6-cyano-9-(4-methoxyphenyl)-9H-purine | 403796-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-cyano-9-(4-methoxyphenyl)-9H-purine
• 英文别名: 9-(4-Methoxy-phenyl)-9h-purine-6-carbonitrile；9-(4-methoxyphenyl)purine-6-carbonitrile
• CAS: 403796-42-9
• 化学式: C₁₃H₉N₅O
• 分子量: 251.247
• InChiKey: VQJPWKSOBVORJG-UHFFFAOYSA-N

物化性质

• 沸点：
  491.9±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  76.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-cyano-9-(4-methoxyphenyl)-9H-purine 在 氨 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 氯仿 为溶剂， 反应 36.0h， 以64%的产率得到N-(4-methoxyphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
  参考文献：
  名称：

  7,8-二氢嘧啶并[5,4-d]嘧啶的高效合成

  摘要：

  7,8-二氢嘧啶并[5,4-d]嘧啶4通过用伯胺处理9-芳基-6-氰基嘌呤1以非常好的产率分离。胺对嘌呤环的 C8 进行亲核攻击，随后咪唑单元开环，随后涉及新形成的脒基和嘧啶环中的氰基取代基的分子内环化产生 7,8-二氢嘧啶[5， 4-d]嘧啶结构 4. 当使用氨代替伯胺时，由于互变异构平衡，化合物 4 进一步快速反应以提供更稳定的嘧啶并 [5,4-d] 嘧啶 6。当嘌呤 1a 和过量的乙醇胺在甲醇中回流加热时，​​芳香结构 6 也被分离出来，以及在室温下，在催化量的 DBU 存在下，将嘌呤 1c 与过量的（4-甲氧基苯基）肼在 THF 中混合。在这两种情况下，产物都是通过前体 7,8-二氢嘧啶并[5,4-d]嘧啶 4 的 Dimroth 重排形成的。 (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

  DOI：

  10.1002/ejoc.200600883
• 作为产物：
  描述：

  原甲酸三乙酯 、 5-amino-1-(4'-methoxyphenyl)-4-(cyanoformimidoyl)imidazole 在 硫酸 作用下， 以 乙腈 为溶剂， 以91%的产率得到6-cyano-9-(4-methoxyphenyl)-9H-purine
  参考文献：
  名称：

  Facile synthesis of 6-cyano-9-substituted-9H-purines and their ring expansion to 8-(arylamino)-4-imino-3-methylpyrimidino[5,4-d]pyrimidines

  摘要：

  6-氰基-9-取代-9H-嘌呤通过将三乙基正形酸酯或三乙基正丙酸酯与相应的(Z)-N1-(芳基或苄基)-N2-(2-氨基-1,2-二氰基乙烯)氨基甲酰胺在回流条件下反应制备，反应产率较高。这些氰基嘌呤与水合的甲胺反应时，生成了8-(芳氨基)-4-亚氨基-3-甲基吡啶并[5,4-d]吡啶，反应发生在咪唑环上，而不是对6-氰基进行加成。所有化合物均已通过光谱数据得到全面表征，并对8-(4-甲氧基苯胺基)-4-亚氨基-3-甲基吡啶并[5,4-d]吡啶进行了X射线晶体结构的测定。

  DOI：

  10.1039/b106539b

文献信息

• Efficient conversion of 6-cyanopurines into 6-alkoxyformimidoylpurines
  作者：M. Alice Carvalho、Teresa M. Esteves、M. Fernanda Proença、Brian L. Booth

  DOI：10.1039/b400171k

  日期：——

  An extremely simple method for the selective synthesis of 9-aryl and 9-alkyl 6-alkoxy or 6-alkoxyformimidoylpurines from the corresponding 6-cyanopurines is described. The reaction is carried out with methanol or ethanol in the presence of DBU. At room temperature, nucleophilic attack by the primary alcohol occurs selectively on the cyano carbon atom, leading to 6-alkoxyformimidoylpurines in good yields. Heating the reaction mixture at a temperature greater than or equal to 78 °C leads to nucleophilic substitution of the substituent in the 6-position by the alkoxy group, generating the corresponding 6-alkoxypurines, also in excellent yields. The 6-alkoxyformimidoylpurines were used as intermediates in the synthesis of 6-carboxamidinopurines by reaction with methylamine (for 9-methylpurine 5a) or methyl ammonium chloride (for 9-arylpurines 5b and 5c).

