2,4-dichloro-6-(4-methoxyphenylamino)pyrimidine | 333404-66-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,4-dichloro-6-(4-methoxyphenylamino)pyrimidine
• 英文别名: (2,6-dichloro-pyrimidin-4-yl)-(4-methoxy-phenyl)-amine；2,6-dichloro-N-(4-methoxyphenyl)pyrimidin-4-amine
• CAS: 333404-66-3
• 化学式: C₁₁H₉Cl₂N₃O
• 分子量: 270.118
• InChiKey: XVDURMABEAUMSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-dichloro-6-(4-methoxyphenylamino)pyrimidine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 正丁醇 为溶剂， 生成 2-N-cyclohexyl-6-N-(4-methoxyphenyl)-4-N-[4-(trifluoromethoxy)phenyl]pyrimidine-2,4,6-triamine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pyrimidine derivatives as sub-micromolar affinity ligands of GalR2

  摘要：

  GalR1 and GalR2 represent unique pharmacological targets for treatment of seizures and epilepsy. A novel series of 2,4,6-triaminopyrimidine derivatives were synthesized and found to have sub-micromolar affinity for GalR2. Optimization of a series of 2,4,6-triaminopyrimidines led to the discovery of several analogs with IC50 values ranging from 0.3 to 1 mu M. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.033
• 作为产物：
  描述：

  2,4,6-三氯嘧啶 、 甲氧苯胺 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以99%的产率得到2,4-dichloro-6-(4-methoxyphenylamino)pyrimidine
  参考文献：
  名称：

  2,4,6-三氯嘧啶。与苯胺反应

  摘要：

  已经研究了2,4,6-三氯嘧啶1与各种4-取代的苯胺2的反应。除含有强吸电子基团的苯胺外，所有苯胺都容易发生单取代。异构体产物3和4的产率平行于环取代基的哈米特常数。当使用乙醇作为溶剂时的主要产物是4-取代的2，6-二氯嘧啶3。光谱和X射线数据证实了这种归属。但是，证明了溶剂对3：4比例的依赖性。在某些情况下，在强迫条件下过量的苯胺会生成2,4-二取代的产物。

  DOI：

  10.1002/jhet.5570370609

文献信息

• 2,4,6-trichloropyrimidine. Reaction with anilines
  作者：Jennifer M. Schomaker、Thomas J. Delia

  DOI：10.1002/jhet.5570370609

  日期：2000.11

  The reaction of 2,4,6-trichloropyrimidine 1 with a variety of 4-substituted anilines 2 has been investigated. Monosubstitution occurs readily for all anilines except those containing strongly electron-withdrawing groups. The yields of the isomeric products 3 and 4 parallel the Hammet constants of the ring substituents. The main product when ethanol was used as the solvent was the 4-substituted-2,6-dichloropyrimidine

  已经研究了2,4,6-三氯嘧啶1与各种4-取代的苯胺2的反应。除含有强吸电子基团的苯胺外，所有苯胺都容易发生单取代。异构体产物3和4的产率平行于环取代基的哈米特常数。当使用乙醇作为溶剂时的主要产物是4-取代的2，6-二氯嘧啶3。光谱和X射线数据证实了这种归属。但是，证明了溶剂对3：4比例的依赖性。在某些情况下，在强迫条件下过量的苯胺会生成2,4-二取代的产物。
• [EN] ANTIVIRAL PYRIMIDINES<br/>[FR] PYRIMIDINES ANTIVIRALES
  申请人：PROGENICS PHARM INC

  公开号：WO2010118367A3

  公开（公告）日：2011-03-10
• Synthesis and biological evaluation of novel pyrimidine derivatives as sub-micromolar affinity ligands of GalR2
  作者：Vasudeva Naidu Sagi、Tianyu Liu、Xiaoying Lu、Tamas Bartfai、Edward Roberts

  DOI：10.1016/j.bmcl.2011.09.033

  日期：2011.12

  GalR1 and GalR2 represent unique pharmacological targets for treatment of seizures and epilepsy. A novel series of 2,4,6-triaminopyrimidine derivatives were synthesized and found to have sub-micromolar affinity for GalR2. Optimization of a series of 2,4,6-triaminopyrimidines led to the discovery of several analogs with IC50 values ranging from 0.3 to 1 mu M. (C) 2011 Elsevier Ltd. All rights reserved.
• 4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2
  作者：Veronique Mesguiche、Rachel J Parsons、Christine E Arris、Johanne Bentley、F.Thomas Boyle、Nicola J Curtin、Thomas G Davies、Jane A Endicott、Ashleigh E Gibson、Bernard T Golding、Roger J Griffin、Philip Jewsbury、Louise N Johnson、David R Newell、Martin E.M Noble、Lan Z Wang、Ian R Hardcastle

  DOI：10.1016/s0960-894x(02)00884-3

  日期：2003.1

  The cyclin dependent kinase (cdk) inhibitor NU6027, 4-cyclohexylmethoxy-5-nitroso-pyrimidine-2,6-diamine (IC50 vs cdk1/cyclinB1 = 2.9 +/- 0.1 muM and IC50 vs cdk2/cyclinA3 = 2.2 +/- 0.6 muM), was used as the basis for the design of a series of 4-alkoxy-2,6-diamino-5-nitrosopyrimidine derivatives. The synthesis and evaluation of 21 compounds as potential inhibitors of cyclin-dependent kinases 1 and 2 is described and the structure-activity relationships relating to NU6027 have been probed. Simple alkoxy- or cycloalkoxy-groups at the O-4-position were tolerated, with the 4-(2-methylbutoxy)-derivative (IC50 vs cdk1/cyclinB1 = 12 +/- 2 muM and cdk2/cyclinA3 = 13 +/- 4 muM) retaining significant activity. Substitutions at the N-6 position were not tolerated. Replacement of the 5-nitroso substituent with ketone, oxime and semicarbazone groups essentially abolished activity. However, the derivative bearing an isosteric 5-formyl group, 2,6-diamino-4-cyclohexylmethoxy-pyrimidine-5-carbaldehyde, showed modest activity (IC50 vs cdk1/cyclinB1 = 35 +/- 3 muM and cdk2/cyclinA3=43 +/- 3 muM). The X-ray crystal structure of the 5-formyl compound bound to cdk2 has been determined to 2.3 Angstrom resolution. The intramolecular H-bond deduced from the structure with NU6027 bound to cdk2 is not evident in the structure with the corresponding formyl compound. Thus the parent compound, 4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine (NU6027), remains the optimal basis for future structure-activity studies for cyclin-dependent kinase inhibitors in this series. (C) 2002 Elsevier Science Ltd. All rights reserved.