6-氯-2-甲基-3,4-联吡啶-5-甲腈 | 84884-31-1

• 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
• 中文名称: 6-氯-2-甲基-3,4-联吡啶-5-甲腈
• 英文名称: 6-chloro-2-methyl<3,4'-bipyridine>-5-carbonitrile
• 英文别名: 6-Chloro-2-methyl-3,4'-bipyridine-5-carbonitrile；2-chloro-6-methyl-5-pyridin-4-ylpyridine-3-carbonitrile
• CAS: 84884-31-1
• 化学式: C₁₂H₈ClN₃
• 分子量: 229.669
• InChiKey: GIBXLQVADBWCND-UHFFFAOYSA-N

物化性质

• 熔点：
  155-157 °C(Solv: chloroform (67-66-3))
• 沸点：
  380.3±42.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  49.6
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  6-氯-2-甲基-3,4-联吡啶-5-甲腈 在 硫酸 作用下， 反应 76.0h， 以83%的产率得到6-chloro-2-methyl<3,4'-bipyridine>-5-carboxamide
  参考文献：
  名称：

  An Efficient and Novel Synthesis of Fused Thiazol-2(3H)-ones

  摘要：

  Reaction of o-bromo aromatic amines (2, 4, 7, 10, 15) with ethyl potassium xanthate gave the corresponding fused thiazol-2(3H)-thiones (16, 19, 22) which in turn were first alkylated with methyl iodide and then treated with sodium methoxide to produce fused thiazol-2(3H)-ones (18, 21, 24). Treatment of 4-(4-pyridinyl)-benzenamine dihydrobromide (1) with DMSO gave 2-bromo-4-(4-pyridinyl)benzenamine (2). Reduction of 4-(4-bromo-3-nitrophenyl)-pyridine (3) with stannous chloride gave 2-bromo-5-(4-pyridinyl)-benzenamine (4). Treatment of 5-bromo-2-methyl[3,4'-bipyridin]-6(1H)-one (5) with phosphorous oxychloride and ammonia sequentially yielded amino compound (7). Hofmann reaction of 2-chloro-6-methyl-[3,4'-bipyridine]-3-carboxamide resulted in amino compound (10). 5-Acyl-6-methylpyridin-2(1H)-ones (11) were converted to 3-bromo-1,6-naphthyridin-2-amines (15) via a four-step sequence.

  DOI：

  10.3987/com-92-6193
• 作为产物：
  描述：

  米力农 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以66%的产率得到6-氯-2-甲基-3,4-联吡啶-5-甲腈
  参考文献：
  名称：

  Imidazo(1,2-a)pyridines. III. Synthesis and Bradycardic Activity of New 5-Imidazo(1,2-a)pyridin-6-ylpyridine Derivatives.

  摘要：

  基于强心药左普利酮（E-1020，1）的数据提示其正性变时效应较米力农（15）弱，我们致力于寻找不同于高藜芦胺衍生物的新型减缓心率药物。在1的吡啶环2-位引入烷氧基、硫醚基和氨基衍生物可产生减缓心率活性，而对血压和心肌收缩力影响不大。芳氧基类似物也能降低心率，其在苯环上邻位带有吸电子基团的成员显示出更高的活性。将咪唑并[1, 2-a]吡啶替换为吡啶后，活性减弱。这些化合物减缓心率的机制似乎是直接作用于窦房结。

  DOI：

  10.1248/cpb.40.1486

文献信息

• 2-(Substituted-amino)-5-(pyridinyl-nicotinonitriles, and their
  申请人：Sterling Drug Inc.

  公开号：US04362734A1

  公开（公告）日：1982-12-07

  Shown are cardiotonically active 2-RR'N-5-PY-6-Q-nicotinonitriles where R is methyl or ethyl, R' is hydrogen or methyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two substituents, and Q is hydrogen or methyl, the latter only when R' is hydrogen, or pharmaceutically acceptable acid-addition salts thereof. Also shown are cardiotonic compositions and a method for increasing cardiac contractility using as active components 2-RR'N-5-PY-6-Q-nicotinonitriles or pharmaceutically acceptable acid-addition salts thereof, where R, R', PY and Q are defined as above. Also shown is the process for preparing said 2-RR'N-5-PY-6-Q-nicotinonitriles by reacting a 2-halo-5-PY-6-Q-nicotinonitrile with an amine of the formula RR'NH.

