5-amino-1-<<2-(acetyloxy)ethoxy>methyl>-1H-imidazole-4-carboxamide | 118966-30-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-amino-1-<<2-(acetyloxy)ethoxy>methyl>-1H-imidazole-4-carboxamide
• 英文别名: 1-<(2-Hydroxyethoxy)methyl>-5-amino-4-carbamoylimidazole；5-amino-1-[2-(acetyloxy)ethoxymethyl]-1H-imidazole-4-carboxamide；1-(2-acetoxyethoxy)methyl-5-amino-4-carbamoyl imidazole；5-amino-1-[[2-(acetyloxy)ethoxy]methyl]-1H-imidazole-4-carboxamide；2-[(5-Amino-4-carbamoylimidazol-1-YL)methoxy]ethyl acetate
• CAS: 118966-30-6
• 化学式: C₉H₁₄N₄O₄
• 分子量: 242.235
• InChiKey: SCOKPTHVGOEBIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  5-amino-1-<<2-(acetyloxy)ethoxy>methyl>-1H-imidazole-4-carboxamide 在 对甲苯磺酰氯 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-(2-acetoxyethoxy)methyl-5-methylamino-7-(N-methylthiocarbamoyl)iminoimidazo<4,5-d><1,3>thiazine
  参考文献：
  名称：

  Kaneko, Chisato; Matsumoto, Hiroatsu; Yamada, Keiko, Chemical and pharmaceutical bulletin, 1988, vol. 36, # 4, p. 1283 - 1288

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(氯甲氧基)乙酸乙酯 、 4-氨基-5-咪唑甲酰胺盐酸盐 在 氢氧化钾 作用下， 生成 5-amino-1-<<2-(acetyloxy)ethoxy>methyl>-1H-imidazole-4-carboxamide
  参考文献：
  名称：

  A simple and efficient synthesis of 9-substituted guanines. Cyclodesulfurization of 1-substituted 5-[(thiocarbamoyl)amino]imidazole-4-carboxamides under aqueous basic conditions

  摘要：

  5-Aminoimidazole-4-carboxamide (AICA) (1a) is 1-alkylated by an improved method. The resulting 5-amino-1-alkylimidazole-4-carboxamides (1b-i) are converted to the corresponding 1-alkyl-5-[(thiocarbamoyl)-amino]imidazole-4-carboxamides (3). These compounds are ring closed under alkaline conditions to 9-substituted guanines (5) in very high yields by treatment with heavy-metal salts in aqueous sodium hydroxide, or, in somewhat lower yields, by S-oxidation with hydrogen peroxide or sodium perborate in aqueous sodium hydroxide.

  DOI：

  10.1021/jo00006a033

文献信息

• Process for the preparation of 9-substituted guanine derivatives
  申请人：A/S Gea Farmaceutisk Fabrik

  公开号：US05223619A1

  公开（公告）日：1993-06-29

  A process for the preparation of 9-substituted quanine derivatives of general formula (I), in which R is C.sub.1 -C.sub.4 -alkyl optionally substituted with one or more hydroxy groups, or R is (.alpha.), benzyl, ribosyl, 2'-deoxyribosyl or (CH.sub.2).sub.n -OR.sup.1 where n is 1 or 2, and R.sup.1 is CH.sub.2 CH.sub.2 OH or (.beta.) or salts thereof, in which a 1-substituted5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide of general formula (III), where R has the same meaning as in formula (I), is cyclized: a) by treatment with a heavy metal salt of the group of Cu-, Ag-, Pb- and Hg-salts in an aqueous alkaline medium containing at least for equivalents of OH-ions at a temperature form about 0.degree. C. to the reflux temperature, or b) by treatment with a peroxy compound in an aqueous alkaline medium at a temperature of about 0.degree.-30.degree. C., whereafter (I) is isolated by treatment with a acid and, if desired, is converted into a salt. The invention further comprises intermediates for use in the preparation of the above-mentioned compounds.

