3-chloro-7-methoxy-6-methyl-1,2,4-benzotriazine 1-oxide | 763132-06-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-chloro-7-methoxy-6-methyl-1,2,4-benzotriazine 1-oxide
• 英文别名: 3-chloro-7-methoxy-6-methyl-1-oxido-1,2,4-benzotriazin-1-ium
• CAS: 763132-06-5
• 化学式: C₉H₈ClN₃O₂
• 分子量: 225.634
• InChiKey: ARYMCAVRYDXAJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-chloro-7-methoxy-6-methyl-1,2,4-benzotriazine 1-oxide 、 四乙基锡 在 四(三苯基膦)钯 作用下， 以 乙腈 为溶剂， 反应 0.33h， 以86%的产率得到3-ethyl-7-methoxy-6-methyl-1,2,4-benzotriazine 1-oxide
  参考文献：
  名称：

  Stille Coupling Reactions in the Synthesis of Hypoxia-Selective 3-Alkyl-1,2,4-Benzotriazine 1,4-Dioxide Anticancer Agents

  摘要：

  The introduction of a 3-alkyl substituent is a key step in the synthesis of 1,2,4-benzotriazine 1,4-dioxide hypoxia-selective anticancer agents, such as SN29751. The Stille reaction of 3-chloro-1,2,4-benzotriazine 1-oxides ( BTOs) 5 was inhibited by the presence of electron donating substituents on the benzo ring, thus limiting the range of compounds available for SAR studies. The use of 3-iodo-BTOs 8 did not provide a significant improvement in the yields of 3-ethyl-BTOs 6. Microwave-assisted Stille coupling of chlorides 5 gave dramatically improved yields, which were consistently superior to those from the corresponding iodides 8. The application of microwave-assisted synthesis extended the range of substituted BTOs available for SAR studies and provided an efficient, scalable synthesis of the investigational anticancer agent, SN29751 ( 1).

  DOI：

  10.1021/jo060986g
• 作为产物：
  描述：

  2-硝基-4-甲氧基-5-甲基苯胺 在 盐酸 、 三氟乙酸 、 sodium nitrite 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 3-chloro-7-methoxy-6-methyl-1,2,4-benzotriazine 1-oxide
  参考文献：
  名称：

  Stille Coupling Reactions in the Synthesis of Hypoxia-Selective 3-Alkyl-1,2,4-Benzotriazine 1,4-Dioxide Anticancer Agents

  摘要：

  The introduction of a 3-alkyl substituent is a key step in the synthesis of 1,2,4-benzotriazine 1,4-dioxide hypoxia-selective anticancer agents, such as SN29751. The Stille reaction of 3-chloro-1,2,4-benzotriazine 1-oxides ( BTOs) 5 was inhibited by the presence of electron donating substituents on the benzo ring, thus limiting the range of compounds available for SAR studies. The use of 3-iodo-BTOs 8 did not provide a significant improvement in the yields of 3-ethyl-BTOs 6. Microwave-assisted Stille coupling of chlorides 5 gave dramatically improved yields, which were consistently superior to those from the corresponding iodides 8. The application of microwave-assisted synthesis extended the range of substituted BTOs available for SAR studies and provided an efficient, scalable synthesis of the investigational anticancer agent, SN29751 ( 1).

  DOI：

  10.1021/jo060986g

文献信息

• Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments
  申请人：Auckland Uniservices Limited

  公开号：EP1468688A2

  公开（公告）日：2004-10-20

  The present invention relates to a synergetistic composition comprising one or more benzoazine-mono-N-oxides, and one or more benzoazine 1,4 dioxides for use in cancer therapy. The invention also provides a range of novel 1,2,4 benzoazine-mono-N-oxides and related analogues. These can be used as potentiators of the cytotoxicity of existing anticancer drugs and therapies for cancer treatment.

  本发明涉及一种协同组合物，包括一种或多种苯并噁唑-单-N-氧化物，以及一种或多种苯并噁唑1,4-二氧化物，用于癌症治疗。 该发明还提供了一系列新颖的1,2,4苯并噁唑-单-N-氧化物及相关类似物。这些可以用作增强现有抗癌药物的细胞毒性和癌症治疗的治疗剂。
• Stille Coupling Reactions in the Synthesis of Hypoxia-Selective 3-Alkyl-1,2,4-Benzotriazine 1,4-Dioxide Anticancer Agents
  作者：Karin Pchalek、Michael P. Hay

  DOI：10.1021/jo060986g

  日期：2006.8.1

  The introduction of a 3-alkyl substituent is a key step in the synthesis of 1,2,4-benzotriazine 1,4-dioxide hypoxia-selective anticancer agents, such as SN29751. The Stille reaction of 3-chloro-1,2,4-benzotriazine 1-oxides ( BTOs) 5 was inhibited by the presence of electron donating substituents on the benzo ring, thus limiting the range of compounds available for SAR studies. The use of 3-iodo-BTOs 8 did not provide a significant improvement in the yields of 3-ethyl-BTOs 6. Microwave-assisted Stille coupling of chlorides 5 gave dramatically improved yields, which were consistently superior to those from the corresponding iodides 8. The application of microwave-assisted synthesis extended the range of substituted BTOs available for SAR studies and provided an efficient, scalable synthesis of the investigational anticancer agent, SN29751 ( 1).