N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-([6-3H]-2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-([6-3H]-2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
• 英文别名: 5-(4-chlorophenyl)-1-(2,4-dichloro-6-tritiophenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide
• 化学式: C₂₂H₂₁Cl₃N₄O
• 分子量: 465.786
• InChiKey: JZCPYUJPEARBJL-OAWTUDSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  利莫那班 在 palladium on activated charcoal 正丁基锂 、 1,10-菲罗啉 、 超重氢 、 1-氯-2-碘乙烷 、 三乙胺 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 3.5h， 生成 N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-([6-3H]-2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Tritiation of SR141716 by metallation-iodination-reduction: tritium-proton nOe study

  摘要：

  中枢大麻素受体拮抗剂 SR141716，N-(哌啶-1-基)-5-(4-氯苯基)-1-(2, 4-二氯苯基)-4-甲基-1H-吡唑-3-甲酰胺，由市售起始材料。芳基肼与二酮缩合，随后碱促进中间体反亚胺的异构化/环化，得到吡唑酸，该吡唑酸通过其酰基氯转化为标题酰肼。通过金属化轻松碘化，然后用碘源进行原位捕获，得到了适度产率的碘化 SR141716。用氚气和催化剂选择性还原碘，同时保留结构中的三个芳基氯原子。氚化的 SR141716 表现出氚-质子 nOe，既明确地确定了氚的位置，又确定了所寻找的二芳基吡唑异构体。这项工作提供了一种制备优选碘化芳基底物的直接方法，该底物在催化还原中寻求选择性和高掺入性方面具有优势。版权所有 © 2002 约翰·威利父子有限公司

  DOI：

  10.1002/jlcr.529

文献信息

• Synthesis, spectral studies and tritiation of the cannabinoid antagonist SR141716A
  作者：Herbert H. Seltzman、F. Ivy Carroll、Jason P. Burgess、Christopher D. Wyrick、David F. Burch

  DOI：10.1039/c39950001549

  日期：——

  An efficient synthesis of the cannabinoid antagonist SR141716A is presented and the structure is established by nOe experiments; tritiated SR141716A is synthesized by a novel sequence of metallation–iodination–tritiation and the labelled site is shown by tritium NMR and tritium–hydrogen nOe experiments.

  提出了一种高效合成大麻素拮抗剂SR141716A的方法，并通过nOe实验确定其结构；采用金属化-碘化-氚化的新顺序合成了氚标记的SR141716A，并通过氚核磁共振及氚-氢nOe实验展示了标记部位。
• Tritiation of SR141716 by metallation-iodination-reduction: tritium-proton nOe study
  作者：Herbert H. Seltzman、F. Ivy Carroll、Jason P. Burgess、Christopher D. Wyrick、David F. Burch

  DOI：10.1002/jlcr.529

  日期：2002.1

  The central cannabinoid receptor antagonist SR141716, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, was synthesized from commercially available starting materials. Condensation of an aryl hydrazine with a diketone followed by base promoted isomerization/cyclization of the intermediate anti-imine gave the pyrazole acid which was converted to the title hydrazide via its acid chloride. Facile iodination via metallation followed by in situ trapping with an iodine source gave a modest yield of the iodinated SR141716. The iodine was selectively reduced with tritium gas and catalyst while retaining the three aryl chlorine atoms in the structure. The tritiated SR141716 exhibited a tritium-proton nOe both definitively identifying the position of the tritium as well as the sought isomer of the diarylpyrazole. This work provides a direct method for the preparation of preferred iodinated aryl substrates that offer advantages where selectivity and high incorporation in catalytic reduction is sought. Copyright © 2002 John Wiley & Sons, Ltd.

  中枢大麻素受体拮抗剂 SR141716，N-(哌啶-1-基)-5-(4-氯苯基)-1-(2, 4-二氯苯基)-4-甲基-1H-吡唑-3-甲酰胺，由市售起始材料。芳基肼与二酮缩合，随后碱促进中间体反亚胺的异构化/环化，得到吡唑酸，该吡唑酸通过其酰基氯转化为标题酰肼。通过金属化轻松碘化，然后用碘源进行原位捕获，得到了适度产率的碘化 SR141716。用氚气和催化剂选择性还原碘，同时保留结构中的三个芳基氯原子。氚化的 SR141716 表现出氚-质子 nOe，既明确地确定了氚的位置，又确定了所寻找的二芳基吡唑异构体。这项工作提供了一种制备优选碘化芳基底物的直接方法，该底物在催化还原中寻求选择性和高掺入性方面具有优势。版权所有 © 2002 约翰·威利父子有限公司