6-ethynyl-9-(tetrahydropyran-2-yl)purine | 333780-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-ethynyl-9-(tetrahydropyran-2-yl)purine
• 英文别名: 6-Ethynyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine；6-ethynyl-9-(oxan-2-yl)purine
• CAS: 333780-80-6
• 化学式: C₁₂H₁₂N₄O
• 分子量: 228.253
• InChiKey: REXLPPQBTQFZPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  52.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-ethynyl-9-(tetrahydropyran-2-yl)purine 在 CoBr(PPh3)3 乙醇 、 Dowex D-50 (H⁺ form) 作用下， 以 甲苯 为溶剂， 反应 5.0h， 生成 6-(1,3-dihydroisobenzofuran-5-yl)-9H-purine
  参考文献：
  名称：

  Cocyclotrimerization of 6-Alkynylpurines with α,ω-Diynes as a Novel Approach to Biologically Active 6-Arylpurines

  摘要：

  Transition metal complex catalyzed cocyclotrimerization of 6-alkynylpurines 1 with various diynes enables the preparation of a plethora of substituted 6-arylpurines 3 in good yields. The most general catalyst for the reaction is a user-friendly system based on a nickel-phosphine complex and reductant (NiBr2(dppe)/Zn) in MeCN. The reaction conditions are compatible with various protective groups on the purine moiety (Bn, THP). As far as other potential catalysts were concerned, only CoBr(PPh3)(3) showed reasonable activity in cocyclotrimerization of alkynylpurines with dipropargyl ether. A comparison of catalytic with stoichiometric approaches and the ligand effect in the catalyst is also given. Cytostatic activity screening of title 6-arylpurines was performed and several moderately active compounds were found.

  DOI：

  10.1021/jo0486342
• 作为产物：
  描述：

  9-(tetrahydropyran-2-yl)-6-[(trimethylsilyl)ethynyl]purine 在 氨 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以70%的产率得到6-ethynyl-9-(tetrahydropyran-2-yl)purine
  参考文献：
  名称：

  Covalent Analogues of DNA Base-Pairs and Triplets IV. Synthesis of Trisubstituted Benzenes Bearing Purine and/or Pyrimidine Rings by Cyclotrimerization of 6-Ethynylpurines and/or 5-Ethynyl-1,3-dimethyluracil

  摘要：

  Ni催化的6-乙炔基嘌呤（3）或5-乙炔基-1,3-二甲基尿嘧啶（4）的环三聚反应生成了1,2,4-三（嘌呤-6-基）苯（7）或1,2,4-三（1,3-二甲基尿嘧啶-5-基）苯（9）。对称的1,3,5-三（嘌呤-6-基）苯（8）作为副产物以极低的收率形式存在。9-苄基-6-乙炔基嘌呤（3a）与4的共环三聚反应生成了三（嘌呤基）苯（7a）作为主要产物，还伴随着1,2-双（9-苄基嘌呤-6-基）-4-（1,3-二甲基尿嘧啶-5-基）苯（10）和其他衍生物和异构体的复杂混合物。化合物7-10是Hoogsteen碱基三联体的类似物。

  DOI：

  10.1135/cccc20021223

文献信息

• Covalent Analogues of DNA Base-Pairs and Triplets V. Synthesis of Purine-Purine and Purine-Pyrimidine Conjugates Connected by Diverse Types of Acyclic Carbon Linkages
  作者：Michal Hocek、Hana Dvořáková、Ivana Císařová

  DOI：10.1135/cccc20021560

  日期：——

  The title 1,2-bis(purin-6-yl)acetylenes, -diacetylenes, -ethylenes and -ethanes were prepared as covalent base-pair analogues starting from 6-ethynylpurines and 6-iodopurines by the Sonogashira cross-coupling or oxidative alkyne-dimerization reactions followed by hydrogenations. 6-[(1,3-Dimethyluracil-5-yl)ethynyl]purine (11) was prepared analogously and hydrogenated to the corresponding purine-pyrimidine conjugates linked via vinylene and ethylene linkers. Unlike the cytostatic bis(purin-6-yl)acetylenes and -diacetylenes, the purine-pyrimidine conjugates were inactive. Crystal structures of bis(purin-6-yl)acetylene 6a, -diacetylene 8a and -ethane 5a were determined by single-crystal X-ray diffraction.

  1,2-双(嘌呤-6-基)乙炔，-二炔，-乙烯和-乙烷作为共价碱对类似物从6-乙炔基嘌呤和6-碘嘌呤出发，通过Sonogashira交叉偶联或氧化炔基二聚反应制备，随后进行氢化反应。类似地制备了6-[(1,3-二甲基尿嘧啶-5-基)乙炔基]嘌呤（11），并将其氢化为相应的嘌呤-嘧啶共轭物，通过乙烯和乙烷连接器连接。与细胞静止作用的双(嘌呤-6-基)乙炔和-二炔不同，嘌呤-嘧啶共轭物无活性。通过单晶X射线衍射测定了双(嘌呤-6-基)乙炔6a，-二炔8a和-乙烷5a的晶体结构。
• Synthesis of Purines Bearing Functionalized C-Substituents by the Conjugate Addition of Nucleophiles to 6-Vinylpurines and 6-Ethynylpurines
  作者：Martin Kuchař、Radek Pohl、Ivan Votruba、Michal Hocek

