in vincristine-resistant P388 cells (P388/VCR cells). Compounds that possessed an arylalkyl substituent on the dihydropyridine ring nitrogen were more potent than verapamil in potentiating the cytotoxicity of vincristine against P388/VCR cells. However, neither drug effectively enhanced the antitumor activity of vincristine in tumor-bearing mice. Introduction of basic nitrogen-containing substituents on the side chain of 1, 4-dihydropyridines gave improved activity in vitro and in vivo. The piperazine derivative 12c and 12o were more than 10 times as potent as verapamil in vitro. Four compounds selected for in vivo testing showed superior antitumor activity in P388/VCR-bearing mice in combination with vincristine. The structure-activity relationships of the compounds are discussed.

  新合成的N-烷基化1,4-二氢吡啶衍生物，在长春新碱耐药的P388细胞（P388/VCR细胞）中检测了其克服多药耐药的能力。在二氢吡啶环氮上带有芳烷基取代基的化合物，比维拉帕米更能增强长春新碱对P388/VCR细胞的细胞毒性。然而，这两种药物均未有效地增强长春新碱在携带肿瘤的小鼠中的抗肿瘤活性。在1,4-二氢吡啶的侧链上引入含有碱性氮的取代基，在体外和体内均能提高活性。哌嗪衍生物12c和12o在体外比维拉帕米强10倍以上。选出四种化合物进行体内测试，它们与长春新碱联合使用时，在携带P388/VCR的肿瘤小鼠中显示出优越的抗肿瘤活性。讨论了化合物的构效关系。
• [Fesipmim]Cl as highly efficient and reusable catalyst for solventless synthesis of dihydropyridine derivatives through Hantzsch reaction
  作者：Akansha Agrwal、Virendra Kasana

  DOI：10.1007/s12039-020-01770-9

  日期：2020.12

  catalyst were measured by vibrating sample magnetometer (VSM). The efficiency of the [Fesipmim]Cl catalyst was checked by using it for the synthesis of different derivatives of dihydropyridine through Hantzsch reaction via a three-component coupling reaction of substituted benzaldehydes, ethyl/ methyl acetoacetate and ammonium acetate. The formation and structures of all the synthesized compounds were confirmed

  摘要 在本研究中，合成了磁性铁氧体纳米粒子（铁氧体NPs）并通过溶胶-凝胶法用二氧化硅（ferrite @ SiO 2 NPs）进行了包覆。然后，制备二氧化硅丙基甲基咪唑氯化物离子液体[Sipmim] Cl，并与上述制备的铁氧体@SiO 2 NPs连接，以合成铁氧体二氧化硅丙基甲基咪唑氯化物[Fesipmim] Cl催化剂。[Fesipmim] Cl催化剂的形成通过傅立叶变换红外（FT-IR）光谱分析确认。X射线衍射（XRD）分析证实了铁氧体NPs和铁氧体@SiO 2 NPs的结构。透射电子显微镜（TEM）证明成功形成了铁素体NP和铁素体@SiO 2NP。扫描电子显微镜（SEM）结果表明，铁氧体NPs，铁素体@SiO 2 NPs和[Fesipmim] Cl的形态发生了变化。通过振动样品磁力计（VSM）测量[Fesipmim] Cl催化剂的磁性。[Fesipmim] Cl催化剂的效率通过使用
• An efficient, metal-free, room temperature aromatization of Hantzsch-1,4-dihydropyridines with urea–hydrogen peroxide adduct, catalyzed by molecular iodine
  作者：Mirela Filipan-Litvić、Mladen Litvić、Vladimir Vinković

  DOI：10.1016/j.tet.2008.04.040

  日期：2008.6

  A mild, highly efficient and metal-free synthetic method for aromatization of 1,4-dihydropyridines employing urea–hydrogen peroxide adduct as oxidant catalyzed by 20 mol % of molecular iodine was developed. The reaction was carried out in ethyl acetate at room temperature and the products were isolated in high to excellent yields. A plausible free-radical mechanism is proposed based on results obtained

