2-pivaloyl-4-chloro-5-trimethylsilylethynylpyrrolo<2,3-d>pyrimidine | 149765-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 2-pivaloyl-4-chloro-5-trimethylsilylethynylpyrrolo<2,3-d>pyrimidine
• CAS: 149765-31-1
• 化学式: C₁₆H₂₁ClN₄OSi
• 分子量: 348.907
• InChiKey: CPMHKLWXVDOYCJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.17±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.82
• 重原子数：
  23.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  70.67
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-pivaloyl-4-chloro-5-trimethylsilylethynylpyrrolo<2,3-d>pyrimidine 在 palladium on activated charcoal sodium hydroxide 、 copper(l) iodide 、 四(三苯基膦)钯 、 四丁基氟化铵 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙二醇甲醚 、 N,N-二甲基甲酰胺 为溶剂， 25.0~100.0 ℃ 、344.73 kPa 条件下， 反应 189.0h， 生成 N-<2-amino-4-diethylamino<(pyrrolo<2,3-d>pyrimidin-5-yl)ethyl>benzoyl>-L-glutamic acid
  参考文献：
  名称：

  The Synthesis of N-{2-Amino-4-substituted [(Pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic Acids as Antineoplastic Agents

  摘要：

  A series of N-{2-amino-4-substituted[(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acids were synthesized. In this current synthesis, compound 2-amino-4-chloro-pyrrolo[2,3-d]pyrimidine (4) was selected as an important precursor for the preparation of key intermediates such as 5b, 10b, 15a and 15b. These highly functionalized pyrrolo[2,3-d]pyrimidines were then later coupled with either 4-ethynylbenzoylglutamate or 4-iodobenzoylglutamate in a palladium catalyzed Heck reaction and thus provided the basic skeleton of the targeted molecules. The availability of the chlorine atom at the 4-position of the pyrrolopyrimidine nucleus has allowed us to introduce different substituents at this position efficiently. By this approach, we were able to prepare a variety of 4-substituted pyrrolo[2,3d]pyrimidine based folate antagonists (2a-2g) which are closely related to the novel thymidylate synthase inhibitor LY231514. In vitro analysis has demonstrated that some of these agents are highly cytotoxic against human leukemic cells (CCRF-CEM) in culture.

  DOI：

  10.3987/com-92-s(t)65
• 作为产物：
  描述：

  2-氨基-4-氯吡咯并[2,3-d]嘧啶 在 吡啶 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 2-pivaloyl-4-chloro-5-trimethylsilylethynylpyrrolo<2,3-d>pyrimidine
  参考文献：
  名称：

  The Synthesis of N-{2-Amino-4-substituted [(Pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic Acids as Antineoplastic Agents

  摘要：

  A series of N-{2-amino-4-substituted[(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acids were synthesized. In this current synthesis, compound 2-amino-4-chloro-pyrrolo[2,3-d]pyrimidine (4) was selected as an important precursor for the preparation of key intermediates such as 5b, 10b, 15a and 15b. These highly functionalized pyrrolo[2,3-d]pyrimidines were then later coupled with either 4-ethynylbenzoylglutamate or 4-iodobenzoylglutamate in a palladium catalyzed Heck reaction and thus provided the basic skeleton of the targeted molecules. The availability of the chlorine atom at the 4-position of the pyrrolopyrimidine nucleus has allowed us to introduce different substituents at this position efficiently. By this approach, we were able to prepare a variety of 4-substituted pyrrolo[2,3d]pyrimidine based folate antagonists (2a-2g) which are closely related to the novel thymidylate synthase inhibitor LY231514. In vitro analysis has demonstrated that some of these agents are highly cytotoxic against human leukemic cells (CCRF-CEM) in culture.

  DOI：

  10.3987/com-92-s(t)65