3,4-dihydro-3-methyl-1,6-naphthyridin-2(1H)-one | 40000-83-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3,4-dihydro-3-methyl-1,6-naphthyridin-2(1H)-one
• 英文别名: 1,2,3,4-Tetrahydro-3-methyl-2-oxo-1,6-naphthyridin；3-methyl-3,4-dihydro-1H-[1,6]naphthyridin-2-one；1,2,3,4-Tetrahydro-3-methyl-2-oxo-1,6-naphthyridine；3-methyl-3,4-dihydro-1H-1,6-naphthyridin-2-one
• CAS: 40000-83-7
• 化学式: C₉H₁₀N₂O
• 分子量: 162.191
• InChiKey: IATCGWRUEGBBQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-3-methyl-1,6-naphthyridin-2(1H)-one 在 palladium on activated charcoal 作用下， 以 萘烷 为溶剂， 反应 48.0h， 以69%的产率得到3-methyl-1H-[1,6]naphthyridin-2-one
  参考文献：
  名称：

  Synthesis of 3-Methyl and 7-Methyl Regio Isomers of Medorinone

  摘要：

  3-aminocrotononitrile (2) 与甲基丙烯酸甲酯 (3) 和 2-丙炔酸甲酯 (9) 反应，分别生成 1,4,5,6-四氢-2,5-二甲基-6-氧代-3-吡啶甲腈 (4) 和 1,6-二氢-2-甲基-6-氧代-3-吡啶甲腈 (10)。 4 与 Bredereck 试剂[双（二甲基氨基）-叔丁氧基甲烷]缩合，以及 6-甲氧基-2-甲基-3-吡啶甲腈（12）与 N,N-二甲基乙酰胺二甲基缩醛缩合，得到相应的烯胺 5 和 13，再与溴化氢环化，分别得到溴萘啶酮 6 和 14。6 脱溴后脱氢得到 3-甲基-1,6-萘啶-2(1H)-酮（8）。 14 在催化还原作用下脱溴，得到 7-甲基-1,6-萘啶-2(1H)-酮 (15)

  DOI：

  10.1055/s-1991-26604
• 作为产物：
  描述：

  2-<2-(dimethylamino)ethenyl>1,4,5,6-tetrahydro-5-methyl-6-oxo-3-pyridinecarbonitrile 在 palladium on activated charcoal 氢溴酸 、 氢气 、 potassium acetate 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 3,4-dihydro-3-methyl-1,6-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Synthesis of 3-Methyl and 7-Methyl Regio Isomers of Medorinone

  摘要：

  3-aminocrotononitrile (2) 与甲基丙烯酸甲酯 (3) 和 2-丙炔酸甲酯 (9) 反应，分别生成 1,4,5,6-四氢-2,5-二甲基-6-氧代-3-吡啶甲腈 (4) 和 1,6-二氢-2-甲基-6-氧代-3-吡啶甲腈 (10)。 4 与 Bredereck 试剂[双（二甲基氨基）-叔丁氧基甲烷]缩合，以及 6-甲氧基-2-甲基-3-吡啶甲腈（12）与 N,N-二甲基乙酰胺二甲基缩醛缩合，得到相应的烯胺 5 和 13，再与溴化氢环化，分别得到溴萘啶酮 6 和 14。6 脱溴后脱氢得到 3-甲基-1,6-萘啶-2(1H)-酮（8）。 14 在催化还原作用下脱溴，得到 7-甲基-1,6-萘啶-2(1H)-酮 (15)

  DOI：

  10.1055/s-1991-26604

文献信息

• [EN] TETRAHYDROQUINOLONES AND AZA-ANALOGUES THEREOF FOR USE AS DPP-IV INHIBITORS IN THE TREATEMENT OF DIABETES<br/>[FR] TETRAHYDROQUINOLONES ET AZA-ANALOGUES ASSOCIES UTILISES EN TANT QU'INHIBITEURS DE LA DPP-IV DANS LE TRAITEMENT DU DIABETE
  申请人：ASTRAZENECA AB

  公开号：WO2005123685A1

  公开（公告）日：2005-12-29

  Compound of formula (I) or a pharmaceutically-acceptable salt thereof, formula (I) wherein Ar is optionally substituted phenyl; R1 is selected from: formula a) or b) (wherein is a single or double bond); R5, R6, R7 and R8 are for example hydrogen or alkyl; R4 is selected from hydrogen, (3-4C)cycloalkyl and optionally substituted (1-4C)alkyl; R10 is for example selected from hydrogen, (1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, hydroxy(1-4C)alkyl, (1-4C)alkoxy, aryl(1-4C)alkyl; Y is carbon and Ring A is optionally substituted phenylene; or each Y may independently be carbon or nitrogen and Ring A is optionally substituted 5- or 6-membered, heteroarylene ring; R11 is selected from hydrogen and optionally substituted phenyl; p is independently at each occurrence 0, 1 or 2; are described. Processes for making such compounds and their use as DPP-IV inhibitors in the treatment of diabetes are also described.

