dimethyl 1,2,4,5-tetrahydro-3-oxobenzocycloheptene-2,4-dicarboxylate | 24790-66-7

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: dimethyl 1,2,4,5-tetrahydro-3-oxobenzocycloheptene-2,4-dicarboxylate
• 英文别名: dimethyl 3-oxo-1,2,4,5-tetrahydrobenzocycloheptene-2,4-dicarboxylate；Dimethyl 3-oxo-2,3,4,5-tetrahydro-1H-benzocycloheptene-2,4-dicarboxylate；dimethyl 3-oxo-1,2,4,5-tetrahydrobenzo[d]cycloheptene-2,4-dicarboxylate；dimethyl 7-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6,8-dicarboxylate；Dimethyl 1,2-benzo-1-cyclohepten-5-one-4,6-dicarboxylate；dimethyl benzo[d]cycloheptenone-6,8-dicarboxylate；dimethyl 7-oxo-5,6,8,9-tetrahydrobenzo[7]annulene-6,8-dicarboxylate
• CAS: 24790-66-7
• 化学式: C₁₅H₁₆O₅
• 分子量: 276.289
• InChiKey: AKTMCFLYKONPOD-UHFFFAOYSA-N

物化性质

• 熔点：
  84-88 °C
• 沸点：
  400.6±45.0 °C(Predicted)
• 密度：
  1.223±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl 1,2,4,5-tetrahydro-3-oxobenzocycloheptene-2,4-dicarboxylate 在 硫酸 、 palladium on activated charcoal 、 氢气 、 硝酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 potassium hydroxide 作用下， 以 甲醇 、 硝基甲烷 、 乙醇 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 生成 1-(6,7-二氢-5H-苯并[6,7]环庚烷并[1,2-c]哒嗪-3-基)-N3-[(7S)-6,7,8,9-四氢-7-(1-吡咯烷基)-5H-苯并环庚烯-2-基]-1H-1,2,4-三唑-3,5-二胺
  参考文献：
  名称：

  Bemcentinib. Tyrosine-protein kinase receptor UFO (Axl) inhibitor, Treatment of cancer

  摘要：

  Increased expression of Axl has been reported in various cancers including colon, esophageal, thyroid, breast, lung, liver and astrocytoma-glioblastoma. Cancer resistance to tyrosine kinase inhibitors and other chemotherapeutics has been correlated with aberrant expression of Axl. These findings support the development of Axl inhibitors in combination with targeted agents to tackle acquired resistance and high Axl levels. Bemcentinib (BGB-324, R-428) is an oral, potent and selective small-molecule inhibitor of Axl kinase in vitro with IC50 values in the low nanomolar range. In preclinical studies, bemcentinib demonstrated efficacy across multiple cancer models. It has also shown a favorable safety profile in clinical studies in cancer patients, and encouraging activity in acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC). Currently, there are phase II studies with bemcentinib ongoing in advanced NSCLC, triple-negative breast cancer, AML and myelodysplastic syndromes, and metastatic melanoma. Orphan drug designation was granted by the U.S. Food and Drug Administration for the treatment of AML.

  DOI：

  10.1358/dof.2018.043.09.2808543
• 作为产物：
  描述：

  1,3-丙酮二羧酸二甲酯 、 1,2-二(溴甲基)苯 生成 dimethyl 1,2,4,5-tetrahydro-3-oxobenzocycloheptene-2,4-dicarboxylate
  参考文献：
  名称：

  AXL INHIBITORS FOR USE IN COMBINATION THERAPY FOR PREVENTING, TREATING OR MANAGING METASTATIC CANCER

  摘要：

  本发明旨在提供一种用于预防、治疗或管理患者的癌症，特别是转移性癌症的方法。该方法包括在给予一种或多种化疗药物的有效剂量的同时，给予一种Axl抑制剂的有效剂量。

  公开号：

  US20170042891A1

文献信息

• Palladium-Catalysed Isomerisation of 2-Vinylidenehydrofurans to 1,3-Dienes and Some Aspects of Their Reactivity
  作者：Abdelkader Ghobsi、Salih Hacini、Laurence Wavrin、Anouk Gaudel-Siri、Agnès Corbères、Cyril Nicolas、Damien Bonne、Jacques Viala、Jean Rodriguez

  DOI：10.1002/ejoc.200800517

  日期：2008.9

  The transformation of easily accessible 2-vinylidenehydrofurans into stable 1,3-dienes has been achieved by using catalytic amounts of palladium(0). These valuable compounds were then engaged in subsequent Diels-Alder reactions giving access to complex heterocyclic cores found in numerous natural products. A rationale for the regioselectivity of the Diels-Alder reactions with vinylfurans has been provided

