2-amino-6-chloro-9-<(2-hydroxyethoxy)methyl>-9H-purine | 81777-49-3

• 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: 2-amino-6-chloro-9-<(2-hydroxyethoxy)methyl>-9H-purine
• 英文别名: 2-amino-6-chloro-9-<(2-hydroxyethoxy)methyl>purine；9-<(2-hydroxyethoxy)methyl>-2-amino-6-chloropurine；2-((2-amino-6-chloro-9H-purin-9-yl)methoxy)ethanol；2-amino-6-chloro-9-(2-hydroxyethoxymethyl)purine；9-((2-Hydroxyethoxy)methyl)-2-amino-6-chloropurine；2-[(2-amino-6-chloropurin-9-yl)methoxy]ethanol
• CAS: 81777-49-3
• 化学式: C₈H₁₀ClN₅O₂
• 分子量: 243.653
• InChiKey: BSFGGUCAZGXDGK-UHFFFAOYSA-N

物化性质

• 沸点：
  555.2±60.0 °C(Predicted)
• 密度：
  1.75±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-amino-6-chloro-9-<(2-hydroxyethoxy)methyl>-9H-purine 在 磷酸 、 adenosine deaminase 作用下， 以89%的产率得到阿昔洛韦
  参考文献：
  名称：

  Nucleic acid related compounds. 37. Convenient and high-yield syntheses of N-[(2-hydroxyethoxy)methyl] heterocycles as "acyclic nucleoside" analogues

  摘要：

  1,3-二氧杂环戊烷与乙酰溴反应，得到（2-乙酰氧乙氧基）溴甲烷（2a），收率为88%。多种嘧啶和三种氯代嘌呤经过三甲基硅基化处理后与2a偶联。相应的N-1和N-9烷基化产物（收率为79-89%）经去乙酰化处理后得到N-[(2-羟基乙氧基)甲基]杂环化合物。2-氨基-6-取代嘌呤衍生物的6-氨基或6-氯取代基经过腺苷脱氨酶顺利水解，得到9-[(2-羟基乙氧基)甲基]鸟苷（无环鸟苷），这是一种有效的抗病毒药物。

  DOI：

  10.1139/v82-081
• 作为产物：
  描述：

  双乙酰阿昔洛韦 在 2,4,6-三甲基吡啶 、 甲醇 、 四乙基氯化铵 、 氨 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 5.17h， 生成 2-amino-6-chloro-9-<(2-hydroxyethoxy)methyl>-9H-purine
  参考文献：
  名称：

  A New Synthesis of Acyclovir Prodrugs.N ²-Acetylacyclovir and 6-Deoxyacyclovir

  摘要：

  9-(2-乙酰氧基乙氧基)-2-氨基-1,9-二氢-6H-嘌呤-6-酮(1b)和 2-乙酰氨基-9-(2-羟基乙氧基)甲基-1、9-[(2-acetoxyethoxy)methyl] -2-乙酰氨基-1,9-二氢-6H-嘌呤-6-酮 (1a)采用区域选择性脱乙酰化程序制备出 9-[(2-乙酰氧基乙氧基)甲基] -2-乙酰氨基-1,9-二氢-6H-嘌呤-6-酮 (N2-acetylacyclovir 3)。化合物 1a 和 1b 经磷酰氯氯化后，分别得到 9-[(2-乙酰氧乙氧基)甲基]-2-乙酰氨基-6-氯-9H-嘌呤（4a）及其 N2-脱乙酰基对应物（4b）。随后在催化转移氢解条件下对 4a 和 4b 进行还原脱氯，再进行脱保护处理，可得到 6-脱氧-阿昔洛韦（7），总收率很高。

  DOI：

  10.1055/s-1990-26904

文献信息

• Synthesis and evaluation of 2-amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine esters as potential prodrugs of acyclovir
  作者：Dae-Kee Kim、Namkyu Lee、Guang-Jin Im、Hun-Taek Kim、Key H. Kim

