4-methoxy-2-methylcinnamanilide | 143268-85-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 4-methoxy-2-methylcinnamanilide
• 英文别名: (E)-N-(4-methoxy-2-methylphenyl)-3-phenylprop-2-enamide
• CAS: 143268-85-3
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: CVFZITFSEYIQTN-DHZHZOJOSA-N

物化性质

• 沸点：
  473.5±45.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  4-methoxy-2-methylcinnamanilide 在 三氯化铝 作用下， 以 氯苯 为溶剂， 反应 3.0h， 以73.2%的产率得到6-hydroxy-8-methyl-2(1H)-quinolinone
  参考文献：
  名称：

  Novel positive inotropic agents: synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives

  摘要：

  A series of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinones has been synthesized and evaluated for positive inotropic activity on the canine heart. Some of these derivatives have a potent activity with none or negative chronotropic effect in isolated, blood-perfused dog heart preparations. They also display a high selectivity for positive inotropic effect over chronotropic and vasodilatory effects in anesthetized dogs. (+/-)-6-[2-Hydroxy-3-[(3-methoxybenzyl)amino]propoxy]-2(1H)-quinolinone (39) and (+/-)-6-[3-(3,4-dimethoxybenzyl)amino]-2-hydroxypropoxy]-2(1H)-quinolinone (40) were further investigated in conscious dogs. After iv administration, they did not affect heart rate or mean blood pressure at the dose producing a 50% increase in the peak of the first derivative of the left ventricular pressure. The compounds (39,OPC-18750, and 40,OPC-18790) are the most promising agents with desirable biological activities, and now are currently undergoing clinical evaluation.

  DOI：

  10.1021/jm00098a003
• 作为产物：
  描述：

  3-苯基-2-丙烯酰氯 、 2-甲基-4-甲氧基苯胺 生成 4-methoxy-2-methylcinnamanilide
  参考文献：
  名称：

  分子间迈克尔加成苯

  摘要：

  描述了苯的第一次分子间迈克尔加成，导致形成3,3-二苯基丙酰苯胺。使2-甲氧基苯胺与肉桂酰氯反应，得到2-甲氧基肉桂酰苯胺（1），将其在80℃下用氯化铝的苯溶液处理，以85％的总收率得到2'-羟基-3,3-二苯基丙酰苯胺（4）。因此，由4-甲氧基-2-甲基肉桂酰胺（5）以76％的产率制备了4'-羟基-2'-甲基-3,3-二苯基丙酰苯胺（6）。

  DOI：

  10.1016/0040-4039(96)01364-0

文献信息

• Lewis Acid Catalyzed Reaction of Cinnamanilides: Competition of Intramolecular and Intermolecular Friedel-Crafts Reaction
  作者：Tai-Chi Wang、Yeh-Long Chen、Kuan-Han Lee、Cherng-Chyi Tzeng

  DOI：10.1055/s-1997-1505

  日期：1997.1

  The first intermolecular Friedel-Crafts reaction of benzene leading to the formation of 3,3-diphenylpropionanilide 7 is described. 4-Methoxyaniline was reacted with cinnamoyl chloride to give 4-methoxycinnamanilide (5a), the treatment of which with aluminum(III) chloride in chlorobenzene at 120°C or in benzene at 80°C afforded exclusively 6-hyddroxyquinolin-2(1H)-one (3a) or 4‘-hydroxy-3,3-diphenylpropionanilide (7a), respectively. The formation of 7a rather than 3a in benzene indicated that an intermolecular Friedel-Crafts reaction occurred prior to the relatively more facile intramolecular ring cyclization. This intermolecular Friedel-Crafts reaction was observed during the attempted ring cyclization of cinnamanilide and its methoxy derivatives in aluminum(III) chloride/benzene. Preparation of 3a can also be achieved in 17% overall yield via the N-oxidation of 6-hydroxyquinoline followed by acetylation and hydrolysis.

  本文介绍了苯分子间的第一个弗里德尔-卡夫斯反应，该反应导致生成 3,3-二苯基丙酰亚胺 7。4-甲氧基苯胺与肉桂酰氯反应生成 4-甲氧基肉桂酰苯胺（5a），将其与氯化铝（III）在氯苯中于 120°C 或在苯中于 80°C 进行处理，可分别得到 6-羟基喹啉-2(1H)-酮（3a）或 4'-羟基-3,3-二苯基丙酰苯胺（7a）。在苯中形成的是 7a 而不是 3a，这表明在相对更容易的分子内环化之前发生了分子间弗里德尔-卡夫斯反应。在尝试肉桂苯胺及其甲氧基衍生物在氯化铝（III）/苯中的环化过程中，也观察到了这种分子间 Friedel-Crafts 反应。通过 6-羟基喹啉的 N-氧化反应，然后进行乙酰化和水解，也可以制备 3a，总产率为 17%。
• QUINOLINE DERIVATIVE OR SALT THEREOF AND REMEDY FOR CARDIAC DISEASES CONTAINING THE SAME
  申请人：KOWA CO. LTD.

