3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine | 134287-59-5

• 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: 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine
• 英文别名: 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazo[1,2-a]purine；3,9-dihydro-3-[(2-hydroxyetoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine；TRIC-ACV；TACV；3-(2-hydroxyethoxymethyl)-5H-imidazo[1,2-a]purin-9-one；3-(2-hydroxyethoxymethyl)-4H-imidazo[1,2-a]purin-9-one
• CAS: 134287-59-5
• 化学式: C₁₀H₁₁N₅O₃
• 分子量: 249.229
• InChiKey: DZPWEUBONKZVQT-UHFFFAOYSA-N

物化性质

• 沸点：
  721.0±68.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  94.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine 在 吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 3-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxymethyl]-5,7-bis-trityl-3,5-dihydro-imidazo[1,2-a]purin-9-one
  参考文献：
  名称：

  A case of unusual sterically driven C-tritylation reaction of tricyclic analogues of acyclovir

  摘要：

  3,9-Dihydro-3-[(2-hydroxyethoxy)methyl] 6-methyl-9-oxo-5H-imidazo[1,2-a]purine (1) and its silylated derivative (2) when tritylated under conditions suitable for regioselective N-5 alkylation underwent instead C-substitution to give 7-trityl (12, 3) and 7-(4-benzhydrylphenyl) (13, 4) derivatives as major and minor products, respectively. Substrates lacking 6-Me group (5, 6) yielded 5-tritylated (10, 7) and 5,7-ditritylated (11, 8) major products and 7-tritylated (9) minor product. The regioselectivity of the reaction seems to be driven mainly by steric hindrance of the 6-Me substituent. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)83029-9
• 作为产物：
  描述：

  阿昔洛韦 在 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine
  参考文献：
  名称：

  3,9-二氢-9-氧代-5H-咪唑并[1,2-a]嘌呤，阿昔洛韦和更昔洛韦的三环类似物的3-取代衍生物的合成及抗病毒活性。

  摘要：

  将9-[（2-羟基乙氧基）甲基]鸟嘌呤（阿昔洛韦，1a）和9-[（1,3-二羟基-2-丙氧基）甲基]鸟嘌呤（DHPG，更昔洛韦，1b）转化为其各自的三环衍生物3 -取代的3,9-二氢-9-氧代-5H-咪唑并[1,2-a]嘌呤2b，3a和3b。1b与溴丙酮反应后，得到6-甲基取代的化合物2b。经由1-（2,2-二乙氧基乙基）中间体4a，b的两步法对于制备在环（3a，b）中未被取代的衍生物是最有效的。新型无环核苷，特别是更昔洛韦衍生物2b，被证明对1型和2型单纯疱疹病毒，水痘带状疱疹病毒和巨细胞病毒具有显着活性。

  DOI：

  10.1021/jm00112a010

文献信息

• Unusual Tritylation Reactions of Tricyclic Analogues of Acyclovir and an Attempt to Elucidate Their Mechanism
  作者：Tomasz Goslinski、Joanna Zeidler、Bozenna Golankiewicz

  DOI：10.1002/(sici)1522-2675(20000216)83:2<373::aid-hlca373>3.0.co;2-n

  日期：2000.2.16

  In reference to our earlier observation that the 3,9-dihydro-3-[ (2-hydroxyethoxy)methyl]-6-methyl-9-oxo-5H-imidazo[1,2-a]purine (6-Me-TACV) tricyclic antiviral agent derived from acyclovir undergoes unusual C-tritylation to 7-trityl and 7-[4-(benzhydryl)phenyl] derivatives enforced by a 6-Mc substituent, we studied tritylation of 6-Ph (1a) and 6-(4-MeOPh) (1b) TACV derivatives. The treatment of 1a and 1b with TrCl in K2CO3/DMF resulted exclusively in the formation of 7-[4-(benzhydryl)phenyl] derivatives 2a, 2b, 3a, 3b, and 4a. inhibition experiments with radical scavengers DNB and DBNO indicated a single-electron-transfer (SET) mechanism for this reaction. Analogous experiments with unsubstituted TACV and 6-Me-TACV suggest that the nature of the substituent at C(6) determines the reaction mechanism. The presence of a 6-aryl substituent results in the exclusive formation of 4-(benzhydryl)phenyl derivatives via a SET mechanism. On the contrary, when C(6) is unsubstituted, trityl derivatives are the only products of the S-N reaction. In the case of 6-Me-TACV, concomitant SET and S-N mechanisms direct the reaction towards 4-(benzhydryl)phenyl and trityl products.