6-pentyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 6-pentyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
• 英文别名: 6-pentylfuro[2,3-d]pyrimidin-2-one；6-pentyl-3H-furo[2,3-d]pyrimidin-2-one；6-pentyl-1H-furo[2,3-d]pyrimidin-2-one
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.244
• InChiKey: FGMSBPRSOVQRQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-pentyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one 、 氯甲基甲基醚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以58%的产率得到3-(methoxymethyl)-6-pentylfuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Efficient palladium-mediated or base-induced 5-endo-dig cyclisation of C5-alkynylated pyrimidine derivatives: conventional and microwave-assisted synthesis of novel furo[2,3-d]pyrimidines

  摘要：

  A series of the novel 5-alkynyl- and furo[2,3-d]pyrimidine derivatives in which the sugar moiety is replaced by a methoxymethyl (MOM) group is synthesised using the Sonogashira cross-coupling reaction under both conventional and microwave conditions, in good to excellent yields. The 5-endo-dig cyclisation of 5-alkynylpyrimidine derivatives promoted by a Pd-catalyst or base gives the corresponding furo[2,3-d]pyrimidines in good yields. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.07.068
• 作为产物：
  描述：

  5-(heptyn-1-yl)uracil 在 copper(l) iodide 、 三乙胺 作用下， 以 甲醇 为溶剂， 以64%的产率得到6-pentyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Inhibition of Mycobacterial Replication by Pyrimidines Possessing Various C-5 Functionalities and Related 2′-Deoxynucleoside Analogues Using in Vitro and in Vivo Models

  摘要：

  Tuberculosis (TB) has become an increasing problem since the emergence of human immunodeficiency virus and increasing appearance of drug-resistant strains. There is an urgent need to advance our knowledge and discover a new class of agents that are distinct than current therapies. Antimycobacterial activities of several 5-alkyl, 5-alkynyl, furanopyrimiclines and related 2'-deoxynucleosides were investigated against Mycobacterium tuberculosis. Compounds with 5-arylalkynyl substituents (23-26,33, 35) displayed potent in vitro antitubercular activity against Mycobacterium bovis and Mycobacterium tuberculosis. The in vivo activity of 5-(2-pyridylethyny1)-uracil (26) and its 2'-deoxycytidine analogue, 5-(2-pyridylethynyI)-2'-deoxycytidine (35), was assessed in BA LB/c mice infected with M. tuberculosis (H 37 Ra). Both compounds 26 and 35 given at a dose of 50 mg/kg for 5 weeks showed promising in vivo efficacy in a mouse model, with the 2'-deoxycytidine derivative being more effective than the uracil analogue and a reference drug o-cycloserine. These data indicated that there is a significant potential in this class of compounds.

  DOI：

  10.1021/jm100568q

文献信息

• Synthesis and biological evaluation of 5-(alkyn-1-yl)-1-(<i>p</i>-toluenesulfonyl)uracil derivatives
  作者：Zlatko Janeba、Jan Balzarini、Graciela Andrei、Robert Snoeck、Erik De Clercq、Morris J Robins

  DOI：10.1139/v06-041

  日期：2006.4.1

  Sonogashira coupling of 5-iodouracil (2) and trimethylsilylacetylene gave 5-(trimethylsilylethynyl)uracil (3), which was deprotected to give 5-ethynyluracil (4). Copper(I)-catalyzed cyclization of 4 gave furo[2,3-d]pyrimidin-2(3H)-one (5). Tosylation of 2 and 4 gave the 1-(p-toluenesulfonyl) derivatives 6 and 7, respectively. The tosylated compound 6 and trimethylsilylacetylene did not undergo Sonogashira coupling, and copper(I)-catalyzed cyclization of 7 did not occur. Coupling of 2 with several terminal alkynes gave 5-(alkyn-1-yl)uracil derivatives (9), which underwent tosylation to produce the targeted 5-(alkyn-1-yl)-1-(p-toluenesulfonyl)uracil compounds (11). Copper(I)-catalyzed cyclization of 9 gave the respective furopyrimidines (10) in low yields. Again, cyclization did not occur with the tosyl derivatives (11). Activity against varicella-zoster virus (VZV) was observed with longer-chain analogues of 9 and 11, and compound 7 showed activity against human cytomegalovirus (HCMV) at near cytotoxic levels.Key words: antiviral screening, furo[2,3-d]pyrimidin-2(3H)-one derivatives, Sonogashira coupling, 1-(p-toluenesulfonyl)pyrimidine derivatives.

