5-amino-1-(2-chlorophenyl)-3-phenyl-1H-pyrazole | 890764-10-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-1-(2-chlorophenyl)-3-phenyl-1H-pyrazole
• 英文别名: 1-(2-chlorophenyl)-3-phenyl-1H-pyrazol-5-amine；2-(2-chlorophenyl)-5-phenylpyrazol-3-amine
• CAS: 890764-10-0
• 化学式: C₁₅H₁₂ClN₃
• mdl: MFCD08445007
• 分子量: 269.733
• InChiKey: AOUSVJASECBRMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-amino-1-(2-chlorophenyl)-3-phenyl-1H-pyrazole 在 三溴化磷 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 1-(2-chlorophenyl)-6-[(formyloxy)methyl]-3-phenyl-1H-pyrazolo-[3,4-d]pyrimidine
  参考文献：
  名称：

  Vilsmeier试剂介导的一锅多重串联反应合成6-[[（甲酰氧基）甲基]-吡唑并嘧啶†

  摘要：

  以5-（2-氯乙酰氨基）吡唑为起始原料，开发了一种新的Vilsmeier试剂介导的一锅反应，用于有效合成6-[（（甲酰氧基）甲基] -1 H-吡唑并[3,4- d ]嘧啶。这种新的多级串联反应，包括Vilsmeier-Haack反应，Morgan-Walls反应，顺序消除，取代和最终水解，可提供高收率的甲酰氧基甲基吡唑并[3,4- d ]嘧啶产物。

  DOI：

  10.1039/c5ra07707a
• 作为产物：
  描述：

  苯甲腈 在 盐酸 、 potassium tert-butylate 作用下， 以 苯 为溶剂， 反应 24.33h， 生成 5-amino-1-(2-chlorophenyl)-3-phenyl-1H-pyrazole
  参考文献：
  名称：

  Substituent Effects of N-(1,3-Diphenyl-1H-pyrazol-5-yl)benzamides on Positive Allosteric Modulation of the Metabotropic Glutamate-5 Receptor in Rat Cortical Astrocytes

  摘要：

  CDPPB [3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide] was recently described as the first centrally active, positive allosteric modulator of rat and human metabotropic glutamate receptor (mGluR) mGluR(5) subtype. We explored the structural requirements for potentiation of glutamate-induced calcium release in naturally expressed mGluR5 in cultured rat astrocytes and increasing affinity for the allosteric antagonist binding site by evaluating 50 analogues of CDPPB. In the fluorometric calcium assay, CDPPB exhibited an EC50 value of 77 +/- 15 nM in potentiating mGluR(5)-mediated responses in cortical astrocytes and a K-i value of 3760 ( 430 nM in displacing [H-3] methoxyPEPy binding in membranes of cultured HEK-293 cells expressing rat mGluR5. The structure-activity relationships showed that electronegative aromatic substituents in the para-position of the benzamide moiety of CDPPB increase potency. Both binding and functional activities were further increased with a halogen atom in the ortho-position of the 1-phenyl ring. These effects of substitution do not match those of either aromatic ring of MPEP [2-methyl-6-(phenylethynyl)-pyridine] for the antagonist allosteric binding site. Combination of the optimal substituents and aromatic positions resulted in 4-nitro-N-(1-(2-fluorophenyl)-3-phenyl-1H-pyrazol-5-yl) benzamide (VU-1545) showing K-i) 156 (29 nM and EC50) 9.6 (1.9 nM in the binding and functional assays, respectively.

  DOI：

  10.1021/jm051252j

文献信息

• One-Pot Acid-Promoted Synthesis of 6-Aminopyrazolopyrimidines from 1<i>H</i>-Pyrazol-5-yl-<i>N</i>,<i>N</i>-dimethylformamidines or 5-Amino-1<i>H</i>-pyrazole-4-carbaldehydes with Cyanamide
  作者：Ching-Chun Tseng、Shuo-En Tsai、Sin-Min Li、Fung Fuh Wong

  DOI：10.1021/acs.joc.9b02653

  日期：2019.12.20

  acid-promoted synthesis of 6-aminopyrazolo[3,4-d]pyrimidine has been developed by treatment of 1H-pyrazol-5-yl-N,N-dimethylformamidines or 5-amino-1H-pyrazole-4-carbaldehydes with cyanamide (NH2C≡N) in an acid-mediated solution. This synthetic route involves four steps of deprotection, imination, the key acid-promoted heterocyclization, and aromatization. On the basis of optimized studies, methanesulfonylchloride

  通过处理1H-吡唑-5-基-N，N-二甲基甲am或5-氨基-1H-吡唑，开发了一种方便高效的一锅酸促进6-氨基吡唑并[3,4-d]嘧啶的合成方法在酸介导的溶液中将-4-甲醛与氰胺（NH2CN）结合使用。该合成途径包括去保护，亚胺化，关键酸促进的杂环化和芳构化的四个步骤。在优化研究的基础上，甲磺酰氯被认为是最好的溶剂。此外，该方法还进行了微波辅助合成技术，以改进主要产物6-氨基吡唑并[3,4-d]嘧啶。此外，我们提出的机制在这项研究中得到证实，这表明N-[（5-氨基-1,3-二芳基-1H-吡唑-4-基）亚甲基]氰酰胺是中间体。
• Evaluation of Electrophilic Heteroaromatic Substitution: Synthesis of Heteroaromatic-Fused Pyrimidine Derivatives via Sequential Three-Component Heterocyclization
  作者：Fung Fuh Wong、Yu-Ying Huang、Chun-Hsi Chang