  DOI：10.1002/ejoc.200600545

  日期：2006.11

  Purines bearing diverse β-substituted ethyl or vinyl groups in position 6 were prepared by the conjugate addition of N-, O- and S-nucleophiles to 6-vinylpurines or 6-ethynylpurines. The scope of this methodology was systematically studied. The addition of amines, alcoholates and thiolates to 6-vinylpurines gave the corresponsing 6-(2-aminoethyl)-, 6-(2-alkoxyethyl)- and 6-[2-(alkylsulfanyl)ethyl]purines

  通过将 N-、O-和 S-亲核试剂共轭加成到 6-乙烯基嘌呤或 6-乙炔基嘌呤，制备在 6 位带有多种 β-取代乙基或乙烯基的嘌呤。系统地研究了这种方法的范围。将胺、醇化物和硫醇化物添加到 6-乙烯基嘌呤中得到相应的 6-(2-氨基乙基)-、6-(2-烷氧基乙基)-和 6-[2-(烷基硫基)乙基]嘌呤。胺与 6-乙炔基嘌呤的加成得到 6-(2-氨基乙烯基)嘌呤，而醇化物和硫醇化物的加入得到 6-(2-二烷氧基乙基)-和 6-[2-双(烷基硫基)乙基]嘌呤。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
• Covalent analogues of DNA base-Pairs and triplets. Part 2: † †For Part I, see ref 1. Synthesis and cytostatic activity of bis(purin-6-yl)acetylenes,-diacetylenes and related compounds
  作者：Michal Hocek、Ivan Votruba

  DOI：10.1016/s0960-894x(02)00077-x

  日期：2002.4

  The title bis(purin-6-yl)acetylenes, -diacetylenes, -ethylenes and -ethanes were prepared as covalent base-pair analogues starting from 6-ethynylpurines and 6-iodopurines by cross-coupling and homo-coupling reactions and hydrogenations. The bis(purin-6-yl)acetylenes and -diacetylenes exhibited significant cytostatic activity in vitro (IC(50)=0.4-1.0 micromol/l).

  通过交叉偶联和均偶联反应和氢化，从6-乙炔基嘌呤和6-碘嘌呤开始，制备标题双（嘌呤-6-基）乙炔，-二乙炔，-乙烯和-乙烷作为共价碱基对类似物。双（嘌呤-6-基）乙炔和-二乙炔在体外表现出显着的细胞抑制活性（IC（50）= 0.4-1.0 micromol / l）。
• Cyclotrimerization of 6-ethynylpurines. Synthesis of 1,2,4- and 1,3,5-tris(purin-6-yl)benzenes as novel Hoogsteen-triplet analogues
  作者：Michal Hocek、Irena G Stará、Ivo Starý、Hana Dvořáková

  DOI：10.1016/s0040-4039(00)01989-4

  日期：2001.1

  Cyclotrimerization reactions of the 9-protected 6-ethynylpurines 4a,b in the presence of various transition metal catalysts were studied. The best results were obtained with Ni(COD)2 or Ni(COD)2/PPh3 to obtain the 1,2,4- and 1,3,5-tris(purin-6-yl)benzenes 5a,b and 6a,b in moderate to good yields (in a 4:1 to 10:1 ratio). This method is suitable for the practical synthesis of the unsymmetrical 1,2,

  研究了9-保护的6-乙炔基嘌呤4a，b在各种过渡金属催化剂存在下的环三聚反应。使用Ni（COD）2或Ni（COD）2 / PPh 3可获得最佳结果，从而获得1,2,4-和1,3,5-三（嘌呤-6-基）苯5a，b和6a，b的产量为中度到良好（比例为4：1到10：1）。该方法适用于不对称的1,2,4-三（嘌呤-6-基）苯5a – c的实际合成，而对称的1,3,5-三（嘌呤-6-基）苯6a，b 通常形成次要产品。
• Cocyclotrimerization of 6-Alkynylpurines with α,ω-Diynes as a Novel Approach to Biologically Active 6-Arylpurines
  作者：Pavel Turek、Martin Kotora、Iva Tišlerová、Michal Hocek、Ivan Votruba、Ivana Císařová

  DOI：10.1021/jo0486342

  日期：2004.12.1

  Transition metal complex catalyzed cocyclotrimerization of 6-alkynylpurines 1 with various diynes enables the preparation of a plethora of substituted 6-arylpurines 3 in good yields. The most general catalyst for the reaction is a user-friendly system based on a nickel-phosphine complex and reductant (NiBr2(dppe)/Zn) in MeCN. The reaction conditions are compatible with various protective groups on the purine moiety (Bn, THP). As far as other potential catalysts were concerned, only CoBr(PPh3)(3) showed reasonable activity in cocyclotrimerization of alkynylpurines with dipropargyl ether. A comparison of catalytic with stoichiometric approaches and the ligand effect in the catalyst is also given. Cytostatic activity screening of title 6-arylpurines was performed and several moderately active compounds were found.