1,6-dimethoxyhexa-2,4-diyne | 20726-67-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,6-dimethoxyhexa-2,4-diyne
• 英文别名: 1,6-dimethoxy-2,4-hexadiyne；2,4-Hexadiyne, 1,6-dimethoxy-
• CAS: 20726-67-4
• 化学式: C₈H₁₀O₂
• 分子量: 138.166
• InChiKey: WAPCAIUCRKHCNY-UHFFFAOYSA-N

物化性质

• 沸点：
  198.0±25.0 °C(Predicted)
• 密度：
  0.987±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,6-dimethoxyhexa-2,4-diyne 在 乙二醇二甲醚溴化镍 、 五甲基二乙烯三胺 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 20.0~50.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 生成 (E)-2-(methoxyethylidene)-5-methoxy-3-pentynoic acid methyl ester
  参考文献：
  名称：

  Activation of carbon dioxide: nickel-catalyzed electrochemical carboxylation of diynes

  摘要：

  The simultaneous activation of carbon dioxide and diynes by electrogenerated LNi(0) complexes (L = bpy, pentamethyldiethylenetriamine: PMDTA) enables the selective incorporation of one molecule of CO2 into the unsaturated systems and the preparative-scale electrosyntheses of carboxylic acids. A series of nonconjugated diynes afforded selectively linear or cyclic adducts depending on the ligand. Diynes bearing both a terminal and an internal triple bond gave exclusive CO2 incorporation into the terminal alkynyl group, regioselectively at the 2-position. The electrocarboxylation of 1,3-diynes with the Ni-PMDTA catalytic system yielded, regio- and stereoselectively, (E)-2-vinylidene-3-yne carboxylic acids in one step. The electrosyntheses were carried out in single-compartment cells fitted with a consumable magnesium anode, and utilized a catalytic amount of an air-stable Ni(II) complex as the catalyst precursor. Cyclic voltammetry studies revealed that both carbon dioxide and the diynes are able to coordinate to LNi(0)-generated species in DMF.

  DOI：

  10.1021/jo00061a038
• 作为产物：
  描述：

  1-iodo-3-methoxy-propyne 在 tris-(dibenzylideneacetone)dipalladium(0) 、 copper(l) iodide 、 三(2-呋喃基)膦 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.83h， 以100%的产率得到1,6-dimethoxyhexa-2,4-diyne
  参考文献：
  名称：

  多糖的寡糖类似物。第5部分。炔烃和卤代炔烃的交叉偶联研究

  摘要：

  优化了均炔丙基醚1与卤代炔丙基醚2a和2b的交叉偶联，并研究了偶联机理。在胺存在下由Pd°和Cu 1促进的偶联产生异二聚体3与同二聚体4和5的混合物（方案1）。优化首先针对抑制均相耦合。同质耦合部分是由于H / I交换（1 + 2a⇌6 + 7）由CuI和一种胺促进。在DMSO中，这种交换（但不是同二聚体的形成）在很大程度上受到抑制。还评估了膦配体的影响。较弱的σ供体（PPh 3除外）导致更快的偶联和更高的异二聚体与同型二聚体比率，其中P（fur）3导致反应最纯净。在[Pd 2（dba）3 ]，CuI和（i-Pr）2 NH存在下，碘代炔烃2a的还原二聚作用也形成了同二聚体（与I 2 ·（i-Pr）2 NH一起）。庞大和受体取代的胺降低了2a的二聚化程度，但是最大的胺类却不能促进偶联。通过使用溴炔2b可获得更好的结果。的二聚化既不2b中，也没有H /间溴交换1和图2b，观察到。1和2b的耦合

  DOI：

  10.1002/hlca.19950780814

文献信息

• TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS
  申请人：Arvinas, Inc.

