methyl 2-((diphenylmethylene)amino)-2-phenylacetate | 171181-53-6

• 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: methyl 2-((diphenylmethylene)amino)-2-phenylacetate
• 英文别名: methyl N-benzhydrylidenephenylglycinate；methyl 2-(benzhydrylideneamino)-2-phenylacetate
• CAS: 171181-53-6
• 化学式: C₂₂H₁₉NO₂
• 分子量: 329.398
• InChiKey: FFQULNDVBDXWTR-UHFFFAOYSA-N

物化性质

• 沸点：
  432.7±45.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-((diphenylmethylene)amino)-2-phenylacetate 在 盐酸 、 sodium hydroxide 、 18-冠醚-6 、 potassium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 2-氨基-2-苯基丁酸
  参考文献：
  名称：

  Structure-Activity Study of Tripeptide Thrombin Inhibitors Using .alpha.-Alkyl Amino Acids and Other Conformationally Constrained Amino Acid Substitutions

  摘要：

  In our continuing effort to design novel thrombin inhibitors, a series of conformationally constrained amino acids (e.g. alpha-alkyl, N-alkyl cyclic, etc.) were utilized in a systematic structure-activity study of the P3, P2, and P1 positions of tripeptide arginal thrombin inhibitors. Early examples of this effort include: D-MePhe-Pro-Arg-H (15), Boc-D-Phg-Pro-Arg-H (18), D-1-Tiq-Pro-Arg-H (23, D-1-Tiq D-1,2,3,4-tetrahydroisoquinolin-1-ylcarbonyl), and Boc-D-Phe-Pro-Arg-H (25).(10a,20) The current work clarifies the contribution of each residue of the tripeptide arginals toward the potent and selective inhibition of thrombin relative to that of t-PA and plasmin. The alpha-methylarginal modification in the P1 residue resulted in analogs 30 (D-MePhe at P3) and 32 (D-1-Tiq at P3) which had lower potency toward thrombin while exhibiting improved selectivity. Analogs modified at the P2 site were found to be very sensitive to the conformational changes induced by variations in side chain ring size with the flexible pipecolinic acid 31 being 2 orders of magnitude less potent at thrombin inhibition than the conformationally constrained azetidine analog 20. Examination of the P3 binding region indicated that alpha-alkylphenylglycine residues resulted in a tendency to exhibit substantial improvements in selectivity over the nonalkylated residues. Combinations of optimal P3 and P2 changes led to compounds TFA-D-Phg(alpha Et)-Azt-Arg-H (16), TFA-D-Phg(alpha Me)-Azt-Arg-H (17), Ac-D-Phg(alpha Me)-Azt-Arg-H (21), TFA-D-Phg(alpha Me)-Pro-Arg-H (27), 30, and 32, which are clearly more selective for thrombin versus plasmin than the nonconformationally constrained compounds.

  DOI：

  10.1021/jm00022a009
• 作为产物：
  描述：

  二苯甲胺 在 18-冠醚-6 、 potassium tert-butylate 、 magnesium sulfate 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 25.0 ℃ 、2.0 MPa 条件下， 反应 43.08h， 生成 methyl 2-((diphenylmethylene)amino)-2-phenylacetate
  参考文献：
  名称：

  通过二氧化碳对芳香亚胺的Umpolung羧化作用获得α-芳基甘氨酸

  摘要：

  通过直接羧化羧化反应实现了一种从芳族亚胺和二氧化碳高效合成α-芳基甘氨酸衍生物的简单且无过渡金属的方法。在叔丁醇钾和18-crown-6的存在下，各种取代的二苯甲亚胺与二氧化碳顺利进行了羧化反应，从而以高至高收率得到了相应的羧化产物。除了提高叔丁醇钾在THF中的溶解度外，18-crown-6在抑制反向质子化或1，3-质子转移异构化以及稳定羧化中间体方面也起着关键作用。

  DOI：

  10.1002/chem.201604623

文献信息

• Amino Acid Schiff Base Bearing Benzophenone Imine As a Platform for Highly Congested Unnatural α-Amino Acid Synthesis
  作者：Yohei Matsumoto、Jun Sawamura、Yumi Murata、Takashi Nishikata、Ryo Yazaki、Takashi Ohshima

  DOI：10.1021/jacs.0c02707

  日期：2020.5.6

  centers. The broad functional group compatibility highlights the mildness of the present catalysis. Notably, we achieved successive β-functionalization and oxidation of amino acid Schiff bases to afford dehydroalanine derivatives bearing tetrasubstituted carbon. A three-component cross-coupling reaction of an amino acid Schiff base, alkyl bromides, and styrene derivatives demonstrated the high utility

