(1S)-6,7-dimethoxy-2-methyl-1-(2,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinoline | 22325-16-2

• 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: (1S)-6,7-dimethoxy-2-methyl-1-(2,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (S)-(+)-cryptostyline III；(1S)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinoline；Cryptostylin III；(1S)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxyphenyl)-3,4-dihydro-1H-isoquinoline
• CAS: 22325-16-2
• 化学式: C₂₁H₂₇NO₅
• 分子量: 373.449
• InChiKey: WAXADPYOTKIQBY-FQEVSTJZSA-N

物化性质

• 沸点：
  462.5±45.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S)-6,7-dimethoxy-2-methyl-1-(2,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinoline 在 甲醇 、 乙酰氯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 11.0h， 生成
  参考文献：
  名称：

  Synthesis of Ultra-Short-Acting Neuromuscular Blocker GW 0430:  A Remarkably Stereo- and Regioselective Synthesis of Mixed Tetrahydroisoquinolinium Chlorofumarates

  摘要：

  [GRAPHICS]The stereo- and regioselective synthesis of ultra-short-acting nondepolarizing neuromuscular blocker GW 0430 (5a) is described. Key steps involved the enantioselective transfer hydrogenation of imine 8 employing Noyori's catalyst, the stereoselective crystallization and methanolysis of trans-betaines 11 and 12, and the stereo- and regioselective trans elimination of hydrogen chloride from 14, The latter transformation allowed complete control of the position of the chloro substituent and stereochemistry at the double bond of the linker in 15.

  DOI：

  10.1021/ol9911573
• 作为产物：
  描述：

  (1S)-6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinolinium formate 、 聚合甲醛 在 甲酸 作用下， 反应 2.0h， 以96%的产率得到(1S)-6,7-dimethoxy-2-methyl-1-(2,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Synthesis of Ultra-Short-Acting Neuromuscular Blocker GW 0430:  A Remarkably Stereo- and Regioselective Synthesis of Mixed Tetrahydroisoquinolinium Chlorofumarates

  摘要：

  [GRAPHICS]The stereo- and regioselective synthesis of ultra-short-acting nondepolarizing neuromuscular blocker GW 0430 (5a) is described. Key steps involved the enantioselective transfer hydrogenation of imine 8 employing Noyori's catalyst, the stereoselective crystallization and methanolysis of trans-betaines 11 and 12, and the stereo- and regioselective trans elimination of hydrogen chloride from 14, The latter transformation allowed complete control of the position of the chloro substituent and stereochemistry at the double bond of the linker in 15.

  DOI：

  10.1021/ol9911573

文献信息

• Stereocontrolled Synthesis of <i>cis-</i>Dibenzoquinolizine Chlorofumarates:  Curare-Like Agents of Ultrashort Duration
  作者：Istvan Kaldor、Paul L. Feldman、Robert A. Mook、John A. Ray、Vicente Samano、Andrea M. Sefler、James B. Thompson、Benjamin R. Travis、Eric E. Boros

  DOI：10.1021/jo010032k

  日期：2001.5.1

  from (1S)-trans-6d, 15 and (+/-)-trans-2,3-dichlorosuccinic anhydride (22), employing a recently disclosed chlorofumarate mixed-diester synthesis. The title compounds (19, 20ab, and 26) displayed curare-like effects of ultrashort duration in rhesus monkeys.

  二苯并喹喔啉9和14与3-卤代-1-丙醇的季铵化反应具有很高的顺式选择性（94-100％顺式），其结果与O-甲基capaurine（7b）的N-甲基化相符，但与拟议的反式相反二苯并[a，h]喹啉嗪甲硫醚10的立体化学和1-苄基和1-苯基异喹啉同类物5b和5c的类似季铵化。在本报告中，我们描述了独特的顺式-二苯并喹啉鎓丙醇15和16的立体选择性制备以及它们转化为双富马酸富马酸酯和混合富马酸酯19、20ab和26的方法。在三个步骤中，对映体选择性地制备了二苯并[a，g]喹啉鎓丙醇15得自二氢异喹啉11。在三乙胺/甲酸和Noyori手性钌催化剂存在下，11的不对称转移氢化生成R-（-）-5'，8-二甲氧基去甲十二烷磺酸（13），产率为98％，ee为87％。在福尔马林/甲酸中对13进行Pictet-Spengler环化，以65％的收率得到二苯并[a，g]喹啉嗪14。在Finkelstein条件下用
• Substituted isoquinolines as ultra short acting neuromuscular blockers
  申请人：Glaxo Wellcome Inc.