  化合物的化学式（I）或其药用可接受的盐，其中化学式（I）中Ar是可选择的取代苯基；R1选自：化学式a）或b）（其中是单键或双键）；R5、R6、R7和R8例如是氢或烷基；R4选自氢、（3-4C）环烷基和可选择的取代（1-4C）烷基；R10例如选自氢、（1-4C）烷基、（3-6C）环烷基（1-4C）烷基、羟基（1-4C）烷基、（1-4C）烷氧基、芳基（1-4C）烷基；Y是碳，环A是可选择的取代苯基；或每个Y可以独立地是碳或氮，环A是可选择的取代的5-或6-成员的杂芳烃环；R11选自氢和可选择的取代苯基；p在每次出现时独立地为0、1或2；描述了制备这类化合物的过程以及它们作为DPP-IV抑制剂在糖尿病治疗中的用途。
• Certain 2-(1H)-pyridinones cardiotonic compositions containing same and
  申请人：Sterling Drug Inc.

  公开号：US04415580A1

  公开（公告）日：1983-11-15

  1-R"-3-Q-4-R'-5-R-1,6-naphthyridin-2(1H)-ones (I) or salts thereof, where R is lower-alkyl, R' is hydrogen or methyl, R" is hydrogen or lower-alkyl, and Q is hydrogen, hydroxy, amino, cyano, carbamyl, carboxy or aminocarbamyl, are useful as cardiotonic agents (I, Q is hydrogen, hydroxy, amino, cyano or carbamyl) and/or intermediates therefor (I, Q is carboxy, aminocarbamyl, hydrogen, amino, cyano or carbamyl). Also shown are 3-Q"-4-R'-5-(RCO)-6-[2-(di-lower-alkylamino)ethenyl]-2(1H)-pyridinones (II) or salts thereof, where R and R' are as above and Q' is hydrogen or cyano, which are useful as cardiotonics (II, Q' is hydrogen) and/or intermediates (II, Q' is cyano or hydrogen). Processes for preparing the compounds of formulas I and II are shown.

  1-R"-3-Q-4-R'-5-R-1,6-萘啶并[2(1H)-酮]（I）或其盐，其中R为低碳基，R'为氢或甲基，R"为氢或低碳基，Q为氢、羟基、氨基、氰基、氨基甲酰基、羧基或氨基甲酰基，可作为心力衰竭药物（I，Q为氢、羟基、氨基、氰基或氨基甲酰基）和/或其中间体（I，Q为羧基、氨基甲酰基、氢、氨基、氰基或氨基甲酰基）。还显示了3-Q"-4-R'-5-(RCO)-6-[2-(二低碳基氨基)乙烯基]-2(1H)-吡啶酮（II）或其盐，其中R和R'如上所述，Q'为氢或氰基，可作为心力衰竭药物（II，Q'为氢）和/或其中间体（II，Q'为氰基或氢）。显示了制备I和II式化合物的过程。
• 5-Alkyl-1,6-naphthyridin-2(1H)-ones and cardiotonic use thereof
  申请人：Sterling Drug Inc.

  公开号：US04517190A1

  公开（公告）日：1985-05-14

  1-R"-3-Q-4-R'-5-R-1,6-naphthyridin-2(1H)-ones (I) or salts thereof, where R is lower-alkyl, R' is hydrogen or methyl, R" is hydrogen or lower-alkyl, and Q is hydrogen, hydroxy, amino, cyano, carbamyl, carboxy or aminocarbamyl, are useful as cardiotonic agents (I, Q is hydrogen, hydroxy, amino, cyano or carbamyl) and/or intermediates therefor (I, Q is carboxy, aminocarbamyl, hydrogen, amino, cyano or carbamyl). Also shown are 3-Q'-4-R'-5-(RCO)-6-[2-(di-lower-alkylamino)ethenyl]-2(1H)-pyridinones (II) or salts thereof, where R and R' are as above and Q' is hydrogen or cyano, which are useful as cardiotonics (II, Q' is hydrogen) and/or intermediates (II, Q' is cyano or hydrogen). Processes for preparing the compounds of formulas I and II are shown.