  非天然 α-氨基酸是合成有机化学中非常宝贵的组成部分，可以提升肽的功能。我们开发了一种新的氨基酸席夫碱催化活化模式，作为高度拥挤的非天然α-氨基酸合成的平台。氧化还原活性铜催化剂能够有效地交叉偶联以构建连续的四取代碳中心。广泛的官能团兼容性突出了本催化剂的温和性。值得注意的是，我们实现了氨基酸席夫碱的连续β-官能化和氧化，以提供带有四取代碳的脱氢丙氨酸衍生物。氨基酸席夫碱、烷基溴和苯乙烯衍生物的三组分交叉偶联反应证明了本方法的高实用性。还使用薄荷醇衍生物作为手性助剂实现了非对映选择性反应，提供对映异构富集的带有 α,β-连续四取代碳的 α-氨基酸。合成的高度拥挤的非天然 α-氨基酸可以被衍生化并整合到肽合成中。
• Synthesis of Hypervalent Iodine(III) Reagents Containing a Transferable (Diarylmethylene)amino Group and Their Use in the Oxidative Amination of Silyl Ketene Acetals
  作者：Kensuke Kiyokawa、Daichi Okumatsu、Satoshi Minakata

  DOI：10.1002/anie.201904971

  日期：2019.6.24

  The preparation of some hypervalent iodine reagents containing a transferable amino group derived from benzophenone imine derivatives is reported. The reagents can be readily prepared and stored as a bench‐stable solid, and were successfully used in the transition‐metal‐free oxidative amination of silyl ketene acetals to afford the corresponding α‐amino esters, the benzophenone imine moieties of which

  据报道制备了一些含有衍生自二苯甲酮亚胺衍生物的可转移氨基的高价碘试剂。该试剂易于制备并以稳定的固体形式存储，已成功用于甲硅烷基酮缩醛的无过渡金属氧化胺化反应，得到相应的α-氨基酯，其二苯甲酮亚胺部分很容易水解，从而导致伯胺的形成。
• Efficient synthesis of functionalized α-aryl α-aminoesters via reaction of polyfunctional diarylzincs with a glycine cation equivalent
  作者：Frédéric Lamaty、René Lazaro、Jean Martinez

  DOI：10.1016/s0040-4039(97)00625-4

  日期：1997.5

  Functionalized diarylzinc reagents, easily available from the corresponding aryl halides by a halogen-lithium exchange followed by transmetalation with ZnCl2 react with a glycine cation equivalent to afford substituted α-aryl α-amino esters in good yields.

  通过卤素-锂交换，然后用ZnCl 2进行金属转移，可容易地从相应的芳基卤化物获得的官能化二芳基锌试剂与甘氨酸阳离子等价物反应，以高收率得到取代的α-芳基α-氨基酯。
• α‐Amination of Carbonyl Compounds by Using Hypervalent Iodine‐Based Aminating Reagents Containing a Transferable (Diarylmethylene)amino Group
  作者：Daichi Okumatsu、Kazuki Kawanaka、Shunpei Kainuma、Kensuke Kiyokawa、Satoshi Minakata

  DOI：10.1002/chem.202203722

  日期：2023.2.16

  Primary resource: Hypervalent iodine-based aminating reagents containing a transferable (diarylmethylene)amino group can be used for the α-amination of simple carbonyl compounds such as esters, amides, and ketones in the presence of a lithium base. The (diarylmethylene)amino groups of the products can be readily modified, thus providing access to primary amines and diarylmethylamines.

  主要资源: 含有可转移（二芳基亚甲基）氨基的高价碘基胺化试剂可用于在锂碱存在下对简单的羰基化合物（如酯、酰胺和酮）进行 α-胺化。产品的（二芳基亚甲基）氨基可以很容易地进行修饰，从而提供获得伯胺和二芳基甲基胺的途径。
• Investigation into the enantioselective protonation of enolate Schiff bases with (R)-pantolactone
  作者：Monique Calmès、Christèle Glot、Jean Martinez

  DOI：10.1016/s0957-4166(00)00500-0

  日期：2001.2

  The effect of several factors on the enantioselective protonation of the enolates of a-amino acid derivatives with (R)-pantolactone were studied. The highest stereoselectivity (74-76% e.e.) was generally observed by associating lithium chloride with LHMDS and by using the optimum temperature for the formation of the enolate. (C) 2001 Published by Elsevier Science Ltd. All rights reserved.