(2S,3S,11bS)-3-(3-fluoromethyl-4-hydroxy-butyrylamino)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl-carbamic acid tert-butyl ester | 916069-89-1

• 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: (2S,3S,11bS)-3-(3-fluoromethyl-4-hydroxy-butyrylamino)-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: ((2S,3S,11bS)-3-((S)-3-fluoromethyl-4-hydroxy-butyrylamino)-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-[[(3S)-3-(fluoromethyl)-4-hydroxybutanoyl]amino]-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl]carbamate
• CAS: 916069-89-1
• 化学式: C₂₅H₃₈FN₃O₆
• 分子量: 495.592
• InChiKey: ORANMAHDSWWRLM-TTYHFUOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,3S,11bS)-3-(3-fluoromethyl-4-hydroxy-butyrylamino)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl-carbamic acid tert-butyl ester 在 2-羟基吡啶 作用下， 以 甲苯 为溶剂， 以20%的产率得到(2S,3S,11bS)-[3-amino-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
• 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 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 33.0h， 生成 (2S,3S,11bS)-3-(3-fluoromethyl-4-hydroxy-butyrylamino)-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

• 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 (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。
• [EN] PROCESS FOR THE PREPARATION OF PYRIDO [2, 1-A] ISOQUINOLINE DERIVATIVES AND POLYMORPHIC FROMS THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE PYRIDO[2,1-A]ISOQUINOLÉINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009027276A1

  公开（公告）日：2009-03-05

  The present invention is concerned with an improved process for the preparation of pyrido[2,l-a]isoquinoline derivatives of formula (I) wherein R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy or lower alkenyl, wherein lower alkyl, lower alkoxy and lower alkenyl may optionally be substituted by lower alkoxycarbonyl, aryl or heterocyclyl, and the pharmaceutically acceptable salts thereof. The invention also relates to two crystalline forms of (2S,3S,11bS)-1-(2-amino-9,10-dimethoxy-1, 3,4,6,7,11b-hexahydro-2H- pyrido[2,l-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride, which are form A and form B and to an amorphous form of said compound.

  本发明涉及一种改进的制备式（I）的吡啶[2，1-a]异喹啉衍生物的方法，其中R1、R2和R3各自独立地为氢、卤素、羟基、低烷基、低烷氧基或低烯基，其中低烷基、低烷氧基和低烯基可选择性地被低烷氧羰基、芳基或杂环基取代，以及其药学上可接受的盐。本发明还涉及（2S，3S，11bS）-1-(2-氨基-9,10-二甲氧基-1,3,4,6,7,11b-六氢-2H-吡啶[2，1-a]异喹啉-3-基)-4(S)-氟甲基-吡咯烷-2-酮二盐酸盐的两种晶体形式，分别为A形和B形，以及该化合物的非晶形式。
• US7956201B2
  申请人：——

  公开号：US7956201B2

  公开（公告）日：2011-06-07