  公开号：US06177445B1

  公开（公告）日：2001-01-23

  Ultra short acting neuromuscular blocking agents of Formula (I) which are useful as skeletal muscle relaxants during emergency intubation procedures, routine surgery and post-operative settings are disclosed, wherein q and t are independently from 0 to 4; X1 and X2 are independently halogen; ha and hb are independenity from 0 to 2; Z1 and Z2 are indepentdently hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl with the proviso that Z1 and Z2 are not both hydrogen; Y1, Y2, and Y3 and Y4 are independently hydrogen, halogen or C1-3 alkoxy; m and p are independently 1 to 6; n and r are independently 0 to 4; with the proviso the if ha and hb are both 0, then r is 0 and n is 0 to 2; R1 to R14 are independently hydrogen, halogen, C1-3 alkoxy, or R2 and R3 together with the carbon atoms to which they are bonded, R5 and R6 together with the carbon atoms to which they are bonded, R9 and R10 together with the carbon atoms to which they are bonded, R12 and R13 together with the carbon atoms to which they are bonded, may independently form a methylenedioxy or ethylenedioxy moiety contained in five- or six-membered ring; W1 and W2 are carbon; and A is a pharmaceutically acceptable anion.

  本发明涉及公式（I）的超短作用神经肌肉松弛剂，其在紧急插管、常规手术和术后情况下作为骨骼肌松弛剂非常有用，其中q和t独立地为0到4；X1和X2独立地为卤素；ha和hb独立地为0到2；Z1和Z2独立地为氢、C1-6烷基、C2-6烯基或C2-6炔基，但须满足Z1和Z2不同时为氢；Y1、Y2、Y3和Y4独立地为氢、卤素或C1-3烷氧基；m和p独立地为1到6；n和r独立地为0到4；但须满足如果ha和hb都为0，则r为0且n为0到2；R1到R14独立地为氢、卤素、C1-3烷氧基，或者R2和R3与它们所结合的碳原子、R5和R6与它们所结合的碳原子、R9和R10与它们所结合的碳原子、R12和R13与它们所结合的碳原子可以独立地形成包含在五元或六元环中的亚甲二氧基或乙撑二氧基基团；W1和W2为碳；A是一种药学上可接受的阴离子。
• Isoquinolines and preparation thereof
  申请人：Avera Pharmaceuticals, Inc.

  公开号：EP1380573A2

  公开（公告）日：2004-01-14

  A compound of Formula (III): wherein Y is selected from the group consisting of hydrogen or methoxy, W comprises a chiral center selected from the group consisting of a carbon atom having an R configuration and a carbon atom having an S configuration, n comprises 0 or 1, and A- comprises a pharmaceutically acceptable anion and process of preparation.

  式（III）化合物： 其中 Y 选自由氢或甲氧基组成的组，W 包括一个手性中心，该手性中心选自由具有 R 构型的碳原子和具有 S 构型的碳原子组成的组，n 包括 0 或 1，A- 包括一个药学上可接受的阴离子，以及制备方法。
• Org Lett. 1999, 1, 1993-1996
  作者：

  DOI：——

  日期：——
• SUBTITUTED ISOQUINOLINES AS ULTRA SHORT ACTING NEUROMUSCULAR BLOCKERS
  申请人：Avera Pharmaceuticals, Inc.

  公开号：EP0975599B1

  公开（公告）日：2003-11-12