  5-iodouracil (2) 与三甲基硅基乙炔的 Sonogashira 偶联得到 5-(三甲基硅乙炔基)脲嘧啶 (3)，经脱保护后得到 5-乙炔基脲嘧啶 (4)。在铜（I）催化下，4 环化得到呋喃并[2,3-d]嘧啶-2(3H)-酮（5）。对 2 和 4 进行对甲苯磺酰基化反应，分别得到 1-（对甲苯磺酰基）衍生物 6 和 7。对甲苯磺酰化的化合物 6 和三甲基硅基乙炔没有发生 Sonogashira 偶联反应，也没有发生铜（I）催化的 7 环化反应。2 与几种末端炔烃偶联后得到 5-(炔-1-基)尿嘧啶衍生物 (9)，这些衍生物经过对甲苯磺酰基化反应生成目标 5-(炔-1-基)-1-(对甲苯磺酰基)尿嘧啶化合物 (11)。在铜(I)催化下，9 的环化反应以低产率生成了相应的呋喃嘧啶（10）。同样，甲苯磺酰基衍生物也没有发生环化反应（11）。9 和 11 的长链类似物对水痘-带状疱疹病毒（VZV）具有活性，化合物 7 对人类巨细胞病毒（HCMV）具有接近细胞毒性水平的活性。
• Inhibition of Mycobacterial Replication by Pyrimidines Possessing Various C-5 Functionalities and Related 2′-Deoxynucleoside Analogues Using in Vitro and in Vivo Models
  作者：Naveen C. Srivastav、Dinesh Rai、Christopher Tse、B. Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1021/jm100568q

  日期：2010.8.26

  Tuberculosis (TB) has become an increasing problem since the emergence of human immunodeficiency virus and increasing appearance of drug-resistant strains. There is an urgent need to advance our knowledge and discover a new class of agents that are distinct than current therapies. Antimycobacterial activities of several 5-alkyl, 5-alkynyl, furanopyrimiclines and related 2'-deoxynucleosides were investigated against Mycobacterium tuberculosis. Compounds with 5-arylalkynyl substituents (23-26,33, 35) displayed potent in vitro antitubercular activity against Mycobacterium bovis and Mycobacterium tuberculosis. The in vivo activity of 5-(2-pyridylethyny1)-uracil (26) and its 2'-deoxycytidine analogue, 5-(2-pyridylethynyI)-2'-deoxycytidine (35), was assessed in BA LB/c mice infected with M. tuberculosis (H 37 Ra). Both compounds 26 and 35 given at a dose of 50 mg/kg for 5 weeks showed promising in vivo efficacy in a mouse model, with the 2'-deoxycytidine derivative being more effective than the uracil analogue and a reference drug o-cycloserine. These data indicated that there is a significant potential in this class of compounds.
• Efficient palladium-mediated or base-induced 5-endo-dig cyclisation of C5-alkynylated pyrimidine derivatives: conventional and microwave-assisted synthesis of novel furo[2,3-d]pyrimidines
  作者：Tatjana Gazivoda Kraljević、Andrea Bistrović、Matea Dedić、Sandra Kraljević Pavelić、Mirela Sedić、Silvana Raić-Malić

  DOI：10.1016/j.tetlet.2012.07.068

  日期：2012.9

  A series of the novel 5-alkynyl- and furo[2,3-d]pyrimidine derivatives in which the sugar moiety is replaced by a methoxymethyl (MOM) group is synthesised using the Sonogashira cross-coupling reaction under both conventional and microwave conditions, in good to excellent yields. The 5-endo-dig cyclisation of 5-alkynylpyrimidine derivatives promoted by a Pd-catalyst or base gives the corresponding furo[2,3-d]pyrimidines in good yields. (C) 2012 Elsevier Ltd. All rights reserved.