7-acetoxy-4-bromomethyl-3-[(2,4-diacetoxy)phenyl]-coumarin | 554430-09-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 7-acetoxy-4-bromomethyl-3-[(2,4-diacetoxy)phenyl]-coumarin
• 英文别名: acetic acid 3-acetoxy-4-(7-acetoxy-4-bromomethyl-2-oxo-2H-chromen-3-yl)-phenyl ester；acetic acid 3-acetoxy-4-(7-acetoxy4-bromomethyl-2-oxo-2H-chromen-3-yl)-phenyl ester；3-(2,4-Diacetoxyphenyl)-4-(bromomethyl)-7-acetoxycoumarin；[4-(bromomethyl)-3-(2,4-diacetyloxyphenyl)-2-oxochromen-7-yl] acetate
• CAS: 554430-09-0
• 化学式: C₂₂H₁₇BrO₈
• 分子量: 489.276
• InChiKey: GOHSNCUPDRMOON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-acetoxy-4-bromomethyl-3-[(2,4-diacetoxy)phenyl]-coumarin 在 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 以90%的产率得到2,8-dihydroxy-11H-chromeno[4,3-c]chromen-5-one
  参考文献：
  名称：

  不对称苯并吡喃苯并吡喃环系统的简便合成

  摘要：

  摘要 描述了一种合成不对称苯并吡喃苯并吡喃环系统的简便方法。该合成的一个关键特征是采用串联脱保护-环化策略来构建四环系统的 C 环。

  DOI：

  10.1016/j.tetlet.2004.06.008
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 在 吡啶 、 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 生成 7-acetoxy-4-bromomethyl-3-[(2,4-diacetoxy)phenyl]-coumarin
  参考文献：
  名称：

  不对称苯并吡喃苯并吡喃环系统的简便合成

  摘要：

  摘要 描述了一种合成不对称苯并吡喃苯并吡喃环系统的简便方法。该合成的一个关键特征是采用串联脱保护-环化策略来构建四环系统的 C 环。

  DOI：

  10.1016/j.tetlet.2004.06.008

文献信息

• Novel heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators
  申请人：——

  公开号：US20040259915A1

  公开（公告）日：2004-12-23

  The present invention is directed to novel heteroatom containing tetracyclic derivatives, pharmaceutical compositions containing them, their use in the treatment and/or prevention of disorders mediated by one or more estrogen receptors and processes for their preparation. The compounds of the invention are useful in the treatment and/or prevention of disorders associated with the depletion of estrogen such as hot flashes, vaginal dryness, osteopenia and osteoporosis; hormone sensitive cancers and hyperplasia of the breast, endometrium, cervix and prostate; endometriosis, uterine fibroids, osteoarthritis and as contraceptive agents, alone or in combination with a progestogen or progestogen antagonist.

  本发明涉及新颖的含杂原子四环衍生物、含有它们的药物组合物、它们在治疗和/或预防由一个或多个雌激素受体介导的疾病中的应用，以及它们的制备方法。本发明的化合物在治疗和/或预防与雌激素耗竭相关的疾病中具有用途，例如热潮红、阴道干燥、骨量减少和骨质疏松症；激素敏感性癌症以及乳腺、子宫内膜、宫颈和前列腺的增生；子宫内膜异位症、子宫肌瘤、骨关节炎，以及作为避孕剂，单独使用或与孕激素或孕激素拮抗剂联合使用。
• A facile synthesis of an unsymmetric benzopyranobenzopyran ring system
  作者：Ramesh M Kanojia、Nareshkumar Jain、Jiayi Xu、Zhihua Sui

  DOI：10.1016/j.tetlet.2004.06.008

  日期：2004.7

  Abstract A facile route to the synthesis of an unsymmetric benzopyranobenzopyran ring system is described. A key feature of this synthesis incorporates a tandem deprotection–cyclization strategy to construct the C-ring of the tetracyclic system.

  摘要 描述了一种合成不对称苯并吡喃苯并吡喃环系统的简便方法。该合成的一个关键特征是采用串联脱保护-环化策略来构建四环系统的 C 环。
• Heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators
  申请人：Janssen Pharmaceutica N.V.

  公开号：US07329654B2

  公开（公告）日：2008-02-12

  The present invention is directed to novel heteroatom containing tetracyclic derivatives, pharmaceutical compositions containing them, their use in the treatment and/or prevention of disorders mediated by one or more estrogen receptors and processes for their preparation. The compounds of the invention are useful in the treatment and/or prevention of disorders associated with the depletion of estrogen such as hot flashes, vaginal dryness, osteopenia and osteoporosis; hormone sensitive cancers and hyperplasia of the breast, endometrium, cervix and prostate; endometriosis, uterine fibroids, osteoarthritis and as contraceptive agents, alone or in combination with a progestogen or progestogen antagonist.

  本发明涉及新颖的含杂原子的四环衍生物，包含它们的制药组合物，以及它们在治疗和/或预防由一个或多个雌激素受体介导的疾病中的使用和制备过程。本发明的化合物在治疗和/或预防与雌激素耗竭相关的疾病方面具有用途，如潮热，阴道干燥，骨质疏松症；激素敏感性癌症和乳腺，子宫内膜，宫颈和前列腺的增生；子宫内膜异位症，子宫肌瘤，骨关节炎以及作为避孕剂，单独或与孕激素或孕激素拮抗剂联合使用。
• Development of a Scalable Synthetic Process for Selective Bromination of 4-Methyl-3,7-Substituted Coumarins
  作者：Xun Li、Nareshkumar Jain、Ronald K. Russell、Robert Ma、Shawn Branum、Jiayi Xu、Zhihua Sui

  DOI：10.1021/op050242p

  日期：2006.3.1

  The hydroxyl-protected coumarin derivatives 6a-e of 4-methyl3-(2,4-dihydroxyphenyl)-7-hydroxycoumarin (4) are key intermediates in the synthesis of unsymmetrical benzopyranobenzopyran compounds, a novel series of selective estrogen receptor modulators (SERMs). Free radical bromination of the 4-methyl group on 7-acetoxy-3-[(2,4-diacetoxy)phenyl]-4-methylcoumarin (6a) with NBS resulted in incomplete reactions and low to moderate yields (25-44%) of 4-bromomethyl product 7a. Lithiation of the 4-methyl group of coumarins 6b (R = SEM), 6c (R = MOM) and 6d (R = Bz) with LDA (1.1 - 1.7 equiv) or LHMDS (1.2-1.7 equiv) generated carbanion in THF at -76 degrees C, which was quenched with bromine (1.5-2.0 equiv) to afford 4-bromomethyl derivatives 7b-d in good yields (80-90%) in small scale reactions (2-20 g). The reaction yields declined to similar to 70% when the scale was increased to >= 80 g. Furthermore, treatment of 3-[(2,4-dimethoxy)phenyl]-7-methoxy-4-methylcoumarin (6e) with LHMDS (1.08 equiv) in THF followed by rapid inverse quenched with NBS (1.10 equiv) in THF at -76 degrees C, selectively produced the desired 4-bromomethyl compound 7e in excellent yield (> 90%) in both small (2-8 g) and large (80-150 g) scale reactions. A non-chromatographic process was developed to prepare 6e. This selective and efficient procedure was successfully transferred to the pilot plant to produce multikilograms of 4-bromomethyl coumarin 7e.
• TETRACYCLIC HETEROCOMPOUNDS AS ESTROGEN RECEPTOR MODULATORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1467998B1

  公开（公告）日：2006-03-29