N-methyl-N-(2-(tert-butyloxycarbonyloxy)ethyl)-4-aminobenzaldehyde | 1352299-88-7

• 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: N-methyl-N-(2-(tert-butyloxycarbonyloxy)ethyl)-4-aminobenzaldehyde
• CAS: 1352299-88-7
• 化学式: C₁₅H₂₁NO₄
• 分子量: 279.336
• InChiKey: BONAWHSIDNSGEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.89
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.84
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-methyl-N-(2-(tert-butyloxycarbonyloxy)ethyl)-4-aminobenzaldehyde 在 sodium metabisulfite 、 四丁基氟化铵 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 5.17h， 生成 4-(5-Bromo-1-methyl-1H-benzo[d]imidazol-2-yl)-N-(2-fluoroethyl)-N-methylaniline
  参考文献：
  名称：

  新型2-芳基苯并咪唑类化合物的合成及生物评价

  摘要：

  在这里，我们描述了新颖的N未取代和N甲基化的2-芳基苯并咪唑衍生物的合成和初步生物学评估，这些衍生物在4- N芳基的位置上具有氟化或羟基化的烷基取代基，并且取代方式不同（H，Br，I）在苯并咪唑环中。对于所选化合物和用于比较目的，还测试了同类苯并噻唑。在一组人类癌细胞系中评估了11种苯并唑衍生物的细胞毒性作用，这些细胞系包括乳腺癌（MCF7），黑素瘤（A375），宫颈（HeLa）和胶质母细胞瘤（U87）。通常，这些化合物对所有测试的细胞均具有中等的细胞毒活性。特别是对于A375和HeLa细胞，N未取代的苯并咪唑2和3比各自的N-甲基化的苯并咪唑同类物（5和7）具有更好的细胞毒性。化合物2的生物分布在U87胶质母细胞瘤细胞中表现出最高的细胞毒活性（IC 50  = 45.2±13.0），使用其18 F标记的对应物（[ 18 F] 2）在CD1小鼠中进行了评估。这些研究表明化合物2可以通过合理的脑吸收（分别在pi

  DOI：

  10.1002/jhet.2575
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 N-甲基-N-(2-羟乙基)-4-氨基苯醛 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以95%的产率得到N-methyl-N-(2-(tert-butyloxycarbonyloxy)ethyl)-4-aminobenzaldehyde
  参考文献：
  名称：

  Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes

  摘要：

  The formation of proteinaceous aggregates is a pathognomonic hallmark of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. To date, the final diagnostic for these diseases can only be achieved by immunostaining of post-mortem brain tissues with the commonly used congo red and Thioflavin T/S amyloid-dyes. The interest in developing amyloid-avid radioprobes to be used for protein aggregates imaging by positron emission tomography has grown substantialy, due to the promise in assisting diagnosis of these disorders. To this purpose, the present work describes the synthesis and characterization of four novel fluorinated styryl benzazole derivatives 1-4 by means of the Wittig reaction, as well as their in vitro evaluation as amyloid-probing agents. All compounds were obtained as mixtures of geometric E and Z isomers, with the preferable formation of the E isomer. Photoisomerization reactions allowed for the maximization of the minor Z isomers. The authentic 1-4E/Z isomers were isolated after purification by column chromatography under dark conditions. Profiting from the fluorescence properties of the different geometric isomers of 1-4, their binding affinities towards amyloid fibrils of insulin, alpha-synuclein and beta-amyloid peptide were also measured. These compounds share similarities with Thioflavin T, interacting specifically with fibrillary species with a red-shift in the excitation wavelengths along with an increase in the fluorescence emission intensity. Apparent binding constants were determined and ranged between 1.22 and 23.96 mu M-1. The present data suggest that the novel fluorinated styryl benzazole derivatives may prove useful for the design of F-18-labeled amyloid radioprobes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.065

文献信息

• X-ray Diffraction Structures of Regioisomers of N-Methylated Benzimidazole Compounds with Interest for the Design of Amyloid-Avid Probes
  作者：Goreti Ribeiro Morais、Isabel C. Santos、Isabel Santos、António Paulo

  DOI：10.1007/s10870-012-0358-x

  日期：2012.10

  This work describes the compounds 5-bromo-1-methyl-2-[N-methyl-N-(2′-O-tert-butylcarbonatethyl)-4′-aminophenyl]-1H-benzo[d]imidazole (4) and 6-bromo-1-methyl-2-[N-methyl-N-(2′-O-tert-butylcarbonatethyl)-4′-aminophenyl]-1H-benzo[d]imidazole (5), C22H26BrN3O3, which correspond to two regioisomers that were obtained by N-methylation of the corresponding 6-bromobenzimidazole derivative. The structures of these two regioisomers have been confirmed in solution by NMR NOESY experiments, as well as in the solid state using single crystal X-ray diffraction analysis. The structures of 4 and 5 comprise two planar benzimidazole and benzene fragments and a disordered aliphatic chain containing a terminal carbamate group. Compound 4 crystallized in the monoclinic P21/c group with unit cell parameters a = 23.0178(7) Å, b = 7.9106(2) Å, c = 11.9758(3) Å, β = 93.340(2)º, V = 2176.90(10) Å3, Z = 4, D = 1.405 Mg/m3. Compound 5 crystallized in the triclinic P-1 group with unit cell parameters a = 6.7187(3) Å, b = 16.5203(10) Å, c = 21.3544(13) Å, α = 109.279(2)º, β = 94.802(2)º, γ = 98.871(2)º, V = 2187.4(2) Å3, Z = 4, D = 1.398 Mg/m3. Two regiosomers of benzimidazole derivatives are reported, including the elucidation of their structures in solution by NMR NOESY experiments and in the solid state by X-ray diffraction studies.

  本研究介绍了 5-溴-1-甲基-2-[N-甲基-N-（2′-O-叔丁基羰基乙基）-4′-氨基苯基]-1H-苯并[d]咪唑（4）和 6-溴-1-甲基-2-[N-甲基-N-（2′-O-叔丁基羰基乙基）-4′-氨基苯基]-1H-苯并[d]咪唑（5）、C22H26BrN3O3，它们对应于通过对相应的 6-溴苯并咪唑衍生物进行 N-甲基化而得到的两种区域异构体。这两种区域异构体的结构已通过核磁共振 NOESY 实验在溶液中得到证实，并通过单晶 X 射线衍射分析在固态中得到证实。4 号和 5 号化合物的结构由两个平面苯并咪唑和苯片段以及一个含有氨基甲酸酯末端基团的无序脂肪族链组成。化合物 4 在单斜 P21/c 组中结晶，单胞参数 a = 23.0178(7) Å, b = 7.9106(2) Å, c = 11.9758(3) Å, β = 93.340(2)º, V = 2176.90(10) Å3, Z = 4, D = 1.405 Mg/m3.化合物 5 以三菱 P-1 族结晶，单胞参数 a = 6.7187(3) Å, b = 16.5203(10) Å, c = 21.3544(13) Å, α = 109.279(2)º, β = 94.802(2)º, γ = 98.871(2)º, V = 2187.4(2) Å3, Z = 4, D = 1.398 Mg/m3.报告了苯并咪唑衍生物的两种外消旋体，包括通过核磁共振 NOESY 实验阐明了它们在溶液中的结构，以及通过 X 射线衍射研究阐明了它们在固态中的结构。