  1-R"-3-Q-4-R'-5-R-1,6-萘啶并[2(1H)-酮]（I）或其盐，其中R为低碳基，R'为氢或甲基，R"为氢或低碳基，Q为氢、羟基、氨基、氰基、氨基甲酰基、羧基或氨基甲酰基，作为强心剂（I，Q为氢、羟基、氨基、氰基或氨基甲酰基）和/或其中间体（I，Q为羧基、氨基甲酰基、氢、氨基、氰基或氨基甲酰基）有用。还显示了3-Q'-4-R'-5-(RCO)-6-[2-(二低碳基氨基)乙烯基]-2(1H)-吡啶酮（II）或其盐，其中R和R'如上所述，Q'为氢或氰基，它们作为强心剂（II，Q'为氢）和/或中间体（II，Q'为氰基或氢）有用。显示了制备公式I和II化合物的过程。
• 3-Substituted-5-alkyl-1,6-naphthyridin-2(1H)-ones, cardiotonic use and
  申请人：Sterling Drug Inc.

  公开号：US04559347A1

  公开（公告）日：1985-12-17

  1-R"-3-Q-4-R'-5-R-1,6-naphthyridin-2(1H)-ones (I) or salts thereof, where R is lower-alkyl, R' is hydrogen or methyl, R" is hydrogen or lower-alkyl, and Q is hydrogen, hydroxy, amino, cyano, carbamyl, carboxy or aminocarbamyl, are useful as cardiotonic agents (I, Q is hydrogen, hydroxy, amino, cyano or carbamyl) and/or intermediates therefor (I, Q is carboxy, aminocarbamyl, hydrogen, amino, cyano or carbamyl). Also shown are 3-Q'-4-R'-5-(RCO)-6-[2-di-lower-alkylamino)ethenyl]-2(1H)-pyridinones (II) or salts thereof, where R and R' are as above and Q' is hydrogen or cyano, which are useful as cardiotonics (II, Q' is hydrogen) and/or intermediates (II, Q' is cyano or hydrogen). Processes for preparing the compounds of formulas I and II are shown.

  1-R"-3-Q-4-R'-5-R-1,6-萘啶-2(1H)-酮(I)或其盐，其中R是低碳基，R'是氢或甲基，R"是氢或低碳基，Q是氢、羟基、氨基、氰基、氨基甲酰基、羧基或氨基甲酰基，可用作心力衰竭药物（I，Q为氢、羟基、氨基、氰基或氨基甲酰基）和/或其中间体（I，Q为羧基、氨基甲酰基、氢、氨基、氰基或氨基甲酰基）。还显示了3-Q'-4-R'-5-(RCO)-6-[2-二-低碳基氨基)乙烯基]-2(1H)-吡啶酮(II)或其盐，其中R和R'如上所述，Q'是氢或氰基，可用作心力衰竭药物（II，Q'为氢）和/或其中间体（II，Q'为氰基或氢）。显示了制备式I和式II化合物的方法。
• 5-(Hydroxyalkyl or alkanoyloxymethyl)-1,6-naphthyridin-2(1H)-one and
  申请人：Sterling Drug Inc.

  公开号：US04532247A1

  公开（公告）日：1985-07-30

  4-R'-5-Q-1,6-naphthyridin-2(1H)-ones (I), where R' is hydrogen or methyl and Q is hydroxymethyl, 1-hydroxyethyl alkanoyloxymethyl or 1-alkanoyloxyethyl, are produced by first reacting 4-R'-5-acetyl(or n-propanoyl)-6-[2-(di-lower-alkylamino]-2(1H)-pyridinone [III] with hydroxylamine or salt thereof to produce 4-R'-5-Q'-1,6-naphthyridin-2(1H)-one-6-oxide (II), where R' is defined as above and Q' is methyl or ethyl; next reacting II with an alkanoic anhydride to produce I where Q is alkanoyloxymethyl or 1-alkanoyloxyethyl; and, then hydrolyzing said alkanoyloxymethyl or -ethyl compound to produce I where Q is hydroxymethyl or 1-hydroxyethyl. Also shown is the cardiotonic use of II and I where Q is hydroxymethyl, 1-hydroxyethyl or alkanoyloxymethyl.

  4-R'-5-Q-1,6-萘啶并[2(1H)-酮]（I），其中R'为氢或甲基，Q为羟甲基，1-羟乙基脂肪酰氧甲基或1-脂肪酰氧乙基，通过首先将4-R'-5-乙酰基（或正丙酰基）-6-[2-(二低烷基)氨基]-2(1H)-吡啶酮[III]与羟胺或其盐反应，生成4-R'-5-Q'-1,6-萘啶并[2(1H)-酮]-6-氧化物（II），其中R'如上所述，Q'为甲基或乙基；然后将II与脂肪酸酐反应，生成Q为脂肪酰氧甲基或1-脂肪酰氧乙基的I；然后水解所述的脂肪酰氧甲基或乙基化合物，生成Q为羟甲基或1-羟乙基的I。还显示了II和Q为羟甲基、1-羟乙基或脂肪酰氧甲基的I的强心作用。