1,5-di(4-methoxyphenyl)-3-trifluoromethyl-1H-pyrazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,5-di(4-methoxyphenyl)-3-trifluoromethyl-1H-pyrazole
• 英文别名: 1,5-bis(4-methoxyphenyl)-3-(trifluoromethyl)pyrazole；1,5-Bis(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole
• 化学式: C₁₈H₁₅F₃N₂O₂
• 分子量: 348.325
• InChiKey: PQOHMVIGLUQKDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  丙烯酸丁酯 、 1,5-di(4-methoxyphenyl)-3-trifluoromethyl-1H-pyrazole 在 palladium diacetate 、 silver carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以77%的产率得到(E)-butyl 3-(1,5-bis(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)acrylate
  参考文献：
  名称：

  通过Pd合成1,3,5-三取代的[4-叔丁基2-（5,5-二氟-2,2-二甲基-6-乙烯基-1,3-二恶烷-4-基）乙酸]吡唑催化的C ？H激活

  摘要：

  所述宝石-difluoromethylenated丙酮化合物2作为HMG-CoA还原酶抑制剂的新的前体有效地合成。在Pd（OAc）2和AgCO 3的存在下，通过Pd催化的1,3,5-三取代的吡唑1的C 4 -H活化的直链烯烃化反应顺利进行。该协议在改善原子经济和防止副产物生成方面具有优势。

  DOI：

  10.1002/cjoc.201201100
• 作为产物：
  描述：

  对甲氧基苯乙酮 在 sodium methylate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 44.0h， 生成 1,5-di(4-methoxyphenyl)-3-trifluoromethyl-1H-pyrazole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors:  Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib)

  摘要：

  A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of ii (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

  DOI：

  10.1021/jm960803q

文献信息

• Synthesis of 1,3,5-Trisubstituted [4-<i>tert</i>-Butyl 2-(5,5-difluoro-2,2-dimethyl-6-vinyl-1,3-dioxan-4-yl)acetate]pyrazoles via a Pd-Catalyzed CH Activation
  作者：Xiaoguang Wang、Xiang Fang、Xueyan Yang、Meng Ni、Fanhong Wu

  DOI：10.1002/cjoc.201201100

  日期：2012.12

  The gem‐difluoromethylenated acetonide 2 was efficiently synthesized as new precursor of HMG‐CoA reductase inhibitor. Straightforward olefination via Pd‐catalyzed C4‐H activation of 1,3,5‐trisubstituted pyrazoles 1 was proceeded smoothly in the presence of Pd(OAc)2 and AgCO3. This protocol has merits in terms of the improved atomic economy and prevention from the generation of by‐products.

  所述宝石-difluoromethylenated丙酮化合物2作为HMG-CoA还原酶抑制剂的新的前体有效地合成。在Pd（OAc）2和AgCO 3的存在下，通过Pd催化的1,3,5-三取代的吡唑1的C 4 -H活化的直链烯烃化反应顺利进行。该协议在改善原子经济和防止副产物生成方面具有优势。
• Methods of treating or preventing a cardiovascular condition using a cyclooxygenase-1 inhibitor
  申请人：——

  公开号：US20030162824A1

  公开（公告）日：2003-08-28

  Methods for treating or preventing one or more cardiovascular conditions in a subject comprising treating the subject with a therapeutically effective amount of a selective cyclooxygenase-1 inhibitor or a pharmaceutically-acceptable salt, tautomer or prodrug thereof alone or in combination with either a drug used in the treatment or prevention of a cardiovascular condition or a non-drug therapy used in the treatment of a cardiovascular condition.

  治疗或预防受试者一种或多种心血管疾病的方法包括使用治疗性有效量的选择性环氧合酶-1抑制剂或其药用可接受的盐、互变异构体或前药单独或与用于治疗或预防心血管疾病的药物或用于心血管疾病治疗的非药物疗法的组合。
• Modified reaction conditions to achieve high regioselectivity in the two component synthesis of 1,5-diarylpyrazoles
  作者：Sunil K. Singh、M. Srinivasa Reddy、S. Shivaramakrishna、D. Kavitha、R. Vasudev、J. Moses Babu、A. Sivalakshmidevi、Y. Koteswar Rao

  DOI：10.1016/j.tetlet.2004.08.100

  日期：2004.10

  The factors affecting regioselectivity during the formation of 1,5-diarylpyrazoles from aryl hydrazines and 1,3-diketones are identified and the regioisomers were characterized by 1D NOESY, LC-NMR and X-ray analyses. A simple alteration in the usual reaction conditions is reported, which allows the exclusive formation of 1,5-diarylpyrazoles. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors:  Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1<i>H</i>-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib)
  作者：Thomas D. Penning、John J. Talley、Stephen R. Bertenshaw、Jeffery S. Carter、Paul W. Collins、Stephen Docter、Matthew J. Graneto、Len F. Lee、James W. Malecha、Julie M. Miyashiro、Roland S. Rogers、D. J. Rogier、Stella S. Yu、Gary D. Anderson、Earl G. Burton、J. Nita Cogburn、Susan A. Gregory、Carol M. Koboldt、William E. Perkins、Karen Seibert、Amy W. Veenhuizen、Yan Y. Zhang、Peter C. Isakson

  DOI：10.1021/jm960803q

  日期：1997.4.1

  A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of ii (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.
• A new and direct route to 3-fluoromethyl substituted pyrazol-4-acrylates via Pd-catalyzed C–H activation
  作者：Xiaoguang Wang、Xiang Fang、Hongyuan Xiao、Dongming Gong、Xueyan Yang、Fanhong Wu

  DOI：10.1016/j.tet.2013.06.058

  日期：2013.8

  Direct C4-H activation of 3-fluoromethyl pyrazoles followed by an oxidative coupling with acrylates, which is perhaps the most direct method for the synthesis of 3-fluoromethyl substituted pyrazol-4-aciylates of biological interest, remains challenging. Here, the first example of the straightforward olefination via Pd-catalyzed C4-H activation of both C3-CF3 and C3-CF2H substituted pyrazoles is reported. The reaction of various C3-CF3 substituted pyrazoles with acrylates proceeds smoothly in the presence of Pd(OAc)(2) and Ag2CO3, whereas olefination of C3-CF2H substituted pyrazoles requires the addition of benzoquinone. A further computational study reveals that reactivity of the pyrazolyl substrates employed are strongly impacted by the substituents of different nature on their C1 or C5 position, which is in good agreement with the experimental data. (C) 2013 Elsevier Ltd. All rights reserved.