5-(4-fluorophenyl)-1-methyl-1H-pyrazole | 689251-78-3

• 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-methyl-1H-pyrazole
• 英文别名: 5-(4-fluorophenyl)-1-methylpyrazole
• CAS: 689251-78-3
• 化学式: C₁₀H₉FN₂
• 分子量: 176.193
• InChiKey: DCGKCBFAIJICIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-fluorophenyl)-1-methyl-1H-pyrazole 在 N-溴代丁二酰亚胺(NBS) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 18.17h， 生成 6-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one
  参考文献：
  名称：

  Discovery of 6-[5-(4-fluorophenyl)-3-methyl-pyrazol-4-yl]-benzoxazin-3-one derivatives as novel selective nonsteroidal mineralocorticoid receptor antagonists

  摘要：

  In the course of our study on selective nonsteroidal mineralocorticoid receptor (MR) antagonists, a series of novel benzoxazine derivatives possessing an azole ring as the core scaffold was designed for the purpose of attenuating the partial agonistic activity of the previously reported dihydropyrrol-2-one derivatives. Screening of alternative azole rings identified 1,3-dimethyl pyrazole 6a as a lead compound with reduced partial agonistic activity. Subsequent replacement of the 1-methyl group of the pyrazole ring with larger lipophilic side chains or polar side chains targeting Arg817 and Gln776 increased MR binding activity while maintaining the agonistic response at the lower level. Among these compounds, 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (37a) showed highly potent in vitro activity, high selectivity versus other steroid hormone receptors, and good pharmacokinetic profiles. Oral administration of 37a in deoxycorticosterone acetate-salt hypertensive rats showed a significant blood pressure-lowering effect with no signs of antiandrogenic effects. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.07.038
• 作为产物：
  描述：

  4-氟苯乙酮 以 乙醇 为溶剂， 反应 6.0h， 生成 5-(4-fluorophenyl)-1-methyl-1H-pyrazole
  参考文献：
  名称：

  PYRAZOLE COMPOUNDS

  摘要：

  本发明涉及其中每个符号如规范中定义的。该化合物具有优越的矿物皮质激素受体拮抗作用，并可用作通过矿物皮质激素受体激活介导的疾病或病况的预防或治疗剂。

  公开号：

  US20100094000A1

文献信息

• Synthesis of 3-Substituted 2-Arylpyridines via Cu/Pd-Catalyzed Decarboxylative Cross-Coupling of Picolinic Acids with (Hetero)Aryl Halides
  作者：Dagmar Hackenberger、Philip Weber、David C. Blakemore、Lukas J. Goossen

  DOI：10.1021/acs.joc.7b00046

  日期：2017.4.7

  A decarboxylative cross-coupling of 3-substituted picolinic acids with (hetero)aryl halides is presented. In the presence of catalytic Cu2O and Pd(1,5-cyclooctadiene)Cl2 with 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl as the ligand, both electron-rich and electron-deficient aryl bromides and chlorides as well as heteroaryl bromides were successfully coupled with various picolinate salts

  提出了3-取代的吡啶甲酸与（杂）芳基卤化物的脱羧交叉偶联。在催化性的Cu 2 O和Pd（1,5-环辛二烯）Cl 2以2-二环己基膦基-2'-（N，N-二甲基氨基）联苯为配体的情况下，富电子和缺电子的芳基溴化物和在温和的条件下，将氯化物以及杂芳基溴化物与各种吡啶甲酸盐成功偶联，收率高达96％。该方案提供了有效的进入2-（杂）芳基吡啶的途径，这是药物发现中一种有吸引力的物质。
• PYRAZOLE COMPOUNDS
  申请人：FUKUMOTO Shoji

  公开号：US20100094000A1

  公开（公告）日：2010-04-15

  The present invention relates to wherein each symbol is as defined in the specification. The compound has a superior mineralocorticoid receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of a disease or condition mediated by the mineralocorticoid receptor activation.

