tert-butyl 1-isoquinolinecarboxylate | 168843-07-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: tert-butyl 1-isoquinolinecarboxylate
• 英文别名: 1-isoquinoline-carboxylic acid, tert-butyl ester；Isoquinoline carboxylic acid t-butyl ester；tert-butyl isoquinoline-1-carboxylate
• CAS: 168843-07-0
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: AKIKSMIYDKLYBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-isoquinolinecarboxylate 在 platinum(IV) oxide 氢气 作用下， 以 乙醇 为溶剂， 生成 tetrahydroisoquinoline-1-tertbutyl formate
  参考文献：
  名称：

  [EN] ACYL ISOINDOLINE DERIVATIVES AND ACYL ISOQUINOLINE DERIVATIVES AS ANTI-VIRAL AGENTS
  [FR] DERIVES D'ACYLE ISOINDOLINE ET D'ACYLE ISOQUINOLINE UTILISES COMME AGENTS ANTIVIRAUX

  摘要：

  Formula（I）的抗病毒剂，其中：R3代表芳基或杂环芳基；R4代表一个或两个取代基，独立选择自氢、C1-6烷基、卤素、ORA、C（O）NRBRC、C（O）RD、CO2H、CO2RD、NRBRC、NREC（O）RD、NRECO2RD、NREC（O）NRFRG、NRESO2RD、SO2NRFRG、SO2RD、硝基、氰基、杂环烷基、杂环芳基、芳基、芳基烷基、杂环芳基烷基或CF3；R5和R6独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；n代表0或1；当n代表0时，R1代表C（O）RH，R2代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；当n代表1时，要么i）R1代表C（O）RH；R2代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；且R7和R8独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；或ii）R1和R2独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；R7代表C（O）RH；且R8代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；RA代表氢、C1-6烷基、芳基烷基、杂环芳基烷基、芳基或杂环芳基；RB和RC独立代表氢、C1-6烷基、芳基或杂环芳基；或RB和RC与它们连接的氮原子一起形成5或6个成员饱和环；RD选自由C1-6烷基、芳基、杂环芳基、芳基烷基和杂环芳基烷基组成的群体；RE代表氢或C1-6烷基；RF和RG独立选择自氢、C1-6烷基、芳基、杂环芳基、芳基烷基和杂环芳基烷基组成的群体；或RF和RG与它们连接的氮原子一起形成5或6个成员饱和环；RH代表羟基或NRBRC；以及其盐、溶剂化合物和酯；但是当RH是羟基时，酯化形成-OR，其中R选择自直链或支链烷基、芳基烷基、芳氧基烷基或芳基，那么R不是叔丁基。提供了它们的制备方法以及在HCV治疗中使用它们的方法。

  公开号：

  WO2004096774A1
• 作为产物：
  描述：

  叔-丁基氯甲酸酯 在 三乙胺 作用下， 以 乙醚 、 苯 为溶剂， 反应 7.0h， 生成 tert-butyl 1-isoquinolinecarboxylate
  参考文献：
  名称：

  Studies on Organometallic Compounds. VII. Reaction of Di-tert-butyl Dicarbonate with .ALPHA.-Trialkylstannyl Derivatives of Pyridine, Quinoline, and Isoquinoline.

  摘要：

  研究发现，二叔丁基二碳酸酯可有效通过三烷基锡基团直接在吡啶核的α位引入叔丁氧羰基。反应中，吡啶、喹啉和异喹啉的α-三烷基锡衍生物与二叔丁基二碳酸酯反应，以良好产率生成相应的α-叔丁氧羰基衍生物，但在吡啶的情况下，除少量多种副产物生成外。

  DOI：

  10.1248/cpb.43.916

文献信息

• METHOD FOR PREPARING (R)-PRAZIQUANTEL
  申请人：SUZHOU TONGLI BIOMEDICAL CO., LTD

  公开号：US20140370556A1

  公开（公告）日：2014-12-18

  The invention relates to a new method for preparing (R)-praziquantel. In the invention, by taking advantage of the high stereo selectivity, site selectivity and region selectivity of an enzyme, an intermediate of a pure optical and chiral (R)-praziquantel are obtained by means of the dynamic kinetic resolution of an enantiomer from the synthesized racemate or derivatives thereof, and the (R)-praziquantel is obtained by using various conventional and mature organic chemical reactions with higher yield. The method of the invention has the potential advantages of easily available raw materials, low cost, environmentally safer process and convenience for large-scale production. Also, the purity of the end product can be more than 98%. By adopting the invention, the quality of the product is improved and a basis for developing high quality of active pharmaceutical ingredients and formulations is established, and thus the pending industrial problem of purifying praziquantel over 30 years becomes solvable.

