4-(8-chloro[1,7]naphthyridin-6-yl)cyclohexanecarboxylic acid | 880466-46-6

• 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-chloro[1,7]naphthyridin-6-yl)cyclohexanecarboxylic acid
• 英文别名: trans-4-(8-chloro-[1,7]naphthyridin-6-yl)-cyclohexanecarboxylic acid；4-(8-Chloro-1,7-naphthyridin-6-yl)cyclohexanecarboxylic acid；4-(8-chloro-1,7-naphthyridin-6-yl)cyclohexane-1-carboxylic acid
• CAS: 880466-46-6
• 化学式: C₁₅H₁₅ClN₂O₂
• 分子量: 290.749
• InChiKey: GIVORNHULGHDDN-UHFFFAOYSA-N

物化性质

• 沸点：
  515.2±50.0 °C(Predicted)
• 密度：
  1.349±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(8-chloro[1,7]naphthyridin-6-yl)cyclohexanecarboxylic acid 、 3-氟苯基硼酸 在 di-μ-bromobis(tri-tert-butylphosphine)dipalladium(I) 、 potassium carbonate 作用下， 以 水 为溶剂， 反应 2.0h， 以58%的产率得到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
• 作为产物：
  描述：

  4-(8-oxo-7,8-dihydro[1,7]naphthyridin-6-yl)cyclohexanecarboxylic acid 在 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 7.5h， 生成 4-(8-chloro[1,7]naphthyridin-6-yl)cyclohexanecarboxylic acid 、 4-(8-chloro[1,7]naphthyridin-6-yl)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。
• 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
  申请人：Jiang Xinglong

  公开号：US20070293678A1

  公开（公告）日：2007-12-20

  A process for the manufacture of isoquinoline and 1,7-naphthyridine derivatives of formula wherein R 1 , R 2 , R 3 , R 4 and X have the meanings as indicated in the specification. The process utilizes readily available starting materials of the formulae or compounds prepared from such starting materials wherein R 1 , R 2 , R 3 and X have meanings as defined for formula (I); and R and R 5 are independently C 1 -C 7 -alkyl.

  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。
• 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
  申请人：Novartis AG

  公开号：EP1791842A1

  公开（公告）日：2007-06-06
• A Scalable Synthesis of a 1,7-Naphthyridine Derivative, a PDE-4 Inhibitor
  作者：Xinglong Jiang、George T. Lee、Edwin B. Villhauer、Kapa Prasad、Mahavir Prashad

  DOI：10.1021/op100124x

  日期：2010.7.16

  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.