(S)-ethyl 3-phenyl-2-(pyridin-2-ylamino)propanoate | 1448586-28-4

• 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: (S)-ethyl 3-phenyl-2-(pyridin-2-ylamino)propanoate
• 英文别名: ethyl (2S)-3-phenyl-2-(pyridin-2-ylamino)propanoate
• CAS: 1448586-28-4
• 化学式: C₁₆H₁₈N₂O₂
• 分子量: 270.331
• InChiKey: NNBKNIMDMRYFBZ-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-ethyl 3-phenyl-2-(pyridin-2-ylamino)propanoate 、 (S)-(-)-α-甲氧基-α-(三氟甲基)苯乙酸 以 氘代氯仿 为溶剂， 生成
  参考文献：
  名称：

  N-Heteroarylation of Chiral α-Aminoesters by Means of Palladium-Catalyzed Buchwald–Hartwig Reaction

  摘要：

  N-Heteroaryl-alpha-amino acid derivatives are valuable pharmacological agents as peptidomimetics. Classical SNAr methods using acid catalysis and elevated temperatures could not be extended to various alpha-amino acids and fairly electrophilic heterocyclic partners. Here, we report a mild and versatile method of N-heteroarylation of chiral alpha-aminoesters without racemization, involving Buchwald-Hartwig conditions. It could be extended to various a-amino acids and azines. This efficient N-heteroarylation leads to (i) a chemical library of putative peptidomimetics combining diverse azaheterocycles with the chiral alpha-aminoesters and their corresponding derivatives (amides, alcohols, etc.) and (ii) arginine derivatives designed as NPFF receptor ligancls.

  DOI：

  10.1021/jo4011427
• 作为产物：
  描述：

  2-氯吡啶 、 (2S)-2-氨基-3-苯丙酸乙酯 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以78%的产率得到(S)-ethyl 3-phenyl-2-(pyridin-2-ylamino)propanoate
  参考文献：
  名称：

  N-Heteroarylation of Chiral α-Aminoesters by Means of Palladium-Catalyzed Buchwald–Hartwig Reaction

  摘要：

  N-Heteroaryl-alpha-amino acid derivatives are valuable pharmacological agents as peptidomimetics. Classical SNAr methods using acid catalysis and elevated temperatures could not be extended to various alpha-amino acids and fairly electrophilic heterocyclic partners. Here, we report a mild and versatile method of N-heteroarylation of chiral alpha-aminoesters without racemization, involving Buchwald-Hartwig conditions. It could be extended to various a-amino acids and azines. This efficient N-heteroarylation leads to (i) a chemical library of putative peptidomimetics combining diverse azaheterocycles with the chiral alpha-aminoesters and their corresponding derivatives (amides, alcohols, etc.) and (ii) arginine derivatives designed as NPFF receptor ligancls.

  DOI：

  10.1021/jo4011427

文献信息

• N-Heteroarylation of Optically Pure α-Amino Esters using the Pd-PEPPSI-IPent^Cl -<i>o</i> -picoline Pre-Catalyst
  作者：Sepideh Sharif、David Mitchell、Michael J. Rodriguez、Jennifer L. Farmer、Michael G. Organ

  DOI：10.1002/chem.201603933

  日期：2016.10.10

  and efficient method for the Pd‐catalyzed N‐heteroarylation of optically pure α‐amino esters was developed. Dichloro[1,3‐bis(2,6‐di‐3‐pentylphenyl)imidazol‐2‐ylidene](o‐picoline)palladium(II) (Pd‐PEPPSI‐IPentCl‐o‐picoline; PEPPSI=pyridine enhanced pre‐catalyst preparation, stabilization, and initiation) was shown to effectively couple a variety of amino acids as the tert‐butyl ester with heteroaryl chlorides

  开发了一种健壮，温和且有效的方法，用于Pd催化的光学纯α-氨基酯的N-杂芳基化反应。二氯[1,3-双（2,6-二-3-戊基苯基）咪唑-2-亚基]（ö甲基吡啶）合钯（II）（PD-PEPPSI-IPent氯- ö甲基吡啶; PEPPSI =吡啶增强预催化剂的制备，稳定化和引发）被证明可以高效地将叔丁酯与叔芳基氯化物等多种氨基酸有效地偶联，并且与酯相邻的酸性质子具有出色的立体保留能力。对照实验表明，消旋作用是碱介导的，使用Pd-PEPPSI-IPent Cl时没有消除Pd介导的β-氢化物的证据。，并且消旋化仅在产物形成后发生，即未芳基化的起始氨基酯在我们的反应条件下不会去质子化。研究还表明，增加氨基酸上酯部分的空间体积（例如，乙基至叔丁基）会大大减慢产品的外消旋作用。