ethyl 6-(2-(4,4,7-trimethylthiochroman-6-yl)ethynyl)-nicotinate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ethyl 6-(2-(4,4,7-trimethylthiochroman-6-yl)ethynyl)-nicotinate
• 英文别名: Ethyl 6-[2-(4,4,7-trimethylthiochroman-6-yl)ethynyl]nicotinate；ethyl 6-[2-(4,4,7-trimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-3-carboxylate
• 化学式: C₂₂H₂₃NO₂S
• 分子量: 365.496
• InChiKey: VUBNMJPQGJUKEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,4,7-trimethyl-6-ethynylthiochroman 、 6-氯烟酸乙酯 、 在 双三苯基磷二氯化钯 氮气 、 乙酸乙酯 、 hexanes 、 silica 作用下， 以 三乙胺 为溶剂， 反应 18.0h， 生成 ethyl 6-(2-(4,4,7-trimethylthiochroman-6-yl)ethynyl)-nicotinate
  参考文献：
  名称：

  Disubstituted acetylenes bearing heteroaromatic and heterobicyclic

  摘要：

  化合物的式子为##STR1## 其中X为S，O或NR'，其中R'为氢或较低烷基；R为氢或较低烷基；A为吡啶基，噻吩基，呋喃基，吡嗪基，嘧啶基或吡嗪啉基；n为0-2；B为H，--COOH或其药学上可接受的盐，酯或酰胺，--CH.sub.2 OH或其醚或酯衍生物，或--CHO或其缩醛衍生物，或--COR.sub.1或其缩酮衍生物，其中R.sub.1为--(CH.sub.2).sub.m CH.sub.3，其中m为0-4，或其药学上可接受的盐。

  公开号：

  US05380877A1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF DISUBSTITUTED ACETYLENES BEARING HETEROAROMATIC AND HETEROBICYCLIC GROUPS<br/>[FR] PROCEDE DE PREPARATION D'ACETYLENES DISUBSTITUES PORTANT DES GROUPES HETEROAROMATIQUES ET HETEROBICYCLIQUES
  申请人：GLENMARK PHARMACEUTICALS LTD

  公开号：WO2005123713A1

  公开（公告）日：2005-12-29

  A process for the preparation of a disubstituted acetylene bearing heteroaromatic and heterobicyclic groups of formula I is provided wherein X is S, O, or NR1 wherein R1 is hydrogen or a C1-C6 straight or branched alkyl group; R is hydrogen or a C1-C6 straight or branched alkyl group; A is a substituted or unsubstituted pyridinyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl group; n is 0-­4; and B is H2 -COOH, -CH2OH, -CHO or a C1-C6 alkyl acetal derivative, -COR2 or a C1­C6 alkyl ketal derivative where R2 is -(CH2),,,CH3 where m is 0-4 or COOR3 wherein R3 is a straight or branched C1-C30 alkyl group, a substituted or unsubstituted C6-C30 aromatic group, a substituted or unsubstituted C3-C30 cycloalkyl, a substituted or unsubstituted C3­C30 cycloalkylalkyl, a substituted or unsubstituted C3-C30 cycloalkenyl, a substituted or unsubstituted C5-C30 aryl, a substituted or unsubstituted C5-C30 arylalkyl, a substituted or unsubstituted C5-C30 heteroaryl, a substituted or unsubstituted C3-C30 heterocyclic ring, a substituted or unsubstituted C4-C30 heterocyclylalkyl, a substituted or unsubstituted C6-C30 heteroarylalkyl, the process comprising a Sonogashira coupling reaction between a compound of formula II wherein X and R have the aforestated meanings, with a compound of formula III wherein X' is a halogen and A, n and B have the aforestated meanings, in the presence of a base and a transition metal catalyst and in a polar aprotic solvent.

  提供一种制备具有式I的含杂芳基和杂双环基的二取代乙炔的过程，其中X为S、O或NR1，其中R1为氢或C1-C6直链或支链烷基基团；R为氢或C1-C6直链或支链烷基基团；A为取代或未取代的吡啶基、噻吩基、呋喃基、吡啶嗪基、嘧啶基或吡啶基团；n为0-4；B为H2-COOH、-CH2OH、-CHO或C1-C6烷基缩醛衍生物、-COR2或C1-C6烷基缩酮衍生物，其中R2为-(CH2)mCH3，其中m为0-4或COOR3，其中R3为直链或支链C1-C30烷基基团、取代或未取代的C6-C30芳基、取代或未取代的C3-C30环烷基、取代或未取代的C3-C30环烷基烷基、取代或未取代的C3-C30环烯基、取代或未取代的C5-C30芳基、取代或未取代的C5-C30芳基烷基、取代或未取代的C5-C30杂芳基、取代或未取代的C3-C30杂环烷基、取代或未取代的C4-C30杂环烷基、取代或未取代的C6-C30杂芳基烷基，所述过程包括将具有上述含义的化合物II与具有上述含义的化合物III进行Sonogashira偶联反应，其中X和R具有上述含义，X'为卤素，A、n和B具有上述含义，在碱和过渡金属催化剂的存在下，在极性无氢溶剂中进行。
• [EN] DISUBSTITUTED ACETYLENES BEARING HETEROAROMATIC AND HETEROBICYCLIC GROUPS HAVING RETINOID-LIKE ACTIVITY<br/>[FR] ACETYLENES DISUBSTITUES A GROUPES HETEROAROMATIQUES ET HETEROBICYCLIQUES PRESENTANT UNE ACTIVITE DE TYPE RETINOIDE
  申请人：ALLERGAN

