ethyl 2-methyl-4-(4-hydroxy-3-methoxyphenyl)-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: ethyl 2-methyl-4-(4-hydroxy-3-methoxyphenyl)-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate
• 英文别名: ethyl 4-(4-hydroxy-3-methoxyphenyl)-2-methyl-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate
• 化学式: C₂₁H₂₀N₂O₄S
• 分子量: 396.467
• InChiKey: IQKKUEYECREODX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  96.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基苯并噻唑 、 乙酰乙酸乙酯 、 香草醛 在 halloysite 作用下， 以 neat (no solvent) 为溶剂， 反应 0.83h， 以88%的产率得到ethyl 2-methyl-4-(4-hydroxy-3-methoxyphenyl)-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate
  参考文献：
  名称：

  利用高岭土高效简便地合成杂环及其机理

  摘要：

  描述了用于新的杂环化合物的高岭土催化的无溶剂合成。使用二酮，醛和三酮的三组分反应可以轻松获得一系列杂环化合物2-氨基苯并噻唑， 尿素 或者 硫脲。三组分高岭土催化Biginelli的机理（使用尿素 和 硫脲）和Biginelli喜欢（使用 2-氨基苯并噻唑）反应已被调查。这是我们首次使用1 H NMR，13 C NMR和ESI-质谱表征来分离和表征关键中间体。机理研究强烈建议使用亚胺3和Knoevenagel型中间体4作为关键中间体。该反应简单，清洁并且在数分钟内获得了良好的产率。

  DOI：

  10.1039/c3ra40993g

文献信息

• Efficient and facile synthesis of heterocycles and their mechanistic consideration using kaolin
  作者：Pramod Kumar Sahu、Praveen Kumar Sahu、Dau Dayal Agarwal

  DOI：10.1039/c3ra40993g

  日期：——

  catalyzed solvent-free synthesis for new heterocyclic compounds is described. A series of heterocyclic compounds can be readily obtained using the three-component reaction of diketones, aldehydes and 2-amino benzothiazole, urea or thiourea. The mechanism of the three component kaolin catalyzed Biginelli (using urea and thiourea) and Biginelli like (using 2-amino benzothiazole) reaction has been investigated

  描述了用于新的杂环化合物的高岭土催化的无溶剂合成。使用二酮，醛和三酮的三组分反应可以轻松获得一系列杂环化合物2-氨基苯并噻唑， 尿素 或者 硫脲。三组分高岭土催化Biginelli的机理（使用尿素 和 硫脲）和Biginelli喜欢（使用 2-氨基苯并噻唑）反应已被调查。这是我们首次使用1 H NMR，13 C NMR和ESI-质谱表征来分离和表征关键中间体。机理研究强烈建议使用亚胺3和Knoevenagel型中间体4作为关键中间体。该反应简单，清洁并且在数分钟内获得了良好的产率。
• POM analyses and evaluation of in vitro antimicrobial, antitumor activity of 4H-pyrimido[2,1-b]benzothiazole derivatives
  作者：Pramod K. Sahu、Praveen K. Sahu、Pushkal Samadhiya、Puran L. Sahu、Dau D. Agarwal

  DOI：10.1007/s00044-016-1589-8

  日期：2016.8

  facile, efficient, and convenient synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives is described using aromatic aldehydes, ethyl acetoacetate, and 2-amino benzothiazole in the presence of l-proline under solvent-free conditions. Present methodology has advantages such as short reaction time, no side products, and easy to work up. Synthesized library compounds have been evaluated for their antitumor

  摘要一种简便，高效和4的简便合成ħ嘧啶并[2,1- b ]苯并噻唑衍生物是使用芳族醛描述，乙酰乙酸乙酯，和2-氨基苯并噻唑在存在升-脯氨酸在无溶剂的条件下。当前的方法具有诸如反应时间短，无副产物和易于加工的优点。已经评估了合成的文库化合物的抗肿瘤和抗微生物活性。此外，我们已经使用分子特性分析将实验工作与理论参数进行了比较，以开发出有关制备嘧啶基苯并噻唑衍生物的新思路，以用于其可能用于治疗癌症和慢性微生物疾病。结论是，Petra / osiris / molinspiration（POM）分析可能被证明是关联4 H -pyrimido [2,1- b]结构特征的合适方法。]苯并噻唑衍生物具有令人满意的抗微生物/抗肿瘤活性，可能有助于开发新型抗药性药物。 图形概要
• Synthesis and Mechanistic Study of Triheterocyclic 4<i>H</i>-Pyrimido[2,1-<i>b</i>]benzothiazole derivatives, One-Pot Three-component Reaction under Solvent-Free Conditions
  作者：Pramod Kumar Sahu、Praveen Kumar Sahu、Yogesh Sharma、Dau Dayal Agarwal

