1,4-dihydro-2,6-dimethyl-4-(5-bromo-2-thienyl)-3,5-pyridinedicarboxylic acid bis-(1,1-methyl ester) | 162229-16-5

• 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: 1,4-dihydro-2,6-dimethyl-4-(5-bromo-2-thienyl)-3,5-pyridinedicarboxylic acid bis-(1,1-methyl ester)
• 英文别名: dimethyl 4-(5-bromo-2-thienyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate；2,6-dimethyl-3,5-dimethoxycarbonyl-4-(5'-bromo-2'-thienyl)-1,4-dihydropyridine；3,5-Dimethyl 4-(5-bromo-2-thienyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate；dimethyl 4-(5-bromothiophen-2-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 162229-16-5
• 化学式: C₁₅H₁₆BrNO₄S
• 分子量: 386.266
• InChiKey: XNQDXCTWEJODIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  92.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,4-dihydro-2,6-dimethyl-4-(5-bromo-2-thienyl)-3,5-pyridinedicarboxylic acid bis-(1,1-methyl ester) 在 三氯一氧化钒 三氯代氧化钒(V) 作用下， 以 二氯甲烷 为溶剂， 反应 1.92h， 以92%的产率得到2,6-dimethyl-3,5-dimethoxycarbonyl-4-(5-bromo-2-thienyl)-pyridine
  参考文献：
  名称：

  Hantzsch-1,4-二氢吡啶与钒（V）盐的快速，高效，室温芳构化：经典技术相对于微波促进反应的优越性

  摘要：

  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。

  DOI：

  10.1016/j.tet.2008.08.103
• 作为产物：
  描述：

  5-溴噻吩-2-甲醛 、 乙酰乙酸甲酯 在 碳酸氢铵 、 glycine nitrate 作用下， 以 乙醇 为溶剂， 反应 0.33h， 以93%的产率得到1,4-dihydro-2,6-dimethyl-4-(5-bromo-2-thienyl)-3,5-pyridinedicarboxylic acid bis-(1,1-methyl ester)
  参考文献：
  名称：

  在可回收甘氨酸硝酸盐对称和非对称1,4-二氢吡啶（GlyNO的多组分多样性导向合成3）的离子液体：使用Q-TOF，ESI-MS / MS用一种机械洞察†往最‡

  摘要：

  多组分反应是产生具有化学多样性的，具有高原子经济性的一组多功能杂环基序的引人注目的策略，从而使转换绿色。如果考虑催化剂的可回收性，相容性和精确机理的探索，这些策略将变得更加丰富。为此，一种廉价且可循环利用的硝酸甘氨酸硝酸盐（GlyNO 3）离子液体已被有效地用于通过以下途径获得高达93％的收率的各种取代的对称和不对称的1,4-二氢吡啶三个组成部分和四个组成部分。在相同的反应条件下获得对称和不对称1,4 DHP的催化剂可回收性和相容性为其实用性带来了更多好处。此外，通过Q-TOF，直接注入电喷雾电离质谱（ESI-MS）监测反应进程，并通过串联MS实验（Q-TOF，ESI-MS）进一步确定了反应中涉及的关键阳离子中间体/ MS），作为机械模型概念的证明。这是第一份揭示汉茨反应主要遵循四个竞争反应途径中的二酮途径的报告。

  DOI：

  10.1039/c4ra02169j

文献信息

• 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。
• Cerebral Antihypoxic Activity of New Thienyldihydropyridines.
  作者：Michel BOULOUARD、Josette LOUCHAHI-RAOUL、Florence HEUDE、Marie-Anne QUERMONNE、Michel CUGNON DE SEVRICOURT、Sylvain RAULT、Max ROBBA

  DOI：10.1248/cpb.43.162

  日期：——

  New thienyldihydropyridines were synthesized according to Hantzsch's method. The antihypoxic activity of these compounds was compared with that of three reference phenyldihydropyridines by means of the skin conductance reaction (SCR)-hypoxia test.

  根据 Hantzsch 方法合成了新的噻吩基二氢吡啶。通过皮肤传导反应（SCR）-缺氧试验，比较了这些化合物与三种参考苯基二氢吡啶类化合物的抗缺氧活性。
• A highly efficient biomimetic aromatization of Hantzsch-1,4-dihydropyridines with t-butylhydroperoxide, catalysed by iron(III) phthalocyanine chloride
  作者：Mirela Filipan-Litvić、Mladen Litvić、Vladimir Vinković

  DOI：10.1016/j.bmc.2008.09.004

  日期：2008.10

  Rapid aromatization of Hantzsch-1,4-DHPswith t-butylhydroperoxide catalysed by iron(III) phthalocyanine chloride is described. The reaction proceeds smoothly at room temperature within 1-35 min and the products of high purity were isolated in excellent yields. To explain the reactivity of this catalytical system plausible mechanism have been proposed to involve formation of high-valent oxoferryl species as in cytochrome P450 itself. (C) 2008 Elsevier Ltd. All rights reserved.
• Remarkably fast and selective aromatization of Hantzsch esters with MoOCl4 and MoCl5: A chemical model for possible biologically relevant properties of molybdenum-containing enzymes
  作者：Mladen Litvić、Maja Regović、Karolina Šmic、Marija Lovrić、Mirela Filipan-Litvić

  DOI：10.1016/j.bmcl.2012.04.043

  日期：2012.6

  Mo(VI) and Mo(V) salts both react selectively with Hantzsch esters to produce substitute pyridines in good-to-excellent yield (75-99%). The remarkable reactivity and selectivity of MoOCl4 under reflux of acetonitrile and MoCl5 in dichloromethane at room temperature encouraged us to propose that molybdenum-containing enzymes (such as xanthine or aldehyde oxidase) also participate to some degree in the metabolism of 1,4-dihydropyridine drugs in the liver analogous to NADH in the respiratory chain. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and activities of a thienyl dihydropyridine series on intracellular calcium in a rat pituitary cell line (GH3/B6)
  作者：M Varache-Lembège、A Nuhrich、V Zemb、G Devaux、P Vacher、AM Vacher、B Dufy

  DOI：10.1016/0223-5234(96)89551-1

  日期：1996.1

  The synthesis of a thienyl dihydropyridine series according to the Hantzsch method is described. The influence of these derivatives on intracellular calcium ([Ca2+]i) in GH3 cells was evaluated in vitro using spectrofluorimetry with indol as Ca2+ fluorescent probe. We compared their effects on [Ca2+]i and hormone release with those of nifedipine. The most active tested compounds on [Ca2+]i were those methylated on the 3-position of the thienyl ring (activity was about 75% of nifedipine). Interestingly, the most efficient compounds on [Ca2+]i were also the most efficient on hormone release.