  公开号：WO1996011686A1

  公开（公告）日：1996-04-25

  (EN) Retinoid-like activity is exhibited by compounds of formula (I) where X is S, O, or NR' where R' is hydrogen or lower alkyl; R is hydrogen or lower alkyl; A is pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; and B is H, -COOH or a pharmaceutically acceptable salt, ester or amide thereof, -CH2OH or an ether or ester derivative, or -CHO or an acetal derivative, or -COR1 or a ketal derivative where R1 is -(CH2)mCH3 where m is 0-4, or a pharmaceutically acceptable salt thereof.(FR) Selon la présente invention, des composés de la formule générale (I) font preuve d'une activité de type rétinoïde. Dans cette formule générale, X est S, O ou NR', R' étant hydrogène ou alklye inférieur; R est hydrogène ou alkyle inférieur; A est pyridyle, thiényle, furyle, pyridazinyle, pyrimidinyle ou pyrazinyle; n est un entier de 0 à 4; et B est H, -COOH ou l'un de ses sels, esters ou amides acceptables du point de vue pharmaceutique, -CH2OH ou un dérivé éther ou ester, ou -CHO ou un dérivé acétal, ou -COR1 ou un dérivé cétal dans lequel R1 est -(CH2)mCH3, m étant un entier de 0 à 4, ou l'un de leurs sels acceptables du point de vue pharmaceutique.

  化合物的通式（I）中，具有类视视黄醇活性，其中X为S、O或NR'，其中R'为氢或低碳基；R为氢或低碳基；A为吡啶基、噻吩基、呋喃基、吡嗪基、嘧啶基或吡咯基；n为0-4；B为H、-COOH或其药学上可接受的盐、酯或酰胺，-CH2OH或其醚或酯衍生物，或-CHO或其缩醛衍生物，或-COR1或其缩酮衍生物，其中R1为-(CH2)mCH3，m为0-4，或其药学上可接受的盐。
• Process for the preparation of disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups
  申请人：Kumar Venkata Siva Bobba

  公开号：US20060106233A1

  公开（公告）日：2006-05-18

  A process for the preparation of a disubstituted acetylene bearing heteroaromatic and heterobicyclic groups of formula I is provided wherein X is S, O, or NR 1 wherein R 1 is hydrogen or a C 1 -C 6 straight or branched alkyl group; R is hydrogen or a C 1 -C 6 straight or branched alkyl group; A is a substituted or unsubstituted pyridinyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl group; n is 0-4; and B is H, —COOH, —CH 2 OH, —CHO or a C 1 -C 6 alkyl acetal derivative, —COR 2 or a C 1 -C 6 alkyl ketal derivative where R 2 is —(CH 2 ) m CH 3 where m is 0-4 or COOR 3 wherein R 3 is a straight or branched C 1 -C 30 alkyl group, a substituted or unsubstituted C 6 -C 30 aromatic group, a substituted or unsubstituted C 3 -C 30 cycloalkyl, a substituted or unsubstituted C 3 -C 30 cycloalkylalkyl, a substituted or unsubstituted C 3 -C 30 cycloalkenyl, a substituted or unsubstituted C 5 -C 30 aryl, a substituted or unsubstituted C 5 -C 30 arylalkyl, a substituted or unsubstituted C 5 -C 30 heteroaryl, a substituted or unsubstituted C 3 -C 30 heterocyclic ring, a substituted or unsubstituted C 4 -C 30 heterocyclylalkyl, a substituted or unsubstituted C 6 -C 30 heteroarylalkyl, the process comprising a Sonogashira coupling reaction between a compound of formula II wherein X and R have the aforestated meanings, with a compound of formula III X′-A-(CH 2 ) n —B  (III) wherein X′ is a halogen and A, n and B have the aforestated meanings, in the presence of a base and a transition metal catalyst and in a polar aprotic solvent.

