tert-butyl 1-(2-bromoethylamino)-1-oxo-3-phenylpropan-2-ylcarbamate | 143799-88-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 1-(2-bromoethylamino)-1-oxo-3-phenylpropan-2-ylcarbamate
• 英文别名: (S)-1-bromo-2-((S)-tert-butoxycarbonylphenylalanylamino)ethane；tert-butyl N-[(2S)-1-(2-bromoethylamino)-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 143799-88-6
• 化学式: C₁₆H₂₃BrN₂O₃
• 分子量: 371.274
• InChiKey: VBCGOMYRGBKIRS-ZDUSSCGKSA-N

物化性质

• 沸点：
  539.3±50.0 °C(Predicted)
• 密度：
  1.297±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-(2-bromoethylamino)-1-oxo-3-phenylpropan-2-ylcarbamate 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 2-(N-Boc-1-amino-2-phenethyl)-2-oxazoline
  参考文献：
  名称：

  从羧酸方便地一锅合成2-恶唑啉。

  摘要：

  使用4-（4,6-二甲氧基-1,3,5-三嗪-2-基）-4-甲基吗啉氯化物（DMT-MM），已经开发出了简单的一锅法制备2-恶唑啉的方法。用DMT-MM在甲醇中处理羧酸和2-卤代乙基铵盐的混合物，然后在KOH存在下回流，得到恶唑啉。

  DOI：

  10.1248/cpb.56.1735
• 作为产物：
  描述：

  N-(叔丁氧羰基)苯丙氨酰甘氨酸甲酯 在 sodium tetrahydroborate 、 四溴化碳 、 三苯基膦 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 tert-butyl 1-(2-bromoethylamino)-1-oxo-3-phenylpropan-2-ylcarbamate
  参考文献：
  名称：

  Higashiura, Kunihiko; Ienaga, Kazuharu, Journal of Chemical Research, Miniprint, 1992, p. 1901 - 1921

  摘要：

  DOI：

文献信息

• Phenylalanine-Based Inactivator of AKT Kinase: Design, Synthesis, and Biological Evaluation
  作者：Thuy Nguyen、Robert A. Coover、Jenson Verghese、Richard G. Moran、Keith C. Ellis

  DOI：10.1021/ml500088x

  日期：2014.5.8

  Strategies to inhibit kinases by targeting the substrate binding site offer many advantages, including naturally evolved selectivity filters, but normally suffer from poor potency. In this work we propose a strategy to design and prepare covalent substrate-competitive kinase inhibitors as a method to improve potency. We have chosen Ala as the model kinase for this work. Using the AKT-GSK3 beta cocrystal structure and a reactive cysteine near the substrate binding site, we have identified phenylalanine (Phe) as an appropriate scaffold for the covalent inactivator portion of these inhibitors. By synthesizing compounds that incorporate cysteine-reactive electrophiles into phenylalanine and testing these compounds as AKT inhibitors, we have identified Boc-Phe-vinyl ketone as a submicromolar inactivator of AKT. We also show that Boc-Phe-vinyl ketone (1) potently inhibits AKT1 and inhibits cell growth in HCT116 and H460 cells nearly as well as AKT inhibitors GSK690693 and MK-2206, (2) is selective for kinases that possess an activation loop cysteine such as AKT, (3) requires the vinyl ketone for inactivation, (4) has inactivation that is time-dependent, and (5) alkylates Cys310 of AKT as shown by mass spectrometry. Identification of Boc-Phe-vinyl ketone as a covalent inactivator of AKT will allow the development of peptide and small-molecule substrate-competitive covalent kinase inhibitors that incorporate additional substrate binding elements to increase selectivity and potency. This proof-of-principle study also provides a basis to apply this strategy to other kinases of the AGC and CAMK families.
• Higashiura, Kunihiko; Ienaga, Kazuharu, Journal of Chemical Research, Miniprint, 1992, p. 1901 - 1921
  作者：Higashiura, Kunihiko、Ienaga, Kazuharu

  DOI：——

  日期：——
• Convenient One-Pot Synthesis of 2-Oxazolines from Carboxylic Acids
  作者：Kazuhito Hioki、Yumiko Takechi、Noriyo Kimura、Hiroyuki Tanaka、Munetaka Kunishima

  DOI：10.1248/cpb.56.1735

  日期：——

  Simple one-pot methods for preparation of 2-oxazolines have been developed using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). Treatment of a mixture of carboxylic acids and 2-haloethylammonium salts with DMT-MM in methanol followed by refluxing in the presence of KOH gives oxazolines.

  使用4-（4,6-二甲氧基-1,3,5-三嗪-2-基）-4-甲基吗啉氯化物（DMT-MM），已经开发出了简单的一锅法制备2-恶唑啉的方法。用DMT-MM在甲醇中处理羧酸和2-卤代乙基铵盐的混合物，然后在KOH存在下回流，得到恶唑啉。