BOC-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide | 138449-24-8

• 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: BOC-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide
• 英文别名: Boc-L-Nap-NMeBzl；Boc-Nal-NMeBzl；Boc-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methyl amide；tert-butyl N-[(2S)-1-[benzyl(methyl)amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamate
• CAS: 138449-24-8
• 化学式: C₂₆H₃₀N₂O₃
• 分子量: 418.536
• InChiKey: CXGBJXRFYNFPAK-QHCPKHFHSA-N

物化性质

• 沸点：
  615.9±55.0 °C(Predicted)
• 密度：
  1.142±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  BOC-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide 在 盐酸 、 1-羟基苯并三唑 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.33h， 生成 Boc-(2S,4R)-Hyp-L-Nap-NMeBzl
  参考文献：
  名称：

  Studies on Neurokinin Antagonists. 4. Synthesis and Structure-Activity Relationships of Novel Dipeptide Substance P Antagonists: N2-[(4R)-4-Hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N-methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and Its Related Compounds

  摘要：

  As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N-2-[N-2-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenylmethyl)-L-phenylalaninamide (2b). The lysine part in 2b was first optimized to a (2S,4R)hydroxyproline derivative (3h),which is 2-fold more potent than 2b in [H-3]SP binding assay using guinea pig lung membranes. Next we modified the 1H-indol-3-ylcarbonyl part in 3h. Introduction; of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity. Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.

  DOI：

  10.1021/jm00039a022
• 作为产物：
  描述：

  Boc-3-(2-萘基)-L-丙氨酸 以85的产率得到BOC-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide
  参考文献：
  名称：

  J. Med. Chem. 1994, 37, 2090-2099

  摘要：

  DOI：

文献信息

• Process Development of a Large-Scale Synthesis of TKA731:  A Tachykinin Receptor Antagonist
  作者：Mahavir Prashad、Denis Har、Bin Hu、Hong-Yong Kim、Michael J. Girgis、Apurva Chaudhary、Oljan Repič、Thomas J. Blacklock、Wolfgang Marterer

  DOI：10.1021/op0341824

  日期：2004.5.1

  leading to the urethane byproduct (I) formation and starting amino acid (2) liberation during the coupling of 2 with N-benzylmethylamine using well-known isobutyl chloroformate mediated mixed carboxylic-carbonic anhydride method, was found to be the symmetrical anhydride (III) formation from 2 as determined by the CO2 offgas formation. A new procedure for the coupling of 2 with N-benzylmethylamine ...

  描述了一种利用二肽 7 和 2-氯-4(3H)-喹唑啉酮 (13) 偶联作为关键步骤的速激肽受体拮抗剂 TKA731 (1) 的高效且无色谱的大规模合成。在六个线性步骤（总共八个步骤）中，从 BOC-1-3-(2-萘基)丙氨酸 (2) 得到 1 的总产率为 63%。这种新的收敛方法避免了在最初发现合成中涉及构建喹唑啉酮环的最后一步中使用甲基碘和甲硫醇副产物的形成。四个色谱也被取消。副反应的主要原因是使用众所周知的氯甲酸异丁酯介导的混合羧酸-碳酸酐法在 2 与 N-苄基甲胺偶联期间形成氨基甲酸酯副产物 (I) 和起始氨基酸 (2) 释放，发现是由 2 形成的对称酸酐 (III)，由 CO2 尾气形成确定。2与N-苄基甲胺偶联的新工艺...
• CO₂ Offgas as a Mechanistic Probe and Scale-up Tool in N-Acylations Using Mixed Anhydrides from Amino Acids and Isobutyl Chloroformate
  作者：Apurva Chaudhary、Michael J. Girgis、Mahavir Prashad、Bin Hu、Denis Har、Oljan Repič、Thomas J. Blacklock

  DOI：10.1021/op034085a

  日期：2003.11.1

  The reaction pathways of an N-acylation reaction, involving a mixed anhydride intermediate produced from reaction of an amino acid with isobutyl chloroformate, were analyzed using a novel technique involving the quantitation of CO2 evolved during various parts of the process. Under the normal mode of addition, in which chloroformate is added to a carboxylate anion solution, the dominant mode of yield

  N-酰化反应的反应途径，涉及由氨基酸与氯甲酸异丁酯反应产生的混合酸酐中间体，使用一种新技术分析了该过程的各个部分中释放的 CO2 的定量。在正常添加模式下，将氯甲酸根添加到羧酸根阴离子溶液中，导致不希望的产物的主要产率损失模式显示为形成对称酸酐，这意味着副产物氨基甲酸酯的形成几乎完全是由于未反应的氯甲酸酯与胺。该结果表明，推断的以正常添加模式存在的高浓度羧酸根阴离子应最小化以减少产率损失。通过证明当进行反向添加（即，将羧酸根阴离子溶液添加到氯甲酸根）时，几乎消除了对称酸酐的形成，证实了这一假设。这些结果，结合相关...
• Using mixed anhydrides from amino acids and isobutyl chloroformate in N-acylations: a case study on the elucidation of mechanism of urethane formation and starting amino acid liberation using carbon dioxide as the probe
  作者：Apurva Chaudhary、Michael Girgis、Mahavir Prashad、Bin Hu、Denis Har、Oljan Repič、Thomas J. Blacklock

  DOI：10.1016/s0040-4039(03)01329-7

  日期：2003.7

  using carbon dioxide offgas as the probe. The main reason for the urethane formation and starting amino acid liberation was found to be the formation of the symmetrical anhydride of the amino acid during the preparation of the mixed carboxylic–carbonic anhydride intermediate, as determined by quantifying the evolved carbon dioxide. New conditions were developed to minimize this side reaction.

  以二氧化碳尾气为探针，阐明了在传统的两步氯甲酸异丁酯介导的N-酰化过程中氨基甲酸酯副产物形成和氨基酸开始释放机理的案例研究。发现氨基甲酸酯的形成和起始氨基酸的释放的主要原因是在混合羧酸-碳酸酐中间体的制备过程中，氨基酸的对称酸酐的形成，这是通过定量析出的二氧化碳确定的。开发了新的条件以最小化该副反应。
• An Efficient and Practical N-Methylation of Amino Acid Derivatives
  作者：Mahavir Prashad、Denis Har、Bin Hu、Hong-Yong Kim、Oljan Repic、Thomas J. Blacklock

  DOI：10.1021/ol0268440

  日期：2003.1.1

  An efficient and practical N-methylation of amino acid derivatives with dimethyl sulfate in the presence of sodium hydride and a catalytic amount of water is described. Reaction of water with sodium hydride generated highly reactive dry sodium hydroxide, which led to much faster reaction rates than powdered sodium hydroxide itself.
• Caliendo; Greco; Grieco, Il Farmaco, 1996, vol. 51, # 3, p. 197 - 201
  作者：Caliendo、Greco、Grieco、Perissutti、Santagada、Calignano、Mancuso、Novellino

  DOI：——

  日期：——