  使用催化量的钯 (0) 已实现将容易获得的 2-亚乙烯基氢呋喃转化为稳定的 1,3-二烯。这些有价值的化合物随后参与了随后的 Diels-Alder 反应，从而获得了在众多天然产物中发现的复杂杂环核。DFT 计算提供了 Diels-Alder 反应与乙烯基呋喃的区域选择性的基本原理。
• AMINOBENZOCYCLOHEPTENE DERIVATIVES, METHODS FOR PREPARING THE SAME AND USES THEREOF IN THERAPY
  申请人：Tarnus-Rondeau Céline

  公开号：US20100069504A1

  公开（公告）日：2010-03-18

  A compound of the general formula (I) as an active principle for treating cancer, specifically tumors, in particular diseases involving inhibition of metalloproteases, such as Aminopeptidase-N. Pharmaceutical compositions comprising the compound of general formula (I). Methods of treatment using the compound of general formula (I).

  一种具有一般化学式（I）的化合物作为治疗癌症的活性成分，特别是肿瘤，特别是涉及金属蛋白酶抑制的疾病，如氨基肽酶-N。包括具有一般化学式（I）的化合物的药物组合物。使用一般化学式（I）的化合物进行治疗的方法。
• New strategy to construct fused/bridged/spiro carbocyclic scaffolds based on the design of novel 6-C synthon precursor
  作者：Jia Liu、Xi Wang、Chang-Liang Sun、Bi-Jie Li、Zhang-Jie shi、Min Wang

  DOI：10.1039/c0ob00660b

  日期：——

  In this article we report a new strategy to build fused/spiro/bridged carbocyclic systems with a novel 6-C synthon from readily available diallyl diacetates through the sequential Pd-catalyzed double allyl alkylation and Diels–Alder annulation. Further exploration on the application of this strategy can construct useful complex scaffolds.

  在本文中，我们报告了一种新的策略，通过连续的钯催化双烯烃烷基化和Diels-Alder环加成，从易得的二烯丙基二酸酯构建带有新型6-C合成单元的融合/螺环/桥联碳环系统。对这一策略的进一步探索可以构建有用的复杂骨架。
• C−C versus C−O Anionic Domino Cycloalkylation of Stabilized Carbanions: Facile One-Pot Stereoselective Preparation of Functionalized Bridged Bicycloalkanones and Cyclic Enol Ethers
  作者：Tania Lavoisier-Gallo、Emmanuelle Charonnet、Jean-Marc Pons、Michel Rajzman、Robert Faure、Jean Rodriguez

  DOI：10.1002/1521-3765(20010302)7:5<1056::aid-chem1056>3.0.co;2-d

  日期：2001.3.2

  cycloalkylation, to synthetically valuable monocyclic or fused polycyclic functionalized enol ethers of high synthetic value. Semiempirical calculations showed a small difference in energy and the late character of the transition states leading to cis and trans isomers of the corresponding fused polycyclic enol ethers. These results, although minimizing the influence of a destabilizing 1,3-interaction

  α,α'-双活化环状或无环酮经历化学选择性碱促进（K2CO3，DBU）一锅 CC 环烷基化，1,3- 和 1,4-二卤化物具有顺式固定构型。该反应产生高度官能化的双环 [3.2.1]octan-9-one 和双环 [4.2.1]nonan-9-one 衍生物，它们很容易通过高产率逆狄克曼裂解转化为七元和八元环. 从反式-1,4-二溴-2-丁烯开始，该转化受立体电子因素的控制，并通过化学和立体选择性的 CO 环烷基化，导致具有合成价值的单环或稠合多环官能化烯醇醚具有高合成价值。半经验计算显示能量的微小差异和导致相应稠合多环烯醇醚顺式和反式异构体的过渡态的后期特征。这些结果虽然最大限度地减少了不稳定的 1,3-相互作用对反应结果的影响，但在质量上与实验结果一致。
• Quadruple Decker [3.3][3.3][3.3]Orthocyclophane Acetal—An Orthocyclophane Ladder
  作者：Shuntaro Mataka、Kouichiro Shigaki、Tsuyoshi Sawada、Yoshihara Mitoma、Masahiko Taniguchi、Thies Thiemann、Kazuya Ohga、Naoyoshi Egashira

  DOI：10.1002/(sici)1521-3773(19981002)37:18<2532::aid-anie2532>3.0.co;2-r

  日期：1998.10.2

  Through clever bridging of orthocyclophanes (in this case by acetalization), molecules such as 1 can be formed with four benzene rings in a stacked face-to-face arrangement. UV/Vis spectroscopic and electrochemical properties of 1 are governed by π-π through-space interactions within the molecule.

  通过邻桥环烷的灵巧桥接（在这种情况下为缩醛化反应），可以以面对面堆叠的方式形成带有四个苯环的分子（如1）。1的UV / Vis光谱和电化学性质受分子内π-π贯穿空间相互作用的支配。