1-(4-methoxyphenyl)-1-phenylsilinan-4-one | 1558028-37-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(4-methoxyphenyl)-1-phenylsilinan-4-one
• 英文别名: 1-(4-Methoxyphenyl)-1-phenylsilinan-4-one
• CAS: 1558028-37-7
• 化学式: C₁₈H₂₀O₂Si
• 分子量: 296.441
• InChiKey: ZKDVYJBBSTUTJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyphenyl)-1-phenylsilinan-4-one 在 5,5-二溴巴比妥酸 、 sodium carbonate 作用下， 以 乙醚 、 甲苯 、 乙腈 为溶剂， 反应 27.5h， 生成 2-chloro-4-ethoxy-N-((6-(4-methoxyphenyl)-6-phenyl-6-sila-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)carbamoyl)-5-(1H-pyrazol-1-yl)benzamide
  参考文献：
  名称：

  含硅GPR81和GPR109A激动剂的合成及药理特性

  摘要：

  GPR81和GPR109A受体介导抗脂解作用，并且是治疗代谢异常（例如血脂异常和2型糖尿病）的潜在药物靶标。仍然需要确定有效的GPR81激动剂作为药理学工具。高通量筛选确定了基于酰脲的GPR81激动剂先导系列，同时对GPR109A受体也有活性。为了扩大化学范围并探索药理作用和药代动力学后果，一系列结构相关的有机硅化合物与6-sila-4、5、6、7-四氢苯并[ d]合成]噻唑骨架并研究其理化性质[辛醇/水分配系数（pH 7.4），在HBSS缓冲液中的溶解度（pH 7.4）]，对大鼠GPR81和GPR109A受体的激动作用以及在人肝微粒体和大鼠中的固有清除率肝细胞。这些有机硅化合物的直接合成为上述GPR81激动剂铅系列的化学范围提供了有价值的扩展，提供了效能和功效SAR，并产生了具有超微摩尔GPR81效能的化合物。这项工作支持将硅化学纳入药物化学工具箱的价值。

  DOI：

  10.1002/cmdc.201500343
• 作为产物：
  描述：

  dimethoxy(4-methoxyphenyl)(phenyl)silane 在 9-硼双环[3.3.1]壬烷 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 5.0h， 生成 1-(4-methoxyphenyl)-1-phenylsilinan-4-one
  参考文献：
  名称：

  Synthesis of 4-Silacyclohexan-1-ones and (4-Silacyclohexan-1-yl)amines Containing the Silicon Protecting Groups MOP (4-Methoxyphenyl), DMOP (2,4-Dimethoxyphenyl), or TMOP (2,4,6-Trimethoxyphenyl): Versatile Si- and C-Functional Building Blocks for Synthesis

  摘要：

  The 4-silacyclohexanones 1-6 were prepared in convenient multistep syntheses, starting from MeSi(OMe)(3) and PhSi(OMe)(3), respectively. Cleavage of the 4-methoxyphenyl (MOP), 2,6-dimethoxyphenyl (DMOP), and 2,4,6-trimethoxyphenyl (TMOP) protecting groups of 4-6 by treatment with HCl/Et2O in CH2Cl2 at 20 degrees C gives the 4-chloro-4-silacyclohexanone 13. Reductive amination of 1-6 with NH3 or i-PrNH2 yields the respective (4-silacyclohexan-1-yl)amines 7-12. Compounds 1-12 and all new precursors synthesized were characterized by elemental analyses (C, H, N) or mass spectrometric investigations (ESI-HRMS) and by NMR spectroscopic studies (H-1, C-13, Si-29). Compounds 1, 3, 5, and 6 and the precursors (MeO)(2)SiPh-(TMOP) (21) and (CH2=CH)(2)SiPh(TMOP) (27) were additionally characterized by single-crystal X-ray diffraction. Compounds 1-12 with their Si- and C-functional groups represent versatile building blocks for synthesis.

