7-methoxy-2-methyl-1-phenyl-3,4-dihydro-1H-isoquinoline | 159465-32-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 7-methoxy-2-methyl-1-phenyl-3,4-dihydro-1H-isoquinoline
• CAS: 159465-32-4
• 化学式: C₁₇H₁₉NO
• 分子量: 253.344
• InChiKey: YANAEXBZPGHPIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-methoxy-2-methyl-1-phenyl-3,4-dihydro-1H-isoquinoline 在 氢溴酸 作用下， 反应 12.0h， 以83%的产率得到N-methyl-7-hydroxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Synthesis and Molecular Modeling of 1-Phenyl-1,2,3,4-tetrahydroisoquinolines and Related 5,6,8,9-Tetrahydro-13bH-dibenzo[a,h]quinolizines as D1 Dopamine Antagonists

  摘要：

  New 1-phenyl-1,2,3,4-tetrahydroisoquinolines and related 5,6,8,9-tetrahydro-13bH-dibenzo[a,h]-quinolizines were prepared as ring-contracted analogs of the prototypical 1-phenyl-2,3,4,5-tetrahydrobenzazepines (e.g., SCH23390) as a continuation of our studies to characterize the antagonist binding pharmacophore of the D-1 dopamine receptor. Receptor affinity was assessed by competition for [H-3]SCH23390 binding sites in rat striatal membranes. The 6-bromo-1-phenyltetrahydroisoquinoline analog 2 of SCH23390 1 had D-1 binding affinity similar to that for the previously reported 6-chloro analog 6, whereas the 6,7-dihydroxy analog 5 had significantly lower D-1 affinity. Conversely, neither 6-monohydroxy- (3) nor 7-monohydroxy-1-phenyltetrahydroisoquinolines (4) had significant affinity for the D-1 receptor. These results demonstrate that 6-halo and 7-hydroxy substituents influence D-1 binding affinity of the 1-phenyltetrahydroisoquinolines in a fashion similar to their effects on 1-phenyltetrahydrobenzazepines. azepines. The conformationally constrained 3-chloro-2-hydroxytetrahydrodibenzoquinolizine 9 had much lower affinity relative to the corresponding, and more flexible, 6-chloro-7-hydroxy-1-phenyltetrahydroisoquinoline 6. Similarly, 2,3-dihydroxytetrahydrodibenzoquinolizine 10 had much lower D-1 affinity compared to dihydrexidine 14, a structurally similar hexahydrobenzo[a]phenanthridine that is a high-affinity full D-1 agonist. Together, these data not only confirm the effects of the halo and hydroxy substitutents on the parent nucleus but demonstrate the pharmacophoric importance of both the nitrogen position and the orientation of the accessory phenyl ring in modulating D-1 receptor affinity and function. Molecular modeling studies and conformational analyses were conducted using the data from these new analogs in combination with the data from compounds previously synthesized. The resulting geometries were used to refine a working model of the D-1 antagonist pharmacophore using conventional quantitative structure-activity relationships and three-dimensional QSAR (CoMFA).

  DOI：

  10.1021/jm00051a008
• 作为产物：
  描述：

  1-苯基-7-甲氧基-3,4-二氢异喹啉 在 sodium tetrahydroborate 、 甲酸 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 9.0h， 生成 7-methoxy-2-methyl-1-phenyl-3,4-dihydro-1H-isoquinoline
  参考文献：
  名称：

  Synthesis and Molecular Modeling of 1-Phenyl-1,2,3,4-tetrahydroisoquinolines and Related 5,6,8,9-Tetrahydro-13bH-dibenzo[a,h]quinolizines as D1 Dopamine Antagonists

  摘要：

  New 1-phenyl-1,2,3,4-tetrahydroisoquinolines and related 5,6,8,9-tetrahydro-13bH-dibenzo[a,h]-quinolizines were prepared as ring-contracted analogs of the prototypical 1-phenyl-2,3,4,5-tetrahydrobenzazepines (e.g., SCH23390) as a continuation of our studies to characterize the antagonist binding pharmacophore of the D-1 dopamine receptor. Receptor affinity was assessed by competition for [H-3]SCH23390 binding sites in rat striatal membranes. The 6-bromo-1-phenyltetrahydroisoquinoline analog 2 of SCH23390 1 had D-1 binding affinity similar to that for the previously reported 6-chloro analog 6, whereas the 6,7-dihydroxy analog 5 had significantly lower D-1 affinity. Conversely, neither 6-monohydroxy- (3) nor 7-monohydroxy-1-phenyltetrahydroisoquinolines (4) had significant affinity for the D-1 receptor. These results demonstrate that 6-halo and 7-hydroxy substituents influence D-1 binding affinity of the 1-phenyltetrahydroisoquinolines in a fashion similar to their effects on 1-phenyltetrahydrobenzazepines. azepines. The conformationally constrained 3-chloro-2-hydroxytetrahydrodibenzoquinolizine 9 had much lower affinity relative to the corresponding, and more flexible, 6-chloro-7-hydroxy-1-phenyltetrahydroisoquinoline 6. Similarly, 2,3-dihydroxytetrahydrodibenzoquinolizine 10 had much lower D-1 affinity compared to dihydrexidine 14, a structurally similar hexahydrobenzo[a]phenanthridine that is a high-affinity full D-1 agonist. Together, these data not only confirm the effects of the halo and hydroxy substitutents on the parent nucleus but demonstrate the pharmacophoric importance of both the nitrogen position and the orientation of the accessory phenyl ring in modulating D-1 receptor affinity and function. Molecular modeling studies and conformational analyses were conducted using the data from these new analogs in combination with the data from compounds previously synthesized. The resulting geometries were used to refine a working model of the D-1 antagonist pharmacophore using conventional quantitative structure-activity relationships and three-dimensional QSAR (CoMFA).