  公开号：US20180155322A1

  公开（公告）日：2018-06-07

  The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，这些化合物可用作雌激素受体（目标蛋白）的调节剂。特别是，本公开涉及包含在一段至少有一种Von Hippel-Lindau配体、一种cereblon配体、凋亡抑制蛋白配体、小鼠双分钟同源2配体或其组合的双功能化合物，这些配体与相应的E3泛素连接酶结合，在另一端有一个与目标蛋白结合的部分，使得目标蛋白被置于泛素连接酶附近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白降解/抑制相关的广泛药理活性。可以通过本公开的化合物和组合物治疗或预防由目标蛋白聚集或积累引起的疾病或障碍。
• Synthesis of Substituted Isoquinolines via Nickel-Catalyzed [2+2+2] Cycloaddition of Alkynes and 3,4-Pyridynes
  作者：Yoshihiro Sato、Toshihiko Iwayama

  DOI：10.3987/com-09-s(s)126

  日期：——

  A novel methodology for the synthesis of substituted isoquinolines via a nickel(0)-catalyzed [2+2+2] cycloaddition of 3,4-pyridynes with two molecules of alkyne has been established. In this reaction, it was found that 2-butyn-1,4-diol derivatives and 1,3-diynes are suitable as substrates and that a propargylic oxygen functionality in alkynes is essential for the reactivity and the selectivity of the

  已经建立了一种通过镍 (0) 催化的 3,4-吡啶与两分子炔烃的 [2+2+2] 环加成合成取代异喹啉的新方法。在该反应中，发现 2-butyn-1,4-diol 衍生物和 1,3-diynes 适合作为底物，并且炔烃中的炔丙基氧官能团对于产物的反应性和选择性至关重要。
• Transition-metal-free variant of Glaser- and Cadiot-Chodkiewicz-type Coupling: Benign access to diverse 1,3-diynes and related molecules
  作者：Dhananjaya Kaldhi、Nagaraju Vodnala、Raghuram Gujjarappa、Arup K. Kabi、Subhashree Nayak、Chandi C. Malakar

  DOI：10.1016/j.tetlet.2020.151775

  日期：2020.4

  Efficient and transition-metal-free transformations towards the synthesis of 1,3-diynes have been described from their corresponding terminal acetylenes or 1,1-dibromo-1-alkenes. The efficiency of molecular iodine as catalyst in aqueous medium, driven the transformation to afford 1,3-diynes in moderate to good yields. The developed reaction conditions revealed appreciable functional group tolerance

  已经从它们相应的末端乙炔或1，1-二溴-1-烯烃描述了向1，3-二炔的合成的高效且无过渡金属的转化。分子碘在水性介质中作为催化剂的效率驱动了转化，以中等至良好的产率提供了1,3-二炔。发达的反应条件揭示了在水性介质中明显的官能团耐受性。此外，已经研究了使用末端炔烃作为易获得的前体来合成1,3-烯炔的无过渡金属方法的范围。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES
  申请人：Arvinas, Inc.

  公开号：US20180179183A1

  公开（公告）日：2018-06-28

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A-RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为快速加速纤维肉瘤（RAF，如c-RAF、A-RAF和/或B-RAF；目标蛋白）的调节剂而发挥作用。具体而言，本公开涉及含有一端为Von Hippel-Lindau、cereblon、凋亡抑制蛋白或鼠双分子同源物2配体的双功能化合物，该配体与相应的E3泛素连接酶结合，并且另一端含有结合目标蛋白RAF的基团，使得目标蛋白与泛素连接酶靠近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由目标蛋白的聚集或积累，或目标蛋白的构成性激活导致的疾病或紊乱。
• Copper salt-catalyzed homo-coupling reaction of potassium alkynyltrifluoroborates: a simple and efficient synthesis of symmetrical 1,3-diynes
  作者：Marcio W. Paixão、Minéia Weber、Antonio L. Braga、Juliano B. de Azeredo、Anna M. Deobald、Hélio A. Stefani

  DOI：10.1016/j.tetlet.2008.02.083

  日期：2008.4

  The copper-catalyzed dimerization of alkynyltrifluoroborates proceeds readily with good yields. The homo-coupling reaction can be effected in DMSO, in the open air, using Cu(OAc)2 as catalyst in the absence of any other additives. A variety of functional groups are tolerated.

  铜催化的炔基三氟硼酸盐的二聚反应容易进行，并且收率很高。均相偶联反应可以在DMSO中，在没有任何其他添加剂的情况下，使用Cu（OAc）2作为催化剂在露天条件下进行。可以容忍各种功能基团。