3,5-dimethyl-1-[2-(trifluoromethyl)phenyl]-1H-pyrazole | 1428183-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3,5-dimethyl-1-[2-(trifluoromethyl)phenyl]-1H-pyrazole
• 英文别名: 3,5-dimethyl-1-[2-(trifluoromethyl)phenyl]pyrazole
• CAS: 1428183-79-2
• 化学式: C₁₂H₁₁F₃N₂
• 分子量: 240.228
• InChiKey: AYTPLEWCZKITPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,5-dimethyl-1-[2-(trifluoromethyl)phenyl]-1H-pyrazole 在 叔丁基过氧化氢 、 Oxone 、 二甲基亚砜 作用下， 反应 9.0h， 生成 bis(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)methanone
  参考文献：
  名称：

  Oxone-DMSO触发亚甲基插入和C（sp 2）-C（sp 3）-HC（sp 2）键形成，以访问功能性双杂环。

  摘要：

  为了制备新型的双杂环支架，实现了新的C（sp 2）–C（sp 3）-H–C（sp 2）键的构建，实现了无金属亚甲基的插入。完整的机理研究包括实验研究和DFT计算，并且以中等到高产率制备了各种对称和不对称的双吡唑以及其他基于吡唑的双杂环分子。不对称吡唑中桥连亚甲基的进一步修饰产生了手性中心，从而扩展了该方法的范围。

  DOI：

  10.1021/acs.joc.9b03477
• 作为产物：
  描述：

  2-(三氟甲基)苯基肼 、 乙酰丙酮 在 silica gel 、 对甲苯磺酸 作用下， 以 neat (no solvent) 为溶剂， 以58%的产率得到3,5-dimethyl-1-[2-(trifluoromethyl)phenyl]-1H-pyrazole
  参考文献：
  名称：

  Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials

  摘要：

  In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 similar to 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.

  DOI：

  10.1021/jm400009c

文献信息

• Direct N-heterocyclization of hydrazines to access styrylated pyrazoles: synthesis of 1,3,5-trisubstituted pyrazoles and dihydropyrazoles
  作者：Vunnam Venkateswarlu、Jaspreet Kour、K. A. Aravinda Kumar、Praveen Kumar Verma、G. Lakshma Reddy、Yaseen Hussain、Aliya Tabassum、Shilpi Balgotra、Sorav Gupta、Abhinandan D. Hudwekar、Ram A. Vishwakarma、Sanghapal D. Sawant

  DOI：10.1039/c8ra04550j

  日期：——

  microwave-assisted method has been developed for the synthesis of tri-substituted pyrazoles via direct N-heterocyclization of hydrazines with metal-acetylacetonate and -dibenzylideneacetonate without using any base or additives. Most importantly, the synthesis of 1-aryl-5-phenyl-3-styryl-1H-pyrazoles was achieved in a single step using hydrochloride salt of various phenylhydrazines and this is the first

  开发了一种微波辅助合成三取代吡唑的方法，该方法通过肼与金属乙酰丙酮化物和二亚苄基丙酮化物的直接N-杂环化来合成三取代吡唑，无需使用任何碱或添加剂。最重要的是，使用各种苯肼的盐酸盐一步合成了1-芳基-5-苯基-3-苯乙烯基-1H-吡唑，这是直接构建这些分子的第一份报告。反应介质和微波条件对于反应过程中选择性产物的形成起着关键作用。本反应探索了使用金属二酮配合物作为反应底物，提供乙酰丙酮和二亚苄基丙酮部分直接参与与肼的环化，以优异的产率形成相应的吡唑。本方案在最终结构中引入了重要的 N-杂环部分，从药物化学的角度来看，该反应具有巨大的应用，特别是在药物发现的后期修饰策略中。
• US8455398B2
  申请人：——

  公开号：US8455398B2

  公开（公告）日：2013-06-04
• Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials
  作者：Dinakaran Murugesan、Alka Mital、Marcel Kaiser、David M. Shackleford、Julia Morizzi、Kasiram Katneni、Michael Campbell、Alan Hudson、Susan A. Charman、Clive Yeates、Ian H. Gilbert

  DOI：10.1021/jm400009c

  日期：2013.4.11

  In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 similar to 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
• Oxone-DMSO Triggered Methylene Insertion and C(sp²)−C(sp³)-H−C(sp²) Bond Formation to Access Functional Bis-Heterocycles
  作者：Jaspreet Kour、Vunnam Venkateswarlu、Praveen K. Verma、Yaseen Hussain、Gurudutt Dubey、Prasad V. Bharatam、Subash C. Sahoo、Sanghapal D. Sawant

  DOI：10.1021/acs.joc.9b03477

  日期：2020.4.3

  Metal-free insertion of a methylene group was achieved for the construction of a new C(sp2)–C(sp3)-H–C(sp2) bond in order to prepare novel bis-heterocyclic scaffolds. The complete mechanistic investigations included experimental study and DFT calculations, and various symmetric and unsymmetric bis-pyrazoles as well as other pyrazole-based bis-heterocyclic molecules were prepared in moderate to high

  为了制备新型的双杂环支架，实现了新的C（sp 2）–C（sp 3）-H–C（sp 2）键的构建，实现了无金属亚甲基的插入。完整的机理研究包括实验研究和DFT计算，并且以中等到高产率制备了各种对称和不对称的双吡唑以及其他基于吡唑的双杂环分子。不对称吡唑中桥连亚甲基的进一步修饰产生了手性中心，从而扩展了该方法的范围。