4-({5-cyclopropyl-3-methyl-1-[(methylsulfanyl)methyl]-1H-pyrazol-4-yl}oxy)-2,6-dimethylbenzonitrile hydrogen sulfate | 1174495-46-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-({5-cyclopropyl-3-methyl-1-[(methylsulfanyl)methyl]-1H-pyrazol-4-yl}oxy)-2,6-dimethylbenzonitrile hydrogen sulfate
• CAS: 1174495-46-5
• 化学式: C₁₈H₂₁N₃OS*H₂O₄S
• 分子量: 425.53
• InChiKey: NVIWFUKCPUDNDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.02
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  125.44
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-({5-cyclopropyl-3-methyl-1-[(methylsulfanyl)methyl]-1H-pyrazol-4-yl}oxy)-2,6-dimethylbenzonitrile hydrogen sulfate 在 Oxone 、 水 作用下， 以 乙酸乙酯 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  Development of a Practical Synthesis of the Progesterone Receptor Antagonist 4-{[3-Cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy}-2,6-dimethylbenzonitrile

  摘要：

  The development and implementation of a scaleable process for the manufacture of the nonsteroidal progesterone receptor antagonist 8 is described. Key aspects of the synthesis include (i) a telescoped chlorination-etherification sequence to prepare diketone 4 and (ii) separation of pyrazole regioisomers 6 and 7 through formation of their hydrogen sulfate salts and selective crystallization, followed by oxidation to 8.

  DOI：

  10.1021/op900110k
• 作为产物：
  描述：

  4-[5-Cyclopropyl-3-methyl-1-(methylsulfanylmethyl)pyrazol-4-yl]oxy-2,6-dimethylbenzonitrile 在 硫酸 作用下， 以 醋酸异丙酯 为溶剂， 反应 12.0h， 生成 4-({5-cyclopropyl-3-methyl-1-[(methylsulfanyl)methyl]-1H-pyrazol-4-yl}oxy)-2,6-dimethylbenzonitrile hydrogen sulfate
  参考文献：
  名称：

  Development of a Practical Synthesis of the Progesterone Receptor Antagonist 4-{[3-Cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy}-2,6-dimethylbenzonitrile

  摘要：

  The development and implementation of a scaleable process for the manufacture of the nonsteroidal progesterone receptor antagonist 8 is described. Key aspects of the synthesis include (i) a telescoped chlorination-etherification sequence to prepare diketone 4 and (ii) separation of pyrazole regioisomers 6 and 7 through formation of their hydrogen sulfate salts and selective crystallization, followed by oxidation to 8.

  DOI：

  10.1021/op900110k

文献信息

• Work-Up Optimization en Route to an Improved Process To Prepare a Progesterone Receptor Antagonist
  作者：Pieter D. de Koning、David J. McManus、George R. Bandurek

  DOI：10.1021/op200145j

  日期：2011.9.16

  When the process to prepare nonsteroidal progesterone receptor antagonist 5 was scaled up, significant problems were encountered, and as a result lower than expected yields were obtained. In particular, the alkylation of pyrazole 2 with chloromethyl methyl sulfide failed to reach completion, and partial degradation of the product occurred during the work-up, resulting in a modest yield of alkylated pyrazole 3a. Further investigation has revealed the root cause of this problem, and an improved, robust process to 5 has been developed.