5-methoxy-1-(2-hydroxyethyl)indole | 714912-36-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-methoxy-1-(2-hydroxyethyl)indole
• 英文别名: 2-(5-methoxy-1H-indol-1-yl)ethan-1-ol；2-(5-methoxy-1H-indol-1-yl)ethanol；2-(5-methoxy-indol-1-yl)-ethanol；1H-Indole-1-ethanol, 5-methoxy-；2-(5-methoxyindol-1-yl)ethanol
• CAS: 714912-36-4
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: JLMZLOXHUQQRIC-UHFFFAOYSA-N

物化性质

• 沸点：
  367.1±22.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  34.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methoxy-1-(2-hydroxyethyl)indole 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 偶氮二甲酸二异丙酯 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 19.0h， 生成 N-(2-(5-methoxy-1H-indol-1-yl)ethyl)-4-methyl-N-(3-phenylprop-2-yn-1-yl)benzenesulfonamide
  参考文献：
  名称：

  通过金催化炔基吲哚的氢化和随后的氧化环化获得氮杂环化苯并[c]咔唑

  摘要：

  在此，我们报道了一种简便有效的合成方法，通过一种新型金（I）催化的炔基吲哚分子内加氢芳基化来构建 azepino[1,2- a ]indoles。在该转化过程中可以很好地耐受多种官能团，并且以中等至优异的产率获得了相应的高度官能化的氮杂[1,2- a ]吲哚骨架。随后的产物氧化得到了有趣且有价值的多环咔唑，它们被广泛用作材料科学的关键组成部分。

  DOI：

  10.1021/acs.orglett.2c02293
• 作为产物：
  描述：

  5-甲氧基吲哚 、 2-溴乙醇 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 生成 5-methoxy-1-(2-hydroxyethyl)indole
  参考文献：
  名称：

  铑（II）催化的1-磺酰基-1,2,3-三唑与吡咯和吲哚环的分子内环化反应：N-桥头氮杂骨架的简便合成

  摘要：

  已经开发了一种便捷有效的合成方法来构建高度功能化的N-桥头a氮骨架，这在生物和制药工业中具有重要意义。通过铑进行反应（II）卡宾氮杂乙烯基中间体，其发起分子内Ç 与吡咯基和吲哚基的环ħ官能化。在温和的反应条件下以高化学选择性，以中等至良好的收率获得了多种a庚因衍生物。所得产物的几种有趣的衍生化方法表明，该方法具有综合价值和实用性。

  DOI：

  10.1002/anie.201400881

文献信息

• β-Amino alcohols from anilines and ethylene glycol through heterogeneous Borrowing Hydrogen reaction
  作者：Pedro J. Llabres-Campaner、Rafael Ballesteros-Garrido、Rafael Ballesteros、Belén Abarca

  DOI：10.1016/j.tet.2017.08.006

  日期：2017.9

  Borrowing Hydrogen (BH), also called Hydrogen Autotransfer (HA), reaction with neat ethylene glycol represents a key step in the preparation of β-amino alcohols. However, due to the stability of ethylene glycol, mono-activation has rarely been achieved. Herein, a combination of Pd/C and ZnO is reported as heterogeneous catalyst for this BH/HA reaction. This system results in an extremely air and moisture

  与纯乙二醇的借入氢（BH）也称为氢自动转移（HA），是制备β-氨基醇的关键步骤。然而，由于乙二醇的稳定性，很少实现单活化。在此，据报道Pd / C和ZnO的组合作为该BH / HA反应的非均相催化剂。该系统产生了极好的空气和湿气稳定性，并且经济的催化剂能够将水中的乙二醇单官能化，而无需进一步活化二醇。在这项工作中，已经探索了不同的二醇和芳族胺，为氨基醇的开发提供了一种新方法。这项研究揭示了两种固体物质的组合如何在异相中提供有趣的催化性能。ZnO激活乙二醇，而Pd / C则负责BH / HA循环。重新芳香化之前的原位BH / HA循环，代表串联异质过程。
• Rhodium(II)‐Catalyzed Intramolecular Annulation of 1‐Sulfonyl‐1,2,3‐Triazoles with Pyrrole and Indole Rings: Facile Synthesis of N‐Bridgehead Azepine Skeletons
  作者：Jin‐Ming Yang、Cheng‐Zhi Zhu、Xiang‐Ying Tang、Min Shi