  提供了一种制备公式I中含有杂原子芳香和杂环的二取代乙炔的方法，其中X为S、O或NR1，其中R1为氢或C1-C6直链或支链烷基；R为氢或C1-C6直链或支链烷基；A为取代或未取代的吡啶基、噻吩基、呋喃基、吡嗪基、嘧啶基或吡嗪基；n为0-4；B为H、-COOH、-CH2OH、-CHO或C1-C6烷基缩醛衍生物、-COR2或C1-C6烷基缩酮衍生物，其中R2为-(CH2)mCH3，其中m为0-4或COOR3，其中R3为直链或支链C1-C30烷基、取代或未取代C6-C30芳香基、取代或未取代C3-C30环烷基、取代或未取代C3-C30环烷基烷基、取代或未取代C3-C30环烯基、取代或未取代C5-C30芳基、取代或未取代C5-C30芳基烷基、取代或未取代C5-C30杂芳基、取代或未取代C3-C30杂环、取代或未取代C4-C30杂环基烷基、取代或未取代C6-C30杂芳基烷基，该方法包括在极性无水溶剂中，在碱和过渡金属催化剂的存在下，通过公式II的化合物与公式III的化合物进行Sonogashira偶联反应，其中X和R具有上述含义，X'为卤素，A、n和B具有上述含义。
• Disubstituted acetylenes bearing a diazinyl group having retinoid like
  申请人：Allergan, Inc.

  公开号：US05354752A1

  公开（公告）日：1994-10-11

  Retinoid-like activity is exhibited by compounds of the formula ##STR1## where X is S, O, or NR' where R' is hydrogen or lower alkyl; R is hydrogen or lower alkyl; A is pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; and B is H, --COOH or a pharmaceutically acceptable salt, ester or amide thereof, --CH.sub.2 OH or an ether or ester derivative, or --CHO or an acetal derivative, or --COR.sub.1 or a ketal derivative where R.sub.1 is --(CH.sub.2).sub.m CH.sub.3 where m is 0-4, or a pharmaceutically acceptable salt thereof.

  化合物的公式为##STR1##，其中X是S、O或NR'，其中R'是氢或较低的烷基；R是氢或较低的烷基；A是吡啶嗪基、嘧啶基或吡嗪基；n为0-4；B是H、--COOH或其药用可接受的盐、酯或酰胺，--CH.sub.2 OH或其醚或酯衍生物，或--CHO或其缩醛衍生物，或--COR.sub.1或其缩酮衍生物，其中R.sub.1为--(CH.sub.2).sub.m CH.sub.3，其中m为0-4，或其药用可接受的盐。
• Process and intermediates for preparing compounds having a disubstituted acetylene moiety and retinoic acid-like biological activity
  申请人：ALLERGAN, INC.

  公开号：EP0419132A2

  公开（公告）日：1991-03-27

  A process is disclosed for the preparation of disubstituted acetylene derivatives having retinoic acid like biological activity, wherein 6-ethynyl-chroman, 6-ethynyl-thio chroman and 6-ethynyl-1,2,3,4-tetrahydroquinoline derivatives of the formula shown below are reacted in the presence of catalysts with halogenated phenyl or heteroaryl derivatives of the formula shown below to provide the disubstituted acety­lenes. In the formulae the symbols have the following meanings, R₁, R₂, R₃, R₄ and R₅ are hydrogen or lower alkyl groups (of 1-6 carbons) where R₁, R₂, R₃, R₄ and R₅ may be identical or different from one another) X is S, O or NR′ where R′ is hydrogen or lower alkyl, Z represents hydrogen, or a metal ion capable of forming a salt with the ethynyl moiety of the molecule, X′ is a leaving group such as a halogeno group, A is phenyl, or heteroaryl such as pyridinyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl or oxazolyl, n is an intetger between 0 to 5, and B is H, -COOH or a pharma­ceutically acceptable salt, ester or amide thereof, -CH₂OH or an ether or ester derivative, or -CHO or an acetal derivative, or -COR₁ or a ketal derivative where R₁ is an alkyl, cycloal­kyl or alkenyl group containing 1 to 5 carbons.

  本发明公开了一种用于制备具有类视黄酸生物活性的二取代炔基衍生物的工艺，其中下式所示的 6-乙炔基-色满、6-乙炔基-硫代色满和 6-乙炔基-1,2,3,4-四氢喹啉衍生物在催化剂存在下与下式所示的卤代苯基或杂芳基衍生物反应，生成二取代炔基。 在式中，符号具有以下含义，R₁、R₂、R₃、R₄ 和 R₅ 是氢或低级烷基（1-6 个碳原子），其中 R₁、R₂、R₃、R₄ 和 R₅ 可以彼此相同或不同）X 是 S、O或NR′，其中R′是氢或低级烷基，Z代表氢或能与分子中的乙炔基形成盐的金属离子，X′是离去基团，如卤代基团、A 是苯基或杂芳基，如吡啶基、噻吩基、呋喃基、哒嗪基、嘧啶基、吡嗪基、噻唑基或噁唑基，n 是 0 至 5 之间的整数，B 是 H、-COOH 或药学上可接受的盐、CH₂OH或其醚或酯衍生物，或-CHO或其缩醛衍生物，或-COR₁或其缩酮衍生物，其中R₁是含 1 至 5 个碳原子的烷基、环烷基或烯基。