1-(β-D-erythro-Pentofuranosyl)-4-(1,2,4-triazol-1-yl)-2(1H)-pyrimidinone | 104105-76-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(β-D-erythro-Pentofuranosyl)-4-(1,2,4-triazol-1-yl)-2(1H)-pyrimidinone
• 英文别名: 4-triazolyl-1-(β-D-ribofuranosyl)-2(1H)-pyrimidinone；4-(1,2,4-triazol-1-yl)-1-(β-D-ribofuranosyl)pyrimidin-2(1H)-one；1-(β-D-ribofuranosyl)-4-(1,2,4-triazol-1-yl)pyrimidin-2-one；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-4-(1,2,4-triazol-1-yl)pyrimidin-2-one；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(1,2,4-triazol-1-yl)pyrimidin-2-one
• CAS: 104105-76-2
• 化学式: C₁₁H₁₃N₅O₅
• 分子量: 295.255
• InChiKey: TYXGGRRHTHFYJA-PEBGCTIMSA-N

物化性质

• 沸点：
  670.6±65.0 °C(Predicted)
• 密度：
  1.89±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  133
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(β-D-erythro-Pentofuranosyl)-4-(1,2,4-triazol-1-yl)-2(1H)-pyrimidinone 在 盐酸羟胺 、 sodium acetate 作用下， 反应 14.0h， 以76%的产率得到1-[(2R,3R,4S,5R)-3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-4-(羟基氨基)嘧啶-2-酮
  参考文献：
  名称：

  从胞苷到MK-4482（EIDD-2801）的简明路线

  摘要：

  到MK-4482（EIDD-2801，A两步路线1）的开发是由酯化和胞苷的hydroxamination的。选择性酰化和直接胺化消除了对保护基团和活化基团的需要，总收率为75％，比报道的17％的收率有明显提高。步骤数从五个转换减少到两个，并且将昂贵的尿苷替换为更多可用的胞苷。

  DOI：

  10.1039/d0cc05944g
• 作为产物：
  描述：

  尿嘧啶核苷 在 吡啶 、 silica gel 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 1-(β-D-erythro-Pentofuranosyl)-4-(1,2,4-triazol-1-yl)-2(1H)-pyrimidinone
  参考文献：
  名称：

  Synthesis and anti-HIV activity of C4-modified pyrimidine nucleosides

  摘要：

  One-pot syntheses provided a series of triazole- and pentafluorophenyloxy-substituted pyrimidine nucleosides. Most of the compounds in the series displayed anti-HIV activities but none as potent as AZT 2. 1-(beta-D-Erythro-pentofuranosyl)-4-pentafluorophenyloxy-2(1H)-pyr imidinone 14 was the most potent and the most selective compound in the series with EC50 = 1.6 microM.

  DOI：

  10.1016/s0014-827x(98)00107-4

文献信息

• Direct synthesis, substitution, and structure of 1-(2′-deoxyβ-D-erythro-pentofuranosyl)-4-pentafluorophenylpyrimidin-2H-one
  作者：Mark P. Wallis、Ian D. Spiers、Carl H. Schwalbe、William Fraser

  DOI：10.1016/0040-4039(95)00587-3

  日期：1995.5

  Direct methods have been developed to access the title nucleoside 1 from 2′-deoxyuridine (dU). The C-4 pentafluorophenyl group of 1 is readily displaced by amine nucleophiles forming N-4 substituted cytosines in good to excellent yields.

  已经开发了直接方法以从2'-脱氧尿苷（dU）访问标题核苷1。的C-4五氟苯基1可容易地通过形成良好N-4取代的胞嘧啶到优异的产率胺亲核试剂置换。
• Studies on Nucleosides and Nucleotides. XII. Carbon-Chain Extension at 5′-Position of Ribonucleosides
  作者：Junji Kimura、Hideyuki Kobayashi、Osamu Miyahara、Oyo Mitsunobu

  DOI：10.1246/bcsj.59.869

  日期：1986.3

  presence of diethyl azodicarboxylate and triphenylphosphine selectively at the 5′-position to give the corresponding 4-(nucleosid-5′-yl-aci-nitro)-2,6-di-t-butylcyclohexa-2,5-dienone (aci-nitro ester of nucleoside) in 39–72% yields along with varied amounts of 5′-deoxy-5′-[N,N′-bis(ethoxycarbonyl)hydrazino]nucleosides. By comparison of the reactions of pyrimidine nucleosides having free 2′- and 3′-hydroxyl

  2,6-二叔丁基-4-硝基苯酚与 O2-甲基尿苷、N3-甲基尿苷或 4-三唑基-1-(β-D-呋喃核糖基)-2(1H)-嘧啶酮在偶氮二甲酸二乙酯和三苯基膦选择性地在 5'-位得到相应的 4-(核苷-5'-基-酰基-硝基)-2,6-二-叔丁基环六-2,5-二烯酮 (核苷的酰基-硝基酯) 39–72% 的产率以及不同数量的 5'-deoxy-5'-[N,N'-bis(ethoxycarbonyl)hydrazino] 核苷。通过比较具有游离 2'-和 3'-羟基的嘧啶核苷与其 2',3'-O-异亚丙基衍生物的反应，aci-nitxo酯与 5'-deoxy-5'-肼基核苷受保护基团以及将偶氮二羧酸二乙酯添加到其他反应物溶液所需的时间的影响。同样，N1，N6，2'3'-O-四苯甲酰腺苷以 83% 的产率提供了预期的酸硝基酯。制备的乙酰硝基酯与稳定的正膦如（乙氧基...
• A High‐Yielding Synthesis of EIDD‐2801 from Uridine**
  作者：Alexander Steiner、Desiree Znidar、Sándor B. Ötvös、David R. Snead、Doris Dallinger、C. Oliver Kappe

  DOI：10.1002/ejoc.202001340

  日期：2020.11.22

  An improved protocol was developed for the synthesis of EIDD‐2801, which is currently in Phase II clinical trials for the treatment of COVID‐19. The process employs uridine as starting material and proceeds through triazolation, one‐pot acetonide protection/esterification and telescoped hydroxyamination/continuous flow acetonide deprotection.

  针对 EIDD-2801 的合成开发了改进的方案，该药物目前正处于治疗 COVID-19 的 II 期临床试验中。该工艺以尿苷为起始原料，经过三唑化、一锅丙酮化物保护/酯化和伸缩式羟胺化/连续流丙酮化物脱保护。
• Nucleic Acid Related Compounds. 87. Nucleophilic Functionalization of Cytidine and 2'-Deoxycytidine Derivatives via Elaboration of the 4-Amino Group into a Readily Displaced 1,2,4-Triazol-4-yl Substituent
  作者：Robert W. Miles、Vicente Samano、Morris J. Robins

  DOI：10.1021/jo00126a078

  日期：1995.10
• Convenient Intermediates for the Preparation of<i>C</i>-4 Modified Derivatives of Pyrimidine Nucleosides
  作者：Anwar Miah、Colin B. Reese、Quanlai Song

  DOI：10.1080/07328319708002521

  日期：1997.1

  4-(4-Nitrophenoxy)-1-(beta-D-ribofuranosyl)pyrimidin-2(1H)-one 15, 5-methyl-4-(1,2,4-triazol-1-yl)-1-(beta-D-2-deoxyribofuranosyl 7a and 4-(4-nitrophenoxy)-1-(beta-D-2-deoxyribofuranosyl)pyrimidin-2(1H)-one 17a, respectively, have been prepared and are recommended as reactive intermediates for the preparation of derivatives of uridine, thymidine and 2'-deoxyuridine which are modified at C-4.