3-[2,4-bis(methoxymethoxy)phenyl]-7-methoxymethoxy-4-methylcoumarin | 554430-40-9

• 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: 3-[2,4-bis(methoxymethoxy)phenyl]-7-methoxymethoxy-4-methylcoumarin
• 英文别名: 3-(2,4-bis-methoxymethoxy-phenyl)-7-methoxymethoxy-4-methyl-chromen-2-one；3-[2,4-Bis(methoxymethoxy)phenyl]-7-(methoxymethoxy)-4-methyl-2H-1-benzopyran-2-one；3-[2,4-bis(methoxymethoxy)phenyl]-7-(methoxymethoxy)-4-methylchromen-2-one
• CAS: 554430-40-9
• 化学式: C₂₂H₂₄O₈
• 分子量: 416.428
• InChiKey: BSMVNWUKMJXAID-UHFFFAOYSA-N

物化性质

• 沸点：
  579.2±50.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  81.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-[2,4-bis(methoxymethoxy)phenyl]-7-methoxymethoxy-4-methylcoumarin 、 甲酸苯酯 在 二异丙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 [3-(2,4-bis-methoxymethoxy-phenyl)-7-methoxymethoxy-2-oxo-2H-chromen-4-yl]-acetaldehyde
  参考文献：
  名称：

  Novel heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators

  摘要：

  本发明涉及包含杂原子的新型四环衍生物，包含它们的药物组合物，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，以及它们的制备过程。发明中的化合物在治疗和/或预防与雌激素耗竭相关的疾病中是有用的，如热潮红、阴道干涩、骨量减少和骨质疏松症；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，并且作为避孕剂，单独使用或与孕激素或孕激素拮抗剂结合使用。

  公开号：

  US20030216463A1
• 作为产物：
  描述：

  2,4-二甲氧基苯乙酸 在 吡啶盐酸盐 、 potassium carbonate 、 三乙胺 作用下， 反应 28.0h， 生成 3-[2,4-bis(methoxymethoxy)phenyl]-7-methoxymethoxy-4-methylcoumarin
  参考文献：
  名称：

  Development of a Scalable Synthetic Process for Selective Bromination of 4-Methyl-3,7-Substituted Coumarins

  摘要：

  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.

  DOI：

  10.1021/op050242p

文献信息

• [EN] TETRACYCLIC HETEROCOMPOUNDS AS ESTROGEN RECEPTOR MODULATORS<br/>[FR] HETERO-COMPOSES TETRACYCLIQUES UTILISABLES COMME MODULATEURS DU RECEPTEUR DES OESTROGENES
  申请人：ORTHO MCNEIL PHARM INC

  公开号：WO2003053977A1

  公开（公告）日：2003-07-03

  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.

  本发明涉及新型含杂原子的四环衍生物、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使用以及它们的制备过程。该发明的化合物在治疗和/或预防与雌激素缺乏有关的疾病方面具有用处，例如潮热、阴道干燥、骨质疏松症和骨质疏松症；激素敏感性癌症和乳腺、子宫内膜、子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药物，单独使用或与孕激素或孕激素拮抗剂组合使用。
• 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。
• TETRACYCLIC HETEROCOMPOUNDS AS ESTROGEN RECEPTOR MODULATORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1467998A1

  公开（公告）日：2004-10-20
• NOVEL HETEROATOM CONTAINING TETRACYCLIC DERIVATIVES AS SELECTIVE ESTROGEN RECEPTOR MODULATORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1569939A1

  公开（公告）日：2005-09-07
• US7105679B2
  申请人：——

  公开号：US7105679B2

  公开（公告）日：2006-09-12