6-<<2-<1,3-bis(benzyloxy)-2-hydroxypropyl>>methyl>-2,4-dimethoxypyrimidine | 139871-38-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-<<2-<1,3-bis(benzyloxy)-2-hydroxypropyl>>methyl>-2,4-dimethoxypyrimidine
• 英文别名: 6-<3-benzyloxy-2-<(benzyloxy)methyl>-2-hydroxypropyl>-2,4-dimethoxypyrimidine；6-(3-benzyloxy-2-(benzyloxymethyl)-2-hydroxypropyl)-2,4-dimethoxypyrimidine；1-(2,6-Dimethoxypyrimidin-4-yl)-3-phenylmethoxy-2-(phenylmethoxymethyl)propan-2-ol
• CAS: 139871-38-8
• 化学式: C₂₄H₂₈N₂O₅
• 分子量: 424.497
• InChiKey: ZKUUQETUPPDPEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-<<2-<1,3-bis(benzyloxy)-2-hydroxypropyl>>methyl>-2,4-dimethoxypyrimidine 在 碘 、 乙酸酐 、 三氯化硼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 101.0h， 生成 2,2-bis(hydroxymethyl)-1H,2H,4H,7H-pyrimido<1,6-c><1,3>oxazine-6,8-dione
  参考文献：
  名称：

  Synthesis of anti-restricted pyrimidine acyclic nucleosides

  摘要：

  A number of pyrimidine acyclic nucleosides which are constrained in the anti conformation have been prepared via treatment of 5,6-dimethyl-2,4-dimethoxypyrimidine or 6-methyl-2,4-dimethoxypyrimidine with 1,3-bis-(benzyloxy)-2-propanone (3) to give 6-[[2-[1,3-bis(benzyloxy)-2-hydroxypropyl]]methyl]-2,4-dimethoxy-5-methylpyrimidine (5a) and 5b, respectively. Using acetic anhydride in DMSO, these compounds were converted to a 2-[[(methylthio)methyl]oxy] intermediate which was annulated to afford 2,2-bis[(benzyloxy)methyl]-8-methoxy-9-methyl-1H,2H,4H-pyrimido[1,6-c][1,3]oxazin-6-one (7a) and 7b, respectively, by using iodine in THF. Nucleophilic replacements at the 8-position and deblocking of 7a and 7b furnished the target compounds, 2,2-bis(hydroxymethyl)-9-methyl-(1H,4H,7H)-pyrimido[1,6-c][1,3]oxazine-6,8-dione (9a) and 9b, and the cytidine derivatives, 8-amino-2,2-bis(hydroxymethyl)-9-methyl-1H,4H-pyrimido[1,6-c][1,3]oxazin-6-one (12a) and 12b. Compounds 8b, 9a, 9b, 10b, 11b, 12a, and 12b were evaluated for activity against herpes viruses and human immunodeficiency virus (HIV). Compound 12a was slightly active against HIV at noncytotoxic concentrations. All other compounds were inactive at the highest concentration tested (100-mu-M).

  DOI：

  10.1021/jo00038a025
• 作为产物：
  描述：

  1,3-双(苄氧基)-2-丙醇 在 N-氯代丁二酰亚胺 、 正丁基锂 、 二甲基硫 、 三乙胺 作用下， 反应 3.42h， 生成 6-<<2-<1,3-bis(benzyloxy)-2-hydroxypropyl>>methyl>-2,4-dimethoxypyrimidine
  参考文献：
  名称：

  Synthesis of anti-restricted pyrimidine acyclic nucleosides

  摘要：

  A number of pyrimidine acyclic nucleosides which are constrained in the anti conformation have been prepared via treatment of 5,6-dimethyl-2,4-dimethoxypyrimidine or 6-methyl-2,4-dimethoxypyrimidine with 1,3-bis-(benzyloxy)-2-propanone (3) to give 6-[[2-[1,3-bis(benzyloxy)-2-hydroxypropyl]]methyl]-2,4-dimethoxy-5-methylpyrimidine (5a) and 5b, respectively. Using acetic anhydride in DMSO, these compounds were converted to a 2-[[(methylthio)methyl]oxy] intermediate which was annulated to afford 2,2-bis[(benzyloxy)methyl]-8-methoxy-9-methyl-1H,2H,4H-pyrimido[1,6-c][1,3]oxazin-6-one (7a) and 7b, respectively, by using iodine in THF. Nucleophilic replacements at the 8-position and deblocking of 7a and 7b furnished the target compounds, 2,2-bis(hydroxymethyl)-9-methyl-(1H,4H,7H)-pyrimido[1,6-c][1,3]oxazine-6,8-dione (9a) and 9b, and the cytidine derivatives, 8-amino-2,2-bis(hydroxymethyl)-9-methyl-1H,4H-pyrimido[1,6-c][1,3]oxazin-6-one (12a) and 12b. Compounds 8b, 9a, 9b, 10b, 11b, 12a, and 12b were evaluated for activity against herpes viruses and human immunodeficiency virus (HIV). Compound 12a was slightly active against HIV at noncytotoxic concentrations. All other compounds were inactive at the highest concentration tested (100-mu-M).

