3-cyano-5-(pyridin-4-yl)-(1H)-pyridin-2-one | 62749-26-2

• 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: 3-cyano-5-(pyridin-4-yl)-(1H)-pyridin-2-one
• 英文别名: 1,2-dihydro-2-oxo-5-(4-pyridinyl)-nicotinonitrile；2-oxo-5-(4-pyridyl)-1,2-dihydropyridin-3-carbonitrile；1,2-Dihydro-2-oxo-5-(4-pyridinyl)-nicotinenitrile；3-Cyan-5-(pyrid-4-yl)-1,2-dihydro-pyrid-2-on；5-(pyridin-4-yl)-3-cyano pyridine-2(1H)-one；5-cyano-[3,4'-bipyridin]-6(1H)-one；2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile
• CAS: 62749-26-2
• 化学式: C₁₁H₇N₃O
• 分子量: 197.196
• InChiKey: SEQOYYYZFNJQSV-UHFFFAOYSA-N

物化性质

• 熔点：
  335-345 °C
• 沸点：
  452.1±45.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  3-cyano-5-(pyridin-4-yl)-(1H)-pyridin-2-one 在 硫酸 、 potassium hydrogencarbonate 作用下， 生成 5-甲酰胺[3,4'-联吡啶]-6(1H)-酮
  参考文献：
  名称：

  3-Cyano-5-(pyridinyl)-2(1H)-pyridinones

  摘要：

  作为心力衰竭药物有用的化合物是1-R-3-Q-5-PY-2(1H)-吡啶酮(I)，其中R是氢、较低的烷基或较低的羟基烷基，Q是氨基（首选）或NHAc，Ac是较低的烷酰基或较低的羧酰基，PY是带有一个或两个较低烷基取代基的4-、3-或2-吡啶基或4-、3-或2-吡啶基。相应的化合物中，Q为硝基、氨基甲酰基、氰基或氢的化合物可用作中间体，Q为氢或氰基的化合物也可用作心力衰竭药物。所述化合物通过以下方法制备：通过将α-PY-β-(R1R2N)丙烯醛(II)与马来酰胺反应，生成1,2-二氢-2-氧代-5-PY-烟酰胺(Ia)，然后将Ia与能够将氨基转化为氨基的试剂反应，生成3-氨基-5-PY-2(1H)-吡啶酮(Ib)；通过将II或α-PY-马隆醛(II')与α-氰基乙酰胺反应，生成1,2-二氢-2-氧代-5-PY-烟酰腈(III)，部分水解III生成Ia；通过将1,2-二氢-2-氧代-5-PY-烟酸(IV)与浓硫酸和浓硝酸混合加热，生成3-硝基-5-PY-2(1H)-吡啶酮(Ic)，然后将Ic还原生成Ib，或者首先将Ic与烷基化剂反应生成1-R'-3-硝基-5-PY-2(1H)-吡啶酮(Id)，再将Id还原生成1-R'-3-氨基-5-PY-2(1H)-吡啶酮(Ib)，其中R'是较低的烷基或较低的羟基烷基。

  公开号：

  US04004012A1
• 作为产物：
  描述：

  3-dimethylamino-2-(4-pyridinyl)-2-propen-1-al 以 水 、 丙二腈 为溶剂， 生成 3-cyano-5-(pyridin-4-yl)-(1H)-pyridin-2-one
  参考文献：
  名称：

  Process for producing 3-cyano-5-(pyridinyl)-2(1H)-pyridinones

  摘要：

  一种制备1,2-二氢-2-氧代-5-(吡啶基)烟酰腈的方法，通过将α-(吡啶基)-β-[二(低烷基)氨基]丙烯醛与马隆腈在低烷醇中反应。该产品可用作心脏强效剂，并且也可用作制备相应的3-氨基-5-(吡啶基-2(1H)-吡啶酮)的中间体，进而用作心脏强效剂。

  公开号：

  US04223149A1

文献信息

• 5-(Pyridinyl)-2(1H)-pyridinones
  申请人：Sterling Drug Inc.

  公开号：US04107315A1

  公开（公告）日：1978-08-15

  Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotinic acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Id to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl. Other derivatives of I where Q is amino are shown.

