methyl 3,5-dimethyl-1H-pyrazole-1-carboxylate | 53921-04-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 3,5-dimethyl-1H-pyrazole-1-carboxylate
• 英文别名: methyl 3,5-dimethylpyrazole-1-carboxylate；DMPE；3,5-dimethyl-pyrazole-1-carboxylic acid methyl ester；1H-Pyrazole-1-carboxylic acid, 3,5-dimethyl-, methyl ester
• CAS: 53921-04-3
• 化学式: C₇H₁₀N₂O₂
• 分子量: 154.169
• InChiKey: HUEYZDMZZGVKRW-UHFFFAOYSA-N

物化性质

• 沸点：
  240.6±43.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  magnesium,ethylbenzene,bromide 、 methyl 3,5-dimethyl-1H-pyrazole-1-carboxylate 以 乙醚 为溶剂， 反应 3.0h， 以42%的产率得到3-苯丙酸甲酯
  参考文献：
  名称：

  New facile alkoxycarbonylating agent, alkyl pyrazole-1-carboxylates. The preparation and the utilities

  摘要：

  Alkyl pyrazole-1-carboxylates (2), which were readily prepared from alkyl chloroformate or carbazate in good yields, were provided as the new facile alkoxycarbonylating agents toward the Grignard reagents for the synthesis of one carbon higher carboxylic esters. Also amines were alkoxycarbonylated by 2 to produce the corresponding urethanes even in an aqueous medium. Benzyl 3,5-dimethylpyrazole-1-carboxylate (2d) could be utilized for the Cbz-protection of amino acids and esters in good yield without any racemization. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)00947-8
• 作为产物：
  描述：

  (3,5-二甲基吡唑-1-基)-三甲基硅烷 在 三乙胺 作用下， 以 苯 为溶剂， 反应 1.5h， 生成 methyl 3,5-dimethyl-1H-pyrazole-1-carboxylate
  参考文献：
  名称：

  Sheludyakov, V. D.; Sheludyakova, S. V.; Kuznetsova, M. G., Journal of general chemistry of the USSR, 1980, vol. 50, # 4, p. 705 - 711

  摘要：

  DOI：

文献信息

• C(sp³)–H Monoarylation of Methanol Enabled by a Bidentate Auxiliary
  作者：Quan Gou、Binfang Yuan、Man Ran、Jian Ren、Ming-zhong Zhang、Xiaoping Tan、Tengrui Yuan、Xing Zhang

  DOI：10.1021/acs.orglett.0c03786

  日期：2021.1.1

  With the assistance of a practical directing group (COAQ), the first catalytic protocol for the palladium-catalyzed C(sp3)–H monoarylation of methanol has been developed, offering an invaluable synthesis means to establish extensive derivatives of crucial arylmethanol functional fragments. Furthermore, the gram-scale reaction, broad substrate scope, excellent functional group compatibility, and even

  在一个实用的指导小组（COAQ）的帮助下，开发了甲醇催化钯催化的C（sp 3）-H单芳基化的第一个催化方案，为建立关键的芳基甲醇功能片段的广泛衍生物提供了宝贵的合成手段。此外，克级反应，广泛的底物范围，出色的官能团相容性，甚至药物的实际合成，都进一步证明了该策略的有效性。
• Layered Zirconium Sulfophenyl Phosphonate as Heterogeneous Catalyst in the Synthesis of Pyrazoles and 4,5,6,7-Tetrahydro-1(2)<i>H</i>-indazoles
  作者：Massimo Curini、Ornelio Rosati、Valerio Campagna、Francesca Montanari、Giancarlo Cravotto、Mauro Boccalini

  DOI：10.1055/s-2005-921904

  日期：——

  Pyrazoles and tetrahydroindazoles may be prepared by condensation of 1,3-diones and hydrazines under layered zirconium sulfophenyl phosphonate catalysis, in solvent-free conditions.