  DOI：10.1002/jhet.1572

  日期：2014.7

  An efficient method has been developed for the preparation of 4H‐pyrimido[2,1‐b]benzothiazole derivatives by the condensation of aldehydes, β‐ketoester, and 2‐amino benzothiazole under solvent and solvent‐free conditions using various catalysts. The reaction uses benzothiazole as a new component, and good yield is obtained at 60–65°C under solvent‐free conditions. Atom economies, good yield, environmentally

  已开发出一种有效的方法来制备4 H-嘧啶[2,1- b在各种溶剂和无溶剂条件下，通过醛，β-酮酸酯和2-氨基苯并噻唑的缩合反应生成]苯并噻唑衍生物。该反应使用苯并噻唑作为新组分，在无溶剂条件下于60–65°C时可获得良好的收率。原子经济，收率高，对环境无害且易于处理是该协议的一些重要功能。本研究表明乙酸和金属催化剂遵循不同的机理。在乙酸中，2-氨基苯并噻唑与苯甲醛反应，生成的中间体与乙酰乙酸乙酯反应生成最终产物，而在金属催化剂存在下，2-氨基苯并噻唑首先与乙酰乙酸乙酯反应，生成的中间体与苯甲醛反应生成嘧啶基[2,1- b]苯并噻唑。
• Design, synthesis and pharmacological evaluation of pyrimidobenzothiazole-3-carboxylate derivatives as selective L-type calcium channel blockers
  作者：Rupesh Chikhale、Sonali Thorat、Amit Pant、Ankush Jadhav、Krishna Chary Thatipamula、Ratnadeep Bansode、G. Bhargavi、Nazira Karodia、M.V. Rajasekharan、Anant Paradkar、Pramod Khedekar

  DOI：10.1016/j.bmc.2015.09.009

  日期：2015.10

  development of calcium channel modulator. A pre-synthetic QSAR was run and on the basis of structure activity relationship a series of twenty three molecules was synthesized and studied by myosin light chain kinase assay (MLCK), Angiotensin Converting Enzyme (ACE) colorimetric assay, non-invasive blood pressure (NIBP) and invasive blood pressure (IBP) methods. Molecules with significant efficacy were studied

  L型电压门控钙通道在各种骨骼和血管平滑肌的收缩中起重要作用，因此在调节血压中起重要作用。二氢吡啶受体已被靶向用于开发新型抗高血压药，二氢嘧啶的结构类似物核之一早已被我们报道为开发钙通道调节剂的潜在药物。运行了合成前的QSAR，并根据结构活性关系合成了一系列二十三个分子，并通过肌球蛋白轻链激酶测定（MLCK），血管紧张素转化酶（ACE）比色测定，无创血压（无创血压（IBBP）和有创血压（IBP）方法。研究了具有显着功效的分子的单晶X射线衍射，分子对接，分子动力学和后合成QSAR。与标准药物硝苯地平相比，NIBP和IBP方法筛选了具有更好的抑制百分率随时间变化的分子。铅化合物2-甲基-4-（3-硝基苯基）-4H-嘧啶基[2,1-b] [1,3]苯并噻唑-3-羧酸酯（26）呈三斜晶结构，聚合物链堆积在晶格中。26位受试者在MLCK分析中表现出的IC50为2.1±1.7μM，具有L型钙通道的选择性
• Preparation and characterization of Lewis acid grafted sulfonated carbon@titania composites for the multicomponent synthesis of 4H-pyrimido[2,1-b]benzothiazoles and benzoxanthenones under solvent-free conditions
  作者：Manmeet Kour、Satya Paul、James H. Clark、Vivek K. Gupta、Rajni Kant

  DOI：10.1016/j.molcata.2015.11.001

  日期：2016.1

  A series of novel and highly efficient Lewis acids covalently grafted over sulfonic acid functionalized carbon@titania composites were successfully synthesized via sulfonation of carbon@titania composites followed by treatment with different Lewis acids like AlCl3, FeCl3, SbCl3, SnCl2, Cu(OAc)(2) and Bi(NO3)(3), The utility of the developed catalysts was explored for the synthesis of a diverse range of 4H-pyrimido[2,1-b]benzothiazoles and benzoxanthenones, and among various catalysts, C/TiO2-SO3-SbCl2 was found to be the most active. We report here the synthesis of five novel compounds and the structure of one of the compounds has also been confirmed by single-crystal X-ray diffraction. All the five prepared composites were characterized by FTIR and ICP-AES analysis, whereas the most active one, C/TiO2-SO3-SbCl2 was further characterized by XRD, EDX, CHNS, SEM, TEM, HRTEM and TGA. The catalyst can be recovered and reused for atleast five runs without any significant impact on catalytic activity and selectivity. The high catalytic activity, thermal stability, simple recovery and reusability, and eco-friendly nature of the catalyst makes the present method to be particularly attractive from the view point of green chemistry. (C) 2015 Elsevier B.V. All rights reserved.