  作为心力衰竭药物有用的化合物是1-R-3-Q-5-PY-2(1H)-吡啶酮（I），其中R是氢、低烷基或低羟基烷基，Q是氨基（首选）、低烷基氨基、二（低烷基）氨基或NHAc，Ac是低脂肪酰基或低羰基脂肪酸酯，PY是具有一个或两个低烷基取代基的4-或3-或2-吡啶基或4-或3-或2-吡啶基。Q为硝基、氨基甲酰基、氰基、卤素或氢的相应化合物可用作中间体，Q为氢或氰基的化合物也可用作心力衰竭药物。所述化合物的制备方法包括：通过将.alpha.-PY-.beta.-(R1R2N)丙烯醛（II）与马来酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酰胺（Ia），然后将Ia与能够将氨基甲酰转化为氨基的试剂反应，生成3-氨基-5-PY-2(1H)-吡啶酮（Ib）；通过将II或.alpha.-PY-马隆醛（II'）与.alpha.-氰基乙酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酰腈（III），然后部分水解III，生成Ia；通过将1,2-二氢-2-氧-5-PY-烟酸（IV）与浓硫酸和浓硝酸的混合物加热，生成3-硝基-5-PY-2(1H)-吡啶酮（Ic），然后将Ic还原生成Ib，或者首先将Ic与烷基化剂反应生成1-R'-3-硝基-5-PY-2(1H)-吡啶酮（Id），再将Id还原生成1-R'-3-氨基-5-PY-2(1H)-吡啶酮（Ib），其中R'是低烷基或低羟基烷基。显示了Q为氨基的I的其他衍生物。
• 3-Amino-5-(pyridinyl)-2(1H)-pyridinones
  申请人：Sterling Drug Inc.

  公开号：US04072746A1

  公开（公告）日：1978-02-07

  Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.-cyanoacetamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinonitrile (III) and partially hydrolyzing III to produce Ia; and, by heating 1,2-dihydro-2-oxo-5-PY-nicotinic acid (IV) with a mixture of concentrated sulfuric acid and concentrated nitric acid to produce 3-nitro-5-PY-2(1H)-pyridinone (Ic) and then either reducing Ic to produce Ib or first reacting Ic with an alkylating agent to produce 1-R'-3-nitro-5-PY-2(1H)-pyridinone (Id) and reducing Id to produce 1-R'-3-amino-5-PY-2(1H)-pyridinone (Ib) where R' is lower-alkyl or lower-hydroxyalkyl. Other derivatives of I where Q is amino are shown.

  作为强心药剂有用的化合物是1-R-3-Q-5-PY-2(1H)-吡啶酮（I），其中R是氢、低烷基或低羟基烷基，Q是氨基（首选）、低烷基氨基、二（低烷基）氨基或NHAc，Ac是低烷酰基或低羰基烷氧基，PY是4-或3-或2-吡啶基或带有一个或两个低烷基取代基的4-或3-或2-吡啶基。相应的化合物中，如果Q是硝基、氨基甲酰基、氰基、卤素或氢，则可用作中间体；其中Q是氢或氰基的化合物也可用作强心药剂。所述化合物的制备方法包括：通过将α-PY-β-(R1R2N)丙烯醛（II）与马来酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酰胺（Ia），然后将Ia与能够将氨基甲酰转化为氨基的试剂反应，生成3-氨基-5-PY-2(1H)-吡啶酮（Ib）；通过将II或α-PY-马隆醛（II'）与α-氰基乙酰胺反应，生成1,2-二氢-2-氧-5-PY-烟酸腈（III），然后部分水解III，生成Ia；通过将1,2-二氢-2-氧-5-PY-烟酸（IV）与浓硫酸和浓硝酸的混合物加热，生成3-硝基-5-PY-2(1H)-吡啶酮（Ic），然后将Ic还原生成Ib，或者首先将Ic与烷基化剂反应，生成1-R'-3-硝基-5-PY-2(1H)-吡啶酮（Id），然后将Id还原生成1-R'-3-氨基-5-PY-2(1H)-吡啶酮（Ib），其中R'是低烷基或低羟基烷基。展示了Q是氨基的I的其他衍生物。
• N-Hydroxy-1,2-dihydro-2-oxo-5-(pyridinyl)-nicotinimidamide and their
  申请人：Sterling Drug Inc.

  公开号：US04305948A1

  公开（公告）日：1981-12-15

  N-Hydroxy-1-R.sub.1 -1,2-dihydro-2-oxo-5-PY-6-R-nicotinimidamides or pharmaceutically-acceptable acid-addition salts thereof, useful as cardiotonic agents, are prepared by reacting 1-R.sub.1 -1,2-dihydro-2-oxo-5-PY-6-R-nicotinonitriles with hydroxylamine and are converted by reaction with polyphosphoric acid to the corresponding cardiotonically useful 1-R.sub.1 -3-amino-5-PY-6-R-2(1H)-pyridinones, where R.sub.1 is hydrogen, lower-alkyl and lower-hydroxyalkyl, R is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents.

