N,N'-dibenzyl-5-hydroxytetrahydropyrimidin-2-one | 245679-88-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N,N'-dibenzyl-5-hydroxytetrahydropyrimidin-2-one
• 英文别名: 1,3-dibenzyl-1,2,3,4,5,6-hexahydro-5-hydroxypyrimidin-2-one；1,3-Dibenzyl-5-hydroxy-1,3-diazinan-2-one
• CAS: 245679-88-3
• 化学式: C₁₈H₂₀N₂O₂
• 分子量: 296.369
• InChiKey: UFYYKKNSHUJPGL-UHFFFAOYSA-N

物化性质

• 沸点：
  508.7±50.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N,N'-dibenzyl-5-hydroxytetrahydropyrimidin-2-one 在 3 A molecular sieve 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 二甲基二环氧乙烷 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 丙酮 为溶剂， 反应 7.0h， 生成 (4S)-1,3-dibenzyl-4-butyl-1,3-diazinane-2,5-dione
  参考文献：
  名称：

  A Highly Flexible Route to 1,2,3,4,5,6- Hexahydro-5-hydroxypyrimidin-2-ones as Potential HIV Protease Inhibitors

  摘要：

  The first asymmetric synthesis of potential HIV protease inhibitors of type II, III and IV is described. Key step of the synthesis is an auxiliary based stereoselective alkylation by means of the (R)-1-amino-2-methoxymethylpyrrolidine (RAMP)- / (S)-1-amino-2-methoxymethylpyrrolidine (SAMP)hydrazone method starting from a readily available key building block, pyrimidin-2,5-dione (6). The synthesis is short and highly versatile in the choice of the substitution pattern as well as the absolute configuration of the alkylated 1,2,3,4,5,6-Hexahydro-5-hydroxypyrimidin-2-ones.

  DOI：

  10.3987/com-03-s(p)51
• 作为产物：
  描述：

  N,N'-dibenzyl-5-benzyloxytetrahydropyrimidin-2-one 在 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 反应 336000.0h， 以68%的产率得到N,N'-dibenzyl-5-hydroxytetrahydropyrimidin-2-one
  参考文献：
  名称：

  New Azt Conjugates as Potent Anti-HIV Agents

  摘要：

  In an attempt to discover anti-HIV agents with much reduced cytotoxicity from the currently available HIV-reverse transcriptase inhibitors, AZT conjugates of cholanic acids, 2-imidazolidone-4- carboxylic acid and its derivatives, and N, N'-disubstituted 5-hydroxy-tetrahydropyrimidin-2-ones have been synthesized and their anti-HIV profiles determined with CEM-SS cell line. The AZT conjugates with 2-imidazolidone-4- carboxylic acid and 2-pyrrolidone-5-carboxylic acid through an ester linkage, and with N,N'-diphenyl-5-hydroxy-tetrahydropyrimidin-2-one through a succinate tether showed significantly higher therapeutic indexes than AZT while they also retained or enhanced AZT's anti-HIV activity. Thus, structural features that favor the desired therapeutic profile of the conjugates appear to include a five-membered ring cyclic urea or lactam, and six-membered ring cyclic urea with N,N'-diphenyl substitution.

  DOI：

  10.1080/15257770500377789

文献信息

• Asymmetric Synthesis of 1,2,3,4,5,6-Hexahydro-5-hydroxypyrimidin-2-ones as Potential HIV-Protease Inhibitors
  作者：Dieter Enders、Lars Wortmann、Barbara Dücker、Gerhard Raabe

  DOI：10.1002/(sici)1522-2675(19990804)82:8<1195::aid-hlca1195>3.0.co;2-n

  日期：1999.8.4
• A Highly Flexible Route to 1,2,3,4,5,6- Hexahydro-5-hydroxypyrimidin-2-ones as Potential HIV Protease Inhibitors
  作者：Dieter Enders、Lars Wortmann、Gerhard Raabe、Barbara Dücker

  DOI：10.3987/com-03-s(p)51

  日期：——

  The first asymmetric synthesis of potential HIV protease inhibitors of type II, III and IV is described. Key step of the synthesis is an auxiliary based stereoselective alkylation by means of the (R)-1-amino-2-methoxymethylpyrrolidine (RAMP)- / (S)-1-amino-2-methoxymethylpyrrolidine (SAMP)hydrazone method starting from a readily available key building block, pyrimidin-2,5-dione (6). The synthesis is short and highly versatile in the choice of the substitution pattern as well as the absolute configuration of the alkylated 1,2,3,4,5,6-Hexahydro-5-hydroxypyrimidin-2-ones.
• New Azt Conjugates as Potent Anti-HIV Agents
  作者：Zhengqing You、Henry Joung Lee

  DOI：10.1080/15257770500377789

  日期：2006.1

  In an attempt to discover anti-HIV agents with much reduced cytotoxicity from the currently available HIV-reverse transcriptase inhibitors, AZT conjugates of cholanic acids, 2-imidazolidone-4- carboxylic acid and its derivatives, and N, N'-disubstituted 5-hydroxy-tetrahydropyrimidin-2-ones have been synthesized and their anti-HIV profiles determined with CEM-SS cell line. The AZT conjugates with 2-imidazolidone-4- carboxylic acid and 2-pyrrolidone-5-carboxylic acid through an ester linkage, and with N,N'-diphenyl-5-hydroxy-tetrahydropyrimidin-2-one through a succinate tether showed significantly higher therapeutic indexes than AZT while they also retained or enhanced AZT's anti-HIV activity. Thus, structural features that favor the desired therapeutic profile of the conjugates appear to include a five-membered ring cyclic urea or lactam, and six-membered ring cyclic urea with N,N'-diphenyl substitution.