tert-butyl (S)-2-((tert-butyldimethylsilyloxy)methyl)aziridine-1-carboxylate | 875762-89-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丙烷
• 英文名称: tert-butyl (S)-2-((tert-butyldimethylsilyloxy)methyl)aziridine-1-carboxylate
• 英文别名: (S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)aziridine-1-carboxylate；tert-butyl (2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]aziridine-1-carboxylate
• CAS: 875762-89-3
• 化学式: C₁₄H₂₉NO₃Si
• 分子量: 287.475
• InChiKey: QKHQXHNZAQKXNI-VPHXOMNUSA-N

物化性质

• 沸点：
  304.4±15.0 °C(Predicted)
• 密度：
  0.978±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  38.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-2-((tert-butyldimethylsilyloxy)methyl)aziridine-1-carboxylate 在 四丁基氟化铵 、 四丁基硫酸氢铵 、 sodium hydroxide 作用下， 以 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 2.5h， 生成 (S)-(-)-tert-butyl (1-(4-bromo-1-tosyl-1H-indol-3-yl)-3-hydroxypropan-2-yl)carbamate
  参考文献：
  名称：

  A concise total synthesis of (−)-indolactam V

  摘要：

  One-pot synthesis of tryptophanol derivative from N-Boc-aziridine and indole has been developed. The ring opening reaction of the aziridine takes place smoothly at -30 degrees C in a regioselective manner and tolerates a wide range of functional groups including halogens attached to the aromatic ring, which was also performed on a gram scale. The resulting tryptophanol derivative was converted to (-)-indolactam V from commercially available 4-bromoindole through a copper-mediated aryl amination in nine steps with an overall yield of 32%. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.04.015
• 作为产物：
  描述：

  [(1S)-2-[[(叔-丁基)二甲基硅烷基]氧基]-1-(羟基甲基)乙基]-氨基甲酸叔-丁酯 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 48.5h， 以50%的产率得到tert-butyl (S)-2-((tert-butyldimethylsilyloxy)methyl)aziridine-1-carboxylate
  参考文献：
  名称：

  [EN] MACROCYCLIC BETA-SECRETASE INHIBITORS
  [FR] INHIBITEURS DE BÊTA-SECRÉTASE MACROCYCLIQUES

  摘要：

  揭示了以下式（I）的新化合物：或其药学上可接受的盐或溶剂，其中R1、R2、R3、n和X如规范中所定义。还揭示了包括式（I）化合物的药物组合物。还揭示了治疗认知或神经退行性疾病如阿尔茨海默病的方法。还揭示了治疗认知或神经退行性疾病的方法，包括向需要此类治疗的患者施用至少一种式（I）化合物和选自-分泌酶抑制剂（不包括式（I）的那些）、HMG-CoA还原酶抑制剂、γ-分泌酶抑制剂、非甾体抗炎药、N-甲基-D-天冬氨酸受体拮抗剂、胆碱酯酶抑制剂和抗淀粉样抗体的化合物组合物的方法。

  公开号：

  WO2006014944A1

文献信息

• [EN] MACROCYCLIC BETA-SECRETASE INHIBITORS<br/>[FR] INHIBITEURS DE BÊTA-SECRÉTASE MACROCYCLIQUES
  申请人：SCHERING CORP

  公开号：WO2006014944A1

  公开（公告）日：2006-02-09

  Disclosed are novel compounds of the formula (I): or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula (I). Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula (I) and at least one compound selected from the group consisting of -secretase inhibitors other than those of formula (I), HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