  开发了一种温和，高效，无金属的合成方法，该方法以20 mol％的分子碘为催化剂，使用脲-过氧化氢加合物作为氧化剂进行1,4-二氢吡啶的芳构化。该反应在室温下在乙酸乙酯中进行，并且以高至优异的产率分离出产物。基于在1，4-二氢吡啶环中具有烷基和芳基取代基的衍生物所获得的结果，提出了一种可能的自由基机理。
• Hantzsch Synthesis of 2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-methoxyphenyl)-1,4-dihydropyridine; a Novel Cyclisation Leading to an Unusual Formation of 1-Amino-2-methoxycarbonyl-3,5-bis(o-methoxyphenyl)-4-oxa-cyclohexan-1-ene
  作者：Mirela Filipan-Litvić、Mladen Litvić、Ivica Cepanec、Vladimir Vinković

  DOI：10.3390/12112546

  日期：——

  Hantzsch condensation of two equivalents of methyl-3-aminocrotonate with (m-and p)-methoxybenzaldehyde afforded the expected products 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-methoxyphenyl)-1,4-dihydropyridine and 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(p-methoxyphenyl)-1,4-dihydropyridine, whereas o-methoxy-benzaldehyde produced mainly 1-amino-2-methoxycarbonyl-3,5-bis(o-methoxy-phenyl)-4-oxa-cyclohexan-1-ene. The structure of the product, not previously reported in theliterature, was determined by 1D and 2D NMR spectra and its MS fragmentation. This isthe first example of cyclisation leading to a substituted pyran rather than 1,4-DHP undertypical Hantzsch reaction conditions. A plausible mechanism for its formation ispostulated.

  将两当量的 3-氨基巴豆酸甲酯与（间和对）甲氧基苯甲醛进行 Hantzsch 缩合，可得到预期产物 2,6-二甲基-3,5-二甲氧基羰基-4-（间甲氧基苯基）-1,4-二氢吡啶和 2,6-二甲基-3,5-二甲氧基羰基-4-（对甲氧基苯基）-1,4-二氢吡啶、而邻甲氧基苯甲醛则主要生成 1-氨基-2-甲氧基羰基-3,5-双（邻甲氧基苯基）-4-氧杂环己-1-烯。通过一维和二维核磁共振波谱及其质谱碎片确定了该产物的结构，该结构此前未在文献中报道过。这是第一个在典型的 Hantzsch 反应条件下环化生成取代吡喃而非 1,4-DHP 的实例。研究人员推测了其形成的合理机制。
• Rapid, efficient, room temperature aromatization of Hantzsch-1,4-dihydropyridines with vanadium(V) salts: superiority of classical technique versus microwave promoted reaction
  作者：Mirela Filipan-Litvić、Mladen Litvić、Vladimir Vinković

  DOI：10.1016/j.tet.2008.08.103

  日期：2008.11

  The aromatization of 1,4-dihydropyridines (1,4-DHPs) employing group 4 (Zr and Hf) and 5 (V, Nb, Ta) elements of periodic system has been studied. The reaction with VOCl3 in dichloromethane at room temperature afforded products, substituted pyridines, in high-to-excellent yield. For the first time, the formation of charge-transfer complexes (CTCs) has been evidenced in preorganization step between

  研究了使用周期系统的第4组（Zr和Hf）和第5组（V，Nb，Ta）元素对1,4-二氢吡啶（1,4-DHPs）进行的芳构化。在室温下与VOCl 3在二氯甲烷中的反应以高至优异的产率提供了产物，取代的吡啶。首次在电子转移之前的1,4-DHP和氧化剂之间的预组织步骤中证明了电荷转移络合物（CTC）的形成。仅在中性溶剂（如二氯甲烷）中形成四氯化碳，其特征是强烈的着色。V 2 O 5将1,4-DHP芳构化在无溶剂介质中，乙酸在回流中的作用优于微波促进的反应。唯一合理的解释是在V 2 O 5的聚合物结构中发现的，该结构缓慢转移了活化反应物所需的微波能量。已发现4-正丙基-1，4-DHP的溶剂极性依赖性氧化脱烷基。出乎意料的是，与在相同反应条件下在二氯甲烷中获得的91％相比，在乙酸中的反应仅提供33％的脱烷基化产物。