1-carbomethoxy-6-methoxy-2-tetralone | 13838-42-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-carbomethoxy-6-methoxy-2-tetralone
• 英文别名: 6-Methoxy-2-oxo-1,2,3,4-tetrahydro-naphthalin-1-carbonsaeuremethylester；methyl 6-methoxy-2-oxo-3,4-dihydro-1H-naphthalene-1-carboxylate
• CAS: 13838-42-1
• 化学式: C₁₃H₁₄O₄
• 分子量: 234.252
• InChiKey: PEJXXLAIAAQBRT-UHFFFAOYSA-N

物化性质

• 沸点：
  144 °C(Press: 0.5 Torr)
• 密度：
  1.205±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-carbomethoxy-6-methoxy-2-tetralone 在 三氯化铝 、 二异丁基氢化铝 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 乙硫醇 、 三氯氧磷 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 22.0h， 生成 2,8-Bis[(tert-butyldimethylsilyl)oxy]-5H-benzo[b]naphtho[2,1-d]pyran-5-ol
  参考文献：
  名称：

  Synthesis and Pharmacology of Conformationally Restricted Raloxifene Analogues:  Highly Potent Selective Estrogen Receptor Modulators

  摘要：

  The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator (SERM) which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. In vivo structure-activity relationships and molecular modeling studies have indicated that the orientation of the basic amine-containing side chain of 1, relative to the stilbene plane, is an important discriminating factor for the maintenance of tissue selectivity. We have constructed a series of analogues of 1 in which this side chain is held in an orientation which is orthogonal to the stilbene plane, similar to the low-energy conformation predicted for raloxifene. Herein, we report on the synthesis of these compounds and on their activity in a series of in vitro and in vivo biological assays reflective of the SERM profile. In particular, we describe their ability to (I) bind the estrogen receptor, (2) antagonize estrogen-stimulated proliferation of MCF-7 cells in vitro, (3) stimulate TGF-beta 3 gene expression in cell culture, (4) inhibit the uterine effects of ethynyl estradiol in immature rats, and (5) potently reduce serum cholesterol and protect against osteopenia in ovariectomized (OVX) rats without estrogen-like stimulation of uterine tissue. These data demonstrate that one of these compounds, LY357489, 4, is among the most potent SERMs described to date with in vivo efficacy on bone and cholesterol metabolism in OVX rats at doses as low as 0.01 mg/kg/d.

  DOI：

  10.1021/jm970688z
• 作为产物：
  描述：

  Methyl 5-(3-methoxyphenyl)-3-oxo-2-(phenyl-lambda3-iodanylidene)pentanoate 在 copper(l) iodide 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以90%的产率得到1-carbomethoxy-6-methoxy-2-tetralone
  参考文献：
  名称：

  芳基取代的碘化碘鎓与氯化铜的分子内环化

  摘要：

  衍生自邻甲氧基苯基，间甲氧基和对甲氧基苯基-3-酮戊酸甲酯的苯基碘鎓碘化物的Cu（I）Cl分解得到相应的5-，6-和7-甲氧基-1-羰基甲氧基-2-四氢萘酮产量。衍生自邻甲氧基苯基，间甲氧基苯基和对甲氧基苯基-3-酮丁酸甲酯的低级同源苯基碘鎓烷基化物仅在间甲氧基苯基的情况下产生类似的1-甲氧基甲氧基-2-茚满酮，而邻甲氧基和对甲氧基苯基被取代碘化碘鎓可产生二聚产物。

  DOI：

  10.1016/s0040-4039(97)00967-2

文献信息

• Pentacyclic compounds, intermediates, processes, compositions, and
  申请人：Eli Lilly and Company

  公开号：US05726186A1

  公开（公告）日：1998-03-10

  The present invention provides compounds of formula I: ##STR1## wherein X is --O-- or --S--, Y is --O--, --S--, --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, or --NR.sup.5 --; R.sup.1, R.sup.2, and R.sup.3 are each independently --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl), --OSO.sub.2 CF.sub.3, Cl, or F; n is 1 or 2; W is CH.sub.2 or C.dbd.O; R.sup.4 is 1-piperidinyl, 2-oxo-1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; R.sup.5 is C.sub.1 -C.sub.3 alkyl, --COC.sub.6 H.sub.5, --CO(C.sub.1 -C.sub.6 alkyl), --C(O)OC.sub.6 H.sub.5, --C(O)O(C.sub.1 -C.sub.6 alkyl), --SO.sub.2 (C.sub.1 -C.sub.6 alkyl), --SO.sub.2 C.sub.6 H.sub.5, or --SO.sub.2 CF.sub.3 ; or a pharmaceutically acceptable salt or solvate thereof.

