1-氯-4-甲氧基-2,3-二甲基苯 | 14804-26-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 1-氯-4-甲氧基-2,3-二甲基苯
• 英文名称: 4-chloro-2,3-dimethylanisole
• 英文别名: 1-Chloro-4-methoxy-2,3-dimethylbenzene
• CAS: 14804-26-3
• 化学式: C₉H₁₁ClO
• 分子量: 170.639
• InChiKey: HHBADVDGSLERMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-氯-4-甲氧基-2,3-二甲基苯 在 N-溴代丁二酰亚胺(NBS) 、 甲酸 、 偶氮二异丁腈 、 碳酸氢钠 、 potassium nitrate 、 三氟乙酸 作用下， 以 甲醇 、 氯苯 为溶剂， 反应 4.17h， 生成 1-methoxy-7-(morphoin-4-yl)-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-2-ylamine
  参考文献：
  名称：

  Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122

  摘要：

  Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.

  DOI：

  10.1021/op200313v
• 作为产物：
  描述：

  2,3-二甲基苯甲醚 在 aluminum oxide 、 sodium chlorite 、 (salen)Mn(III) 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以85%的产率得到1-氯-4-甲氧基-2,3-二甲基苯
  参考文献：
  名称：

  Selective aromatic chlorination of activated arenes with sodium chlorite, (salen)manganese(III) complex, and alumina in dichloromethane

  摘要：

  烷基苯醚与氯化钠在二氯甲烷中，在（salen）锰（III）配合物和预加载少量水的氧化铝存在下，在温和条件下生成了具有异常高对位选择性的单氯化产物。基于NaClO₂的两相体系也可以成功用于对取代苯酚和多甲氧基苯的区域选择性单氯化。关键词：芳香族氯化、烷基芳基醚、氯化钠、（salen）锰（III）配合物、氧化铝。

  DOI：

  10.1139/v97-625

文献信息

• Selective aromatic chlorination of activated arenes with sodium chlorite, (salen)manganese(III) complex, and alumina in dichloromethane
  作者：Masao Hirano、Shigetaka Yakabe、Hiroyuki Monobe、Takashi Morimoto

  DOI：10.1139/v97-625

  日期：1997.12.1

  The reaction of alkyl phenyl ethers with sodium chlorite in dichloromethane in the presence of a (salen)manganese(III) complex and alumina preloaded with a small amount of water afforded monochlorination products with unusually high para selectivities under mild conditions. The NaClO₂-based biphasic system can also be successfully used for the regioselective monochlorination of substituted anisoles and polymethoxybenzenes. Keywords: aromatic chlorination, alkyl aryl ethers, sodium chlorite, (salen)manganese(III) complex, alumina.

  烷基苯醚与氯化钠在二氯甲烷中，在（salen）锰（III）配合物和预加载少量水的氧化铝存在下，在温和条件下生成了具有异常高对位选择性的单氯化产物。基于NaClO₂的两相体系也可以成功用于对取代苯酚和多甲氧基苯的区域选择性单氯化。关键词：芳香族氯化、烷基芳基醚、氯化钠、（salen）锰（III）配合物、氧化铝。
• 2-(Aminomethyl)phenols, a new class of saluretic agents. 1. Effects of nuclear substitution
  作者：G. E. Stokker、A. A. Deana、S. J. DeSolms、E. M. Schultz、R. L. Smith、E. J. Cragoe、J. E. Baer、C. T. Ludden、H. F. Russo

  DOI：10.1021/jm00186a024

  日期：1980.12

  A series of 2-(aminomethyl)phenols was synthesized and tested in rats and dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration. The most active compounds belong to a subseries of 4-alkyl-6-halo derivatives of which 2, 2-(aminomethyl)-4-(1,1-dimethylethyl)-6-iodophenol, is the most active. Compound 2 also possesses significant

  合成了一系列2-（氨基甲基）酚，并在大鼠和狗中测试了其利尿和利尿活性。这些化合物中的许多在静脉内或口服给药时表现出高活性。活性最高的化合物属于4-烷基-6-卤代衍生物的子系列，其中2，2-（氨基甲基）-4-（1,1-二甲基乙基）-6-碘酚是最具活性的。化合物2还具有显着的降压活性，这是一种辅助药理参数，可将2与本系列制备的其他化合物区分开。此外，2显示局部利尿和抗炎活性。
• ¹³C N.M.R. STUDIES: VIII. ¹³C SPECTRA OF SOME SUBSTITUTED ANISOLES
  作者：K. S. Dhami、J. B. Stothers

  DOI：10.1139/v66-425

  日期：1966.12.1

  The 13C nuclear magnetic resonance spectra of a series of 40 substituted anisoles have been obtained to investigate the effects of substitution on the aromatic and methoxyl carbon shieldings. This work extends our studies on the variations of chemical shifts of carbon nuclei in side chains of aryl derivatives. The question of steric hindrance to conjugative interaction of a methoxyl group with an aromatic

  已经获得了一系列 40 种取代苯甲醚的 13C 核磁共振谱，以研究取代对芳烃和甲氧基碳屏蔽的影响。这项工作扩展了我们对芳基衍生物侧链中碳核化学位移变化的研究。基于目前的结果考虑了甲氧基与芳环的共轭相互作用的空间位阻问题。提供了两个邻位都被取代的化合物中空间效应的证据。
• INHIBITORS OF p38
  申请人：Bemis Guy W.

  公开号：US20110281878A1

  公开（公告）日：2011-11-17

  The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

  本发明涉及p38的抑制剂，p38是一种哺乳动物蛋白激酶，参与细胞增殖、细胞死亡和对细胞外刺激的反应。本发明还涉及制备这些抑制剂的方法。本发明还提供了包含本发明抑制剂的药物组合物，并提供了利用这些组合物治疗和预防各种疾病的方法。
• Biphasic electrophilic halogenation of activated aromatics and heteroaromatics with N-halosuccinimides catalyzed by perchloric acid
  作者：Yuri Goldberg、Howard Alper

  DOI：10.1021/jo00063a028

  日期：1993.5

  Catalytic amounts of 70% perchloric acid (0.1-10, mostly 0.1-1, mol %, based on substrate) initiate the regioselective halogenation of activated aromatics [mesitylene, 1,3-dimethoxybenzene, 2,3-dimethylanisole, o-xylene] and heteroaromatics [thiophene, its 2-methyl, 2-halo (chloro, bromo, iodo), and 3-bromo derivatives] with N-halosuccinimide (NXS, X = Cl or Br) in two-phase solid-liquid systems (NXS/hexane or NXS/CCl4) at room temperature to give ring-halogenated products in high yields. For example, thiophene is transformed to 2-halo or 2,5-dihalo derivatives (yield 82-98%) using 1 or 2 equiv of NXS, respectively. Unsymmetrical 2,5-dihalothiophenes are obtained in 70-82% yield by reacting 2-halothiophenes with an appropriate NXS. The reaction of 3-bromothiophene with NBS affords 2,3-dibromothiophene in 93-99% yield. 1,3-Dimethoxybenzene and 2,3-dimethylanisole are halogenated regiospecifically at the 4 position to give the corresponding products in 81-94% yield.