(2E)-1,1-dimethylethyl 3-(5-pyrimidinyl)-2-propenoate | 154844-41-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2E)-1,1-dimethylethyl 3-(5-pyrimidinyl)-2-propenoate
• 英文别名: tert-Butyl (2E)-3-(pyrimidin-5-yl)prop-2-enoate；tert-butyl (E)-3-pyrimidin-5-ylprop-2-enoate
• CAS: 154844-41-4
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.244
• InChiKey: HWEDVZJCCYKDBA-SNAWJCMRSA-N

物化性质

• 沸点：
  318.0±17.0 °C(Predicted)
• 密度：
  1.106±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2E)-1,1-dimethylethyl 3-(5-pyrimidinyl)-2-propenoate 在 Petroselinum crispum phenylalanine ammonialyase (1U) ammonium hydroxide 、 三氟乙酸 作用下， 反应 24.0h， 生成 β-(5-Pyrimidinyl)-L-alanine
  参考文献：
  名称：

  Phenylalanine Ammonia-Lyase: The Use of Its Broad Substrate Specificity for Mechanistic Investigations and Biocatalysis—Synthesis ofL-Arylalanines

  摘要：

  Several fluoro- and chlorophenylalanines were found to be good substrates of phenylalanine ammonialyase (PAL/EC 4.3.1.5) from parsley. The enantiomerically pure L-amino acids were obtained in goad yields by reaction of the corresponding cinnamic acids with 5M ammonia solution (buffered to pH 10) in the presence of PAL. The kinetic constants for nine different fluoro- and chlorophenylalanines do not provide a rigorous proof for but are consistent with the previously proposed mechanism comprising an electrophilic attack of the methylidene-imidazolone cofactor of PAL at the aromatic nucleus as a first chemical step. In the resulting Friedel-Crafts-type sigma complex the beta-protons are activated for abstraction and consequently the pro-S is abstracted by an enzymic base. Results from semiempirical calculations combined with a proposed partial active site model showed a correlation between the experimental kinetic constants and the change in polarization of the pro-S Cd-H bond and heat of formation of the ir complexes, thus making the electrophilic attack at the neutral aromatic ring plausible. Furthermore, while 5-pyrimidinylalanine was found to be a moderately good substrate of PAL, 2-pyrimidinylalanine was an inhibitor.

  DOI：

  10.1002/1521-3765(20000915)6:18<3386::aid-chem3386>3.0.co;2-5
• 作为产物：
  描述：

  5-溴嘧啶 、 丙烯酸叔丁酯 在 palladium diacetate 三乙胺 作用下， 反应 72.0h， 以67%的产率得到(2E)-1,1-dimethylethyl 3-(5-pyrimidinyl)-2-propenoate
  参考文献：
  名称：

  杂环β-氨基酸的合成。β-氨基-5-嘧啶丙酸及其衍生物的简便制备方法。

  摘要：

  通过5-溴嘧啶和丙烯酸叔丁酯之间的Heck偶联获得的新型（2E）-1,1-二甲基乙基-3-（5-嘧啶基）-2-丙酸酯在氨饱和的叔丁醇中进行近乎定量的迈克尔加成反应。迄今未知的β-氨基-5-嘧啶丙酸酯。该反应序列的合成效用通过以克为单位进行制备来证明。描述了酯向游离氨基酸和Cbz-N-保护的氨基酸的转化。的叔丁基酯和N-保护的β氨基酸在肽和peptidomimic合成是有用的。

  DOI：

  10.1016/s0040-4039(00)61438-7

文献信息

• Synthesis of heterocyclic β-amino acids. A convenient preparation of β-amino-5-pyrimidinepropanoic acid and derivatives.
  作者：Philippe R. Bovy、Joseph G. Rico

  DOI：10.1016/s0040-4039(00)61438-7

  日期：1993.12

  The novel (2E)-1,1-dimethylethyl-3-(5-pyrimidinyl)-2-propenoate , obtained by Heck coupling between 5-bromopyrimidine and tert-butyl acrylate undergoes nearly quantitative Michael addition in t-butanol saturated with ammonia to the hitherto unknown β-amino-5-pyrimidinepropanoic ester . The synthetic utility of this reactions sequence is demonstrated by preparation of on a multigram scale. The transformation

  通过5-溴嘧啶和丙烯酸叔丁酯之间的Heck偶联获得的新型（2E）-1,1-二甲基乙基-3-（5-嘧啶基）-2-丙酸酯在氨饱和的叔丁醇中进行近乎定量的迈克尔加成反应。迄今未知的β-氨基-5-嘧啶丙酸酯。该反应序列的合成效用通过以克为单位进行制备来证明。描述了酯向游离氨基酸和Cbz-N-保护的氨基酸的转化。的叔丁基酯和N-保护的β氨基酸在肽和peptidomimic合成是有用的。
• HETEROARYL DERIVATIVES AS PROTEIN KINASE INHIBITORS
  申请人：Honold Konrad

  公开号：US20090318428A1

  公开（公告）日：2009-12-24

  Objects of the present invention are the compounds of formula I their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates, the preparation of the above-mentioned compounds, medicaments containing them and their manufacture, as well as the use of the above-mentioned compounds in the control or prevention of illnesses such as cancer.

  本发明的对象是公式I的化合物及其药学上可接受的盐、对映体形式、非对映异构体和外消旋体，上述化合物的制备，含有它们的药物以及它们的制造，以及上述化合物在控制或预防癌症等疾病方面的使用。
• GAMMA-HYDROXY-2-(FLUOROALKYLAMINOCARBONYL)-1-PIPERAZINEPENTANAMIDES AS HIV PROTEASE INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1242426B1

  公开（公告）日：2007-10-31
• US8067599B2
  申请人：——

  公开号：US8067599B2

  公开（公告）日：2011-11-29
• Phenylalanine Ammonia-Lyase: The Use of Its Broad Substrate Specificity for Mechanistic Investigations and Biocatalysis—Synthesis ofL-Arylalanines
  作者：Andreas Gloge、Jerzy Zoń、Ágnes Kövári、László Poppe、János Rétey

  DOI：10.1002/1521-3765(20000915)6:18<3386::aid-chem3386>3.0.co;2-5

  日期：2000.9.15

  Several fluoro- and chlorophenylalanines were found to be good substrates of phenylalanine ammonialyase (PAL/EC 4.3.1.5) from parsley. The enantiomerically pure L-amino acids were obtained in goad yields by reaction of the corresponding cinnamic acids with 5M ammonia solution (buffered to pH 10) in the presence of PAL. The kinetic constants for nine different fluoro- and chlorophenylalanines do not provide a rigorous proof for but are consistent with the previously proposed mechanism comprising an electrophilic attack of the methylidene-imidazolone cofactor of PAL at the aromatic nucleus as a first chemical step. In the resulting Friedel-Crafts-type sigma complex the beta-protons are activated for abstraction and consequently the pro-S is abstracted by an enzymic base. Results from semiempirical calculations combined with a proposed partial active site model showed a correlation between the experimental kinetic constants and the change in polarization of the pro-S Cd-H bond and heat of formation of the ir complexes, thus making the electrophilic attack at the neutral aromatic ring plausible. Furthermore, while 5-pyrimidinylalanine was found to be a moderately good substrate of PAL, 2-pyrimidinylalanine was an inhibitor.