Carmegliptin dihydrochloride | 813452-14-1

• 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: Carmegliptin dihydrochloride
• 英文别名: (4S)-1-[(2S,3S,11bS)-2-amino-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-3-yl]-4-(fluoromethyl)pyrrolidin-2-one;dihydrochloride
• CAS: 813452-14-1
• 化学式: C20H30Cl2FN3O3
• 分子量: 450.4
• InChiKey: DDKJYXSAKVWFLS-LSKWAPIISA-N

物化性质

• 熔点：
  >275 °C

计算性质

• 辛醇/水分配系数(LogP)：
  2.36
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  68
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  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 、 (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 、 盐酸 以 异丙醇 为溶剂， 反应 64.0h， 以to afford the title compound (2.04 g, 91%)的产率得到Carmegliptin dihydrochloride
  参考文献：
  名称：

  Pyrido [2,1-a] isoquinoline derivatives

  摘要：

  本发明提供了公式（I）1中所示的化合物，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性糖尿病和糖耐量受损。

  公开号：

  US20040259903A1

文献信息

• PROCESS FOR THE PREPARATION OF PYRIDO[2,1-a] ISOQUINOLINE DERIVATIVES
  申请人：Abrecht Stefan

  公开号：US20090163718A1

  公开（公告）日：2009-06-25

  The present invention relates to a novel process for the preparation of pyrido[2,1-a]isoquinoline derivatives of the formula wherein R 2 , R 3 and R 4 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy and lower alkenyl, wherein lower alkyl, lower alkoxy and lower alkenyl may optionally be substituted by a group consisting of lower alkoxycarbonyl, aryl and heterocyclyl, and the pharmaceutically acceptable salts thereof. The pyrido[2,1-a]isoquinoline derivatives of the formula I are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV.

  本发明涉及一种用于制备式中的吡啶[2,1-a]异喹啉衍生物的新型过程R2，R3和R4分别独立地选自由氢，卤素，羟基，较低烷基，较低烷氧基和较低烯基的群，其中较低烷基，较低烷氧基和较低烯基可以选择性地被较低烷氧羰基，芳基和杂环烷基的群取代，以及其药学上可接受的盐。式I的吡啶[2,1-a]异喹啉衍生物对与DPP IV相关的疾病的治疗和/或预防是有用的。
• 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。