(1R)-2-tert-butoxy-1-methyl-2-oxoethyl (2R)-2-(5-chloro-2-iodoanilino)-4-oxobutanoate | 252349-38-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (1R)-2-tert-butoxy-1-methyl-2-oxoethyl (2R)-2-(5-chloro-2-iodoanilino)-4-oxobutanoate
• 英文别名: [(2R)-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl] (2R)-2-(5-chloro-2-iodoanilino)-4-oxobutanoate
• CAS: 252349-38-5
• 化学式: C₁₇H₂₁ClINO₅
• 分子量: 481.715
• InChiKey: NLCSNOYCSSXFAN-ZWNOBZJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R)-2-tert-butoxy-1-methyl-2-oxoethyl (2R)-2-(5-chloro-2-iodoanilino)-4-oxobutanoate 在 四(三苯基膦)钯 lithium hydroxide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 甲苯 、 乙腈 为溶剂， 反应 7.5h， 生成 sodium (2R,4E)-7-chloro-4-(2-oxo-1-phenyl-3-pyrrolidinylidene)-1,2,3,4-tetrahydro-2-quinolinecarboxylate
  参考文献：
  名称：

  Novel Stereocontrolled Addition of Allylmetal Reagents to α-Imino Esters:  Efficient Synthesis of Chiral Tetrahydroquinoline Derivatives

  摘要：

  To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA receptor, an efficient distereoselective route was set up. The addition of suitable allyltin reagents to chiral N-aryl alpha-imino esters (R-(+)-tert-butyl lactate used as chiral auxiliary), gave the corresponding a amino acid-type derivative in high chemical yield and optical purity. This allylation reaction represents a novel example of efficient long-range stereodifferentiation process. In the last part of the synthesis, a regioselective Heck-type cyclization reaction enabled preparation of the target tetrasubstituted exocycle and trisubtituted endocycle double bond derivatives.

  DOI：

  10.1021/jo020327d
• 作为产物：
  描述：

  (1R)-2-tert-butoxy-1-methyl-2-oxoethyl acrylate 在 sodium periodate 、 四氧化锇 、 四氯化钛 、 臭氧 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 16.58h， 生成 (1R)-2-tert-butoxy-1-methyl-2-oxoethyl (2R)-2-(5-chloro-2-iodoanilino)-4-oxobutanoate
  参考文献：
  名称：

  Novel Stereocontrolled Addition of Allylmetal Reagents to α-Imino Esters:  Efficient Synthesis of Chiral Tetrahydroquinoline Derivatives

  摘要：

  To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA receptor, an efficient distereoselective route was set up. The addition of suitable allyltin reagents to chiral N-aryl alpha-imino esters (R-(+)-tert-butyl lactate used as chiral auxiliary), gave the corresponding a amino acid-type derivative in high chemical yield and optical purity. This allylation reaction represents a novel example of efficient long-range stereodifferentiation process. In the last part of the synthesis, a regioselective Heck-type cyclization reaction enabled preparation of the target tetrasubstituted exocycle and trisubtituted endocycle double bond derivatives.

  DOI：

  10.1021/jo020327d

文献信息

• Process Development and Scale Up of a Glycine Antagonist
  作者：Adam Banks、Gary F. Breen、Darren Caine、John S. Carey、Christopher Drake、Michael A. Forth、Asa Gladwin、Simone Guelfi、Jerome F. Hayes、Paolo Maragni、David O. Morgan、Paul Oxley、Alcide Perboni、Matthew E. Popkin、Fiona Rawlinson、Guillaume Roux

  DOI：10.1021/op9001824

  日期：2009.11.20

  A synthetic route amenable to large-scale synthesis of the glycine antagonist (2R,4E)-7-chloro-4-(2-oxo-1-phenyl-pyyrrolidin-3-ylidene)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid, (2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-penta-ol 12 is presented. The route consists of four stages of chemistry. Stage 1 starts from 5-chloro-2-iodoaniline hydrochloride and is a three-step telescoped stage consisting

  适用于大规模合成甘氨酸拮抗剂（2 R，4 E）-7-氯-4-（2-氧代-1-苯基-吡咯烷基-3-亚吡啶）-1,2,3,4的合成路线提出了-四氢喹啉-2-羧酸，（2 R，3 R，4 R，5 S）-6-（甲基氨基）己烷-1,2,3,4,5-戊醇12。该路线包括四个化学阶段。阶段1从5-氯-2-碘苯胺盐酸盐开始，是一个三步伸缩阶段，包括与乙二醛乙酯形成亚胺，使用乙烯基氧基三甲基硅烷进行曼尼希反应以及随后的与（2-氧代-1-苯基-3-的Wittig反应）吡咯烷基）三苯基溴化phosph。第一阶段产品（4 E）-2 [（（5-氯-2-碘代苯基）氨基] -4-（2-氧代-1-苯基-吡咯烷-3-亚叉基）丁酸乙酯17经过酶催化的动力学拆分以制备单（2 R）-对映体19作为乙酯。第3阶段是分子内Heck反应，得到（2 R，4 E）-7-氯-4-（2-氧代-1-苯基-吡咯烷烃-3-亚烷基）-1,2,3,4-四氢喹啉-2
• Chiral tetrahydroquinoline derivatives as potent anti-hyperalgesic agents in animal models of sustained inflammation and chronic neuropathic pain
  作者：Romano Di Fabio、Giuseppe Alvaro、Barbara Bertani、Daniele Donati、Domenica Maria Pizzi、Gabriella Gentile、Giorgio Pentassuglia、Simone Giacobbe、Simone Spada、Emiliangelo Ratti、Mauro Corsi、Mauro Quartaroli、Robert J. Barnaby、Giovanni Vitulli

  DOI：10.1016/j.bmcl.2006.12.022

  日期：2007.3

  Chiral tetrahydroquinoline derivatives have been prepared by an asymmetric Mannich-type condensation reaction using commercially available vinyloxyethylsilane and a N-arylimino R-(+)-t-butyl lactate ester, in the presence of a catalytic amount of metal triflates as Lewis acids. This synthetic approach gave rise to the target aldehyde intermediate in moderate facial diastereoselectivity and in high chemical yield. This efficient route enabled to scale up the synthesis of an orally bioavailable glycine antagonist showing outstanding in vivo anti-hyperalgesic activity in different animal models of sustained inflammation and chronic neuropathic pain. (c) 2006 Elsevier Ltd. All rights reserved.