  DOI：

  10.1021/jo00038a025

文献信息

• Synthesis and in vitro antiproliferative evaluation of novel N-alkylated 6-isobutyl- and propyl pyrimidine derivatives
  作者：Tatjana Gazivoda Kraljević、Nataša Ilić、Višnja Stepanić、Lana Sappe、Jasna Petranović、Sandra Kraljević Pavelić、Silvana Raić-Malić

  DOI：10.1016/j.bmcl.2014.04.079

  日期：2014.7

  A series of novel N-alkylated C-6-isobutyl- or -propyl pyrimidine derivatives were synthesized and their antiproliferative effect was evaluated on a panel of tumor cell lines including leukemia cell line K562 and normal diploid human fibroblasts. N-methoxymethylated 5-methylpyrimidin-2,4-dione with di (benzyloxy)isobutyl at C-6 (14b) showed the strongest effect on the cell growth at micromolar concentrations. Mechanisms of action for the lipophilic compound 14b predicted in silico, pointed to its anticancer and antimetastatic potential exerted through inhibition of DNA or RNA polymerases and adhesion molecules. The latter mechanism has been supported in vitro for adherent tumor cell lines. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis of C-6 Pyrimidine Acyclic Nucleoside Analogs as Potential Antiviral Agents
  作者：Ling-Yih Hsu、Dean S. Wise、William M. Shannon、John C. Drach、Leroy B. Townsend

  DOI：10.1080/15257779408013263

  日期：1994.3

  A number of pyrimidine acyclic nucleosides in which the acyclic moiety is attached to the C-6 position rather than N-1 of the pyrimidine ring have been prepared. This was accomplished via treatment of lithiated 2,4-methoxy-5,6-dimethylpyrimidine, or, 2,4-dimethoxy-6-methylpyrimidine with 1,3-bis-(benzyloxy)-2-propanone, benzyl chloromethyl ether or oxirane, respectively, to give the corresponding key intermediates 6-[3-benzyloxy-2-[(benzyloxy)methyl]-2-hydroxypropyl]-2,4- dimethoxy-5-methylpyrimidine (2a), 6-[3-benzyloxy-2-[(benzyloxy)methyl]-2-hydroxypropyl]-2,4-dimethoxypyrimidine (2b), 6-(2-benzyloxyethyl)-2,4-dimethoxy-5-methylpyrimidine (3), and 2,4-dimethoxy-6-(3-hydroxypropyl)-5-methylpyrimidine (4a). After acidic hydrolysis, followed by debenzylation with boron trichloride these key intermediates were converted to the target C-6 pyrimidine acyclic derivatives. Compounds 6-8b, 11-13, 15, 16, 20, 22, 26, and 29-32 were evaluated for activity against herpes viruses and human immunodeficiency virus. None of the compounds were active against the viruses nor were they cytotoxic at the highest concentration tested.
• Synthesis of anti-restricted pyrimidine acyclic nucleosides
  作者：Ling Yih Hsu、Dean S. Wise、Louis S. Kucera、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jo00038a025

  日期：1992.6

  A number of pyrimidine acyclic nucleosides which are constrained in the anti conformation have been prepared via treatment of 5,6-dimethyl-2,4-dimethoxypyrimidine or 6-methyl-2,4-dimethoxypyrimidine with 1,3-bis-(benzyloxy)-2-propanone (3) to give 6-[[2-[1,3-bis(benzyloxy)-2-hydroxypropyl]]methyl]-2,4-dimethoxy-5-methylpyrimidine (5a) and 5b, respectively. Using acetic anhydride in DMSO, these compounds were converted to a 2-[[(methylthio)methyl]oxy] intermediate which was annulated to afford 2,2-bis[(benzyloxy)methyl]-8-methoxy-9-methyl-1H,2H,4H-pyrimido[1,6-c][1,3]oxazin-6-one (7a) and 7b, respectively, by using iodine in THF. Nucleophilic replacements at the 8-position and deblocking of 7a and 7b furnished the target compounds, 2,2-bis(hydroxymethyl)-9-methyl-(1H,4H,7H)-pyrimido[1,6-c][1,3]oxazine-6,8-dione (9a) and 9b, and the cytidine derivatives, 8-amino-2,2-bis(hydroxymethyl)-9-methyl-1H,4H-pyrimido[1,6-c][1,3]oxazin-6-one (12a) and 12b. Compounds 8b, 9a, 9b, 10b, 11b, 12a, and 12b were evaluated for activity against herpes viruses and human immunodeficiency virus (HIV). Compound 12a was slightly active against HIV at noncytotoxic concentrations. All other compounds were inactive at the highest concentration tested (100-mu-M).