  DOI：10.1016/s0968-0896(98)80026-6

  日期：1998.12

  2-Amino -6-fluoro-9-(2-hydroxyethoxymethyl)purine (2) and its ester derivatives 4a-d were synthesized as potential prodrugs of acyclovir, and were evaluated for their oral acyclovir bioavailability in rats and in vivo antiviral efficacy in HSV-1-infected mice. Treatment of 2-amino-6-chloro-9-(2-hydroxyethoxymethy (3) with trimethylamine in THF/DMF (4:1) followed by a reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2 in 78% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O, (EtCO)(2)O, (n-PrCO)(2)O, or (i-PrCO)(2)O) in DMF in the presence of a catalytic amount of DMAP at room temperature produced the esters 4a-d in 90-98% yields. Of the prodrugs tested in rats, the isobutyrate 4d achieved the highest mean urinary recovery of acyclovir (51%) that is 5.7-fold higher than that of acyclovir (9%) and comparable to that of valacyclovir (50%). The prodrug 4d protected dose-dependently the mortality of HSV-1-infected mice, and the group treated with 4d at a dose of 400 mg/kg showed the longest mean survival day (14.6 +/- 3.1 days) (mean +/- S.D.). (C) 1998 Elsevier Science Ltd. All rights reserved.
• STIMAC, ANTON;KOBE, JOZE, LAB. MICROCOMPUT., 9,(1990) N, C. 461-464
  作者：STIMAC, ANTON、KOBE, JOZE

  DOI：——

  日期：——
• Nucleic acid related compounds. 37. Convenient and high-yield syntheses of <i>N</i>-[(2-hydroxyethoxy)methyl] heterocycles as "acyclic nucleoside" analogues
  作者：Morris J. Robins、Peter W. Hatfield

  DOI：10.1139/v82-081

  日期：1982.3.1

  Treatment of 1,3-dioxolane with acetyl bromide gave (2-acetoxyethoxy)methyl bromide (2a) in 88% yield. A number of pyrimidines and three chloropurines were trimethylsilylated and coupled with 2a. The respective N-1 and N-9 alkylated products (obtained in 79–89% yields) were deacetylated to give N-[(2-hydroxyethoxy)methyl] heterocycles. The 6-amino or 6-chloro substituent of the 2-amino-6-substituted-purine derivatives was hydrolyzed smoothly with adenosine deaminase to give 9-[(2-hydroxyethoxy)methyl]guanine (acycloguanosine), the potent antiviral agent.

  1,3-二氧杂环戊烷与乙酰溴反应，得到（2-乙酰氧乙氧基）溴甲烷（2a），收率为88%。多种嘧啶和三种氯代嘌呤经过三甲基硅基化处理后与2a偶联。相应的N-1和N-9烷基化产物（收率为79-89%）经去乙酰化处理后得到N-[(2-羟基乙氧基)甲基]杂环化合物。2-氨基-6-取代嘌呤衍生物的6-氨基或6-氯取代基经过腺苷脱氨酶顺利水解，得到9-[(2-羟基乙氧基)甲基]鸟苷（无环鸟苷），这是一种有效的抗病毒药物。
• A New Synthesis of Acyclovir Prodrugs.<i>N</i> ²-Acetylacyclovir and 6-Deoxyacyclovir
  作者：Anton Štimac、Jože Kobe

  DOI：10.1055/s-1990-26904

  日期：——

  9-(2-Acetoxyethoxy)-2-amino-1,9-dihydro-6H-purin-6-one (1b) and 2-acetylamino-9-(2-hydroxyethoxy)methyl-1,9-dihydro-6H-purin-6-one (N2-acetylacyclovir 3) were prepared from 9-[(2-acetoxyethoxy)methyl] -2-acetylamino-1,9-dihydro-6H-purin-6-one (1a) using regioselective deacetylation procedures. Compounds 1a and 1b were chlorinated with phosphoryl chloride to give 9-[(2-acetoxyethoxy)methyl]-2-acetylamino-6-chloro-9H-purine (4a) and its N2-deacetylated counterpart (4b), respectively. Subsequent reductive dechlorination of 4a and 4b under conditions of catalytic transfer hydrogenolysis followed by deprotection afforded 6-deoxy-acyclovir (7) in a good overall yield.

  9-(2-乙酰氧基乙氧基)-2-氨基-1,9-二氢-6H-嘌呤-6-酮(1b)和 2-乙酰氨基-9-(2-羟基乙氧基)甲基-1、9-[(2-acetoxyethoxy)methyl] -2-乙酰氨基-1,9-二氢-6H-嘌呤-6-酮 (1a)采用区域选择性脱乙酰化程序制备出 9-[(2-乙酰氧基乙氧基)甲基] -2-乙酰氨基-1,9-二氢-6H-嘌呤-6-酮 (N2-acetylacyclovir 3)。化合物 1a 和 1b 经磷酰氯氯化后，分别得到 9-[(2-乙酰氧乙氧基)甲基]-2-乙酰氨基-6-氯-9H-嘌呤（4a）及其 N2-脱乙酰基对应物（4b）。随后在催化转移氢解条件下对 4a 和 4b 进行还原脱氯，再进行脱保护处理，可得到 6-脱氧-阿昔洛韦（7），总收率很高。