  一种制备一般式（I）中的9-取代喹啉衍生物的方法，其中R是C.sub.1-C.sub.4-烷基，可选择性地取代一个或多个羟基，或R是（α）、苄基、核糖基、2'-脱氧核糖基或（CH.sub.2）.sub.n-OR.sup.1，其中n为1或2，R.sup.1为CH.sub.2CH.sub.2OH或（β）或其盐，其中一种一般式（III）的1-取代5-(硫代氨基)-1H-咪唑-4-羧酰胺在具有与公式（I）中相同含义的R的情况下被环化：a）通过在含有至少四当量OH-离子的水性碱性介质中，以从大约0°C到沸点温度的温度进行处理，处理与Cu-、Ag-、Pb-和Hg-盐组的重金属盐，或b）通过在水性碱性介质中以约0°C至30°C的温度处理过氧化物化合物处理，之后通过与酸处理分离出（I），如有需要，转化为盐。该发明还包括用于制备上述化合物的中间体。
• A series of novel acyclic nucleosides. II. Synthesis of acyclic nucleosides bearing an imidazo[4,5-<i>d</i>] [1,3]oxazine ring
  作者：Hiroatsu Matsumoto、Chisato Kaneko、Takeo Mori、Yoshihisa Mizuno

  DOI：10.1002/jhet.5570270525

  日期：1990.7

  Novel acyclic nucleosides 3a,b,c where N-1 of acyclovir is replaced by oxygen atom were prepared. Thus, 1-[(2-acetoxyethoxy)methyl]-5-amino-4-ethoxycarbonylimidazole (9) was treated with ethoxycarbonyl isothiocyanate or benzoyl isothiocyanate to give 11e,f. Methylation of the latter with methyl iodide afforded S-methylisothiourea derivative 12f which was treated with alkali and subsequently the mixture

  制备了新的无环核苷3a，b，c，其中无环鸟苷的N-1被氧原子取代。因此，用乙氧基羰基异硫氰酸酯或苯甲酰基异硫氰酸酯处理1-[（（2-乙酰氧基乙氧基）甲基] -5-氨基-4-乙氧基羰基咪唑（9），得到11e，f。后者用碘甲烷甲基化，得到S-甲基异硫脲衍生物12f，将其用碱处理，然后将混合物中和，得到5-氨基-3-[（2-羟基乙氧基）甲基] -3 H-咪唑并[4,5-]。d ] [1，3]恶嗪-7-一（3a）。化合物3b，c[（2-羟基乙氧基）甲基]咪唑-4-羧酸甲酯（ -被处理乙酸酐或丙酸酐与钠5-氨基1中得到7将其制得）通过5-氨基- [（2-乙酰氧基乙氧基）甲基] -咪唑-4-羧酰胺（5）。对无环氧嘧啶类似物的细胞毒性和针对1型单纯疱疹病毒（HSV-1）的活性的评估表明，所测试的所有衍生物均无活性，但与阿昔洛韦相比，其细胞毒性相似或更低。
• [EN] A PROCESS FOR THE PREPARATION OF 9-SUBSTITUTED GUANINE DERIVATIVES AND INTERMEDIATES FOR USE IN THE PROCESS
  申请人：A/S GEA FARMACEUTISK FABRIK