  本发明涉及其中每个符号如规范中定义的。该化合物具有优越的矿物皮质激素受体拮抗作用，并可用作通过矿物皮质激素受体激活介导的疾病或病况的预防或治疗剂。
• Palladium-catalysed direct diarylations of pyrazoles with aryl bromides: a one step access to 4,5-diarylpyrazoles
  作者：Abdelilah Takfaoui、Liqin Zhao、Rachid Touzani、Pierre H. Dixneuf、Henri Doucet

  DOI：10.1016/j.tetlet.2014.01.079

  日期：2014.3

  The palladium-catalysed direct arylation of pyrazoles with aryl halides, using PdCl(C3H5)(dppb)/KOAc catalyst, reveals a similar reactivity of C4 and C5 CH bonds of pyrazoles, whereas the C3 CH bond is almost unreactive, and gives access in one step to a variety of 4,5-diarylpyrazoles. This CH bond functionalisation reaction tolerates a variety of substituents on the aryl bromide such as nitro, cyano

  使用PdCl（C 3 H 5）（dppb）/ KOAc催化剂，钯催化吡唑与芳基卤化物的直接芳基化反应显示出吡唑的C4和C5 C H键具有相似的反应性，而C3 C H键几乎不具有反应性，并一步一步即可获得各种4,5-二芳基吡唑类化合物。该C H键官能化反应容许芳基溴化物上的各种取代基，例如硝基，氰基，甲酰基，丙酰基，酯，氯，氟或三氟甲基。
• Agent for preventing or treating neuropathy
  申请人：Momose Yu

  公开号：US20060004069A1

  公开（公告）日：2006-01-05

  The present invention provides an agent for preventing or treating neuropathy having superior action and low toxicity. This agent comprises a compound represented by the formula: wherein ring A is a 5-membered aromatic heterocycle containing 2 or more nitrogen atoms, which may further have substituent(s); B is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a divalent acyclic hydrocarbon group; Z is —O—, —S—, —NR 2 —, —CONR 2 — or —NR 2 CO— (R 2 is a hydrogen atom or an optionally substituted alkyl group); Y is a bond or a divalent acyclic hydrocarbon group; R 1 is an optionally substituted cyclic group, an optionally substituted amino group or an optionally substituted acyl group, provided that when the 5-membered aromatic heterocycle represented by ring A is imidazole, then Z should not be —O—, or a salt thereof.

  本发明提供了一种用于预防或治疗神经病的药剂，具有优异的作用和低毒性。该药剂包括以下式子所表示的化合物：其中环A是一个含有2个或更多氮原子的5元芳香杂环，可以进一步具有取代基；B是一个可选取代的碳氢化合物基团或可选取代的杂环基团；X是一个二价的无环碳氢基团；Z是—O—、—S—、—NR2—、—CONR2—或—NR2CO—（其中R2是氢原子或可选取代的烷基基团）；Y是一个键或一个二价的无环碳氢基团；R1是一个可选取代的环基、可选取代的氨基或可选取代的酰基，但当环A所表示的5元芳香杂环是咪唑时，Z不应为—O—，或其盐。
• N1-Selective Methylation of Pyrazoles via α-Halomethylsilanes as Masked Methylating Reagents
  作者：Emma Yang、Derek M. Dalton

  DOI：10.1021/acs.joc.3c02841

  日期：2024.3.15

  The development of a highly selective N-methylation of pyrazole heterocycles using commercially available, bench-stable α-halomethylsilanes as masked methylating reagents is described. Sterically bulky α-halomethylsilanes significantly improve the selectivity of N-alkylation over traditional methylating reagents and readily undergo protodesilylation in the presence of a fluoride source and water to

  描述了使用市售的、实验室稳定的 α-卤甲基硅烷作为掩蔽甲基化试剂开发吡唑杂环的高选择性 N-甲基化。与传统的甲基化试剂相比，空间庞大的 α-卤甲基硅烷显着提高了 N-烷基化的选择性，并且在氟化物源和水存在下很容易进行原脱甲硅烷基化，得到N-甲基吡唑。使用一系列吡唑底物以良好的产率实现了 92:8 至 >99:1 N1/N2 区域异构比的选择性。