4-[4-(tert-butoxycarbonyl)-1,4-diazepan-1-yl]benzoic acid | 303134-14-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[4-(tert-butoxycarbonyl)-1,4-diazepan-1-yl]benzoic acid
• 英文别名: 4-(4-Boc-1,4-diazepan-1-YL)benzoic acid；4-[4-[(2-methylpropan-2-yl)oxycarbonyl]-1,4-diazepan-1-yl]benzoic acid
• CAS: 303134-14-7
• 化学式: C₁₇H₂₄N₂O₄
• 分子量: 320.389
• InChiKey: ODLYPZPRQQWXQS-UHFFFAOYSA-N

物化性质

• 沸点：
  489.1±40.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-(tert-butoxycarbonyl)-1,4-diazepan-1-yl]benzoic acid 在 吡啶 、 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 ammonium chloride 、 三乙酰氧基硼氢化钠 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 84.58h， 生成 ethyl (3-[(3-cyanobenzoyl)amino]-2-{[4-(4-methyl-1,4-diazepan-1-yl)benzoyl]amino}phenoxy)acetate
  参考文献：
  名称：

  Synthesis and biological activity of novel 1,2-disubstituted benzene derivatives as factor Xa inhibitors

  摘要：

  Factor Xa (fXa) is a serine protease that plays a pivotal role in the coagulation cascade. High-tbroughput screening of the Yamanouchi compound library yielded lead compound I with the ability to inhibit fXa at micromolar concentrations. To improve its fXa inhibitory activity and its oral anticoagulant activity, the linker between benzamidine and the central benzene ring was modified and a carboxyl group was introduced at the central benzene ring. The resulting compounds 40b (YM-203552), 41a (YM-202054), and 41c (YM-203558) exhibited potent fXa inhibitory activity and oral anticoagulant activity. In particular, YM-203558 exhibited the most potent oral anticoagulant activity, prolonging PT more than 3-fold at 0.5 and 2.0h. Additionally, these compounds showed a high degree of selectivity for other serine proteases. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.005
• 作为产物：
  描述：

  2,2,2,4'-四氟苯乙酮 在 sodium hydroxide 、 三乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 4-[4-(tert-butoxycarbonyl)-1,4-diazepan-1-yl]benzoic acid
  参考文献：
  名称：

  一种制备 4-氮取代苯甲酸的实用方法

  摘要：

  描述了一种有效且实用的制备 4-氮取代苯甲酸的方法。我们的方法包括 2,2,2,4'-四氟苯乙酮与胺的芳香取代，然后是苯甲酸的卤仿反应。在该方法中，即使对于亲核性较低的 7-、8-和 9-元胺 1 当量。使用时，相应的苯甲酸以中等至极好的收率获得。由于包括纯化在内的实验步骤简单，该方法适用于大规模合成。

  DOI：

  10.1246/cl.2006.1090

文献信息

• A Practical Method for the Preparation of 4-Nitrogen-substituted Benzoic Acids
  作者：Tsuyoshi Shinozuka、Akira Nakao、Keiji Saito、Satoru Naito

  DOI：10.1246/cl.2006.1090

  日期：2006.10

  efficient and practical method for the preparation of 4-nitrogen-substituted benzoic acids is described. Our method consists of the aromatic substitution of 2,2,2,4'-tetrafluoroacetophenone with amines, followed by haloform reaction to the benzoic acids. In this method, even though for the less nucleophilic 7-, 8-, and 9-membered amines 1 equiv. was used, corresponding benzoic acids were obtained in moderate

  描述了一种有效且实用的制备 4-氮取代苯甲酸的方法。我们的方法包括 2,2,2,4'-四氟苯乙酮与胺的芳香取代，然后是苯甲酸的卤仿反应。在该方法中，即使对于亲核性较低的 7-、8-和 9-元胺 1 当量。使用时，相应的苯甲酸以中等至极好的收率获得。由于包括纯化在内的实验步骤简单，该方法适用于大规模合成。
• Synthesis and biological activity of novel 1,2-disubstituted benzene derivatives as factor Xa inhibitors
  作者：Hiroyuki Koshio、Fukushi Hirayama、Tsukasa Ishihara、Ryouta Shiraki、Takeshi Shigenaga、Yuta Taniuchi、Kazuo Sato、Yumiko Moritani、Yoshiyuki Iwatsuki、Seiji Kaku、Naoko Katayama、Tomihisa Kawasaki、Yuzo Matsumoto、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2004.11.005

  日期：2005.2

  Factor Xa (fXa) is a serine protease that plays a pivotal role in the coagulation cascade. High-tbroughput screening of the Yamanouchi compound library yielded lead compound I with the ability to inhibit fXa at micromolar concentrations. To improve its fXa inhibitory activity and its oral anticoagulant activity, the linker between benzamidine and the central benzene ring was modified and a carboxyl group was introduced at the central benzene ring. The resulting compounds 40b (YM-203552), 41a (YM-202054), and 41c (YM-203558) exhibited potent fXa inhibitory activity and oral anticoagulant activity. In particular, YM-203558 exhibited the most potent oral anticoagulant activity, prolonging PT more than 3-fold at 0.5 and 2.0h. Additionally, these compounds showed a high degree of selectivity for other serine proteases. (C) 2004 Elsevier Ltd. All rights reserved.