  公开号：WO1990011283A1

  公开（公告）日：1990-10-04

  (EN) A process for the preparation of 9-substituted guanine derivatives of general formula (I), in which R is C1-C4-alkyl optionally substituted with one or more hydroxy groups, or R is ($g(a)), benzyl, ribosyl, 2'-deoxyribosyl or (CH2)n-OR1 where n is 1 or 2, and R1 is CH2CH2OH or ($g(b)) or salts thereof, in which a 1-substituted 5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide of general formula (III), where R has the same meaning as in formula (I), is cyclized: a) by treatment with a heavy metal salt of the group of Cu-, Ag-, Pb- and Hg-salts in an aqueous alkaline medium containing at least four equivalents of OH-ions at a temperature from about 0°C to the reflux temperature, or b) by treatment with a peroxy compound in an aqueous alkaline medium at a temperature of about 0-30°C, whereafter (I) is isolated by treatment with acid and, if desired, is converted into a salt. The invention further comprises intermediates for use in the preparation of the above-mentioned compounds.(FR) L'invention concerne un procédé de préparation de dérivés de guanine substitués en position 9, selon la formule générale (I), dans laquelle R représente alcoyle C1-C4 facultativement remplacé par un ou plusieurs groupes hydroxy, où R représente ($g(a)), benzyle, ribosyle, 2'-désoxyribosyle ou (CH2)n-OR1 où n représente 1 ou 2, et R1 représente CH2CH2OH ou ($g(b)), ou leurs sels, dans lequel un 5-(thiocarbamoyle) amino-1H-imidazole-4-carboxamide substitué en position 1, de la formule générale (III), dans laquelle R est défini comme dans la formule (I), est cyclisé: a) par traitement à l'aide d'un sel de métal lourd du groupe composé de sels de Cu, Ag, Pb et Hg dans un milieu alcalin aqueux contenant au moins quatre équivalents d'ions OH-, à température comprise entre environ 0°C et la température de reflux ou b) par traitement à l'aide d'un composé peroxy dans un milieu alcalin aqueux à une température comprise entre environ 0 et 30°C, après quoi (I) est isolé par traitement à l'acide, et si désiré, est transformé en un sel. L'invention comprend en outre des intermédiaires utilisés dans la préparation des composés précités.

  一种制备9-取代鸟嘌呤衍生物的方法，其一般式为（I），其中R是C1-C4烷基，可选择地取代一个或多个羟基，或者R是（$g(a)），苄基，核糖基，2'-去氧核糖基或（CH2）n-OR1，其中n为1或2，R1为CH2CH2OH或（$g(b)）或其盐，其中通过将一种一般式（III）的1-取代5-（硫氨酰）氨基-1H-咪唑-4-羧酰胺，其中R与公式（I）中的含义相同，进行环化：a）通过在含有至少四当量OH-离子的水性碱性介质中，用Cu-、Ag-、Pb-和Hg-盐中的重金属盐处理，在0°C至沸点温度范围内进行，或b）通过在水性碱性介质中使用过氧化物化合物，在约0-30°C的温度下进行处理，然后通过酸处理分离出（I），如有需要，转化为盐。该发明还包括用于制备上述化合物的中间体。
• 5-Cyanoamino-4-imidazolecarboxamide and Nitrosative Guanine Deamination:  Experimental Evidence for Pyrimidine Ring-Opening during Deamination
  作者：Ming Qian、Rainer Glaser

  DOI：10.1021/ja0389523

  日期：2004.3.3

  5-Cyanoamino-4-imidazolecarboxamide 4a (R = CH2-O-CH2-CH2-OH) has been synthesized, purified, and fully characterized by MS, MS/MS, HRMS, IR spectroscopy, and by 1H and 13C NMR spectroscopy. It is shown that cyclization of 4a yields the guanine 6a and the isoguanine 12a. Our findings provide experimental evidence in support of our hypothesis that the formation of oxanine and xanthine in nitrosative guanine deamination may proceed via pyrimidine ring-opened intermediates. The observed formation of 6a from the amide 4a (XH2 = NH2) shows that, in analogy, oxanine can be formed from 3 (XH = OH). The formation of 12a from 4a reveals for the first time the possibility that oxanine might be formed by a second pathway that involves electrocyclic reaction of 3. Finally, the new chemistry suggests the possibility for a new dG-to-dG cross-link.
• ALNEDE, VZHUSTORGE;SLAUSEN, FINN PRIESS;JUHL-CHRISTENSEN, JZHUSTORGEN;MSS+, J. ORG. CHEM., 56,(1991) N, C. 2139-2143
  作者：ALNEDE, VZHUSTORGE、SLAUSEN, FINN PRIESS、JUHL-CHRISTENSEN, JZHUSTORGEN、MSS+

  DOI：——

  日期：——