N-[1-(3-chloro-4-methoxyphenyl)ethyl]formamide | 1027563-54-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-[1-(3-chloro-4-methoxyphenyl)ethyl]formamide
• CAS: 1027563-54-7
• 化学式: C₁₀H₁₂ClNO₂
• 分子量: 213.664
• InChiKey: IEBWEOAMNOZZNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[1-(3-chloro-4-methoxyphenyl)ethyl]formamide 在 N-甲基吡咯烷酮 、 盐酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 反应 5.0h， 生成 4-Chloro-1-[1-(3-chloro-4-methoxyphenyl)ethylamino]phthalazine-6-carbonitrile
  参考文献：
  名称：

  4-Benzylamino-1-chloro-6-substituted Phthalazines:  Synthesis and Inhibitory Activity toward Phosphodiesterase 5

  摘要：

  We synthesized various 4-benzylamino-1-chloro-6-substituted phthalazines (15) and 4-benzylamino-1-chloro-7-substituted phthalazines (16) and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) purified from porcine platelets. The PDE5-inhibitory activities of 15 were greater than those of the isomers (16). The preferred substituent at the 4-position of phthalazine was a (3-chloro-4-methoxybenzyl)amino group, and those at the B-position were cyano, nitro, and trifluoromethyl groups. Compounds 15a (IC50 = 4.8 nM), 15f (3.5 nM), and 15i (5.3 nM) were more potent inhibitors than E4021 (8.6 nM). Compounds 15a and 15f also showed vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F-2 alpha (10(-5) M). The EC50 values for vasorelaxant action of 15a, 15f, and E4021 were 150, 160, and 980 nM, respectively. These results show that novel PDE5 inhibitors possessing a potent vasorelaxant effect may exist among phthalazine derivatives.

  DOI：

  10.1021/jm970815r
• 作为产物：
  描述：

  2-氯苯甲醚 、 alkaline earth salt of/the/ methylsulfuric acid 在 三氯化铝 、 甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 N-[1-(3-chloro-4-methoxyphenyl)ethyl]formamide
  参考文献：
  名称：

  4-Benzylamino-1-chloro-6-substituted Phthalazines:  Synthesis and Inhibitory Activity toward Phosphodiesterase 5

  摘要：

  We synthesized various 4-benzylamino-1-chloro-6-substituted phthalazines (15) and 4-benzylamino-1-chloro-7-substituted phthalazines (16) and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) purified from porcine platelets. The PDE5-inhibitory activities of 15 were greater than those of the isomers (16). The preferred substituent at the 4-position of phthalazine was a (3-chloro-4-methoxybenzyl)amino group, and those at the B-position were cyano, nitro, and trifluoromethyl groups. Compounds 15a (IC50 = 4.8 nM), 15f (3.5 nM), and 15i (5.3 nM) were more potent inhibitors than E4021 (8.6 nM). Compounds 15a and 15f also showed vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F-2 alpha (10(-5) M). The EC50 values for vasorelaxant action of 15a, 15f, and E4021 were 150, 160, and 980 nM, respectively. These results show that novel PDE5 inhibitors possessing a potent vasorelaxant effect may exist among phthalazine derivatives.

  DOI：

  10.1021/jm970815r

文献信息

• Hydroarylation of enamides enabled by HFIP <i>via</i> a hexafluoroisopropyl ether as iminium reservoir
  作者：Nicolas Zeidan、Sergiu Bicic、Robert J. Mayer、David Lebœuf、Joseph Moran

  DOI：10.1039/d2sc02012b

  日期：——

  Here we describe that HFIP greatly expands the scope with respect to both reaction partners of the Brønsted acid-catalyzed hydroarylation of enamides. The reaction is fast and practical and can be performed on the gram scale. A hexafluoroisopropyl ether intermediate was isolated from the reaction mixture and was shown to convert to the product when resubmitted to the reaction conditions. Extensive

  在这里，我们描述了 HFIP 极大地扩展了 Brønsted 酸催化烯酰胺加氢芳基化的两个反应伙伴的范围。该反应快速实用，可在克级进行。从反应混合物中分离出六氟异丙醚中间体，并显示当重新接受反应条件时转化为产物。广泛的动力学研究和计算表明，六氟异丙醚形成迅速，可作为关键阳离子中间体的缓释储存器，防止底物在反应条件下发生低聚。鉴于本研究中阳离子中间体的亲电性相对较低，HFIP 似乎也可能积极参与其他涉及更多亲电碳阳离子的反应。
• 4-Benzylamino-1-chloro-6-substituted Phthalazines:  Synthesis and Inhibitory Activity toward Phosphodiesterase 5
  作者：Nobuhisa Watanabe、Yasuhiro Kabasawa、Yasutaka Takase、Masayuki Matsukura、Kazuki Miyazaki、Hiroki Ishihara、Kohtarou Kodama、Hideyuki Adachi

  DOI：10.1021/jm970815r

  日期：1998.8.1

  We synthesized various 4-benzylamino-1-chloro-6-substituted phthalazines (15) and 4-benzylamino-1-chloro-7-substituted phthalazines (16) and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) purified from porcine platelets. The PDE5-inhibitory activities of 15 were greater than those of the isomers (16). The preferred substituent at the 4-position of phthalazine was a (3-chloro-4-methoxybenzyl)amino group, and those at the B-position were cyano, nitro, and trifluoromethyl groups. Compounds 15a (IC50 = 4.8 nM), 15f (3.5 nM), and 15i (5.3 nM) were more potent inhibitors than E4021 (8.6 nM). Compounds 15a and 15f also showed vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F-2 alpha (10(-5) M). The EC50 values for vasorelaxant action of 15a, 15f, and E4021 were 150, 160, and 980 nM, respectively. These results show that novel PDE5 inhibitors possessing a potent vasorelaxant effect may exist among phthalazine derivatives.