6-chloro-5-(prop-2-en-1-yl)pyrimidin-4-amine | 454685-45-1

• 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: 6-chloro-5-(prop-2-en-1-yl)pyrimidin-4-amine
• 英文别名: 4-amino-5-allyl-6-chloropyrimidine；4-amino-6-chloro-5-allylpyrimidine；6-Chloro-5-prop-2-enylpyrimidin-4-amine
• CAS: 454685-45-1
• 化学式: C₇H₈ClN₃
• 分子量: 169.614
• InChiKey: WJTWTSJZTVGLHL-UHFFFAOYSA-N

物化性质

• 沸点：
  309.9±37.0 °C(Predicted)
• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-5-(prop-2-en-1-yl)pyrimidin-4-amine 在 platinum on activated charcoal bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四(三苯基膦)钯 、 氢碘酸 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 、 三(邻甲基苯基)磷 、 sodium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙酸乙酯 、 乙腈 为溶剂， 20.0~70.0 ℃ 、405.3 kPa 条件下， 生成 5-[3-(3-Bromo-phenyl)-propyl]-6-(6-morpholin-4-yl-pyridin-3-ylethynyl)-pyrimidin-4-ylamine
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship of 6-Alkynylpyrimidines as Potent Adenosine Kinase Inhibitors

  摘要：

  Adenosine (ADO) is an extracellular signaling molecule within the central and peripheral nervous system. Its concentration is increased at sites of tissue injury and inflammation. One of the mechanisms by which antinociceptive and antiinflammatory effects of ADO can be enhanced consists of inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO. Novel nonnucleoside AK inhibitors based on 4-amino-6-alkynylpyrimidines were prepared, and the importance of the length of the linker at the 5-position for high affinity AK inhibition was demonstrated. Compounds with 2- and 3-atom linkers were the most potent AK inhibitors. Optimization of their physicochemical properties led to 31a and 37a that effectively reduced pain and inflammation in animal models.

  DOI：

  10.1021/jm020049a
• 作为产物：
  描述：

  烯丙基丙二酸二乙酯 在 氨 、 sodium ethanolate 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 6-chloro-5-(prop-2-en-1-yl)pyrimidin-4-amine
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship of 6-Alkynylpyrimidines as Potent Adenosine Kinase Inhibitors

  摘要：

  Adenosine (ADO) is an extracellular signaling molecule within the central and peripheral nervous system. Its concentration is increased at sites of tissue injury and inflammation. One of the mechanisms by which antinociceptive and antiinflammatory effects of ADO can be enhanced consists of inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO. Novel nonnucleoside AK inhibitors based on 4-amino-6-alkynylpyrimidines were prepared, and the importance of the length of the linker at the 5-position for high affinity AK inhibition was demonstrated. Compounds with 2- and 3-atom linkers were the most potent AK inhibitors. Optimization of their physicochemical properties led to 31a and 37a that effectively reduced pain and inflammation in animal models.

  DOI：

  10.1021/jm020049a

文献信息

• 一种4-氯-7H-吡咯并[2,3-d]嘧啶的合成方法
  申请人：华东师范大学

  公开号：CN107011347B

  公开（公告）日：2019-01-18

  本发明公开了一种4‑氯‑7H‑吡咯并[2,3‑d]嘧啶的合成方法，该化合物是合成治疗类风湿性关节炎JAK抑制剂—鲁索替尼、托法替尼的重要中间体，其合成方法：以化合物Ⅰ(4,6‑二氯‑5‑烯丙基嘧啶)为起始原料，与氨气发生亲核取代反应生成化合物Ⅱ；然后化合物Ⅱ与臭氧反应并还原生成化合物Ⅲ；最后在酸性环境下自身关环生成化合物Ⅳ，即终产物4‑氯‑7H‑吡咯并[2,3‑d]嘧啶，合成路线如下式所示。本发明的合成工艺原料低廉易得，合成路线简短，成本低收率高，易于工业化生产。
• 一种制备4-氯-7H-吡咯并[2,3-d]嘧啶的制备方法
  申请人：南京格亚医药科技有限公司

  公开号：CN110343112A

  公开（公告）日：2019-10-18

  本发明提供一种4‑氯‑7H‑吡咯并[2，3‑d]嘧啶的制备方法，包括下列步骤：(1)将式(I)化合物在二氯甲烷溶剂中与氨水反应转化为式(II)；(2)式(II)化合物在高碘酸钠及过渡金属钌催化下发生反应得到式(III)化合物；(3)式(III)化合物在酸性条件下，自身发生闭环反应生成最后目标产物4‑氯‑7H‑吡咯并[2，3‑d]嘧啶。该方法制备4‑氯‑7H‑吡咯并[2，3‑d]嘧啶初始原料易获得，且反应过程中废液比较容易处理，各步反应条件温和，纯化较易，操作简单可行，收率较高。
• An improved synthesis of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine
  作者：Yu-Liu Zhang、Cheng-Tao Xu、Ting Liu、Yong Zhu、Yu Luo

  DOI：10.1007/s10593-018-2320-0

  日期：2018.6

  An improved seven-step synthesis of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine from dimethyl malonate with 31% overall yield is described. The procedure is operationally simple and practical for the synthesis of the 4-chloro-7H-pyrrolo[2,3-d]pyrimidine building block.
• Design, Synthesis, and Structure−Activity Relationship of 6-Alkynylpyrimidines as Potent Adenosine Kinase Inhibitors
  作者：Arthur Gomtsyan、Stanley Didomenico、Chih-Hung Lee、Mark A. Matulenko、Ki Kim、Elizabeth A. Kowaluk、Carol T. Wismer、Joe Mikusa、Haixia Yu、Kathy Kohlhaas、Michael F. Jarvis、Shripad S. Bhagwat

  DOI：10.1021/jm020049a

  日期：2002.8.1

  Adenosine (ADO) is an extracellular signaling molecule within the central and peripheral nervous system. Its concentration is increased at sites of tissue injury and inflammation. One of the mechanisms by which antinociceptive and antiinflammatory effects of ADO can be enhanced consists of inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO. Novel nonnucleoside AK inhibitors based on 4-amino-6-alkynylpyrimidines were prepared, and the importance of the length of the linker at the 5-position for high affinity AK inhibition was demonstrated. Compounds with 2- and 3-atom linkers were the most potent AK inhibitors. Optimization of their physicochemical properties led to 31a and 37a that effectively reduced pain and inflammation in animal models.