(S)-2-amino-9,10-dimethoxy-1,6,7,11b-tetrahydro-4H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester | 1012065-67-6

• 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: (S)-2-amino-9,10-dimethoxy-1,6,7,11b-tetrahydro-4H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester
• 英文别名: ethyl (11bS)-2-amino-9,10-dimethoxy-4,6,7,11b-tetrahydro-1H-benzo[a]quinolizine-3-carboxylate
• CAS: 1012065-67-6
• 化学式: C₁₈H₂₄N₂O₄
• 分子量: 332.4
• InChiKey: KJLKBWRENGBSKF-HNNXBMFYSA-N

物化性质

• 沸点：
  484.7±45.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-9,10-dimethoxy-1,6,7,11b-tetrahydro-4H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester 、 二碳酸二叔丁酯 在 氢气 、 甲醇 、 水 、 sodium methylate 、 formamide 作用下， 以 2,2,2-三氟乙醇 为溶剂， 40.0~50.0 ℃ 、3.0 MPa 条件下， 反应 19.0h， 生成 ethyl (2S,3S,11bS)-2-amino-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizine-3-carboxylate
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF PYRIDO [ 2-1-A] ISOQUINOLINE DERIVATIVES BY CATALYTIC ASYMMETRIC HYDROGENATION OF AN ENAMINE

  摘要：

  本发明涉及一种制备式为的吡啶并[2,1-a]异喹啉衍生物的方法，其中R2、R3和R4如规范中所定义，包括以下步骤：a）在手性二膦配体存在下，对式为的烯胺进行催化不对称氢化，其中R1为低碳基；b）引入氨基保护基Prot；c）酰胺化酯，形成式为的酰胺，其中R2、R3、R4和Prot如规范中所定义。

  公开号：

  US20080076925A1
• 作为产物：
  描述：

  (S)-2-amino-9,10-dimethoxy-1,6,7,11b-tetrahydro-4H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester, (S,S)-2,3-bisbenzoyloxysuccinic acid salt 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.08h， 以98%的产率得到(S)-2-amino-9,10-dimethoxy-1,6,7,11b-tetrahydro-4H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF PYRIDO [2,1-a] ISOQUINOLINE DERIVATIVES COMPRISING OPTICAL RESOLUTION OF AN ENAMINE

  摘要：

  本发明涉及一种制备式为pyrido[2,1-a]异喹啉衍生物的方法，其中R1、R2、R3和R4在规范中有定义，包括在具有手性分离剂的存在下，光学分辨式为R1为低级烷基的恩酰胺，形成式为RCO2-的手性(S)-恩酰胺盐。

  公开号：

  US20080071087A1

文献信息

• PROCESS FOR THE PREPARATION OF PYRIDO [2,1-A] ISOQUINOLINE DERIVATIVES COMPRISING OPTICAL RESOLUTION OF AN ENAMINE
  申请人：Abrecht Stefan

  公开号：US20130018191A1

  公开（公告）日：2013-01-17

  This invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula wherein R 1 , R 2 , R 3 and R 4 are defined in the specification, comprising the optical resolution of an enamine of the formula wherein R 1 is lower alkyl, in the presence of an optical active resolving agent to form an (S)-enamine salt of the formula wherein RCO 2 − is the conjugate base of the resolving agent.

  本发明涉及一种制备式为pyrido [2,1-a] isoquinoline衍生物的过程，其中R1、R2、R3和R4在说明书中定义，包括在光学活性分离剂的存在下对式为的烯胺进行光学分辨，以形成式为的（S）-烯胺盐，其中RCO2-是分离剂的共轭碱基。
• Process For The Preparation Of Pyrido [2,1-A] Isoquinoline Derivatives Comprising Optical Resolution Of An Enamine
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150126743A1

  公开（公告）日：2015-05-07

  This invention relates to a process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R 1 , R 2 , R 3 and R 4 are defined in the specification, comprising the optical resolution of an enamine of the formula wherein R 1 is lower alkyl, in the presence of an optical active resolving agent to form an (S)-enamine salt of the formula wherein RCO 2 − is the conjugate base of the resolving agent.

  本发明涉及一种制备式为pyrido[2,1-a]isoquinoline衍生物的方法，其中R1、R2、R3和R4在规范中有定义，包括在光学活性分离剂的存在下，对式为的烯胺进行光学分辨，以形成式为的(S)-烯胺盐，其中RCO2-是分离剂的共轭碱基。
• PROCESS FOR THE PREPARATION OF PYRIDO[2,1-A]ISOQUINOLINE DERIVATIVES COMPRISING OPTICAL RESOLUTION OF AN ENAMINE
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2066667B1

  公开（公告）日：2011-08-31
• Process for the Preparation of Pyrido [2,1-a] Isoquinoline Derivatives by Catalytic Asymmetric Hydrogenation of an Enamine
  申请人：Abrecht Stefan

  公开号：US20120010413A1

  公开（公告）日：2012-01-12

  The invention relates to a process for the preparation of pyrido[2,1-a] isoquinoline derivatives of the formula wherein R 2 , R 3 and R 4 are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula wherein R 1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula wherein R 2 , R 3 , R 4 and Prot are as defined in the specification.
• PROCESS FOR THE PREPARATION OF PYRIDO[2,1-a] ISOQUINOLINE DERIVATIVES BY CATALYTIC ASYMMETRIC HYDROGENATION OF AN ENAMINE
  申请人：Hoffmann-La Roche Inc.

  公开号：US20130109859A1

  公开（公告）日：2013-05-02

  The invention relates to a process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R 2 , R 3 and R 4 are as defined in the specification, comprising the steps of a) catalytic asymmetric hydrogenation of an enamine of the formula wherein R 1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula wherein R 2 , R 3 , R 4 and Prot are as defined in the specification.