N-isopropyl-3-phenylpropanamidate | 56146-87-3

• 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-isopropyl-3-phenylpropanamidate
• 英文别名: N-iso-propyl-3-phenylpropanamide；N-isopropyl-3-phenylpropionamide；N-isopropyl-3-phenylpropanamide；N-isopropylbenzenepropanamide；3-phenyl-N-propan-2-ylpropanamide
• CAS: 56146-87-3
• 化学式: C₁₂H₁₇NO
• mdl: MFCD00465426
• 分子量: 191.273
• InChiKey: ZYRLCOGVOHEKBK-UHFFFAOYSA-N

物化性质

• 熔点：
  90-91 °C(Solv: dichloromethane (75-09-2); hexane (110-54-3))
• 沸点：
  358.8±21.0 °C(Predicted)
• 密度：
  0.982±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-isopropyl-3-phenylpropanamidate 在 (μ₃,η²,η³,η⁵-acenaphthylene)Ru(CO)7 α-Me3Si-γ-Me3SiO-poly[oxy(methylsilanediyl)] 作用下， 以 various solvent(s) 为溶剂， 反应 24.0h， 以66%的产率得到N-异丙基-3-苯基-1-丙胺
  参考文献：
  名称：

  钌催化的仲酰胺与氢硅烷的还原和还原性N-烷基化：通过明智地选择氢化硅烷来实际合成仲胺和叔胺

  摘要：

  甲羰基三钌簇，（μ 3，η 2，η 3，η 5 -acenaphthylene）的Ru 3（CO）7（1）催化仲酰胺与氢硅烷的反应，生成仲胺，叔胺和甲硅烷基烯胺的混合物。通过使用较高浓度的催化剂（3 mol％）和使用双官能氢硅烷（例如1,1,3,3-四甲基二硅氧烷），可以实现具有完全选择性的仲胺的生产。对反应混合物进行酸性处理后，可得到相应的铵盐，可用碱进行处理，从而为分离高纯度仲胺提供了一种简便的方法。相反，通过使用较低浓度的催化剂（1mol％）和聚合氢硅氧烷（PMHS）作为还原剂，以高选择性形成叔胺。用PMHS还原将钌催化剂和有机副产物封装到不溶性有机硅树脂中。这两个反应歧管适用于各种仲酰胺，并且实用性在于该程序提供所需的仲胺或叔胺作为单一产物。产品仅被少量的钌和硅残留物污染。基于产物和观察到的副产物以及NMR研究，还描述了反应的机理方案。

  DOI：

  10.1021/jo070591c
• 作为产物：
  描述：

  2,2-difluoro-N-isopropyl-6-phenyl-2H-1,3l³,2l⁴-dioxaborinin-4-amine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 25.0 ℃ 、100.0 kPa 条件下， 以88%的产率得到N-isopropyl-3-phenylpropanamidate
  参考文献：
  名称：

  Hydrogenation of BF2 complexes with 1,3-dicarbonyl ligands

  摘要：

  The catalytic hydrogenation (H-2, Pd/C) of a set of BF2 complexes with a 1,3-dicarbonyl Structural unit leading to monocarbonyl compounds has been studied. The transformation presented is general for the aryl-substituted derivatives and occurs under mild conditions (H-2, 1 bar, 25 degrees C) in methanol or THF. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.01.017

文献信息

• BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：US20190300521A1

  公开（公告）日：2019-10-03

  The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为SMARCA2或BRM（靶蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合Von Hippel-Lindau E3泛素连接酶的配体，另一端结合靶蛋白的双功能化合物，使得靶蛋白与泛素连接酶靠近以实现靶蛋白的降解（和抑制）。本公开展示了与靶蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由靶蛋白聚集或积累导致的疾病或紊乱。
• TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20180125821A1

  公开（公告）日：2018-05-10

  The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为tau蛋白的调节剂具有实用性。具体而言，本公开涉及含有一端结合到E3泛素连接酶的VHL或cereblon配体，另一端结合到tau蛋白的双功能化合物，使得tau蛋白与泛素连接酶靠近，以实现tau蛋白的降解（和抑制）。本公开展示了与tau蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由tau蛋白聚集或积累导致的疾病或紊乱。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES
  申请人：Arvinas, Inc.

  公开号：US20190151295A1

  公开（公告）日：2019-05-23

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为白细胞介素-1受体相关激酶4（IRAK-4；目标蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合E3泛素连接酶的Von Hppel-Lindau、cereblon配体的双功能化合物，另一端结合目标蛋白的部分，使得目标蛋白靠近泛素连接酶以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由目标蛋白聚集或积累导致的疾病或紊乱。
• Ruthenium Catalyzed C–H Selenylations of Aryl Acetic Amides and Esters via Weak Coordination
  作者：Zhengyun Weng、Xinyue Fang、Meicui He、Linghui Gu、Jiafu Lin、Zheyu Li、Wenbo Ma

  DOI：10.1021/acs.orglett.9b02196

  日期：2019.8.16

  An efficient ruthenium-catalyzed direct C–H selenylation of aryl acetic amides and esters has been achieved via distal weakly coordination. Notable features of this protocol including broad substrate scope, wide functional group tolerance, and good regioselectivity. In addition, diaryl disulfides were also successfully applied to this reaction under slightly modified conditions.

  通过远端弱配位，已经实现了有效的钌催化芳基乙酰胺和酯的直接C–H硒化反应。该协议的显着特征包括广泛的底物范围，广泛的官能团耐受性和良好的区域选择性。另外，二芳基二硫化物也已在稍微改变的条件下成功地用于该反应。
• Heterobicyclic pyrazole compounds and methods of use
  申请人：Blake F. James

  公开号：US20070238726A1

  公开（公告）日：2007-10-11

  Compounds of Formulas Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  化合物Ia和Ib的结构，以及其立体异构体、几何异构体、互变异构体、溶剂合物、代谢物和药学上可接受的盐，可用于抑制受体酪氨酸激酶并治疗由此介导的疾病。公开了使用化合物Ia和Ib的结构，以及其立体异构体、几何异构体、互变异构体、溶剂合物和药学上可接受的盐的方法，用于体外、体内和体内诊断、预防或治疗哺乳动物细胞中的这类疾病，或相关的病理条件。