  DOI：10.1021/jo301463m

  日期：2012.10.5

  A new sequential three-component heterocyclization was developed by reacting aromatic and heterocyclic substrates, including aminobenzenes, 1-aminonaphthalene, 2-aminopyrazines, 5-aminopyrazoles, 3-aminopyridine, 5-aminopyrimidine, 5-aminoquinoline, and 8-aminoquinoline, with formamide in the presence of PBr3. The reaction gave the corresponding pyrazolo[3,4-d]pyrimidines in good yields (59–96%), except

  通过使芳香族和杂环底物（包括氨基苯，1-氨基萘，2-氨基吡嗪，5-氨基吡唑，3-氨基吡啶，5-氨基嘧啶，5-氨基喹啉和8-氨基喹啉）与甲酰胺反应，开发了一种新的顺序三组分杂环化方法在PBr 3存在下。除氨基苯和3-氨基吡啶外，该反应以较高的收率（59-96％）得到了相应的吡唑并[3,4- d ]嘧啶。提出了包括三步酰胺化，亲电取代亚胺化和氧化环化的合理反应机理，以解决杂环化问题。发现反应的反应性与芳族或杂环底物的亲电子性成比例。
• One-Flask Synthesis of Pyrazolo[3,4-d]pyrimidines from 5-Aminopyrazoles and Mechanistic Study
  作者：Wan-Ping Yen、Shuo-En Tsai、Naoto Uramaru、Hiroyuki Takayama、Fung Wong

  DOI：10.3390/molecules22050820

  日期：——

  converted into pyrazolo[3,4-d]pyrimidines. The experiments demonstrated that the reaction intermediates were the chemical equivalents of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl)formamidines. The rate of the reaction could be described as being proportional to the reactivity of amine reactants during intermolecular heterocyclization, especially when hexamethyldisilazane was used.

  开发了一种新颖的单烧瓶合成方法，其中5-氨基吡唑在PBr 4存在下与N，N-取代的酰胺反应。然后加入六甲基二硅氮烷进行杂环化，以合适的产率产生相应的吡唑并[3，4-d]嘧啶。因此，这些一瓶反应涉及Vilsmeier酰胺化，亚胺化反应和顺序的分子间杂环化。为了研究反应机理，我们设计了一系列4-甲酰基-1,3-二苯基-1H-吡唑-5-基-N，N-二取代甲s，它们被视为4-（亚氨基甲基）-1的化学当量，制备了3-二苯基-1H-吡唑-5-基-甲am并将其成功转化为吡唑并[3，4-d]嘧啶。实验表明，反应中间体是4-（亚氨基甲基）-1的化学当量，3-二苯基-1H-吡唑-5-基）甲idine。反应速率可以描述为与分子间杂环化过程中胺反应物的反应性成比例，特别是在使用六甲基二硅氮烷的情况下。
• One-pot, telescoped synthesis of N-aryl-5-aminopyrazoles from anilines in environmentally benign conditions
  作者：Maura Marinozzi、Gloria Marcelli、Andrea Carotti、Benedetto Natalini

  DOI：10.1039/c3ra47541g

  日期：——

  An efficient synthetic approach to synthesize N-aryl-5-aminopyrazoles from anilines via a one-pot, telescoped reaction performed in entirely aqueous conditions has been developed. This protocol provides a rapid, convenient method to prepare N-aryl-5-aminopyrazoles, useful building blocks for the synthesis of several bicyclic nitrogen heterocycles, by avoiding the isolation of the toxic intermediate arylhydrazines and the use of a metallic reductant.

  我们开发出了一种高效的合成方法，通过完全在水性条件下进行的一锅伸缩反应，从苯胺合成 N-芳基-5-氨基吡唑。该方法避免了分离有毒的芳基肼中间体和使用金属还原剂，为制备 N-芳基-5-氨基吡唑提供了一种快速、便捷的方法，而 N-芳基-5-氨基吡唑是合成多种双环氮杂环的有用构筑基块。
• Tandem Oxidative Reaction of 1,3-Diarylpropenes and 5-Aminopyrazoles
  作者：Dongping Cheng、Jing-Hua Li、Xiaoliang Xu、Huafang Gu、Hongshuang Xia、Yawei Wang

  DOI：10.1055/a-2145-5916

  日期：2023.12

  The reaction of 5-aminopyrazoles with 1,3-diarylpropenes mediated by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, with subsequent intramolecular cyclization and dehydroaromatization in the presence of Cu(OTf)2/tert-butyl hydroperoxide, gave a series of pyrazolo[3,4-b]pyridines in moderate to excellent yields. The reaction has the advantages of high atom economy, a wide substrate scope, and a one-pot procedure.

  摘要在 2,3-二氯-5,6-二氰基-1,4-苯醌介导下，5-氨基吡唑与 1,3-二芳基丙烯发生反应，随后在 Cu(OTf)2/ 叔丁基过氧化氢存在下发生分子内环化和脱氢芳香化反应，得到一系列吡唑并[3,4-b]吡啶，收率中等到极好。该反应具有原子经济性高、底物范围广和一锅反应等优点。