  DOI：10.1002/anie.201400881

  日期：2014.5.12

  method has been developed to construct highly functionalized N‐bridgehead azepine skeletons, which are of great importance in biological and pharmaceutical industry. The reaction proceeds through a rhodium(II) azavinyl carbene intermediate, which initiated the intramolecular CH functionalization with pyrrolyl and indolyl rings. A variety of azepine derivatives were obtained in moderate to good yields under

  已经开发了一种便捷有效的合成方法来构建高度功能化的N-桥头a氮骨架，这在生物和制药工业中具有重要意义。通过铑进行反应（II）卡宾氮杂乙烯基中间体，其发起分子内Ç 与吡咯基和吲哚基的环ħ官能化。在温和的反应条件下以高化学选择性，以中等至良好的收率获得了多种a庚因衍生物。所得产物的几种有趣的衍生化方法表明，该方法具有综合价值和实用性。
• Cu(I)-Catalyzed Intramolecular Tandem Cyclization of <i>N</i>-Indole-Tethered Cyclopropenes: Synthesis of Functionalized Hydrogenated Diazabenzo[<i>a</i>]cyclopenta[<i>cd</i>]azulene Derivatives
  作者：Peng-Hua Li、Song Yang、Tong-Gang Hao、Qin Xu、Min Shi

  DOI：10.1021/acs.orglett.9b00864

  日期：2019.5.3

  A Cu(I)-catalyzed [3 + 2] intramolecular cycloaddition reaction of N-indole-tethered cyclopropenes is presented in this paper. This reaction starts from the formation of π-allyl cationic intermediate or its resonance-stabilized metal carbenoid intermediate upon activation of cyclopropene with Cu(I) catalyst and a Friedel–Crafts-type cyclization to give functionalized hydrogenated diazabenzo[a]cyclopenta[cd]azulenes

  本文提出了Cu（I）催化的N吲哚系环丙烯的[3 + 2]分子内环加成反应。该反应始于在用Cu（I）催化剂活化环丙烯并进行Friedel-Crafts型环化反应以形成官能化的氢化二氮杂苯并[ a ]环戊[ cd ]之后，形成π-烯丙基阳离子中间体或其共振稳定的金属类化合物中间体。天青石的产量高到极好，dr值中等到良好。可以实现该环加成反应的不对称变体，从而得到具有中等ee值的所需产物。
• Synthesis of 3-Fluoro-2-hetarylindoles and 3,3-Difluoro-2-hetarylindolines through Lewis Acid-Catalyzed Formation of 3,3-Difluoroindolium Ions
  作者：Jacqueline Zi Mei Fong、Simon Sze Shiong Choo、Jean-Alexandre Richard、Marc V. Garland、Liangfeng Guo、Charles W. Johannes、Tuan Minh Nguyen

  DOI：10.1002/ejoc.201403443

  日期：2015.2

  Synthesis of 3-fluoro-2-hetarylindoles through addition of hetarenes to 3,3-difluoroindolium ions generated in situ by Zn(OTf)2-catalyzed oxazolidine ring opening is described. Indoles, pyrroles and alkyl-substituted furans can be used as hetaryl nucleophiles to afford a range of 3-fluoro-2-hetarylindole products 6 in 56–95 % yields. A diverse array of 3,3-difluorinated 2-hetarylindolines 7 can also

