3-((1-methyl-1H-pyrazol-4-yl)methyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-amine | 1403324-85-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 3-((1-methyl-1H-pyrazol-4-yl)methyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-amine
• 英文别名: 3-[(1-Methylpyrazol-4-yl)methyl]-1,2,4,5-tetrahydro-3-benzazepin-7-amine；3-[(1-methylpyrazol-4-yl)methyl]-1,2,4,5-tetrahydro-3-benzazepin-7-amine
• CAS: 1403324-85-5
• 化学式: C₁₅H₂₀N₄
• 分子量: 256.351
• InChiKey: WRDULLTVRRPUFQ-UHFFFAOYSA-N

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：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-((1-methyl-1H-pyrazol-4-yl)methyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-amine 在 N-溴代丁二酰亚胺(NBS) 、 氢溴酸 作用下， 以 甲醇 、 水 为溶剂， 反应 1.5h， 生成 7-[(1-methyl-1H-pyrazol-4-yl)methyl]-6,7,8,9-tetrahydro-5H-[1,3]thiazolo[4,5-h][3]benzazepin-2-amine
  参考文献：
  名称：

  Efficient and scalable synthesis of thiazole fused benzazepine as a D2 partial agonist

  摘要：

  The development of an efficient and scalable synthetic route to prepare the selective D2 partial agonist (1) is described here. Regioselective nitration of tetrahydrobenzazepine 2, followed by reductive amination, hydrogenation, and oxidative cyclization afforded 1 in good yield, without the need of column chromatography. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.08.035
• 作为产物：
  描述：

  7-硝基-2,3,4,5-四氢-1H-苯并[d]氮杂卓 在 palladium 10% on activated carbon 、 氢气 、 sodium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 3-((1-methyl-1H-pyrazol-4-yl)methyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-amine
  参考文献：
  名称：

  Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists

  摘要：

  Dopamine (D-2) partial agonists (D2PAs) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics. Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D-2 partial agonists. These compounds have good selectivity, CNS drug-like properties and tunable D-2 partial agonism. One of the key compounds, 8h, has good in vitro/in vivo ADME characteristics, and is active in a rat amphetamine-induced locomotor activity model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.023

文献信息

• Preparation of two D2 partial agonists in C-14 and stable isotope labeled forms
  作者：Charles S. Elmore、Mark E. Powell、Hui Xiong、Ye Wu、Lijuan Wang、David Saunders、Rebecca A. Urbanek

  DOI：10.1002/jlcr.2951

  日期：2012.7

  prepared in stable isotope and C-14 labeled forms. Both compounds contained an aminothiazole ring, and the C-14 label was introduced into the ring using KS14CN. However, the use of KS14CN to form [14C]-2 gave poor results; therefore, benzoyl [14C]isothiocyanate was used instead, which led to a much improved yield. The stable isotope labeled forms were prepared with the label in the side chain from [2H5]ethyl

  为了支持开发治疗多巴胺水平失衡导致的疾病的计划，以稳定同位素和 C-14 标记形式制备了两种候选药物 1 和 2。两种化合物都包含一个氨基噻唑环，并且使用 KS14CN 将 C-14 标记引入到环中。然而，使用 KS14CN 形成 [14C]-2 的结果很差；因此，改用苯甲酰[14C]异硫氰酸酯，从而大大提高了产率。稳定同位素标记的形式是由 [2H5]-1 的 [2H5] 乙基碘和 1-[13C] 甲基 [15N2] 吡唑 [13C] 甲醛在侧链中的标记制备的，后者依次由 [羰基-13C]DMF、[15N2] 硫酸肼和 [13C] 甲基碘用于 [13C2, 15N2]-2。版权所有 © 2012 John Wiley & Sons, Ltd.
• Efficient and scalable synthesis of thiazole fused benzazepine as a D2 partial agonist
  作者：Hui Xiong、Ye Wu、Scott G. Lehr、William Blackwell、Gary Steelman、Jim Hulsizer、Rebecca A. Urbanek

  DOI：10.1016/j.tetlet.2012.08.035

  日期：2012.10

  The development of an efficient and scalable synthetic route to prepare the selective D2 partial agonist (1) is described here. Regioselective nitration of tetrahydrobenzazepine 2, followed by reductive amination, hydrogenation, and oxidative cyclization afforded 1 in good yield, without the need of column chromatography. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists
  作者：Rebecca A. Urbanek、Hui Xiong、Ye Wu、William Blackwell、Gary Steelman、Jim Rosamond、Steven S. Wesolowski、James B. Campbell、Minli Zhang、Becky Brockel、Daniel V. Widzowski

  DOI：10.1016/j.bmcl.2012.11.023

  日期：2013.1

  Dopamine (D-2) partial agonists (D2PAs) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics. Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D-2 partial agonists. These compounds have good selectivity, CNS drug-like properties and tunable D-2 partial agonism. One of the key compounds, 8h, has good in vitro/in vivo ADME characteristics, and is active in a rat amphetamine-induced locomotor activity model. (C) 2012 Elsevier Ltd. All rights reserved.