(2S,3S,11bS)-[3-((4S)-4-(fluoromethyl)-2-oxo-pyrrolidin-1-yl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]-carbamic acid tert-butyl ester | 813452-16-3

• 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: (2S,3S,11bS)-[3-((4S)-4-(fluoromethyl)-2-oxo-pyrrolidin-1-yl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]-carbamic acid tert-butyl ester
• 英文别名: [(S,S,S)-3-((S)-4-fluoromethyl-2-oxo-pyrrolidin-1-yl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]-carbamic acid tert-butyl ester；((2S,3S,11bS)-3-((4S)-fluoromethyl-2-oxo-pyrrolidin-1-yl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl)-carbamic acid tert-butyl ester；tert-butyl N-[(2S,3S,11bS)-3-[(4S)-4-(fluoromethyl)-2-oxopyrrolidin-1-yl]-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl]carbamate
• CAS: 813452-16-3
• 化学式: C₂₅H₃₆FN₃O₅
• 分子量: 477.576
• InChiKey: ZKBIZSYATOJUSX-TTYHFUOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  80.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3S,11bS)-[3-((4S)-4-(fluoromethyl)-2-oxo-pyrrolidin-1-yl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以91%的产率得到(S)-1-((2S,3S,11bS)-2-amino-9, 10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4-fluoromethyl-pyrrolidin-2-one
  参考文献：
  名称：

  卡格列汀的发现：一种有效且长效的二肽基肽酶IV抑制剂，可用于治疗2型糖尿病

  摘要：

  针对一类基于S1特异性口袋中具有非芳族取代基的氨基苯并[ a ]喹唑啉的DPP-IV抑制剂的设计，合成和SAR进行了描述。选择其代表卡格列汀（8p）进行临床开发。还介绍了其与酶复合的X射线结构以及2型糖尿病动物模型中的早期功效数据。

  DOI：

  10.1016/j.bmcl.2009.12.024
• 作为产物：
  描述：

  (+/-)-2-amino-9,10-dimethoxy-1,6,7,11b-tetrahydro-4H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester 在 6-氯吡啶-2-醇 、 sodium tetrahydroborate 、 三乙胺 、 三氟乙酸 、 potassium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 35.0h， 生成 (2S,3S,11bS)-[3-((4S)-4-(fluoromethyl)-2-oxo-pyrrolidin-1-yl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  c

  摘要：

  DOI：

  c

文献信息

• Pyrido [2,1-a] isoquinoline derivatives
  申请人：——

  公开号：US20040259903A1

  公开（公告）日：2004-12-23

  The present invention provides compounds of formula (I) 1 wherein R 1 , R 2 , R 3 and R 4 are as indicated in the description, or a pharmaceutically acceptable salt thereof. The compounds are useful for the treatment of diseases which are associated with DPP-IV, such as diabetes, particularly non-insulin dependent diabetes mellitus, and impaired glucose tolerance.

  本发明提供了式（I）的化合物，其中R1、R2、R3和R4如描述中所示，或其药学上可接受的盐。这些化合物可用于治疗与DPP-IV相关的疾病，如糖尿病，特别是非胰岛素依赖型糖尿病和糖耐量受损。
• 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：US20080076925A1

  公开（公告）日：2008-03-27

  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.

  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。
• 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：US20080071087A1

  公开（公告）日：2008-03-20

  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]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。
• Process for the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one useful in the preparation of the DPP-IV inhibitor (S)-1 ((2S,3S,11bS)-2-amino-9,10-dimethoxy-1,3,4,6,7, 11b-hexahydro-2h-pyrido[2,1-a] isoquinolin-3-yl)-4-fluoromethyl-pyrrolidin-2-one
  申请人：Abrecht Stefan

  公开号：US20060270853A1

  公开（公告）日：2006-11-30

  This invention relates to a process of the preparation of the novel intermediate (S)-4-fluoromethyl-dihydro-furan-2-one of the formula and with its use for the manufacture of pyrido[2,1-a]isoquinoline derivatives of the formula which are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV.

  本发明涉及制备新中间体(S)-4-氟甲基-二氢呋喃-2-酮的方法，其化学式为：并利用该中间体制备式为：的吡啶[2,1-a]异喹啉衍生物，这些衍生物对于治疗和/或预防与DPP IV相关的疾病是有用的。
• PROCESS FOR THE PREPARATION OF (S)-4-FLUOROMETHYL-DIHYDRO-FURAN-2-ONE
  申请人：Zutter Ulrich

  公开号：US20080108816A1

  公开（公告）日：2008-05-08

  The present invention relates to a process of the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one of the formula by employing a dialkylmalonate of the formula wherein R 1b is lower alkyl, and the use of this process for the manufacture of DPP-IV inhibitors that are useful for the treatment and/or prophylaxis of diseases such as diabetes.

  本发明涉及一种制备(S)-4-氟甲基二氢呋喃-2-酮的方法，该方法采用式为其中R1为低级烷基的二烷基丙二酸酯，并且利用该方法制造DPP-IV抑制剂，该抑制剂可用于治疗和/或预防糖尿病等疾病。