Imidazole-1-carbothioic acid O-{(S)-1-[(4R,5S,6R)-6-benzyl-1,3-bis-cyclopropylmethyl-5-(2-methoxy-ethoxymethoxy)-2-oxo-hexahydro-pyrimidin-4-yl]-2-phenyl-ethyl} ester | 210635-03-3

• 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: Imidazole-1-carbothioic acid O-{(S)-1-[(4R,5S,6R)-6-benzyl-1,3-bis-cyclopropylmethyl-5-(2-methoxy-ethoxymethoxy)-2-oxo-hexahydro-pyrimidin-4-yl]-2-phenyl-ethyl} ester
• 英文别名: O-[(1S)-1-[(4R,5S,6R)-6-benzyl-1,3-bis(cyclopropylmethyl)-5-(2-methoxyethoxymethoxy)-2-oxo-1,3-diazinan-4-yl]-2-phenylethyl] imidazole-1-carbothioate
• CAS: 210635-03-3
• 化学式: C₃₅H₄₄N₄O₅S
• 分子量: 632.824
• InChiKey: YHTLCLFKBFQWHF-LVVLYVGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  45
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Imidazole-1-carbothioic acid O-{(S)-1-[(4R,5S,6R)-6-benzyl-1,3-bis-cyclopropylmethyl-5-(2-methoxy-ethoxymethoxy)-2-oxo-hexahydro-pyrimidin-4-yl]-2-phenyl-ethyl} ester 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以20 mg的产率得到(4R,5R,6R)-4-Benzyl-1,3-bis-cyclopropylmethyl-5-(2-methoxy-ethoxymethoxy)-6-phenethyl-tetrahydro-pyrimidin-2-one
  参考文献：
  名称：

  Stereospecific, Stereoselective Rearrangement of Hexahydro-1,3-diazepin-2-ones to Tetrahydropyrimidin-2-ones and Imidazolidin-2-ones, a Useful Route for the Synthesis of HIV Protease Inhibitors

  摘要：

  We have discovered that hexahydro-5,6-dihydroxy-1,3-diazepin-2-ones can undergo a stereospecific, stereoselective-rearrangement, ring-contraction reaction to give the corresponding tetrahydro-5-hydroxypyrimidin-2-ones. This reaction is very general and proceeds in excellent yields. The rearrangement proceeds through the formation of the aziridinium cationic intermediate I, which is subsequently opened by nucleophilic attack (S(N)2) at the less hindered carbon to give the rearranged product. The X-ray structure determination of the rearranged product (17a; Figure 1) confirmed the structure and the stereochemical assignments and is consistent with:the proposed mechanism. When the urea nitrogens are not substituted, the aziridine product can be isolated, and its structure (24; Figure 2) was also confirmed by X-ray analysis. The aziridine product can be used as a mono N-protecting group to synthesize differentially disubstituted N,N'-dialkylated tetrahydropyrimidin-2-one analogues. The tetrahydro-5-hydroxypyrimidin-2-ones can further undergo a second stereospecific, stereoselective-rearrangement, ring-contraction reaction to give the corresponding imidazolidinones. This second rearrangement is also very general and proceeds in good yields. These tetrahydro-5-hydroxypyrimidin-2-ones and imidazolidinones have previously been shown to be potent HIVPR inhibitors.

  DOI：

  10.1021/jo980533e
• 作为产物：
  描述：

  Chloro-acetic acid (S)-1-[(4R,5S,6R)-6-benzyl-1,3-bis-cyclopropylmethyl-5-(2-methoxy-ethoxymethoxy)-2-oxo-hexahydro-pyrimidin-4-yl]-2-phenyl-ethyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 生成 Imidazole-1-carbothioic acid O-{(S)-1-[(4R,5S,6R)-6-benzyl-1,3-bis-cyclopropylmethyl-5-(2-methoxy-ethoxymethoxy)-2-oxo-hexahydro-pyrimidin-4-yl]-2-phenyl-ethyl} ester
  参考文献：
  名称：

  Stereospecific, Stereoselective Rearrangement of Hexahydro-1,3-diazepin-2-ones to Tetrahydropyrimidin-2-ones and Imidazolidin-2-ones, a Useful Route for the Synthesis of HIV Protease Inhibitors

  摘要：

  We have discovered that hexahydro-5,6-dihydroxy-1,3-diazepin-2-ones can undergo a stereospecific, stereoselective-rearrangement, ring-contraction reaction to give the corresponding tetrahydro-5-hydroxypyrimidin-2-ones. This reaction is very general and proceeds in excellent yields. The rearrangement proceeds through the formation of the aziridinium cationic intermediate I, which is subsequently opened by nucleophilic attack (S(N)2) at the less hindered carbon to give the rearranged product. The X-ray structure determination of the rearranged product (17a; Figure 1) confirmed the structure and the stereochemical assignments and is consistent with:the proposed mechanism. When the urea nitrogens are not substituted, the aziridine product can be isolated, and its structure (24; Figure 2) was also confirmed by X-ray analysis. The aziridine product can be used as a mono N-protecting group to synthesize differentially disubstituted N,N'-dialkylated tetrahydropyrimidin-2-one analogues. The tetrahydro-5-hydroxypyrimidin-2-ones can further undergo a second stereospecific, stereoselective-rearrangement, ring-contraction reaction to give the corresponding imidazolidinones. This second rearrangement is also very general and proceeds in good yields. These tetrahydro-5-hydroxypyrimidin-2-ones and imidazolidinones have previously been shown to be potent HIVPR inhibitors.

  DOI：

  10.1021/jo980533e

文献信息

• Stereospecific, Stereoselective Rearrangement of Hexahydro-1,3-diazepin-2-ones to Tetrahydropyrimidin-2-ones and Imidazolidin-2-ones, a Useful Route for the Synthesis of HIV Protease Inhibitors
  作者：George V. De Lucca

  DOI：10.1021/jo980533e

  日期：1998.7.1

  We have discovered that hexahydro-5,6-dihydroxy-1,3-diazepin-2-ones can undergo a stereospecific, stereoselective-rearrangement, ring-contraction reaction to give the corresponding tetrahydro-5-hydroxypyrimidin-2-ones. This reaction is very general and proceeds in excellent yields. The rearrangement proceeds through the formation of the aziridinium cationic intermediate I, which is subsequently opened by nucleophilic attack (S(N)2) at the less hindered carbon to give the rearranged product. The X-ray structure determination of the rearranged product (17a; Figure 1) confirmed the structure and the stereochemical assignments and is consistent with:the proposed mechanism. When the urea nitrogens are not substituted, the aziridine product can be isolated, and its structure (24; Figure 2) was also confirmed by X-ray analysis. The aziridine product can be used as a mono N-protecting group to synthesize differentially disubstituted N,N'-dialkylated tetrahydropyrimidin-2-one analogues. The tetrahydro-5-hydroxypyrimidin-2-ones can further undergo a second stereospecific, stereoselective-rearrangement, ring-contraction reaction to give the corresponding imidazolidinones. This second rearrangement is also very general and proceeds in good yields. These tetrahydro-5-hydroxypyrimidin-2-ones and imidazolidinones have previously been shown to be potent HIVPR inhibitors.