5-(4-fluorophenyl)-1-(4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole | 188817-07-4

• 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-(4-fluorophenyl)-1-(4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole
• 英文别名: 1-(p-nitrophenyl)-5-(p-fluorophenyl)-3-trifluoromethylpyrazole；5-(4-Fluoro-phenyl)-1-(4-nitro-phenyl)-3-trifluoromethyl-1H-pyrazole；5-(4-fluorophenyl)-1-(4-nitrophenyl)-3-(trifluoromethyl)pyrazole
• CAS: 188817-07-4
• 化学式: C₁₆H₉F₄N₃O₂
• 分子量: 351.26
• InChiKey: KFMKDAFANAIVEZ-UHFFFAOYSA-N

物化性质

• 熔点：
  98 °C
• 沸点：
  454.0±45.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(4-fluorophenyl)-1-(4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole 在 palladium on activated charcoal 吡啶 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 N-[4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]methanesulfonamide
  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
• 作为产物：
  描述：

  4-氟苯乙酮 在 sodium methylate 作用下， 以 甲醇 、 甲基叔丁基醚 、 2,2,2-三氟乙醇 为溶剂， 生成 5-(4-fluorophenyl)-1-(4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole
  参考文献：
  名称：

  [EN] NOVEL COMPOUNDS AS ROR GAMMA MODULATORS
  [FR] NOUVEAUX COMPOSÉS UTILISÉS EN TANT QUE MODULATEURS DE ROR GAMMA

  摘要：

  本公开涉及式(I)的化合物及其药用盐，其中环A、环B、L、R1、R2、R3、R4、R5、Ra、Rb、n、m、p和q如本文所定义，这些化合物作为视黄酸相关孤儿受体γt（RORγt）调节剂具有活性。这些化合物可以预防、抑制或抑制RORγt的作用，因此在治疗RORγt介导的疾病、紊乱、综合症或症状方面具有用处，例如疼痛、炎症、慢性阻塞性肺病（COPD）、哮喘、类风湿性关节炎、结肠炎、多发性硬化症、牛皮癣、神经退行性疾病和癌症。

  公开号：

  WO2017021879A1

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。
• The reaction of aryl and heteroarylhydrazines with aryl-trifluoromethyl β-diketones
  作者：Shiv P. Singh、Vinod Kumar、Ranjana Aggarwal、Jose Elguero

  DOI：10.1002/jhet.5570430428

  日期：2006.7

  We report the results obtained when five aromatic or heteroaromatic hydrazines react with six β-diketones bearing trifluoromethyl and aryl substituents. Forty-two compounds have been isolated corresponding to two isomeric trifluoromethyl pyrazoles and the intermediate 5-CF3, 5-OH pyrazolines. The results have provided useful information for establishing the mechanism of the synthesis of pyrazoles.

  我们报告了当五个芳香族或杂芳香族肼与六个带有三氟甲基和芳基取代基的β-二酮反应时获得的结果。四十二个化合物已被分离出对应于两个同分异构的三氟甲基吡唑和中间体5-CF 3，5-OH吡唑啉。该结果为建立吡唑的合成机理提供了有用的信息。
• PROCESS FOR THE PREPARATION OF ROR GAMMA MODULATORS
  申请人：Glenmark Pharmaceuticals S.A.

  公开号：EP3686187A1

  公开（公告）日：2020-07-29

  The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, ring B, L, R1, R2, R3, R4, R5, Ra, Rb, n, m, p and q are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer.

  本公开涉及式（I）化合物及其药学上可接受的盐类，其中环 A、环 B、L、R1、R2、R3、R4、R5、Ra、Rb、n、m、p 和 q 如本文所定义，它们作为视黄醇相关孤儿受体 gamma t（RORγt）的调节剂具有活性。这些化合物可防止、抑制或抑制 RORγt 的作用，因此可用于治疗 RORγt 介导的疾病、失调、综合症或病症，如疼痛、炎症、慢性阻塞性肺病、哮喘、类风湿性关节炎、结肠炎、多发性硬化症、银屑病、神经退行性疾病和癌症。
• Compounds as ROR gamma modulators
  申请人：Glenmark Pharmaceuticals S.A.

  公开号：US10344024B2

  公开（公告）日：2019-07-09

  The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, ring B, L, R1, R2, R3, R4, R5, Ra, Rb, n, m, p and q are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer.

  本公开涉及式（I）化合物及其药学上可接受的盐类，其中环 A、环 B、L、R1、R2、R3、R4、R5、Ra、Rb、n、m、p 和 q 如本文所定义，它们作为视黄醇相关孤儿受体 gamma t（RORγt）的调节剂具有活性。这些化合物可防止、抑制或抑制 RORγt 的作用，因此可用于治疗 RORγt 介导的疾病、失调、综合症或病症，如疼痛、炎症、慢性阻塞性肺病、哮喘、类风湿性关节炎、结肠炎、多发性硬化症、银屑病、神经退行性疾病和癌症。
• 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.