  DOI：

  10.1021/jm00051a008

文献信息

• Oxidative cyanation of tertiary amines for facile synthesis of tetrahydroisoquinolines with quaternary centers
  作者：Yue Ji、Xue Zhang、Ya Wu、Ze-Lin Dang、Wei-Wei Han、Si-Chang Wang、San-Bao Dong、Qun-Zheng Zhang

  DOI：10.1016/j.tetlet.2022.154175

  日期：2022.11

  facile and efficient synthesis of tetrahydroisoquinolines with quaternary centers has been successfully realized by orchestrating a sequential process consisted of N-bromosuccinimide oxidation and cyanation of tertiary amines. This compatible combination protocol enables one-pot synthesis of α-cyano tetrahydroisoquinolines containing a quaternary center with up to 99% yield.

  通过协调由N-溴代琥珀酰亚胺氧化和叔胺氰化组成的顺序过程，已经成功地实现了具有季中心的四氢异喹啉的简便有效合成。这种兼容的组合方案能够一锅合成含有季铵中心的 α-氰基四氢异喹啉，产率高达 99%。
• 一种α,α-二取代四氢异喹啉类化合物的合成方法
  申请人：西安石油大学

  公开号：CN114516835B

  公开（公告）日：2023-08-15

  本发明提供一种α，α‑二取代四氢异喹啉化合物的合成方法，将式(1)所示的四氢异喹啉类化合物加至有机溶剂中，并加入氧化剂和碱性添加剂，进行氧化反应，随后再加入三甲基氰硅烷和有机溶剂，进行亲核加成反应，得到式(2)α，α‑二取代四氢异喹啉类化合物；其中，Rx为‑H、‑F、‑Cl、‑CH3和‑OCH3中的一种或两种；R1和R2各自独立的为‑H、‑CH3或‑OCH3；所述氧化剂为N‑溴代丁二酰亚胺、N‑碘代丁二酰亚胺、N‑氯代丁二酰亚胺、二溴海因或三氯异氰尿酸。本发明方法能实现α，α‑二取代四氢异喹啉类化合物的合成，反应条件温和且产物收率高。
• Concise Redox Deracemization of Secondary and Tertiary Amines with a Tetrahydroisoquinoline Core via a Nonenzymatic Process
  作者：Yue Ji、Lei Shi、Mu-Wang Chen、Guang-Shou Feng、Yong-Gui Zhou

  DOI：10.1021/jacs.5b06659

  日期：2015.8.26

  A concise deracemization of racemic secondary and tertiary amines with a tetrahydroisoquinoline core has been successfully realized by orchestrating a redox process consisted of N-bromosuccinimide oxidation and iridum-catalyzed asymmetric hydrogenation. This compatible redox combination enables one-pot, single-operation deracemization to generate chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines with up to 98% ee in 93% yield, offering a simple and scalable synthetic technique for chiral amines directly from racemic starting materials.
• Synthesis and Molecular Modeling of 1-Phenyl-1,2,3,4-tetrahydroisoquinolines and Related 5,6,8,9-Tetrahydro-13bH-dibenzo[a,h]quinolizines as D1 Dopamine Antagonists
  作者：Deborah L. Minor、Steven D. Wyrick、Paul S. Charifson、Val J. Watts、David E. Nichols、Richard B. Mailman

  DOI：10.1021/jm00051a008

  日期：1994.12

  New 1-phenyl-1,2,3,4-tetrahydroisoquinolines and related 5,6,8,9-tetrahydro-13bH-dibenzo[a,h]-quinolizines were prepared as ring-contracted analogs of the prototypical 1-phenyl-2,3,4,5-tetrahydrobenzazepines (e.g., SCH23390) as a continuation of our studies to characterize the antagonist binding pharmacophore of the D-1 dopamine receptor. Receptor affinity was assessed by competition for [H-3]SCH23390 binding sites in rat striatal membranes. The 6-bromo-1-phenyltetrahydroisoquinoline analog 2 of SCH23390 1 had D-1 binding affinity similar to that for the previously reported 6-chloro analog 6, whereas the 6,7-dihydroxy analog 5 had significantly lower D-1 affinity. Conversely, neither 6-monohydroxy- (3) nor 7-monohydroxy-1-phenyltetrahydroisoquinolines (4) had significant affinity for the D-1 receptor. These results demonstrate that 6-halo and 7-hydroxy substituents influence D-1 binding affinity of the 1-phenyltetrahydroisoquinolines in a fashion similar to their effects on 1-phenyltetrahydrobenzazepines. azepines. The conformationally constrained 3-chloro-2-hydroxytetrahydrodibenzoquinolizine 9 had much lower affinity relative to the corresponding, and more flexible, 6-chloro-7-hydroxy-1-phenyltetrahydroisoquinoline 6. Similarly, 2,3-dihydroxytetrahydrodibenzoquinolizine 10 had much lower D-1 affinity compared to dihydrexidine 14, a structurally similar hexahydrobenzo[a]phenanthridine that is a high-affinity full D-1 agonist. Together, these data not only confirm the effects of the halo and hydroxy substitutents on the parent nucleus but demonstrate the pharmacophoric importance of both the nitrogen position and the orientation of the accessory phenyl ring in modulating D-1 receptor affinity and function. Molecular modeling studies and conformational analyses were conducted using the data from these new analogs in combination with the data from compounds previously synthesized. The resulting geometries were used to refine a working model of the D-1 antagonist pharmacophore using conventional quantitative structure-activity relationships and three-dimensional QSAR (CoMFA).