2,4-dimethoxy-6-(2-hydroxyethyl)-5-methylpyrimidine | 156569-32-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,4-dimethoxy-6-(2-hydroxyethyl)-5-methylpyrimidine
• 英文别名: 2,4-dimethoxy-5-methyl-6-(1-hdroxyethyl)pyrimidine；2-(2,6-dimethoxy-5-methylpyrimidin-4-yl)ethanol
• CAS: 156569-32-3
• 化学式: C₉H₁₄N₂O₃
• 分子量: 198.222
• InChiKey: QBLLKCNSJSRSMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.34
• 重原子数：
  14.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.47
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2,4-dimethoxy-6-(2-hydroxyethyl)-5-methylpyrimidine 在 盐酸 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 6-methoxy-5-methyl-3,4-dihydro-1H-pyrimido[1,6-c][1,3]oxazin-8-one
  参考文献：
  名称：

  Synthesis of 1-Hydroxy-10-methyl-pyrimido [1, 6-C][1, 3]oxazine and the Oxazepine Derivative, Structural Mimicry of Anti-Constrained Acyclic Thymidine

  摘要：

  A number of pyrimido[1,6-c][1,3]oxazine and -oxazepine derivatives, mimicry analogs of anti-constrained acyclic thymidine, have been prepared via treatment of lithiated 5,6-dimethyl-2,4-dimethoxypyrimidine with benzylchloromethyl ether or oxiran to furnish 2,4-dimethoxy-6-(1-benzyloxyethyl)-5-methylpyrimidine (2) and 2,4-dimethoxy-6-(1 -hydroxypropyl)-5-methylpyrimidine (8), respectively. Debenzylation of 2 afforded 2,4-dimethoxy-6-(1-hydroxyethyl)-5-methylpyrimidine (3). Chloromethylation of 3 and 8 with paraformaldehyde and gaseous hydrogen chloride produced reactive chloromethyl ether intermediates which were converted to the cyclized products 9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1,6-c][1,3]-oxazine (5) and -oxazepine (9)-6,8-dione, respectively. By using selenium dioxide, allylic oxidation of 5 and 9 afforded the target compounds, a racemic mixture of (+/-) 1-hydroxy-9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1,6-c][1,3]-oxazine (6) and -oxazepine (10)-6, 8-dione, respectively. Compounds 5, 6, 7, 9, and 10 were evaluated for activity against human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). All of these compounds were inactive.

  DOI：

  10.1080/07328319608002449
• 作为产物：
  描述：

  2,4-二甲氧基-5,6-二甲基嘧啶 在 palladium on activated charcoal 氢气 、 lithium diisopropyl amide 作用下， 以 甲醇 为溶剂， -55.0 ℃ 、344.73 kPa 条件下， 反应 21.5h， 生成 2,4-dimethoxy-6-(2-hydroxyethyl)-5-methylpyrimidine
  参考文献：
  名称：

  Synthesis of 1-Hydroxy-10-methyl-pyrimido [1, 6-C][1, 3]oxazine and the Oxazepine Derivative, Structural Mimicry of Anti-Constrained Acyclic Thymidine

  摘要：

  A number of pyrimido[1,6-c][1,3]oxazine and -oxazepine derivatives, mimicry analogs of anti-constrained acyclic thymidine, have been prepared via treatment of lithiated 5,6-dimethyl-2,4-dimethoxypyrimidine with benzylchloromethyl ether or oxiran to furnish 2,4-dimethoxy-6-(1-benzyloxyethyl)-5-methylpyrimidine (2) and 2,4-dimethoxy-6-(1 -hydroxypropyl)-5-methylpyrimidine (8), respectively. Debenzylation of 2 afforded 2,4-dimethoxy-6-(1-hydroxyethyl)-5-methylpyrimidine (3). Chloromethylation of 3 and 8 with paraformaldehyde and gaseous hydrogen chloride produced reactive chloromethyl ether intermediates which were converted to the cyclized products 9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1,6-c][1,3]-oxazine (5) and -oxazepine (9)-6,8-dione, respectively. By using selenium dioxide, allylic oxidation of 5 and 9 afforded the target compounds, a racemic mixture of (+/-) 1-hydroxy-9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1,6-c][1,3]-oxazine (6) and -oxazepine (10)-6, 8-dione, respectively. Compounds 5, 6, 7, 9, and 10 were evaluated for activity against human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). All of these compounds were inactive.

  DOI：

  10.1080/07328319608002449

文献信息

• 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 1-Hydroxy-10-methyl-pyrimido [1, 6-C][1, 3]oxazine and the Oxazepine Derivative, Structural Mimicry of Anti-Constrained Acyclic Thymidine
  作者：Ling-Yih Hsu、Dean S. Wise、John C. Drach、Leroy B. Townsend

  DOI：10.1080/07328319608002449

  日期：1996.9

  A number of pyrimido[1,6-c][1,3]oxazine and -oxazepine derivatives, mimicry analogs of anti-constrained acyclic thymidine, have been prepared via treatment of lithiated 5,6-dimethyl-2,4-dimethoxypyrimidine with benzylchloromethyl ether or oxiran to furnish 2,4-dimethoxy-6-(1-benzyloxyethyl)-5-methylpyrimidine (2) and 2,4-dimethoxy-6-(1 -hydroxypropyl)-5-methylpyrimidine (8), respectively. Debenzylation of 2 afforded 2,4-dimethoxy-6-(1-hydroxyethyl)-5-methylpyrimidine (3). Chloromethylation of 3 and 8 with paraformaldehyde and gaseous hydrogen chloride produced reactive chloromethyl ether intermediates which were converted to the cyclized products 9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1,6-c][1,3]-oxazine (5) and -oxazepine (9)-6,8-dione, respectively. By using selenium dioxide, allylic oxidation of 5 and 9 afforded the target compounds, a racemic mixture of (+/-) 1-hydroxy-9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1,6-c][1,3]-oxazine (6) and -oxazepine (10)-6, 8-dione, respectively. Compounds 5, 6, 7, 9, and 10 were evaluated for activity against human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). All of these compounds were inactive.