  吡唑和四氢吲哒唑可以通过在无溶剂条件下，层状锆磺苯膦酸盐催化剂的作用下，由1,3-二酮和肼缩合制备得到。
• Migration tendencies of functional groups toward sigmatropic rearrangement in 3,3-disubstituted 3H-pyrazoles
  作者：Peter Sciess、Henri Stalder

  DOI：10.1016/s0040-4039(00)92734-5

  日期：——

  3,3-Disubstituted 3H-pyrazoles - aromatise through an intramolecular sigmatropic 1,5-(1,2-) shift of one of the quaternary groups. From a kinetic study of the uncatalysed and of the acid catalysed isomerisation reaction migration tendencies of functional groups in sigmatropic rearrangement toward neutral and toward cationic centers are obtained.

  3,3-二取代的3H-吡唑-通过四元基团之一的分子内σ1,5-（1,2-）转移而芳香化。通过对未催化的和酸催化的异构化反应的动力学研究，获得了在σ重排的官能团向中性中心和向阳离子中心迁移的趋势。
• Alberola, Angel; Calvo, Luis; Ortega, Alfonso Gonzalez, Heterocycles, 1999, vol. 51, # 11, p. 2675 - 2686
  作者：Alberola, Angel、Calvo, Luis、Ortega, Alfonso Gonzalez、Sadaba, M. Luisa、Sanudo, M. Carmen、Granda, Santiago Garcia、Rodriguez, Elena Garcia

  DOI：——

  日期：——
• A novel, potent, oral active and safe antinociceptive pyrazole targeting kappa opioid receptors
  作者：Gabriela Trevisan、Mateus F. Rossato、Cristiani I.B. Walker、Sara M. Oliveira、Fernanda Rosa、Raquel Tonello、Cássia R. Silva、Pablo Machado、Aline A. Boligon、Marcos A.P. Martins、Nilo Zanatta、Hélio G. Bonacorso、Margareth L. Athayde、Maribel A. Rubin、João B. Calixto、Juliano Ferreira

  DOI：10.1016/j.neuropharm.2013.06.011

  日期：2013.10

  Pyrazole compounds are an intriguing class of compounds with potential analgesic activity; however, their mechanism of action remains unknown. Thus, the goal of this study was to explore the antinociceptive potential, safety and mechanism of action of novel 1-pyrazole methyl ester derivatives, which were designed by molecular simplification, using in vivo and in vitro methods in mice. First, tree 1-pyrazole methyl ester derivatives (DMPE, MPFE, and MPCIE) were tested in the capsaicin test and all presented antinociceptive effect; however the MPCIE (methyl 5-trichloromethyl-3-methyl-1H-pyrazolel-carboxylate) was the most effective. Thus, we selected this compound to assess the effects and mechanisms in subsequent pain models. MPCIE produced antinociception when administered by oral, intraperitoneal, intrathecal and intraplantar routes and was effective in the capsaicin and the acetic acid-induced nociception tests. Moreover, this compound reduced the hyperalgesia in diverse clinically-relevant pain models, including postoperative, inflammatory, and neuropathic nociception in mice. The antinociception produced by orally administered MPCIE was mediated by kappa-opioid receptors, since these effects were prevented by systemically pre-treatment with naloxone and the kappa-opioid receptor antagonist nor-binaltorphimine. Moreover, MPCIE prevented binding of the kappa-opioid ligand [H-3]-CI-977 in vitro (IC50 of 0.68 (032-1.4) mu M), but not the TRPV1 ([H-3]-resiniferatoxin) or the alpha(2)-adrenoreceptor ([H-3]-idazoxan) binding. Regarding the drug-induced side effects, oral administration of MPCIE did not produce sedation, constipation or motor impairment at its active dose. In addition, MPCIE was readily absorbed after oral administration. Taken together, these results demonstrate that MPCIE is a novel, potent, orally active and safe analgesic drug that targets kappa-opioid receptors. (C) 2013 Elsevier Ltd. All rights reserved.