  展示的是具有心脏强心作用的2-RR'N-5-PY-6-Q-烟酰腙，其中R为甲基或乙基，R'为氢或甲基，PY为4-或3-吡啶基或带有一或两个取代基的4-或3-吡啶基，Q为氢或甲基，仅当R'为氢时才为甲基，或其药学上可接受的酸加成盐。还显示了心脏强心组合物和使用2-RR'N-5-PY-6-Q-烟酰腙或其药学上可接受的酸加成盐作为活性成分来增加心脏收缩力的方法，其中R、R'、PY和Q的定义如上所述。还显示了通过将2-卤代-5-PY-6-Q-烟酰腙与RR'NH的胺反应制备所述2-RR'N-5-PY-6-Q-烟酰腙的过程。
• 3-Cyan-pyridine, Verfahren zu ihrer Herstellung und ihre pharmazeutische Verwendung
  申请人：ARZNEIMITTELWERK DRESDEN GmbH

  公开号：EP0200024A2

  公开（公告）日：1986-11-05

  Die Erfindung betrifft neue, in 2-Stellung mit Oxaalkylamino-, Aminoalkylamino- oder Oxaalkyloxy-Gruppen substituierte 3-Cyan-pyridine, die in 5-Stellung Pyridyl- oder Phenylreste enthalten. Die Verbindungen weisen kardiotonische, antiarrhythmische, vasodilatatorische, bronchodilatatorische sowie antiallergische Wirkungen auf.

  本发明涉及在 2 位被氧杂烷基氨基、氨基烷基氨基或氧杂烷氧基取代并在 5 位含有吡啶基或苯基的新 3-氰基吡啶。 这些化合物具有强心、抗心律失常、血管扩张、支气管扩张和抗过敏作用。
• Hagen; Klauschenz; Rumler, Pharmazie, 1990, vol. 45, # 3, p. 189 - 190
  作者：Hagen、Klauschenz、Rumler、Hagen、Heer、Mitzner、Niedrich、Lohmann

  DOI：——

  日期：——
• Klauschenz; Rumler; Hagen, Pharmazie, 1989, vol. 44, # 1, p. 23 - 25
  作者：Klauschenz、Rumler、Hagen、Hagen、Heer、Mitzner、Niedrich

  DOI：——

  日期：——
• Synthesis and cardiotonic activity of 6-substituted 5-cyano-(3,4′-bipyridine)-1′-oxides and related compounds: molecular structure of 5-cyano-6-morpholino-(3,4′-bipyridine)-1′-oxide (AWD 122–239)
  作者：E Klauschenz、V Hagen、B Wiesner、A Hagen、G Reck、EG Krause

  DOI：10.1016/0223-5234(94)90035-3

  日期：1994.1

  6-Chloro-3,4'-bipyridine-1-oxides 5 and 5-cyano-1,6-dihydro-2-methyl-6-oxo-3,4'-bipyridine-1'-oxide 7 have been prepared from the corresponding pyridine derivatives by oxidation using peracetic acid. Reaction of 5 with various amines gave the 6-substituted compounds 6. Some of the synthesized products 6 were subsequently converted by derivation into related analogues 8, 9 and 10. In this series 5-cyano-6-morpholino-(3,4'-bipyridine)-1'-oxide (AWD 122-239, 6a), exhibited remarkable positive inotropic potency in spontaneously beating isolated guinea-pig atria as well as in anesthetized pigs. Additionally, 6a showed nearly no inhibition of cyclic AMP phosphodiesterase III. The molecular and crystal structures were determined together with the molecular electrostatic potential and structure-activity relationships are discussed. The obtained results clearly indicate compound 6a as a new type of cardiotonic.