  公开号：EP0638571A1

  公开（公告）日：1995-02-15

  A quinoline derivative represented by general formula (1), a medicinally acceptable salt thereof, and a remedy for cardiac diseases containing the same, wherein ring A represents a furan, dihydrofuran or dioxolane ring, R¹ represents hydroxy, carboxy, alkoxycarbonyl, etc., R²s may be the same or different from each other and each represents hydrogen, alkyl, etc., R³ and R⁴ may be the same or different from each other and each represents hydrogen, halogen, alkyl, amino, alkoxy, etc., R⁵, R⁶, R⁷ and R⁸ may be the same or different from one another and each represents hydrogen or alkyl, m represents an integer of 0 to 3, and symbol ...... means that there may be a double bond formed by R⁶ and R⁸. The compound (1) has a positively inotropic effect on myocardia and an antiarrhythmic effect and can dilate blood vessels without extremely increasing the heart rate. Therefore, a remedy for cardiac diseases containing the same as the active ingredient is remarkably useful for treating cardiac insufficiency, arrhythmia, and so forth.

  一种由通式(1)代表的喹啉衍生物、其药用盐以及含有该衍生物的治疗心脏病的药物，其中环A代表呋喃、二氢呋喃或二氧戊环，R¹代表羟基、羧基、烷氧羰基等，R²s可以相同或不同，各自代表氢、烷基等、R³ 和 R⁴ 可以相同或互不相同，各自代表氢、卤素、烷基、氨基、烷氧基等，R⁵、R⁶、R⁷ 和 R⁸ 可以相同或互不相同，各自代表氢或烷基，m 代表 0 至 3 的整数，符号 ...... 表示 R⁶ 和 R⁸ 可以形成双键。化合物(1)对心肌具有正性肌力作用和抗心律失常作用，并能扩张血管而不会极度增加心率。因此，以该化合物为有效成分的心脏疾病治疗药物对治疗心功能不全、心律失常等有显著作用。
• US5576324A
  申请人：——

  公开号：US5576324A

  公开（公告）日：1996-11-19
• Novel positive inotropic agents: synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives
  作者：Takafumi Fujioka、Shuji Teramoto、Toyoki Mori、Tetsumi Hosokawa、Takumi Sumida、Michiaki Tominaga、Youichi Yabuuchi

  DOI：10.1021/jm00098a003

  日期：1992.10

  A series of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinones has been synthesized and evaluated for positive inotropic activity on the canine heart. Some of these derivatives have a potent activity with none or negative chronotropic effect in isolated, blood-perfused dog heart preparations. They also display a high selectivity for positive inotropic effect over chronotropic and vasodilatory effects in anesthetized dogs. (+/-)-6-[2-Hydroxy-3-[(3-methoxybenzyl)amino]propoxy]-2(1H)-quinolinone (39) and (+/-)-6-[3-(3,4-dimethoxybenzyl)amino]-2-hydroxypropoxy]-2(1H)-quinolinone (40) were further investigated in conscious dogs. After iv administration, they did not affect heart rate or mean blood pressure at the dose producing a 50% increase in the peak of the first derivative of the left ventricular pressure. The compounds (39,OPC-18750, and 40,OPC-18790) are the most promising agents with desirable biological activities, and now are currently undergoing clinical evaluation.
• An intermolecular Michael addition of benzene
  作者：Tai-chi Wang、Yeh-Long Chen、Kuan-Han Lee、Cherng-Chyi Tzeng

  DOI：10.1016/0040-4039(96)01364-0

  日期：1996.8

  The first intermolecular Michael addition of benzene leading to the formation of 3,3-diphenylpropionanilide is described. 2-Methoxyaniline was reacted with cinnamoyl chloride to give 2-methoxycinnamanilide (1) which was treated with aluminum chloride in benzene at 80°C to afford 2′-hydroxy-3,3-diphenylpropionanilide (4) in an 85% overall yield. Accordingly, 4′-hydroxy-2′-methyl-3,3-diphenylpropionanilide

  描述了苯的第一次分子间迈克尔加成，导致形成3,3-二苯基丙酰苯胺。使2-甲氧基苯胺与肉桂酰氯反应，得到2-甲氧基肉桂酰苯胺（1），将其在80℃下用氯化铝的苯溶液处理，以85％的总收率得到2'-羟基-3,3-二苯基丙酰苯胺（4）。因此，由4-甲氧基-2-甲基肉桂酰胺（5）以76％的产率制备了4'-羟基-2'-甲基-3,3-二苯基丙酰苯胺（6）。