5-amino-4-(6-methoxy-2-methylpyridin-3-yl)-3-methyl-1H-pyrazole-1-carboxamide | 1266353-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-amino-4-(6-methoxy-2-methylpyridin-3-yl)-3-methyl-1H-pyrazole-1-carboxamide
• 英文别名: 5-Amino-4-(6-methoxy-2-methylpyridin-3-yl)-3-methylpyrazole-1-carboxamide；5-amino-4-(6-methoxy-2-methylpyridin-3-yl)-3-methylpyrazole-1-carboxamide
• CAS: 1266353-36-9
• 化学式: C₁₂H₁₅N₅O₂
• 分子量: 261.283
• InChiKey: WKVYWRATGVCMEH-UHFFFAOYSA-N

物化性质

• 沸点：
  447.1±55.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-amino-4-(6-methoxy-2-methylpyridin-3-yl)-3-methyl-1H-pyrazole-1-carboxamide 在 N-甲基吗啉 、 N,N-二异丙基乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 7.0h， 生成 Pexacerfont; 8-(6-甲氧基-2-甲基-3-吡啶基)-2,7-二甲基-N-[(1R)-1-甲基丙基]吡唑并[1,5-a]-1,3,5-三嗪-4-胺
  参考文献：
  名称：

  The Development of a Robust Process for a CRF₁ Receptor Antagonist

  摘要：

  A scalable and robust process was developed for the preparation of pexacerfont (2), a pyrazolotriazine corticotropin-releasing factor receptor 1 antagonist (CRF1). The formation of the core hydroxypyrazolotriazine moiety was achieved through two consecutive cyclizations of a semicarbazide, employing reaction conditions that are significantly milder than those reported in the literature. Further conversion to the key chloropyrazolotriazine intermediate was accomplished through a novel catalytic process using phosphorous oxychloride as the chlorinating agent. The active pharmaceutical ingredient 2 was obtained in > 99.5% purity with a 68% overall yield for the six synthetic steps.

  DOI：

  10.1021/op100270u
• 作为产物：
  描述：

  2-(6-甲氧基-2-甲基吡啶-3-基)乙腈 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 水 、 异丙醇 为溶剂， 反应 10.5h， 生成 5-amino-4-(6-methoxy-2-methylpyridin-3-yl)-3-methyl-1H-pyrazole-1-carboxamide
  参考文献：
  名称：

  The Development of a Robust Process for a CRF₁ Receptor Antagonist

  摘要：

  A scalable and robust process was developed for the preparation of pexacerfont (2), a pyrazolotriazine corticotropin-releasing factor receptor 1 antagonist (CRF1). The formation of the core hydroxypyrazolotriazine moiety was achieved through two consecutive cyclizations of a semicarbazide, employing reaction conditions that are significantly milder than those reported in the literature. Further conversion to the key chloropyrazolotriazine intermediate was accomplished through a novel catalytic process using phosphorous oxychloride as the chlorinating agent. The active pharmaceutical ingredient 2 was obtained in > 99.5% purity with a 68% overall yield for the six synthetic steps.

  DOI：

  10.1021/op100270u

文献信息

• <i>N-N</i>migration of a carbamoyl group in a pyrazole derivative revealed by NMR
  作者：Charles Pathirana、Chris Sfouggatakis、Venkatapuram Palaniswamy

  DOI：10.1002/mrc.3921

  日期：2013.3

  interpretation of 1D and 2D (HMQC, HMBC) NMR data where (1)H-(15)N HMBC correlations revealed the position of carbamoyl group attachment on the pyrazole. Comparison of structures of the target-compound and the by-product showed that the latter resulted from N-N migration of the carbamoyl group in the target-compound.

  在合成5-氨基-4-（6-甲氧基-2-甲基吡啶-3-基）-3-甲基-1H-吡唑-1-羧酰胺（参见方案1）时，副反应生成了3-氨基-作为副产物的4-（6-甲氧基-2-甲基吡啶-3-基）-5-甲基-1H-吡唑-1-羧酰胺与目标化合物形成平衡。副产物的结构通过1D和2D（HMQC，HMBC）NMR数据的解释得以阐明，其中（1）H-（15）N HMBC相关性揭示了氨基甲酰基在吡唑上的附着位置。比较目标化合物和副产物的结构表明，后者是由氨基甲酰基在目标化合物中的NN迁移引起的。
• Org. Process Res. Dev. 2011, 15, 343-352
  作者：

  DOI：——

  日期：——
• The Development of a Robust Process for a CRF₁ Receptor Antagonist
  作者：Sévrine Broxer、Monica A. Fitzgerald、Chris Sfouggatakis、Jessica L. Defreese、Evan Barlow、Gerald L. Powers、Michael Peddicord、Bao-Ning Su、Yue Tai-Yuen、Charles Pathirana、James P. Sherbine

  DOI：10.1021/op100270u

  日期：2011.3.18

  A scalable and robust process was developed for the preparation of pexacerfont (2), a pyrazolotriazine corticotropin-releasing factor receptor 1 antagonist (CRF1). The formation of the core hydroxypyrazolotriazine moiety was achieved through two consecutive cyclizations of a semicarbazide, employing reaction conditions that are significantly milder than those reported in the literature. Further conversion to the key chloropyrazolotriazine intermediate was accomplished through a novel catalytic process using phosphorous oxychloride as the chlorinating agent. The active pharmaceutical ingredient 2 was obtained in > 99.5% purity with a 68% overall yield for the six synthetic steps.