  DOI：

  10.1021/om401208y

文献信息

• Synthesis of Silacyclohexanones from Divinylsilanes and Allylamines by a Rh-Catalyzed Cyclization
  作者：Jiawei Guo、Song Liu、Qinjiao Pang、Hongyun Zhang、Lu Gao、Li Chen、Zhenlei Song

  DOI：10.1021/acs.orglett.1c04183

  日期：2022.1.21

  An efficient synthesis of silacyclohexanones bearing a variety of silyl substituents has been developed by a [Rh(coe)2Cl]2/PCy3-catalyzed cyclization of divinylsilanes with Jun’s allylamine. The silacyclohexanones can be oxidized with DDQ to give the corresponding silacyclohexadienones, which are further transformed into silicon analog of 2-deoxystreptamine or exo-alkylidenesilacyclohexadienes.

  通过[Rh(coe) 2 Cl] 2 /PCy 3催化的二乙烯基硅烷与Jun's烯丙胺的环化，开发了一种有效合成具有多种甲硅烷基取代基的硅环己酮。硅杂环己酮可以用 DDQ 氧化得到相应的硅环己二烯酮，其进一步转化为 2-脱氧链霉胺或外亚烷基硅环己二烯的硅类似物。
• Synthesis of 4-Silacyclohexan-1-ones and (4-Silacyclohexan-1-yl)amines Containing the Silicon Protecting Groups MOP (4-Methoxyphenyl), DMOP (2,4-Dimethoxyphenyl), or TMOP (2,4,6-Trimethoxyphenyl): Versatile Si- and C-Functional Building Blocks for Synthesis
  作者：Markus Fischer、Christian Burschka、Reinhold Tacke

  DOI：10.1021/om401208y

  日期：2014.2.24

  The 4-silacyclohexanones 1-6 were prepared in convenient multistep syntheses, starting from MeSi(OMe)(3) and PhSi(OMe)(3), respectively. Cleavage of the 4-methoxyphenyl (MOP), 2,6-dimethoxyphenyl (DMOP), and 2,4,6-trimethoxyphenyl (TMOP) protecting groups of 4-6 by treatment with HCl/Et2O in CH2Cl2 at 20 degrees C gives the 4-chloro-4-silacyclohexanone 13. Reductive amination of 1-6 with NH3 or i-PrNH2 yields the respective (4-silacyclohexan-1-yl)amines 7-12. Compounds 1-12 and all new precursors synthesized were characterized by elemental analyses (C, H, N) or mass spectrometric investigations (ESI-HRMS) and by NMR spectroscopic studies (H-1, C-13, Si-29). Compounds 1, 3, 5, and 6 and the precursors (MeO)(2)SiPh-(TMOP) (21) and (CH2=CH)(2)SiPh(TMOP) (27) were additionally characterized by single-crystal X-ray diffraction. Compounds 1-12 with their Si- and C-functional groups represent versatile building blocks for synthesis.
• Synthesis and Pharmacological Properties of Silicon-Containing GPR81 and GPR109A Agonists
  作者：Marcel Geyer、Johannes A. Baus、Ola Fjellström、Eric Wellner、Linda Gustafsson、Reinhold Tacke

  DOI：10.1002/cmdc.201500343

  日期：2015.12

  The GPR81 and GPR109A receptors mediate antilipolytic effects and are potential drug targets for the treatment of metabolic disorders such as dyslipidemia and type 2 diabetes. There is still a need to identify potent GPR81 agonists as pharmacological tools. A high‐throughput screen identified an acylurea‐based GPR81 agonist lead series, with activities at the GPR109A receptor as well. To expand the

  GPR81和GPR109A受体介导抗脂解作用，并且是治疗代谢异常（例如血脂异常和2型糖尿病）的潜在药物靶标。仍然需要确定有效的GPR81激动剂作为药理学工具。高通量筛选确定了基于酰脲的GPR81激动剂先导系列，同时对GPR109A受体也有活性。为了扩大化学范围并探索药理作用和药代动力学后果，一系列结构相关的有机硅化合物与6-sila-4、5、6、7-四氢苯并[ d]合成]噻唑骨架并研究其理化性质[辛醇/水分配系数（pH 7.4），在HBSS缓冲液中的溶解度（pH 7.4）]，对大鼠GPR81和GPR109A受体的激动作用以及在人肝微粒体和大鼠中的固有清除率肝细胞。这些有机硅化合物的直接合成为上述GPR81激动剂铅系列的化学范围提供了有价值的扩展，提供了效能和功效SAR，并产生了具有超微摩尔GPR81效能的化合物。这项工作支持将硅化学纳入药物化学工具箱的价值。