(5-chloro-2-hydroxyphenyl)dimorpholinomethane | 146801-09-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (5-chloro-2-hydroxyphenyl)dimorpholinomethane
• 英文别名: 4-chloro-2-(dimorpholinomethyl)phenol；5-chlorosalicylaldehyde morpholinal；4-chloro-2-(dimorpholin-4-ylmethyl)phenol
• CAS: 146801-09-4
• 化学式: C₁₅H₂₁ClN₂O₃
• 分子量: 312.796
• InChiKey: JTHRXIMTMHYRIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.71
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  45.17
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (5-chloro-2-hydroxyphenyl)dimorpholinomethane 反应 0.05h， 生成 4-(7-chloro-9-(2-methyl-1H-indol-3-yl)-2,3,4,4a,9,9a-hexahydro-1H-xanthen-4a-yl)morpholine
  参考文献：
  名称：

  The hit-to-lead optimization of 1,2,3,4,4a,9a-hexahydro-1H-xanthenes as glucocorticoid receptor antagonists

  摘要：

  The structure activity relationship (SAR) study of a 1,2,3,4,4a,9a-hexahydro-1H-xanthene series of selective, human glucocorticoid receptor alpha (hGR alpha) antagonists is reported. Compounds were screened using hydroxyapatite-based GR binding and MMTV-Luc co-transfection reporter gene assays. Four different regions of the scaffold were modified to assess the effects on hGRa antagonism and related potency. Compound 8d exhibits an 8-fold better bioactivity than the original hit 1a, as well as an improved chemical stability, which make it a promising lead for the subsequent optimization. (C) 2014 Ming-Wei Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2014.03.017
• 作为产物：
  描述：

  吗啉 、 5-氯代水杨醛 反应 0.33h， 以97%的产率得到(5-chloro-2-hydroxyphenyl)dimorpholinomethane
  参考文献：
  名称：

  Novel approach to 3,3-dimethyl-4-morpholino-3,4-dihydrocoumarins via hetero-Diels–Alder reaction

  摘要：

  A new four-step synthetic procedure has been developed to prepare 3,3-dimethyl-4-morpholino-3,4-dihydrocoumarins from substituted salicylaldehydes, morpholine, and isobutyraldehyde. It involves aminal formation, deamination, enamine formation, hetero-Diels-Alder reaction, hydrolysis, and oxidation. The aminal formation, subsequent one-pot domino deamination, enamine formation, and hetero-Diels-Alder reaction were achieved in microwave-assisted catalyst-free conditions. The following hydrolysis and oxidation steps, performed conventionally, gave quantitative yields. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.06.083

文献信息

• Synthesis of hexa-, tetra-, and dihydroxanthene derivatives from salicylaldehyde aminals
  作者：L. Yu. Ukhin、V. A. Kharlanov、E. V. Solomovich、O. V. Shishkin

  DOI：10.1007/bf02494643

  日期：1999.5

  Salicylaldehyde aminals react with cyclohexanone upon heating to form tetrahydroxanthene derivatives. The structure of one of these derivatives,viz., 5,7-dichloro-4a-morpholino-1,2,3,4-tetrahydro-4aH-xanthene, was established by X-ray diffraction analysis. The scheme of the reaction was suggested, which involves cycloaddition of intermediateo-methylenequinone (from aminal) and enamine (from cyclohexanone)

  水杨醛缩醛胺在加热时与环己酮反应形成四氢氧杂蒽衍生物。这些衍生物之一的结构，即 5,7-dichloro-4a-morpholino-1,2,3,4-tetrahydro-4aH-xanthene，通过 X 射线衍射分析确定。建议的反应方案包括中间体-亚甲基醌（来自胺醛）和烯胺（来自环己酮）的环加成。水杨醛缩醛胺与由环己酮形成的烯胺反应可以依次得到六氢氧杂蒽、四氢氧杂蒽和二氢氧杂蒽的衍生物。开发了合成这些化合物的程序。 N-取代的 4a-氨基-7-硝基-1,2,3,4-四氢-4aH-呫吨也通过二烷基铵 2-甲酰基-4-硝基苯氧化物与上述烯胺。
• ——
  作者：L. Yu. Ukhin

  DOI：10.1023/a:1023923226389

  日期：——

  Fusion of 2-methylindole with morphinals of substituted salicylaldehydes (in a ratio of 1 : 1) afforded 3-[(2-hydroxyaryl)morpholinomethyl]-2-methylindoles as normal products of the Mannich reaction. In some cases, the reactions with an excess of 2-methylindole resulted in unusual condensation accompanied by the replacement of the OH group by the morpholino group to form bis(2-methylindol-3-yl)(2-morpholinoaryl)methanes.