  揭示了以下式（I）的新化合物：或其药学上可接受的盐或溶剂，其中R1、R2、R3、n和X如规范中所定义。还揭示了包括式（I）化合物的药物组合物。还揭示了治疗认知或神经退行性疾病如阿尔茨海默病的方法。还揭示了治疗认知或神经退行性疾病的方法，包括向需要此类治疗的患者施用至少一种式（I）化合物和选自-分泌酶抑制剂（不包括式（I）的那些）、HMG-CoA还原酶抑制剂、γ-分泌酶抑制剂、非甾体抗炎药、N-甲基-D-天冬氨酸受体拮抗剂、胆碱酯酶抑制剂和抗淀粉样抗体的化合物组合物的方法。
• 11-Step Total Synthesis of Teleocidins B-1–B-4
  作者：Hugh Nakamura、Kosuke Yasui、Yuzuru Kanda、Phil S. Baran

  DOI：10.1021/jacs.8b13697

  日期：2019.1.30

  A unified and modular approach to the teleocidin B family of natural products is presented that proceeds in 11 steps and features an array of interesting strategies and methods. Indolactam V, the known biosynthetic precursor to this family, was accessed through electrochemical amination, Cu-mediated aziridine opening, and a remarkable base-induced macrolactamization. Guided by a desire to minimize

  提出了一种针对天然产物 Teleocidin B 家族的统一和模块化方法，该方法分 11 个步骤进行，并具有一系列有趣的策略和方法。Indolactam V 是该家族已知的生物合成前体，通过电化学胺化、Cu 介导的氮丙啶开放和显着的碱诱导大环内酰胺化获得。在最小化让步步骤的愿望的指导下，CH 硼酸化和 Sigman-Heck 变换的战术组合使 Teleocidins 的聚合、立体控制合成成为可能。
• 一种LZC696中间体及其合成方法
  申请人：上海博氏医药科技有限公司

  公开号：CN105237560B

  公开（公告）日：2018-07-06

  本发明公开了一种化合物，所述化合物为(R)‑叔丁基(1‑((1,1’联苯)‑4‑基)3‑((叔丁基二甲基硅基)氧)丙烷‑2‑基)氨基甲酸酯，其结构式如式A所示：A。采用这种化合物合成LZC696中间体，整个工艺过程没有昂贵的试剂和原料，无对氧气敏感反应，纯化程序简单，只需要在化合物3和最终产品重结晶纯化就可以达到商业化使用纯度。本发明合成工艺成本低，简单环保，适合工业化放量生产。
• Syntheses of Potent, Selective, and Orally Bioavailable Indazole-Pyridine Series of Protein Kinase B/Akt Inhibitors with Reduced Hypotension
  作者：Gui-Dong Zhu、Viraj B. Gandhi、Jianchun Gong、Sheela Thomas、Keith W. Woods、Xiaohong Song、Tongmei Li、R. Bruce Diebold、Yan Luo、Xuesong Liu、Ran Guan、Vered Klinghofer、Eric F. Johnson、Jennifer Bouska、Amanda Olson、Kennan C. Marsh、Vincent S. Stoll、Mulugeta Mamo、James Polakowski、Thomas J. Campbell、Ruth L. Martin、Gary A. Gintant、Thomas D. Penning、Qun Li、Saul H. Rosenberg、Vincent L. Giranda

  DOI：10.1021/jm0701019

  日期：2007.6.1

  Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80% homology with Akt in the kinase domain, our efforts have focused on structure-activity relationship (SAR) studies of the phenyl moiety, in an attempt to address the cardiovascular liability and further improve the Akt potency. A novel and efficient synthetic route toward diversely substituted phenyl derivatives of 7 was developed utilizing a copper-mediated aziridine ring-opening reaction as the key step. To improve the selectivity of these Akt inhibitors over other protein kinases, a nitrogen atom was incorporated into selected phenyl analogues of 7 at the C-6 position of the methyl indazole scaffold. These modifications resulted in the discovery of inhibitor 37c with greater potency (IC50 = 0.6 nM vs Akt), selectivity, and improved cardiovascular safety profile. The SARs, pharmacokinetic profile, and CV safety of selected Akt inhibitors will be discussed.
• WO2008/106128
  申请人：——

  公开号：——

  公开（公告）日：——