  本发明涉及一种制备(R)-吡喹酮的新方法。本发明利用酶的高立体选择性、位点选择性和区域选择性，通过从合成的外消旋体或其衍生物中动力学地拆分对映体，获得一种纯光学手性的(R)-吡喹酮中间体，并利用各种常规和成熟的有机化学反应，得到(R)-吡喹酮，其产量更高。本发明的方法具有易得的原材料、低成本、环境更安全的工艺和便于大规模生产的潜在优点。此外，最终产品的纯度可以超过98%。通过采用本发明，产品的质量得到了提高，建立了开发高质量活性药物成分和配方的基础，从而解决了30多年来净化吡喹酮的悬而未决的工业问题。
• US9068214B2
  申请人：——

  公开号：US9068214B2

  公开（公告）日：2015-06-30
• US9139859B2
  申请人：——

  公开号：US9139859B2

  公开（公告）日：2015-09-22
• Studies on Organometallic Compounds. VII. Reaction of Di-tert-butyl Dicarbonate with .ALPHA.-Trialkylstannyl Derivatives of Pyridine, Quinoline, and Isoquinoline.
  作者：Yutaka YAMAMOTO、Hidekazu OUCHI、Takuo TANAKA

  DOI：10.1248/cpb.43.916

  日期：——

  Di-tert-butyl dicarbonate was found to be effective for direct introduction of a tert-butoxycarbonyl group at the α-position of the pyridine nucleus via the trialkylstannyl group; reaction of α-trialkylstannyl derivatives of pyridine, quinoline, and isoquinoline with di-tert-butyl dicarbonate gave the corresponding α-tert-butoxycarbonyl derivatives in good yields, althrough small amounts of a variety of by-products were formed except in the case of pyridine.

  研究发现，二叔丁基二碳酸酯可有效通过三烷基锡基团直接在吡啶核的α位引入叔丁氧羰基。反应中，吡啶、喹啉和异喹啉的α-三烷基锡衍生物与二叔丁基二碳酸酯反应，以良好产率生成相应的α-叔丁氧羰基衍生物，但在吡啶的情况下，除少量多种副产物生成外。
• [EN] ACYL ISOINDOLINE DERIVATIVES AND ACYL ISOQUINOLINE DERIVATIVES AS ANTI-VIRAL AGENTS<br/>[FR] DERIVES D'ACYLE ISOINDOLINE ET D'ACYLE ISOQUINOLINE UTILISES COMME AGENTS ANTIVIRAUX
  申请人：GLAXO GROUP LTD

  公开号：WO2004096774A1

  公开（公告）日：2004-11-11

  Anti-viral agents of Formula (I) wherein: R3 represents aryl or heteroaryl; R4 represents one or two substituents independently selected from hydrogen, C 1-6alkyl, halo, ORA , C(O)NRBRC, C(O)RD, CO2H, CO2RD, NRBRC, NRE C(O)RD, NRECO2RD, NREC(O)NRFRG, NRESO2RD, SO2NRFRG, SO2RD, nitro, cyano, heterocyclyl, heteroaryl, aryl, arylalkyl heteroarylalkyl or CF3; R5 and R6 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; n represents 0 or 1; when n represents 0, R1 represents C(O)RH and R2 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; when n represents 1, either i) R1 represents C(O)RH; R2 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; and R7 and R8 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; or ii) R1 and R2 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; R7 represents C(O)RH; and R8 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; RA represents hydrogen, C1-6alkyl, arylalkyl, heteroarylalkyl, aryl or heteroaryl; RB and RC independently represent hydrogen, C1-6alkyl, aryl or heteroaryl; or RB and RC together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group; RD is selected from the group consisting of C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl; RE represents hydrogen or C1-6alkyl; RF and RG are independently selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl; or RF and RG together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group; RH represents hydroxy or NRBRC; and salts, solvates and esters thereof; provided that when RH is hydroxy, which is esterified to form -OR where R is selected from straight or branched chain alkyl, aralkyl, aryloxyalkyl, or aryl, then R is other than tert-butyl. Processes for their preparation and methods of using them in HCV treatment are provided.

  Formula（I）的抗病毒剂，其中：R3代表芳基或杂环芳基；R4代表一个或两个取代基，独立选择自氢、C1-6烷基、卤素、ORA、C（O）NRBRC、C（O）RD、CO2H、CO2RD、NRBRC、NREC（O）RD、NRECO2RD、NREC（O）NRFRG、NRESO2RD、SO2NRFRG、SO2RD、硝基、氰基、杂环烷基、杂环芳基、芳基、芳基烷基、杂环芳基烷基或CF3；R5和R6独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；n代表0或1；当n代表0时，R1代表C（O）RH，R2代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；当n代表1时，要么i）R1代表C（O）RH；R2代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；且R7和R8独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；或ii）R1和R2独立代表氢、C1-6烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；R7代表C（O）RH；且R8代表C1-6烷基、杂环烷基、芳基烷基或杂环芳基烷基；RA代表氢、C1-6烷基、芳基烷基、杂环芳基烷基、芳基或杂环芳基；RB和RC独立代表氢、C1-6烷基、芳基或杂环芳基；或RB和RC与它们连接的氮原子一起形成5或6个成员饱和环；RD选自由C1-6烷基、芳基、杂环芳基、芳基烷基和杂环芳基烷基组成的群体；RE代表氢或C1-6烷基；RF和RG独立选择自氢、C1-6烷基、芳基、杂环芳基、芳基烷基和杂环芳基烷基组成的群体；或RF和RG与它们连接的氮原子一起形成5或6个成员饱和环；RH代表羟基或NRBRC；以及其盐、溶剂化合物和酯；但是当RH是羟基时，酯化形成-OR，其中R选择自直链或支链烷基、芳基烷基、芳氧基烷基或芳基，那么R不是叔丁基。提供了它们的制备方法以及在HCV治疗中使用它们的方法。