  N-羟基-1-R.sub.1-1,2-二氢-2-氧-5-PY-6-R-烟酰亚胺或其药用酸盐，可用作心力衰竭药物，通过将1-R.sub.1-1,2-二氢-2-氧-5-PY-6-R-烟酰腈与羟胺反应制备，然后通过与多聚磷酸反应转化为相应的有益心力药物的1-R.sub.1-3-氨基-5-PY-6-R-2(1H)-吡啶酮，其中R.sub.1为氢、较低烷基和较低羟基烷基，R为氢或较低烷基，PY为4-或3-吡啶基或带有一个或两个较低烷基取代基的4-或3-吡啶基。
• 5-(Pyridinyl)-1H-pyrazolo[3,4-b]pyridine-3-amines, their use as
  申请人：Sterling Drug Inc.

  公开号：US04264603A1

  公开（公告）日：1981-04-28

  1-R-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridin-3-amines or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a 2-halo-5-PY-6-Q-nicotinonitrile with 1-R-hydrazine, where R is hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl or lower-alkoxyalkyl, Q is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Also shown are cardiotonic compositions and method for increasing cardiac contractility using said compounds or salts.

  用于作为心力增强剂的1-R-5-PY-6-Q-1H-吡唑并[3,4-b]吡啶-3-胺或其药用可接受的酸盐，通过将2-卤代-5-PY-6-Q-烟酰腈与1-R-肼反应制备，其中R为氢、较低的烷基、较低的羟基烷基、2,3-二羟基丙基或较低的烷氧基烷基，Q为氢或较低的烷基，PY为4-或3-吡啶基或带有一个或两个较低的烷基取代基的4-或3-吡啶基。还显示了心力增强剂组合物和使用所述化合物或盐增加心脏收缩力的方法。
• 5-(Pyridinyl)-1H-pyrazolo[3,4-b]pyridin-3-amines and their cardiotonic
  申请人：Sterling Drug Inc.

  公开号：US04361568A1

  公开（公告）日：1982-11-30

  1-R-3-(NB)-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridines or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a 1-R-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridin-3-amine with a lower-alkanoic acid and reducing agent to produce 1-R-3-(NB)-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridine (I) where NB is NHR.sub.1 or NR.sub.1 R.sub.2, with a mixture of formic acid and formaldehyde to produce I where NB is N(CH.sub.3).sub.2 or with a lower-acylating agent to produce I where NB is NHAc and, if desired, reacting the 3-(NHAc) compound with a reducing agent to prepare the corresponding 3-NHR.sub.1 compound, where R is lower-alkyl, lower-hydroxyalkyl, lower-acyloxy-(lower-alkyl) or lower-alkoxy-alkyl, Q is hydrogen or lower-alkyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, and NB is selected from NHR.sub.1, NR.sub.1 R.sub.2 or NHAc where R.sub.1 and R.sub.2 are each lower-alkyl and Ac is lower-acyl. Also shown are cardiotonic compositions and method for increasing cardiac contractility using said compounds or salts.

  1-R-3-(NB)-5-PY-6-Q-1H-吡唑并[3,4-b]吡啶或其药用酸盐，可作为心力衰竭药物，通过将1-R-5-PY-6-Q-1H-吡唑并[3,4-b]吡啶-3-胺与低碳酸和还原剂反应制备出1-R-3-(NB)-5-PY-6-Q-1H-吡唑并[3,4-b]吡啶(I)，其中NB为NHR.sub.1或NR.sub.1 R.sub.2，通过甲酸和甲醛的混合物产生I，其中NB为N(CH.sub.3).sub.2，或者通过低酰化剂产生I，其中NB为NHAc，并且如果需要，将3-(NHAc)化合物与还原剂反应以制备相应的3-NHR.sub.1化合物，其中R为低烷基、低羟基烷基、低酰氧基-(低烷基)或低烷氧基烷基，Q为氢或低烷基，PY为4-或3-吡啶基或带有一个或两个低烷基取代基的4-或3-吡啶基，NB选自NHR.sub.1、NR.sub.1 R.sub.2或NHAc，其中R.sub.1和R.sub.2各自为低烷基，Ac为低酰基。同时还展示了心力衰竭药物组合物和使用所述化合物或盐来增加心脏收缩力的方法。