ethyl 4-[3-[5-(methylsulfamoylmethyl)-1H-indol-3-yl]propyl]piperazine-1-carboxylate | 201798-98-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 4-[3-[5-(methylsulfamoylmethyl)-1H-indol-3-yl]propyl]piperazine-1-carboxylate
• CAS: 201798-98-3
• 化学式: C₂₀H₃₀N₄O₄S
• 分子量: 422.549
• InChiKey: LUHIABOQFBNJHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-[3-[5-(methylsulfamoylmethyl)-1H-indol-3-yl]propyl]piperazine-1-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以95%的产率得到N-Methyl-C-[3-(3-piperazin-1-yl-propyl)-1H-indol-5-yl]-methanesulfonamide
  参考文献：
  名称：

  An Efficient Fischer Indole Synthesis of Avitriptan, a Potent 5-HT_1D Receptor Agonist

  摘要：

  An efficient synthesis of the antimigraine drug candidate avitriptan (1, BMS 180048) is reported. The key step is a two-phase Fischer indolization reaction between hydrazine 6 and 5-chlorovaleraldehyde, 20, to give the chloropropylindole 35, which is susceptible to acid-catalyzed degradation under the reaction conditions required for its formation. Sequential coupling of 35 with piperazine, 26, and 4-chloro-5-methoxypyrimidine, 24, gives the title compound in 40-45% overall yield. Significant improvements in the syntheses of the known starting materials, hydrazine 6, 5-chlorovaleraldehyde, 20, and 4-chloro-5-methoxypyrimidine, 24, were also achieved.

  DOI：

  10.1021/jo971368q
• 作为产物：
  描述：

  N-哌嗪甲酸乙酯 、 N-methyl-3-(3'-chloropropyl)-1H-indolyl-5-methanesulfonamide 在 sodium carbonate 、 sodium iodide 作用下， 以 乙醇 为溶剂， 以90%的产率得到ethyl 4-[3-[5-(methylsulfamoylmethyl)-1H-indol-3-yl]propyl]piperazine-1-carboxylate
  参考文献：
  名称：

  An Efficient Fischer Indole Synthesis of Avitriptan, a Potent 5-HT_1D Receptor Agonist

  摘要：

  An efficient synthesis of the antimigraine drug candidate avitriptan (1, BMS 180048) is reported. The key step is a two-phase Fischer indolization reaction between hydrazine 6 and 5-chlorovaleraldehyde, 20, to give the chloropropylindole 35, which is susceptible to acid-catalyzed degradation under the reaction conditions required for its formation. Sequential coupling of 35 with piperazine, 26, and 4-chloro-5-methoxypyrimidine, 24, gives the title compound in 40-45% overall yield. Significant improvements in the syntheses of the known starting materials, hydrazine 6, 5-chlorovaleraldehyde, 20, and 4-chloro-5-methoxypyrimidine, 24, were also achieved.

  DOI：

  10.1021/jo971368q

文献信息

• An Efficient Fischer Indole Synthesis of Avitriptan, a Potent 5-HT_1D Receptor Agonist
  作者：Paul R. Brodfuehrer、Bang-Chi Chen、Thomas R. Sattelberg、Patrick R. Smith、Jayachandra P. Reddy、Derron R. Stark、Sandra L. Quinlan、J. Gregory Reid、John K. Thottathil、Shaopeng Wang

  DOI：10.1021/jo971368q

  日期：1997.12.1

  An efficient synthesis of the antimigraine drug candidate avitriptan (1, BMS 180048) is reported. The key step is a two-phase Fischer indolization reaction between hydrazine 6 and 5-chlorovaleraldehyde, 20, to give the chloropropylindole 35, which is susceptible to acid-catalyzed degradation under the reaction conditions required for its formation. Sequential coupling of 35 with piperazine, 26, and 4-chloro-5-methoxypyrimidine, 24, gives the title compound in 40-45% overall yield. Significant improvements in the syntheses of the known starting materials, hydrazine 6, 5-chlorovaleraldehyde, 20, and 4-chloro-5-methoxypyrimidine, 24, were also achieved.