4-[8-(3-fluorophenyl)[1,7]naphthyridin-6-yl]-trans-cyclohexanecarboxylic acid | 880466-44-4

• 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: 4-[8-(3-fluorophenyl)[1,7]naphthyridin-6-yl]-trans-cyclohexanecarboxylic acid
• 英文别名: 4-(8-(3-trifluorophenyl)-1,7-naphthyridin-6-yl)-cyclohexanecarboxylic acid；trans-4-[8-(3-fluoro-phenyl)-[1,7]naphthyridin-6-yl]-trans-cyclohexanecarboxylic acid；4-[8-(3-fluorophenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylic Acid
• CAS: 880466-44-4
• 化学式: C₂₁H₁₉FN₂O₂
• 分子量: 350.392
• InChiKey: XWVBOPKUSVZZPJ-UHFFFAOYSA-N

物化性质

• 熔点：
  168-170 °C
• 沸点：
  552.6±50.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[8-(3-fluorophenyl)[1,7]naphthyridin-6-yl]-trans-cyclohexanecarboxylic acid 、 水 、 sodium hydroxide 、 在 乙腈 、 水 作用下， 以 乙腈 为溶剂， 反应 22.0h， 以to give 4-[8-(3-fluoro-phenyl)-[1,7]naphthyridin-6-yl]-trans-cyclohexanecarboxylic acid (trans >98%) as a white solid的产率得到
  参考文献：
  名称：

  Process For The Preparation Of 6, 8-Subs Tituted '1, 7 Naphthpyridin Derivatives By Reacting The 8-Halo-'1, 7 Naphthpyrid In-Derivate With An Organic Boronic Acid Derivatives And Intermadiates Of This Process

  摘要：

  一种制备公式中R1、R2、R3、R4和X所示的异喹啉和1,7-萘啉衍生物的工艺。该工艺利用公式（I）中定义的具有所述含义的R1、R2、R3和X的易得的起始材料或从这些起始材料制备的化合物，其中R和R5独立地为C1-C7烷基。

  公开号：

  US20070293678A1
• 作为产物：
  描述：

  3-吡啶乙腈 在 水 、 氢溴酸 、 双氧水 、 sodium carbonate 、 溶剂黄146 、 三苯基膦 、 lithium hydroxide 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 二甲氨基甲酰氯 、 锌 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 79.5h， 生成 4-[8-(3-fluorophenyl)[1,7]naphthyridin-6-yl]-trans-cyclohexanecarboxylic acid
  参考文献：
  名称：

  A Scalable Synthesis of a 1,7-Naphthyridine Derivative, a PDE-4 Inhibitor

  摘要：

  A six-step synthesis of a 4-[8-(3-fluorophenyl)[1,7]naphthyridin-6-yl]-trans-cyclohexanecarboxylic acid with an overall yield of 27% starting from 2-cyano-3-methylpyridine, cyclohexane-1,4-dicarboxylic acid dimethyl ester, and 3-fluorophenylboronic acid is described. The trans stereochemistry in the cyclohexane moiety was achieved through a series of equilibration steps at different stages of the synthesis.

  DOI：

  10.1021/op100124x

文献信息

• [EN] PROCESS FOR THE PREPARATION OF 6, 8-SUBSTITUTED `1, 7 NAPHTHPYRIDIN DERIVATIVES BY REACTING THE 8-HALO-`1, 7 NAPHTHPYRIDIN-DERIVATE WITH AN ORGANIC BORONIC ACID DERIVATIVES AND INTERMADIATES OF THIS PROCESS<br/>[FR] PROCESSUS DE PREPARATION DE DERIVES DE `1, 7!NAPHTHPYRIDINE 6, 8-SUBSTITUES PAR REACTION DE 8-HALO-DERIVAT DE `1, 7!NAPHTHPYRIDINE AVEC DES DERIVES D'ACIDE BORIQUE ORGANIQUE ET INTERMEDIAURES DE CE PROCESSUS
  申请人：NOVARTIS AG

  公开号：WO2006031959A1

  公开（公告）日：2006-03-23

  A process for the preparation of compounds of formula (I) wherein R1 is C1-C20-alkyl optionally substituted by one or two of hydroxy, C3-C12­cycloalkyl, C6-C12-aryl, C1-C7-alkoxy, thiol, C1-C7-alkylthio or carboxy, or R1 is C3-C12-cycloalkyl optionally substituted by one or two of C1-C7-alkyl, hydroxy, C1­C7-alkoxy, CI-C7-alkylthio or carboxy, or R1 is C6-C12-aryl optionally substituted by one, two, three or four substituents selected from C1-C7-alkyl, halo; hydroxy, C1-C7-alkoxy, C1-C7-alkylthio and nitro, or R1 is heteroaryl optionally substituted by C1-C7- alkyl, Cl-C7-alkoxy or halo; R2 and R3 are independently hydrogen or C1-C20-alkoxy; R4 is C6-C12-aryl optionally substituted by one, two, three or four substituents selected from C1-C7-alkyl, halo, hydroxy, C1-C7-alkoxy, C1-C7-alkylthio and nitro, or R4 is heteroaryl optionally substituted by C1-C7,- alkyl, C1-C7-alkoxy or halo; and X is N or CH; or a salt thereof; which process comprises coupling compounds of formula (VI) and Y is chloro or bromo in the presence of a catalyst and a base with a compound of the formula (VII) and R6 and R7 are hydrogen or, C1-C7-alkyl, or R6 and R7 combined are C2-C3 alkylene optionally substituted by one or two of C1-C4­-alkyl that together with the boron and the oxygen atoms form a 5- or 6-membered ring.

