10-Bromo-8-chloro-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one | 861405-87-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 10-Bromo-8-chloro-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one
• 英文别名: 7-bromo-9-chloro-6-hydroxy-2-[(1S)-1-hydroxy-3,3-dimethylbutyl]-1-methoxy-8-methyl-10H-benzo[b][1,5]benzodioxocin-12-one
• CAS: 861405-87-0
• 化学式: C₂₂H₂₄BrClO₆
• 分子量: 499.786
• InChiKey: RRKFQBGZNBJQEW-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  10-Bromo-8-chloro-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 copper(l) iodide 、 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 7-Methyl-bicyclo[2.2.1]heptane-7-carboxylic acid 4-chloro-2-ethyl-9-((S)-1-hydroxy-3,3-dimethyl-butyl)-8-methoxy-3-methyl-7-oxo-5H,7H-6,12-dioxa-dibenzo[a,d]cycloocten-1-yl ester
  参考文献：
  名称：

  Dibenzodioxocinones—A new class of CETP inhibitors

  摘要：

  Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor. The compound suffered from very low stability in plasma. Optimisation by partial synthesis started from 1 and led to low-nanomolar inhibitors with good stability in rat plasma. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.073
• 作为产物：
  描述：

  1-methoxy-8-methyl-6-(3-methylbutoxy)-12-oxo-10H-benzo[b][1,5]benzodioxocine-2-carbaldehyde 在 N-氯代丁二酰亚胺 、 N-溴代丁二酰亚胺(NBS) 、 三氯化铁 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 生成 10-Bromo-8-chloro-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one
  参考文献：
  名称：

  Dibenzodioxocinones—A new class of CETP inhibitors

  摘要：

  Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor. The compound suffered from very low stability in plasma. Optimisation by partial synthesis started from 1 and led to low-nanomolar inhibitors with good stability in rat plasma. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.073

文献信息

• A Further Improved Synthesis of a Dibenzodioxocinone CETP Inhibitor
  作者：Zhi-Hua Sun、Erkang Fan、Guo-Qiang Lin

  DOI：10.1055/s-0029-1217757

  日期：2009.10

  A newly improved synthesis of a dibenzodioxocinone CETP inhibitor is described. Key features of the synthetic route include a chiral ligand induced alkyl addition to aldehyde and the use of triethylborane for improved selective alkylation of brominated phenyl ring.

  描述了一种新改进的二苯并二噁烷酮 CETP 抑制剂的合成方法。合成路线的关键特点包括一个手性配体诱导的烷基添加到醛上，以及使用三乙基硼烷以改善溴化苯环的选择性烷基化。
• Direct B-Alkyl Suzuki-Miyaura Cross-Coupling of Trialkyl- boranes with Aryl Bromides in the Presence of Unmasked Acidic or Basic Functions and Base-Labile Protections under Mild Non-Aqueous Conditions
  作者：Bing Wang、Hui-Xia Sun、Zhi-Hua Sun、Guo-Qiang Lin

  DOI：10.1002/adsc.200800630

  日期：2009.2

  Abstractmagnified imageAn efficient and chemoselective palladium‐catalyzed direct B‐alkyl Suzuki–Miyaura cross‐coupling of trialkylboranes with diversely functionalized aryl bromides is described. A wide variety of unmasked acidic or basic functions are tolerated. The mild non‐aqueous conditions are compatible with aldehydes, ketones, nitriles, chloro substitution as well as base‐labile phenolic Piv and TBS protecting groups. The anhydrous conditions were found to be advantageous for aryl bromide substrates. A potent CEPT inhibitor was efficiently synthesised using this protocol.
• Dibenzodioxocinones—A new class of CETP inhibitors
  作者：David Brückner、Frank-Thorsten Hafner、Volkhart Li、Carsten Schmeck、Joachim Telser、Alexandros Vakalopoulos、Gabriele Wirtz

  DOI：10.1016/j.bmcl.2005.05.073

  日期：2005.8

  Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor. The compound suffered from very low stability in plasma. Optimisation by partial synthesis started from 1 and led to low-nanomolar inhibitors with good stability in rat plasma. (c) 2005 Elsevier Ltd. All rights reserved.