  本文介绍了一种极其简单的方法，可从相应的 6-氰基嘌呤中选择性合成 9-芳基和 9-烷基 6-烷氧基或 6-烷氧基甲酰亚胺基嘌呤。反应是在 DBU 存在下与甲醇或乙醇进行的。在室温下，伯醇的亲核作用选择性地作用于氰基碳原子，从而生成产率较高的 6-烷氧基甲酰亚胺基嘌呤。在高于或等于 78 °C 的温度下加热反应混合物，6-位上的取代基就会被烷氧基亲核取代，生成相应的 6-烷氧基嘌呤，收率也非常高。这些 6-烷氧基甲酰亚胺基嘌呤被用作中间体，通过与甲胺（9-甲基嘌呤 5a）或甲基氯化铵（9-芳基嘌呤 5b 和 5c）反应合成 6-甲脒基嘌呤。
• A Mild Approach to the Synthesis of 4-Amino-8-(arylamino)pyrimido[5,4-d]pyrimidine 3-Oxides
  作者：Alexandra Ribeiro、M. Alice Carvalho、M. Fernanda Proença

  DOI：10.1002/ejoc.200900216

  日期：2009.10

  The reaction of benzylhydroxylamine with 6-cyanopurines leads to the formation of 7-benzyloxy-8-imino-7,8-dihydropyrimido[5,4-d]pyrimidines. The hydrochloride of these compounds, isolated upon addition of aqueous hydrochloric acid, is a convenient precursor of the pyrimido[5,4-d]pyrimidine N-oxides when a suspension of the salt is refluxed in ethanol or acetonitrile. Refluxing a solution of the same

  苄基羟胺与 6-氰基嘌呤的反应导致形成 7-benzyloxy-8-imino-7,8-dihydropyrimido[5,4-d]pyrimidines。当盐的悬浮液在乙醇或乙腈中回流时，这些化合物的盐酸盐在加入盐酸水溶液后分离，是嘧啶并[5,4-d]嘧啶N-氧化物的方便前体。回流相同盐的乙醇溶液，产生 Dimroth 重排产物。（© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009）
• Synthesis and in vitro evaluation of substituted pyrimido[5,4-d]pyrimidines as a novel class of Antimycobacterium tuberculosis agents
  作者：Ana H. Bacelar、M. Alice Carvalho、M. Fernanda Proença

  DOI：10.1016/j.ejmech.2010.03.047

  日期：2010.7

  Novel pyrimido[5,4-d]pyrimidines were efficiently synthesized and evaluated for antibacterial activity against Mycobacterium tuberculosis strain H(37)Rv. This new structural class of compounds showed high activity against the bacilli. The activity depends on the substituents present in N-3 and C-8 of the pyrimido[5,4-d]pyrimidine core. Compounds having a 4-MeOC(6)H(4), a Ph or a 4-FC(6)H(4) group as the substituent on C-8 and a 4'-pyridinyl, a Ph or 2'-furyl group as the substituent on N-3 were active. The highest activity was registered for compounds having 4-FC(6)H(4) or 4-MeOC(6)H(4) as substituents in C-8 and a heteroaryl group as substituent in N-3. The new compounds showed high potency and promising antitubercular activity, as is the case of N[8-[(4-fluorophenyl)amino]-4-iminopyrimido[5,4-d]pyrimidin-3(4H)-yl]isonicotinamide with an IC(90) = 3.58 mu g/mL, and should be regarded as new hits for further development as a novel class of Antimycobacterium tuberculosis agents. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Reactions of 9-Aryl-6-cyanopurines with Primary Amines
  作者：Amal Al-Azmi、K. Anita Kumari

  DOI：10.3987/com-09-11713

  日期：——

  Two structural isomers (9-aryl-6-cyanopurines and imidazole-4,5-dicarbonitriles) were isolated from the reaction of (Z)-Nl-aryl-N2-(2-amino-l,2-dicyanovinyl)formamidines with triethyl orthoacetate or propionate. On the other hand, 9-aryl-6-cyanopurines were the only product, when triethyl orthoformate was used. The reaction of 9-aryl-6-cyanopurines with hydroxylamine hydrochloride in dichloromethane/ethanol at room temperature furnished 6-amidinopurines, while reaction with primary amines afforded pyrimido[5,4-d]pyrimidines. In addition, 9-aryl-6-cyanopurines reacted with hydrazine monohydrate under mild conditions to give 4-imino-N8-arylpyrimido[5,4-d]pyrimidines. The latter furnished novel pyrimido[4,5-e][1,2,4]triazolo[1,5-c]pyrimidines when refluxed with an excess of triethyl orthoesters. The new compounds were fully characterized and single crystal X-ray analyses have been carried out on 9-(4-methoxyphenyl)-9H-purine-6-carboximidamide and 2-methyl1-[(E)-p-tolyliminomethyl]-1H-imidazole-4,5-dicarbonitrile.
• Unexpected Behaviour of 6-Cyanopurines Towards Secondary Amines
  作者：Amal Al-Azmi、K. Anita Kumari

  DOI：10.3987/com-13-12695

  日期：——

  Reaction of 6-cyanopurines with excess dimethylamine and excess piperidine at room temperature or by reflux-respectively-yielded a mixture of 6-purinecarboximidamides and N,N-dialkylpurines or piperidin-1-yl(purin-6-yl)methanimine and (piperidin-1-yl)-9H-purine, respectively. 6-Purinecarboximidamides were initially formed from the reaction, whereas N,N-dialkylpurines were detected in the mixture 30 min afterward. Both purines appeared to be generated from different mechanistic pathways.