methyl (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-2,4-pentadienoate | 180867-78-1

• 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: methyl (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-2,4-pentadienoate
• 英文别名: SB 223706；methyl (2Z,4E)-5-(5,6-dichloroindol-2-yl)-2-methoxy-2,4-pentadienoate；methyl (2Z,4E)-5-(5,6-dichloro-1H-indol-2-yl)-2-methoxypenta-2,4-dienoate
• CAS: 180867-78-1
• 化学式: C₁₅H₁₃Cl₂NO₃
• 分子量: 326.179
• InChiKey: VUONTIGZNJVBHV-WLXMHCNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-2,4-pentadienoate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成 5-(5,6-dichloro-2-indolyl)-2-methoxy-2,4-pentadienoic acid
  参考文献：
  名称：

  合成破骨细胞抑制剂SB-242784

  摘要：

  破骨细胞抑制剂SB-242784（1）是由关键的吲哚中间体4制备的。有机锡2c与溴化丙烯酸酯11的“ Stille”交叉偶联提供了二烯12，它也是通过烯炔16的还原异构化过程获得的。溴酰胺3是由相应的酸制备7将其容易地从溴丙酮酸获得。

  DOI：

  10.1016/s0040-4039(03)00544-6
• 作为产物：
  描述：

  methyl (Z)-3-bromo-2-methoxyacrylate 在 双(乙腈)氯化钯(II) 、 tris-(dibenzylideneacetone)dipalladium(0) cesium fluoride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 2.0h， 生成 methyl (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-2,4-pentadienoate
  参考文献：
  名称：

  三组分钯催化的偶联反应合成2-二烯基吲哚SB 242784

  摘要：

  描述了使用新型一锅法Castro-Stephens-Suzuki反应作为关键反应合成SB 242784的方法。

  DOI：

  10.1016/s0040-4039(98)02161-3

文献信息

• Synthesis of 2-dienylindole, SB 242784, by a three-component palladium-catalyzed coupling reaction
  作者：Marvin S. Yu、Lewilynn Lopez de Leon、Michael A. McGuire、Glen Botha

  DOI：10.1016/s0040-4039(98)02161-3

  日期：1998.12

  The synthesis of SB 242784 using a novel one-pot Castro-Stephens-Suzuki reaction as the key reaction is described.

  描述了使用新型一锅法Castro-Stephens-Suzuki反应作为关键反应合成SB 242784的方法。
• Indole derivatives for the treatment of osteoporosis
  申请人：SmithKline Beecham SpA

  公开号：US20040010012A1

  公开（公告）日：2004-01-15

  A compound of formula (I), or a salt thereof, or a solvate thereof, wherein Ra represents a group R 5 which is hydrogen, alkyl or optionally substituted aryl and Rb represents a moiety of formula (a), wherein X represents a hydroxy or an alkoxy group wherein the alkyl group may be substitued or unsubstituted or X represents a group NR s R t wherein R s and R t each independently represent hydrogen, alkyl, substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted arylalkyl, an optionally substituted heterocyclic group or an optionally substituted heterocyclylalkyl group, or R s and R t together with the nitrogen to which they arm attached form a heterocyclic group; R 1 represents an alkyl or a substituted or unsubstituted aryl group; and R 2 , R 3 and R 4 each independently represent hydrogen, alkyl, aryl or substituted aryl; R 6 and R 7 each independently represent hydrogen, hydroxy, amino, alkoxy, optionally substituted aryloxy, optionally substituted benzyloxy, alkylamino, dialkylamino, halo, trifluoromethyl, trifluoromethoxy, nitro, alkyl, carboxy, carbalkoxy, carbamoyl, alkylcarbamoyl, or R 6 and R 7 together represent methylenedioxy, carbonyldioxy or carbonyldiamino; and R 8 represents hydrogen, hydroxy, alkynoyl, alkyl, aminoalkyl, hydroxyalkyl, carboxyalky, carbalkoxyalkyl, carbamoyl or aminosulphonyl; a process for preparing such a compound, a pharmaceutical composition containing such a compound and the use of such a compound in medecine.

  化合物的式子（I），或其盐或溶剂化物，其中Ra代表R5基团，该基团为氢，烷基或可选取代的芳基基团，而Rb代表式（a）的基团，其中X代表羟基或烷氧基基团，其中烷基基团可以被取代或未取代，或X代表NRsRt基团，其中Rs和Rt各自独立地代表氢，烷基，取代的烷基，可选取代的烯基，可选取代的芳基，可选取代的芳基烷基，可选取代的杂环基团或可选取代的杂环基团烷基，或Rs和Rt与它们连接的氮原子一起形成一个杂环基团；R1代表烷基或取代或未取代的芳基基团；而R2、R3和R4各自独立地代表氢，烷基，芳基或取代的芳基；R6和R7各自独立地代表氢，羟基，氨基，烷氧基，可选取代的芳氧基，可选取代的苯甲氧基，烷基氨基，二烷基氨基，卤素，三氟甲基，三氟甲氧基，硝基，烷基，羧基，羧酸烷酯，氨基甲酰基，烷基氨基甲酰基，或R6和R7一起代表亚甲二氧基，羰基二氧基或羰基二氨基；而R8代表氢，羟基，炔基酰基，烷基，氨基烷基，羟基烷基，羧基烷基，碳酰氧基烷基，氨基甲酰基或氨基磺酰基；制备这种化合物的过程，含有这种化合物的药物组成物以及这种化合物在医学中的使用。
• 5-(5,6-Dichloro-2-indolyl)-2-methoxy-2,4-pentadienamides:  Novel and Selective Inhibitors of the Vacuolar H⁺-ATPase of Osteoclasts with Bone Antiresorptive Activity
  作者：Stefania Gagliardi、Guy Nadler、Emanuela Consolandi、Carlo Parini、Marcel Morvan、Marie-Nöelle Legave、Pietro Belfiore、Andrea Zocchetti、Geoffrey D. Clarke、Ian James、Ponnal Nambi、Maxine Gowen、Carlo Farina

