2,6-dimethyl-4-(trifluoromethyl)nicotinonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,6-dimethyl-4-(trifluoromethyl)nicotinonitrile
• 英文别名: 2,6-Dimethyl-4-(trifluoromethyl)-3-pyridinecarbonitrile；2,6-dimethyl-4-(trifluoromethyl)pyridine-3-carbonitrile
• 化学式: C₉H₇F₃N₂
• 分子量: 200.163
• InChiKey: VLZSWIZOZAREIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,6-dimethyl-4-(trifluoromethyl)nicotinonitrile 在 过氧化脲素 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 以62%的产率得到3-cyano-2,6-dimethyl-4-(trifluoromethyl)pyridine 1-oxide
  参考文献：
  名称：

  Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-O-methyltransferase

  摘要：

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.

  DOI：

  10.1021/jm1001524
• 作为产物：
  描述：

  三氟乙酰丙酮 、 3-氨基巴豆腈 以 乙醇 为溶剂， 反应 8.0h， 以73%的产率得到2,6-dimethyl-4-(trifluoromethyl)nicotinonitrile
  参考文献：
  名称：

  A Convenient and Regioselective Synthesis of 4-Trifluoromethylpyridines

  摘要：

  三氟甲基取代的β-二酮与一级烯胺，如β-氨基巴豆腈和乙基β-氨基巴豆酸酯，在区域选择性反应下，可以提供中等至良好的产率的4-三氟甲基吡啶。

  DOI：

  10.1055/s-1997-1354

文献信息

• Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-<i>O</i>-methyltransferase
  作者：László E. Kiss、Humberto S. Ferreira、Leonel Torrão、Maria João Bonifácio、P. Nuno Palma、Patrício Soares-da-Silva、David A. Learmonth

  DOI：10.1021/jm1001524

  日期：2010.4.22

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.
• A Convenient and Regioselective Synthesis of 4-Trifluoromethylpyridines
  作者：Isamu Katsuyama、Seiya Ogawa、Yoshihiro Yamaguchi、Kazumasa Funabiki、Masaki Matsui、Hiroshige Muramatsu、Katsuyoshi Shibata

  DOI：10.1055/s-1997-1354

  日期：1997.11

  Trifluoromethyl-substituted β-diketones regioselectively react with primary enamines such as β-aminocrotononitrile and ethyl β-aminocrotonate, providing moderate to good yields of 4-trifluoro-methylpyridines.

  三氟甲基取代的β-二酮与一级烯胺，如β-氨基巴豆腈和乙基β-氨基巴豆酸酯，在区域选择性反应下，可以提供中等至良好的产率的4-三氟甲基吡啶。