[(R)-5-(4-methoxy-benzyl)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-carbamic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester | 1083065-09-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: [(R)-5-(4-methoxy-benzyl)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-carbamic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester
• 英文别名: [(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] N-[(7R)-5-[(4-methoxyphenyl)methyl]-6-oxo-7H-benzo[d][1]benzazepin-7-yl]carbamate
• CAS: 1083065-09-1
• 化学式: C₃₃H₃₈N₂O₄
• 分子量: 526.676
• InChiKey: IDKCDWYJGGDAKW-BVXIIPPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(R)-5-(4-methoxy-benzyl)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-carbamic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester 在 lithium diisopropyl amide 、 三甲基氯硅烷 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 24.08h， 以31.5%的产率得到[(S)-5-(4-methoxy-benzyl)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-carbamic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester
  参考文献：
  名称：

  PROCESS FOR PREPARATION OF ENANTIOMERICALLY PURE COMPOUNDS

  摘要：

  该发明涉及一种用于光学分辨二苯并[b,d]氮杂环己酮衍生物的过程，其化学式为II，其中R1为氢或卤素，R2为C1-4烷基，可选择性地取代为C3-7环烷基或苄基，苄基可选择性地取代为C1-4烷氧基，以获得化学式为I的(S)-7-氨基-5H,7H-二苯并[b,d]氮杂环己酮，其中R1如化合物II的情况。化学式为I的(S)-7-氨基-5H,7H-二苯并[b,d]氮杂环己酮可用作手性构建块，用于制备马隆酰胺衍生物，这些衍生物有潜力作为γ-分泌酶抑制剂，因此可能在治疗阿尔茨海默病和癌症方面有用。

  公开号：

  US20080293933A1
• 作为产物：
  描述：

  NA无结构图 、 (1R,2S,5R)-Menthyl chloroformate 在 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.42h， 以42.4%的产率得到[(S)-5-(4-methoxy-benzyl)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-carbamic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester
  参考文献：
  名称：

  Improved synthesis of (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one, a building block for γ-secretase inhibitors

  摘要：

  An improved synthesis of (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one (1), involving a selective crystallization of epimeric menthylcarbamates for the resolution step followed by simultaneous cleavage of the carbamate and the lactam protecting group is described. Epimerization conditions of the undesired epimer have also been determined. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.08.090

文献信息

• Process for preparation of enantiomerically pure compounds
  申请人：Hoffmann-La Roche Inc.

  公开号：US07579464B2

  公开（公告）日：2009-08-25

  The invention relates to a process for the optical resolution of a dibenzo[b,d]azepinone derivative of formula II, wherein R1 is hydrogen or halogen and R2 is either C1-4-alkyl optionally substituted with C3-7-cycloalkyl or benzyl which is optionally substituted with C1-4-alkoxy, to obtain a (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one of formula I, wherein R1 is as in the compound of formula II. The (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one of formula I can be used as a chiral building block for the preparation of malonamide derivatives which have the potential to act as γ-secretase inhibitors and therefore may be useful in the treatment of Alzheimer's disease and cancer.

  本发明涉及一种用于光学分离二苯并[b，d]氮杂环己酮衍生物的过程，其中式II中R1为氢或卤素，R2为C1-4烷基，可选地被C3-7环烷基或苄基取代，苄基可选地被C1-4烷氧基取代，以获得式I中的(S)-7-氨基-5H,7H-二苯并[b，d]氮杂环己酮，其中R1如式II中化合物所述。式I中的(S)-7-氨基-5H,7H-二苯并[b，d]氮杂环己酮可用作手性构建块，用于制备马隆酰胺衍生物，其具有作为γ-分泌酶抑制剂的潜力，因此可能在治疗阿尔茨海默病和癌症方面有用。
• PROCESS FOR PREPARATION OF ENANTIOMERICALLY PURE COMPOUNDS
  申请人：Hoffmann-Emery Fabienne

  公开号：US20080293933A1

  公开（公告）日：2008-11-27

  The invention relates to a process for the optical resolution of a dibenzo[b,d]azepinone derivative of formula II, wherein R 1 is hydrogen or halogen and R 2 is either C 1-4 -alkyl optionally substituted with C 3-7 -cycloalkyl or benzyl which is optionally substituted with C 1-4 -alkoxy, to obtain a (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one of formula I, wherein R 1 is as in the compound of formula II. The (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one of formula I can be used as a chiral building block for the preparation of malonamide derivatives which have the potential to act as γ-secretase inhibitors and therefore may be useful in the treatment of Alzheimer's disease and cancer.

  该发明涉及一种用于光学分辨二苯并[b,d]氮杂环己酮衍生物的过程，其化学式为II，其中R1为氢或卤素，R2为C1-4烷基，可选择性地取代为C3-7环烷基或苄基，苄基可选择性地取代为C1-4烷氧基，以获得化学式为I的(S)-7-氨基-5H,7H-二苯并[b,d]氮杂环己酮，其中R1如化合物II的情况。化学式为I的(S)-7-氨基-5H,7H-二苯并[b,d]氮杂环己酮可用作手性构建块，用于制备马隆酰胺衍生物，这些衍生物有潜力作为γ-分泌酶抑制剂，因此可能在治疗阿尔茨海默病和癌症方面有用。
• Improved synthesis of (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one, a building block for γ-secretase inhibitors
  作者：Fabienne Hoffmann-Emery、Roland Jakob-Roetne、Alexander Flohr、Fritz Bliss、Reinhard Reents

  DOI：10.1016/j.tetlet.2009.08.090

  日期：2009.11

  An improved synthesis of (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one (1), involving a selective crystallization of epimeric menthylcarbamates for the resolution step followed by simultaneous cleavage of the carbamate and the lactam protecting group is described. Epimerization conditions of the undesired epimer have also been determined. (C) 2009 Elsevier Ltd. All rights reserved.