  描述了 3-氟-2-杂芳基吲哚的合成方法，即通过将杂环烃加成​​到由 Zn(OTf)2 催化的恶唑烷开环原位生成的 3,3-二氟吲哚离子上。吲哚、吡咯和烷基取代的呋喃可用作杂芳基亲核试剂，以 56-95% 的产率提供一系列 3-氟-2-杂芳基吲哚产物 6。一系列不同的 3,3-二氟化 2-杂芳基二氢吲哚 7 也可以通过串联顺序工艺以 43-84% 的产率合成，该工艺涉及芴烯亲核加成、HF 消除和氟环化反应。我们通过 1H NMR 和 UV/Vis 光谱的研究表明，3,3-二氟化 2-杂芳基二氢吲哚具有有趣的取代基依赖性酸致变色特性。还研究了所选化合物 6 和 7 的紫外吸收和荧光光谱。
• [EN] USE OF alpha-PHENYLTHIOCARBOXYLIC AND alpha-PHENYLOXYCARBOXYLIC ACIDS WITH SERUM-GLUCOSE-LOWERING AND SERUM-LIPID-LOWERING ACTIVITY<br/>[FR] UTILISATION D'ACIDES 20040708WO03059875A2SIGMA TAU IND FARMACEUTI [IT], et al200307241,74-7,14,17,18,20-26PX1-7,10,15PXWINEGAR D A ET AL: "Role of peroxisome proliferator-activated receptors in atherosclerosis", CURRENT OPINION IN CARDIOVASCULAR, PULMONARY AND RENAL INVESTIGATIONAL DRUGS 2000 UNITED KINGDOM, vol. 2, no. 3, 2000, pages 233 - 243, XP008029337, ISSN: 1464-8482WINEGAR D A ET ALRole of peroxisome proliferator-activated receptors in atherosclerosisCURRENT OPINION IN CARDIOVASCULAR, PULMONARY AND RENAL INVESTIGATIONAL DRUGS 2000 UNITED KINGDOM2000231464-8482233243page 236, left-hand column, last paragraph237L1,2<table>1</table>X1,2,7,8,10-12,15XBROOKS D A ET AL: "Design and synthesis of 2-methyl-2-{4-[2-(5-methyl-2- aryloxazol-4-yl)ethoxy]phenoxy}propionic acids: a new class of dual PPARalpha/gamma agonists", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 44, no. 13, 21 June 2001 (2001-06-21), pages 2061 - 2064, XP002184099, ISSN: 0022-2623BROOKS D A ET ALDesign and synthesis of 2-methyl-2-{4-[2-(5-methyl-2- aryloxazol-4-yl)ethoxy]phenoxy}propionic acids: a new class of dual PPARalpha/gamma agonistsJOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US2001062144130022-262320612064Chart 1<table>1</table>2063R1,2X1-3,7,10-12,15XLALEZARI I ET AL: "LR-16 A COMPOUND WITH POTENT EFFECTS ON THE OXYGEN AFFINITY OF HEMOGLOBIN ON BLOOD CHOLESTEROL AND ON LOW DENSITY LIPOPROTEIN", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 85, no. 16, 1988, 1988, pages 6117 - 6121, XP001161155, ISSN: 0027-8424LALEZARI I ET ALLR-16 A COMPOUND WITH POTENT EFFECTS ON THE OXYGEN AFFINITY OF HEMOGLOBIN ON BLOOD CHOLESTEROL AND ON LOW DENSITY LIPOPROTEINPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES1988198885160027-842461176121Scheme 1page 6117, abstractX1,2,10-12,15XUS3262850AMOSS JONES WILLIAM GLYNNE, et al19660726111719X1,2,10-12,15XGB1422679AFUNAI PHARMACEUTICAL IND LTD19760128112126X1,2,7,10-12,15XGRONOWITZ S ET AL: "POTENTIAL HYPOLIPIDEMIC AGENTS XIX. SYNTHESIS AND LIPID-LOWERING PROPERTIES OF THIOPHENE DERIVATIVES RELATED TO CLOFIBRATE", ACTA PHARMACEUTICA SUECICA, XX, XX, vol. 15, no. 5, 1978, pages 361 - 367, XP001053343, ISSN: 0001-6675GRONOWITZ S ET ALPOTENTIAL HYPOLIPIDEMIC AGENTS XIX. SYNTHESIS AND LIPID-LOWERING PROPERTIES OF THIOPHENE DERIVATIVES RELATED TO CLOFIBRATEACTA