(2S,4R)-1-benzyl 4-methyl 4-azido-2-methylpiperidine-1,4-dicarboxylate | 1227685-19-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,4R)-1-benzyl 4-methyl 4-azido-2-methylpiperidine-1,4-dicarboxylate
• 英文别名: 1-benzyl 4-methyl (2S,4R)-4-azido-2-methylpiperidine-1,4-dicarboxylate；1-benzyl 1-methyl (2S,4R)-4-azido-2-methylpiperidine-1,4-dicarboxylate；1-O-benzyl 4-O-methyl (2S,4R)-4-azido-2-methylpiperidine-1,4-dicarboxylate
• CAS: 1227685-19-9
• 化学式: C₁₆H₂₀N₄O₄
• 分子量: 332.359
• InChiKey: VBAIXWAGKVSDQP-BLLLJJGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4R)-1-benzyl 4-methyl 4-azido-2-methylpiperidine-1,4-dicarboxylate 在 sodium tetrahydroborate 、 potassium phosphate 、 copper(l) iodide 、 sodium ethanolate 、 溶剂黄146 、 甲基磺酰氯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N'-二甲基乙二胺 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 26.0h， 生成 (5R,7S)-benzyl 1-(3-fluorophenyl)-7-methyl-2-oxo-1,8-diazaspiro[4.5]dec-3-ene-8-carboxylate
  参考文献：
  名称：

  Stereoselective Synthesis of Spiropiperidines as BACE-1 Aspartyl Protease Inhibitors via Late Stage N-Arylation of a 1,8-Diazaspiro[4.5]dec-3-en-2-one Pharmacophore

  摘要：

  A stereoselective synthesis of spiropiperidine compounds, exemplified by compound 1, was developed, which was based upon the late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore. Previously, compound 1 was prepared in low overall yield from piperidinone 2 via the Strecker reaction. A new route was developed, which employed the stereospecific Corey-Link reaction of an enantiomerically pure trichloromethylcarbinol to give a template compound amenable to late stage N-arylation.

  DOI：

  10.1021/jo400016m
• 作为产物：
  描述：

  (S)-1-CBZ-2-甲基-4-哌啶酮 在 sodium azide 、 18-冠醚-6 、 magnesium chloride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 为溶剂， 反应 24.5h， 生成 (2S,4R)-1-benzyl 4-methyl 4-azido-2-methylpiperidine-1,4-dicarboxylate
  参考文献：
  名称：

  Novel Sultam Compounds

  摘要：

  本发明揭示了化合物及其在规范中定义的Formula I（I）结构下的药用盐。同时还揭示了相应的药物组合物、治疗方法、合成方法和中间体。

  公开号：

  US20130150376A1

文献信息

• [EN] LACTAMS AS BETA SECRETASE INHIBITORS<br/>[FR] LACTAMES EN TANT QU'INHIBITEURS DE BÊTA-SÉCRÉTASE
  申请人：PFIZER

  公开号：WO2010058333A1

  公开（公告）日：2010-05-27

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment methods of synthesis, and intermediates are also disclosed.

  本文披露了化合物及其药学上可接受的盐，其中这些化合物具有规范中定义的Formula (I)的结构。同时还披露了相应的药物组合物、治疗方法、合成方法和中间体。
• Novel Sultam Compounds
  申请人：Brodney Michael Aaron

  公开号：US20130150376A1

  公开（公告）日：2013-06-13

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  本发明揭示了化合物及其在规范中定义的Formula I（I）结构下的药用盐。同时还揭示了相应的药物组合物、治疗方法、合成方法和中间体。
• Stereoselective Synthesis of Spiropiperidines as BACE-1 Aspartyl Protease Inhibitors via Late Stage <i>N</i>-Arylation of a 1,8-Diazaspiro[4.5]dec-3-en-2-one Pharmacophore
  作者：Che-Wah Lee、Ricardo Lira、Jason Dutra、Kevin Ogilvie、Brian T. O’Neill、Michael Brodney、Christopher Helal、Joseph Young、Erik Lachapelle、Subas Sakya、John C. Murray

  DOI：10.1021/jo400016m

  日期：2013.3.15

  A stereoselective synthesis of spiropiperidine compounds, exemplified by compound 1, was developed, which was based upon the late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore. Previously, compound 1 was prepared in low overall yield from piperidinone 2 via the Strecker reaction. A new route was developed, which employed the stereospecific Corey-Link reaction of an enantiomerically pure trichloromethylcarbinol to give a template compound amenable to late stage N-arylation.