  本发明提供了式I的化合物：##STR1## 其中X为- O-或-S-，Y为- O-，- S-，- CH.sub.2-，- CH.sub.2 CH.sub.2-，- CH.dbd.CH-或-NR.sup.5-；R.sup.1，R.sup.2和R.sup.3各自独立地为- H，- OH，- O（C.sub.1-C.sub.4烷基），- OCOC.sub.6H.sub.5，- OCO（C.sub.1-C.sub.6烷基），- OSO.sub.2（C.sub.4-C.sub.6烷基），- OSO.sub.2CF.sub.3，- Cl或- F；n为1或2；W为CH.sub.2或C.dbd.O；R.sup.4为1-哌啶基，2-氧代-1-哌啶基，1-吡咯烷基，甲基-1-吡咯烷基，二甲基-1-吡咯烷基，2-氧代-1-吡咯烷基，4-吗啉基，二甲基氨基，二乙基氨基或1-己亚甲基亚胺基；R.sup.5为C.sub.1-C.sub.3烷基，- COC.sub.6H.sub.5，- CO（C.sub.1-C.sub.6烷基），- C（O）OC.sub.6H.sub.5，- C（O）O（C.sub.1-C.sub.6烷基），- SO.sub.2（C.sub.1-C.sub.6烷基），- SO.sub.2C.sub.6H.sub.5或- SO.sub.2CF.sub.3；或其药学上可接受的盐或溶剂。
• A Facile Method for the Solution and Solid-Phase Synthesis of Substituted [3.3.1] Bicycles
  作者：K. C. Nicolaou、Jeffrey A. Pfefferkorn、Guo-Qiang Cao、Sanghee Kim、Jilali Kessabi

  DOI：10.1021/ol990791d

  日期：1999.9.1

  [reaction: see text] Interest in bicyclic natural products from the Guttiferae classification has led to the development of an improved method for the selenium-mediated cyclization of alkenyl-substituted beta-dicarbonyls (I) to form a variety of bicyclo[3.3.1]nonan-9-ones (II) both in solution and on solid support.

  [反应：见正文]对古蒂科分类中的双环天然产物的兴趣已导致开发了一种改进的方法，该方法用于硒介导的烯基取代的β-二羰基（I）的环化反应以形成多种双环[3.3.1]溶液和固体支持物上的] nonan-9-ones（II）。
• Ring fragmentation processes resulting from acid catalysed diazo ketone cyclisations
  作者：Oliver E. Hutt、Lewis N. Mander、Anthony C. Willis

  DOI：10.1016/j.tetlet.2005.05.009

  日期：2005.7

  The initial products from the cyclisation of hexahydrophenanthryl diazo ketones with participation by either the alkene bonds or the aromatic ring (Ar1,4) undergo rearrangement by 1,2 bond shifts or unexpected bond fission. Benzocyclo-octanyl ketones were formed from the latter process.

  六氢菲基重氮酮在烯烃键或芳环（Ar 1,4）的参与下环化的初始产物会发生1,2键移位或意外的键裂，从而发生重排。苯并环辛基酮是由后一种方法形成的。
• Pentacyclic compounds, intermediates, processes, compositions, and methods
  申请人：ELI LILLY AND COMPANY

  公开号：EP0761669B1

  公开（公告）日：2000-11-22
• O-Arylation versus C-Arylation:  Copper-Catalyzed Intramolecular Coupling of Aryl Bromides with 1,3-Dicarbonyls
  作者：Yewen Fang、Chaozhong Li

  DOI：10.1021/jo060747t

  日期：2006.8.1

  The copper-catalyzed intramolecular coupling of aryl bromides with 1,3-dicarbonyls via a six-membered ring closure was examined. With CuI (10 mol %) as the catalyst, N,N'-dimethylethylenediamine as the ligand, and Cs2CO3 as the base, the reactions of alpha-(2-bromobenzyl)-beta-keto esters in THF at refluxing temperature afforded the corresponding substituted 4H-1-benzopyrans in high yields via O-arylation. On the other hand, the reactions of delta-(2-bromophenyl)-beta-keto esters in refluxing dioxane led to the formation of 3,4-dihydronaphthalen-2(1H)-one derivatives via C-arylation.