3-{4-[2-(4-Fluoro-phenyl)-2-morpholin-4-yl-ethyl]-piperazin-1-yl}-2-methyl-1-phenyl-propan-1-one | 89011-85-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-{4-[2-(4-Fluoro-phenyl)-2-morpholin-4-yl-ethyl]-piperazin-1-yl}-2-methyl-1-phenyl-propan-1-one
• 英文别名: 3-[4-[2-(4-Fluorophenyl)-2-morpholin-4-ylethyl]piperazin-1-yl]-2-methyl-1-phenylpropan-1-one
• CAS: 89011-85-8
• 化学式: C₂₆H₃₄FN₃O₂
• 分子量: 439.573
• InChiKey: IRGMEZVYFZTDHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  36
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-[4-[2-(4-fluorophenyl)-2-morpholin-4-ylethyl]piperazin-1-yl]-2-methyl-1-phenylpropan-1-one;dihydrochloride 、 ammonium hydroxide 以68%的产率得到
  参考文献：
  名称：

  VEJDELEK, Z.;PROTIVA, M., COLLECT. CZECH. CHEM. COMMUN., 1983, 48, N 10, 2977-2988

  摘要：

  DOI：

文献信息

• Potential antitussives: Synthesis and pharmacology of a series of 1-[2-amino-2-(4-fluorophenyl)ethyl]-4-(2-benzoylpropyl)piperazines
  作者：Zdeněk Vejdělek、Miroslav Protiva

  DOI：10.1135/cccc19832977

  日期：——

  Compound V, obtained by a reaction of 2-chloro-4'-fluoroacetophenone with 1-(ethoxycarbonyl)piperazine, was reduced with sodium borohydride to the amino alcohol VIf. The hydrochloride of VIf was treated with thionyl chloride to give the hydrochloride of 1-[2-chloro-2-(4-fluorophenyl)ethyl]-4-(ethoxycarbonyl)piperazine (VIg). The crude VIg was subjected to substitution reactions with diethylamine, pyrrolidine, piperidine, morpholine and 1-methylpiperazine in benzene at 60 °C. The obtained aminocarbamates VIa-VIe were hydrolyzed with concentrated ethanolic potassium hydroxide and gave the amines VIIa-VIIe. Mannich reactions of the hydrochlorides of these compounds with paraformaldehyde and propiophenone (and 4-hydroxypropiophenone, respectively) resulted in the title compounds IIIa-IIIe, IVa,b and IVd,e. Only substances IIIa and IIId were found to have an antitussic activity in rats and guinea-pigs comparable to that of eprazinone (I). In higher doses they brought about central depression, ataxia and ptosis in mice and some of them adrenolytic and hypotensive effects in rats.

  通过将2-氯-4'-氟乙酰苯酮与1-(乙氧羰基)哌嗪反应得到化合物V，然后用硼氢化钠还原为氨基醇VIf。将VIf的盐酸盐与亚硫酰氯处理得到1-[2-氯-2-(4-氟苯基)乙基]-4-(乙氧羰基)哌嗪的盐酸盐（VIg）。粗制的VIg在苯中与二乙胺、吡咯烷、哌啶、吗啉和1-甲基哌嗪进行取代反应，产生氨基氨基甲酸酯VIa-VIe。用浓缩的乙醇钾氢氧化物水解VIa-VIe，得到胺类物质VIIa-VIIe。这些化合物的盐酸盐与多聚甲醛和丙酮苯酮（和对羟基丙酮苯酮，分别）进行Mannich反应，得到标题化合物IIIa-IIIe、IVa,b和IVd,e。只有IIIa和IIId这两种物质在大鼠和豚鼠中显示出与依普拉津酮（I）相当的止咳活性。在较高剂量下，它们会导致小鼠出现中枢抑制、共济失调和上睑下垂，部分物质在大鼠中还表现出肾上腺素拮抗和降压作用。
• VEJDELEK, Z.;PROTIVA, M., COLLECT. CZECH. CHEM. COMMUN., 1983, 48, N 10, 2977-2988
  作者：VEJDELEK, Z.、PROTIVA, M.

  DOI：——

  日期：——