4,6-dichloro-2-methyl-5-phenylpyrimidine | 31778-27-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4,6-dichloro-2-methyl-5-phenylpyrimidine
• 英文别名: 4,6-dichloro-2-methyl-5-phenyl-pyrimidine；4,6-Dichlor-2-methyl-5-phenyl-pyrimidin
• CAS: 31778-27-5
• 化学式: C₁₁H₈Cl₂N₂
• 分子量: 239.104
• InChiKey: MJIRECIIDKZUGR-UHFFFAOYSA-N

物化性质

• 熔点：
  160 °C
• 沸点：
  319.4±42.0 °C(Predicted)
• 密度：
  1.318±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-2-methyl-5-phenylpyrimidine 在 bis-triphenylphosphine-palladium(II) chloride ammonium hydroxide 、 copper(l) iodide 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 3.0h， 生成 5-(4-Chlorophenyl)-6-phenylethynylpyrimidin-4-ylamine
  参考文献：
  名称：

  4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors

  摘要：

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.029
• 作为产物：
  描述：

  2-methyl-5-phenylpyrimidine-4,6-diol 在 三氯氧磷 作用下， 以50%的产率得到4,6-dichloro-2-methyl-5-phenylpyrimidine
  参考文献：
  名称：

  4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors

  摘要：

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.029

文献信息

• Heterocyclic Amplifiers of Phleomycin. VII. Phenyl-, Tolyl-, Phenoxy- and Benzyl-pyrimidines; also Some Carbocyclic Analogues
  作者：DJ Brown、BJ Cronin、S Lan、G Nardo

  DOI：10.1071/ch9850825

  日期：——

  Synthetic routes are described for 5-phenyl-, 5-p-chlorophenyl-, 2-p-tolyl-, 2- and 4-benzyl- and 4-phenoxy-pyrimidines, each bearing a sulfur-, nitrogen- or oxygen-linked basic side chain; also to analogous biphenyls and a diphenylmethane . These compounds were required for evaluation as amplifiers of phleomycin.

  本文介绍了 5-苯基、5-对氯苯基、2-对甲苯基、2-和 4-苄基以及 4-苯氧基嘧啶的合成路线，每种嘧啶都带有与硫、氮或氧相连的碱性侧链；还介绍了类似联苯和二苯基甲烷的合成路线。需要对这些化合物进行评估，以确定其是否可作为博来霉素的放大剂。
• Basford et al., Journal of the Chemical Society, 1947, p. 1354,1360
  作者：Basford et al.

  DOI：——

  日期：——
• 728. The ultra-violet absorption spectra of phenylpyrimidines
  作者：Allison Maggiolo、Peter B. Russell

  DOI：10.1039/jr9510003297

  日期：——
• 4-Amino-5-aryl-6-arylethynylpyrimidines: Structure–activity relationships of non-nucleoside adenosine kinase inhibitors
  作者：Mark A. Matulenko、Ernest S. Paight、Robin R. Frey、Arthur Gomtsyan、Stanley DiDomenico、Meiqun Jiang、Chih-Hung Lee、Andrew O. Stewart、Haixia Yu、Kathy L. Kohlhaas、Karen M. Alexander、Steve McGaraughty、Joseph Mikusa、Kennan C. Marsh、Steven W. Muchmore、Clarissa L. Jakob、Elizabeth A. Kowaluk、Michael F. Jarvis、Shripad S. Bhagwat

  DOI：10.1016/j.bmc.2006.12.029

  日期：2007.2

  A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-yipyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.