  DOI：10.1021/jm9800144

  日期：1998.5.1

  The vacuolar H+-ATPase (V-ATPase) located on the ruffled border of the osteoclast, is a proton pump which is responsible for secreting the massive amounts of protons that are required for the bone resorption process. With the aim to identify new agents which are able to prevent the excessive bone resorption associated with osteoporosis, we have designed a novel class of potent and selective inhibitors of the osteoclast proton pump, starting from the structure of the specific V-ATPase inhibitor bafilomycin A(1). Compounds 3a-d potently inhibited the V-ATPase in chicken osteoclast membranes (IC50 = 60-180 nM) and were able to prevent bone resorption by human osteoclasts in vitro at low-nanomolar concentrations. Notably, the EC50 of compound 3c in this assay was 45-fold lower than the concentration required for half-maximal inhibition of the V-ATPase from human kidney cortex. These results support the validity of the osteoclast proton pump as a useful molecular target to produce novel inhibitors of bone resorption, potentially useful as antiosteporotic agents.
• (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide, a novel, potent and selective inhibitor of the osteoclast V-ATPase
  作者：Guy Nadler、Marcel Morvan、Isabelle Delimoge、Pietro Belfiore、Andrea Zocchetti、Ian James、Denise Zembryki、Elizabeth Lee-Rycakzewski、Carlo Parini、Emanuela Consolandi、Stefania Gagliardi、Carlo Farina

  DOI：10.1016/s0960-894x(98)00660-x

  日期：1998.12

  Optimisation of a novel series of osteoclast ATPase inhibitors led to (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-( 1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (1) that was the most potent compound in an in vitro osteoclast ATPase assay and in human bone resorption assays. Two of the possible geometric isomers have also been prepared and shown to be significantly less potent than 1. (C) 1998 Elsevier Science Ltd. All rights reserved.
• [EN] 2-VINYL INDOLES, PYRIDO AND AZEPINO INDOLE DERIVATIVES, 2-ALKYNYL INDOLES, 2-ALKYNYL BENZO[b]FURANS, THEIR PRECURSORS AND NOVEL PROCESSES FOR THE PREPARATION THEREOF<br/>[FR] 2-VINYLINDOLES, DÉRIVÉS PYRIDO ET AZÉPINOINDOLE, 2-ALCYNYLINDOLES, 2-ALCYNYLBENZO[b]FURANNES, LEURS PRÉCURSEURS ET LEURS NOUVEAUX PROCÉDÉS DE PRÉPARATION
  申请人：LAUTENS MARK

  公开号：WO2007134421A1

  公开（公告）日：2007-11-29

  [EN] The present invention relates to the preparation of 2-vinyl indoles from ortho-gem-dibromovinylaniline compounds and alkene reagents using a palladium pre-catalyst, a base, and, in some instances, a ligand or additive. The present invention also relates to the preparation of pyrido and azepino derivatives via a palladium-catalyzed tandem intramolecular Buchwald-Hartwig amination and Heck coupling reaction of appropriately functionalized ortho-gem-dibromovinylanilines. The present invention also relates to the preparation of 2-alkynyl indoles from ortho-gem-dibromovinylaniline compounds and alkyne reagents using a palladium pre-catalyst, a copper pre-catalyst, a base, and a ligand. Novel processes for the preparation of benzo[b]furan compounds are also disclosed, wherein the 2-alkynyl benzo[b]furans are prepared from ortho-gem-dibromovinylphenol compounds and alkyne reagents using a palladium pre-catalyst, a copper pre-catalyst, a base, and a ligand.
  [FR] La présente invention concerne la préparation de 2-vinylindoles à partir de composés ortho-gem-dibromovinylanilineet de réactifs alcène, préparation dans laquelle on utilise un pré-catalyseur à base de palladium, une base, et, parfois, un ligand ou un additif. La présente invention concerne également la préparation de dérivés pyrido et azépino par l'intermédiaire d'une réaction intramoléculaire tandem catalysée par le palladium d'amination de Buchwald-Hartwig et de couplage de Heck d'ortho-gem-dibromovinylanilines convenablement fonctionnalisés. La présente invention concerne également la préparation de 2-alcynylindoles à partir de composés ortho-gem-dibromovinylaniline et de réactifs alcyne effectuée en utilisant un pré-catalyseur à base de palladium, un pré-catalyseur à base de cuivre, une base et un ligand. La présente invention concerne également des nouveaux procédés de préparation de composés benzo[b]furanne, où les 2-alcynylbenzo[b]furannes sont préparés à partir de composés ortho-gem-dibromovinylphénol et de réactifs alcyne en utilisant un pré-catalyseur à base de palladium, un pré-catalyseur à base de cuivre, une base et un ligand.