  一种制备化合物的方法，化合物的结构式为（I），其中R1是C1-C20烷基，可以选择地被一个或两个氢氧基、C3-C12环烷基、C6-C12芳基、C1-C7烷氧基、硫醇、C1-C7烷硫基或羧基取代；或者R1是C3-C12环烷基，可以选择地被一个或两个C1-C7烷基、氢氧基、C1-C7烷氧基、C1-C7烷硫基或羧基取代；或者R1是C6-C12芳基，可以选择地被一个、两个、三个或四个从C1-C7烷基、卤素、氢氧基、C1-C7烷氧基、C1-C7烷硫基和硝基中选取的取代基取代；或者R1是杂环芳基，可以选择地被C1-C7烷基、Cl-C7烷氧基或卤素取代；R2和R3独立地是氢或C1-C20烷氧基；R4是C6-C12芳基，可以选择地被一个、两个、三个或四个从C1-C7烷基、卤素、氢氧基、C1-C7烷氧基、C1-C7烷硫基和硝基中选取的取代基取代；或者R4是杂环芳基，可以选择地被C1-C7烷基、C1-C7烷氧基或卤素取代；X是N或CH；或其盐；该方法包括在催化剂和碱的存在下，通过偶联结合结构式为（VI）的化合物和Y为氯或溴的化合物，与结构式为（VII）的化合物反应，其中R6和R7是氢或C1-C7烷基，或者R6和R7组合成C2-C3烷基，可以选择地被一个或两个从C1-C4烷基取代，与硼和氧原子一起形成5-或6-成员环。
• Naphthyridine derivatives, their preparation and their use as phosphodiesterase isoenzyme 4 (pde4) inhibitors
  申请人：——

  公开号：US20040254212A1

  公开（公告）日：2004-12-16

  The invention relates to compounds of formula I 1 in free or salt form, where R 1 is a monovalent aromatic group having up to 10 carbon atoms, and R 2 is a cycloaliphatic group having up to 8 ring carbon atoms. Compositions containing them, methods for their preparation and their use as pharmaceuticals are also described.

  该发明涉及公式I1的化合物，以自由或盐形式存在，其中R1是具有最多10个碳原子的单价芳香基团，而R2是具有最多8个环碳原子的环烷基团。还描述了包含它们的组合物，它们的制备方法以及它们作为药物的用途。
• Naphthyridine derivatives, their preparation and their use as phosphodiesterase isoenzyme 4 (PDE4) inhibitors
  申请人：Novartis AG

  公开号：US07273875B2

  公开（公告）日：2007-09-25

  The invention relates to compounds of formula I in free or salt form, where R1 is a monovalent aromatic group having up to 10 carbon atoms, and R2 is a cycloaliphatic group having up to 8 ring carbon atoms. Compositions containing them, methods for their preparation and their use as pharmaceuticals are also described.

  本发明涉及公式I的化合物，其以自由或盐形式存在，其中R1是具有最多10个碳原子的一价芳香基团，而R2是具有最多8个环状碳原子的环状脂肪族基团。还描述了含有它们的组合物，它们的制备方法以及它们作为药物的用途。
• ORTHO-BENZYLPHENOL MONO(METH)ACRYLATE MONOMERS SUITABLE FOR MICROSTRUCTURED OPTICAL FILMS
  申请人：Hunt Bryan V.

  公开号：US20090275720A1

  公开（公告）日：2009-11-05

  Optical films having a polymerized microstructured surface and polymerizable resin compositions are described comprising at least one ortho-benzylphenol mono(meth)acrylate monomer.

  本文描述了具有聚合微结构表面的光学薄膜和聚合性树脂组合物，其中包括至少一种正苯基酚单（甲基）丙烯酸酯单体。
• Use of naphthyridine derivatives as medicaments
  申请人：Novartis AG

  公开号：EP2286813A2

  公开（公告）日：2011-02-23

  Compounds of formula I in free or salt form for the preparation of a medicament for the treatment of pulmonary hypertension, where R1 and R2 have the meanings as indicated in the specification. Pharmaceutical compositions that contain the compounds are also described.

  式 I 的化合物 游离或盐形式，用于制备治疗肺动脉高压的药物，其中 R1 和 R2 的含义如说明书所示。还描述了含有该化合物的药物组合物。