PHARMACEUTICA SUECICA, XX, XX19781550001-6675361367<table>1</table>3641X1,3,10-12,15XDURIEZ P ET AL: "POST-STATIN APPROACHES TO HYPERLIPIDAEMIA", EXPERT OPINION ON INVESTIGATIONAL DRUGS, ASHLEY PUBLICATIONS LTD., LONDON, GB, vol. 7, no. 12, December 1998 (1998-12-01), pages 1997 - 2009, XP000892408, ISSN: 1354-3784DURIEZ P ET ALPOST-STATIN APPROACHES TO HYPERLIPIDAEMIAEXPERT OPINION ON INVESTIGATIONAL DRUGS, ASHLEY PUBLICATIONS LTD., LONDON, GB1998127121354-37841997200920023.1Y1-15YBROWN P J ET AL: "A Ureido-Thiobutyric Acid (GW9578) is a subtype-Selective PPARalpha Agonist with Potent lipid-Lowering Activity", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 42, no. 19, 9 April 1999 (1999-04-09), pages 3785 - 3788, XP002128791, ISSN: 0022-2623BROWN P J ET ALA Ureido-Thiobutyric Acid (GW9578) is a subtype-Selective PPARalpha Agonist with Potent lipid-Lowering ActivityJOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US1999040942190022-262337853788Chart 1page 3787, left-hand column, last paragraphY1-15YGUERRE-MILLO MICHELE ET AL: "Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 275, no. 22, 2 June 2000 (2000-06-02), pages 16638 - 16642, XP002275720, ISSN: 0021-9258GUERRE-MILLO MICHELE ET ALPeroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposityJOURNAL OF BIOLOGICAL CHEMISTRY20000602275220021-9258166381664216641R3Y1-15YZHANG BEI B ET AL: "New approaches in the treatment of type 2 diabetes", CURRENT OPINION IN CHEMICAL BIOLOGY, vol. 4, no. 4, August 2000 (2000-08-01), pages 461 - 467, XP002275721, ISSN: 1367-5931ZHANG BEI B ET ALNew approaches in the treatment of type 2 diabetesCURRENT OPINION IN CHEMICAL BIOLOGY200008441367-5931461467463L31Y1-15YHAWKE ROY L ET AL: "Potent hypocholesterolemic activity of novel ureido phenoxyisobutyrates correlates with their intrinsic fibrate potency and not with their ACAT inhibitory activity", JOURNAL OF LIPID RESEARCH, vol. 38, no. 6, 1997, pages 1189 - 1203, XP002275722, ISSN: 0022-2275HAWKE ROY L ET ALPotent hypocholesterolemic activity of novel ureido phenoxyisobutyrates correlates with their intrinsic fibrate potency and not with their ACAT inhibitory activityJOURNAL OF LIPID RESEARCH19973860022-227511891203entire documentAA
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2004056355A1

  公开（公告）日：2004-07-08

  The use is described of derivatives of α-phenylthiocarboxylic and α-phenyloxycarboxylic acids with formula (I): in which the substituents have the meanings described in the text, for the preparation of a medicine for the prophylaxis and treatment of diabetes, particularly type 2 diabetes, its complications, the various forms of insulin resistance, and hyperlipidaemias.

  本文描述了使用具有以下公式（I）的α-苯基硫代羧酸和α-苯基氧羧酸的衍生物进行制备药物，用于预防和治疗糖尿病，特别是2型糖尿病、其并发症、各种形式的胰岛素抵抗和高脂血症。其中，取代基的含义在文本中有描述。