4-bromomethyl-3-[(2,4-dimethoxy)phenyl]-7-methoxycoumarin | 749901-81-3

• 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: 4-bromomethyl-3-[(2,4-dimethoxy)phenyl]-7-methoxycoumarin
• 英文别名: 3-(2,4-Dimethoxyphenyl)-4-(bromomethyl)-7-methoxycoumarin；4-(bromomethyl)-3-(2,4-dimethoxyphenyl)-7-methoxychromen-2-one
• CAS: 749901-81-3
• 化学式: C₁₉H₁₇BrO₅
• 分子量: 405.245
• InChiKey: KRBYROAQCFZALW-UHFFFAOYSA-N

物化性质

• 沸点：
  551.1±50.0 °C(Predicted)
• 密度：
  1.429±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-bromomethyl-3-[(2,4-dimethoxy)phenyl]-7-methoxycoumarin 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 以89%的产率得到2,8-dihydroxy-11H-chromeno[4,3-c]chromen-5-one
  参考文献：
  名称：

  通过4-甲基香豆素的碳负离子化学合成新型的四环色烯

  摘要：

  通过锂化将各种取代基引入4-甲基香豆素的甲基上，然后与各种亲电子试剂反应。发现6'-苯环上烷氧基的存在对于该反应的成功至关重要。该方法提供了合成4-甲基香豆素甲基的方便的合成途径。这种方法的应用在生物学上具有重要意义的新型四环色烯环系统的合成中得到了展示（n  = 1-3）。

  DOI：

  10.1016/j.tetlet.2006.06.047
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-bromomethyl-3-[(2,4-dimethoxy)phenyl]-7-methoxycoumarin
  参考文献：
  名称：

  四环杂化合物的合成作为选择性雌激素受体调节剂。第1部分。放大开发2,5,8取代的5,11-二氢色酚[4,3- c ]苯二甲基衍生物的工艺开发

  摘要：

  不对称的苯并吡喃并苯并吡喃化合物是新型的选择性雌激素受体调节剂（SERM）。开发了一种可重现的非色谱方法，以制备数百克数量的5-（4-（2-（2-哌啶-1-基）乙氧基）苯基）-5,11-二氢苯并[4,3 - c ]苯二甲基-2,8 -二基-双（2，2-二甲基丙酸酯）（14）。经过三个扩大规模的推广活动后，该11步合成的总产率从0.17％提高到7.1％。

  DOI：

  10.1021/op700020f

文献信息

• [EN] FUSED TETRACYCLIC HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES TÉTRACYCLIQUES FUSIONNÉS ET LEURS MÉTHODES D'UTILISATION POUR LE TRAITEMENT DE MALADIES VIRALES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015094998A1

  公开（公告）日：2015-06-25

  The present invention relates to novel Fused Tetracyclic Heterocyclic Compounds of Formula I: (I), wherein A, A', R2A, R2B, R7, R8, R9, and R10 are defined herein. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HCV and the prophylaxis, treatment, or delay in the onset of disease caused by HCV. The present invention also relates to pharmaceutical compositions comprising at least one Fused Tetracyclic Heterocyclic Compound, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines, and methods of using the Fused Tetracyclic Heterocyclic Compounds for treating or preventing HCV infection in a patient.

  本发明涉及新型融合的四环杂环化合物，其化学式为I：(I)，其中A、A'、R2A、R2B、R7、R8、R9和R10在本发明中定义。这些化合物及其药用可接受的盐对于预防或治疗HCV感染以及预防、治疗或推迟由HCV引起的疾病的发生是有用的。本发明还涉及包含至少一种融合的四环杂环化合物的药物组合物，可选地与其他抗病毒剂、免疫调节剂、抗生素或疫苗联合使用，以及使用这些融合的四环杂环化合物来治疗或预防患者中HCV感染的方法。
• [EN] FUSED TETRACYCLIC HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES<br/>[FR] COMPOSÉS TÉTRACYCLIQUES HÉTÉROCYCLIQUES CONDENSÉS ET LEURS PROCÉDÉS D'UTILISATION POUR LE TRAITEMENT DE MALADIES VIRALES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015089810A1

  公开（公告）日：2015-06-25

  The present invention relates to novel Fused Tetracyclic Heterocyclic Compounds of Formula (I): wherein A, A', R2A, R2B, R7, R8, R9 and R10 are defined herein. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HCV and the prophylaxis, treatment, or delay in the onset of disease caused by HCV. The present invention also relates to pharmaceutical compositions comprising at least one Fused Tetracyclic Heterocyclic Compound, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines, and methods of using the Fused Tetracyclic Heterocyclic Compounds for treating or preventing HCV infection in a patient.

  本发明涉及新型融合的四环杂环化合物，其具有以下公式(I)：其中A，A'，R2A，R2B，R7，R8，R9和R10的定义如本文所述。这些化合物及其药用可接受的盐对于预防或治疗HCV感染以及预防、治疗或延缓HCV引起的疾病发作是有用的。本发明还涉及包含至少一种融合的四环杂环化合物的药物组合物，可选地与其他抗病毒药、免疫调节剂、抗生素或疫苗组合使用，以及使用这些融合的四环杂环化合物来治疗或预防患者中HCV感染的方法。
• 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。
• 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.
• FUSED TETRACYCLIC HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
  申请人：KOZLOWSKI Joseph

  公开号：US20170217940A1

  公开（公告）日：2017-08-03

  The present invention relates to novel Fused Tetracyclic Heterocyclic Compounds of Formula I: (I), wherein A, A′, R 2A , R 2B , R 7 , R 8 , R 9 , and R 10 are defined herein. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HCV and the prophylaxis, treatment, or delay in the onset of disease caused by HCV. The present invention also relates to pharmaceutical compositions comprising at least one Fused Tetracyclic Heterocyclic Compound, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines, and methods of using the Fused Tetracyclic Heterocyclic Compounds for treating or preventing HCV infection in a patient.