tert-butyl 4-methylphenethylcarbamate | 1190890-96-0

• 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: tert-butyl 4-methylphenethylcarbamate
• 英文别名: (2-(4-tolyl)ethyl)carbamic acid tert-butyl ester；(2-p-tolylethyl)carbamic acid tert-butyl ester；tert-butyl [2-(4-methylphenyl)ethyl]carbamate；tert-Butyl4-methylphenethylcarbamate；tert-butyl N-[2-(4-methylphenyl)ethyl]carbamate
• CAS: 1190890-96-0
• 化学式: C₁₄H₂₁NO₂
• 分子量: 235.326
• InChiKey: BCIGATJTDFUJGB-UHFFFAOYSA-N

物化性质

• 沸点：
  355.3±21.0 °C(Predicted)
• 密度：
  1.008±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-methylphenethylcarbamate 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 mineral oil 为溶剂， 反应 8.5h， 生成 甲基-(2-对甲苯-乙基)胺
  参考文献：
  名称：

  Palladium-Catalyzed C(sp²)–H Olefination of Free Primary and Secondary 2-Phenylethylamines: Access to Tetrahydroisoquinolines

  摘要：

  A rapid construction of THIQs by a Pd(II)-catalyzed C(sp(2))-H olefination of free primary and secondary 2-phenylethylamines with high step- and atom-economy was reported. Notably, no substituent was required at the alpha-position to the amino group of the 2-phenylethylamines. The substrate scope was broad, and the reaction could also be applied to generate THIQs from the biologically active molecules such as the drug molecule baclofen and phenylalanine ester.

  DOI：

  10.1021/acs.joc.9b01769
• 作为产物：
  描述：

  N-formyl-N-vinyl-carbamic acid tert-butyl ester 在 环己硫醇 、 10-苯基-10H-吩噻嗪 、 sodium formate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 反应 16.0h， 生成 tert-butyl 4-methylphenethylcarbamate
  参考文献：
  名称：

  区域选择性芳乙胺合成的催化策略

  摘要：

  报道了一种用于合成高度特权苯乙胺药效团的温和、模块化和实用的催化系统。该系统使用独特的有机催化剂组合来促进电子和氢原子的转移，可将乙烯基胺衍生物与各种芳基卤化物（包括芳基氯）直接加氢芳基化。这种通用且高度化学选择性的方案提供了范围广泛的具有完全区域控制的芳乙胺产品。该过程的实用性因其可扩展性和一系列生物活性小分子的模块化合成而突出。

  DOI：

  10.1021/jacs.9b01077

文献信息

• THERAPEUTIC AGENT FOR CEREBRAL INFARCTION
  申请人：Nakao Akira

  公开号：US20120196824A1

  公开（公告）日：2012-08-02

  The invention provides a therapeutic drug for ischemic stroke. The therapeutic drug has the formula (I) wherein each symbol is as defined herein, or a pharmacologically acceptable salt thereof, or a solvate thereof, as an active ingredient.

  这项发明提供了一种用于缺血性中风的治疗药物。该治疗药物具有如下式（I）的化学式，其中每个符号如本文所定义，或其药理学上可接受的盐，或其溶剂化物，作为活性成分。
• KYNURENINE PRODUCTION INHIBITOR
  申请人：Amishiro Nobuyoshi

  公开号：US20110237584A1

  公开（公告）日：2011-09-29

  Provided is a kynurenine production inhibitor comprising a nitrogen-containing heterocyclic compound represented by formula (I): (wherein R 50 and R 51 may be the same or different and each represent a hydrogen atom or the like, G 1 and G 2 may be the same or different and each represent a nitrogen atom or the like, X represents formula (III): (wherein m 1 and m 2 may be the same or different and each represent an integer of 0 or 1, Y represents an oxygen atom or the like, and R 6 and R 7 may be the same or different and each represent a hydrogen atom or the like), R 1 represents optionally substituted lower alkyl or the like, R 2 represents a hydrogen atom or the like, and R 3 represents optionally substituted lower alkyl or the like), and the like.

  提供的是一种色氨酸代谢抑制剂，包括由式(I)表示的含氮杂环化合物：（其中R50和R51可以相同也可以不同，每个代表氢原子或类似物，G1和G2可以相同也可以不同，每个代表氮原子或类似物，X表示式(III)：（其中m1和m2可以相同也可以不同，每个代表0或1的整数，Y表示氧原子或类似物，R6和R7可以相同也可以不同，每个代表氢原子或类似物），R1表示可选择地取代的低碳烷基或类似物，R2表示氢原子或类似物，R3表示可选择地取代的低碳烷基或类似物），等等。
• [EN] PCSK9 ANTAGONIST COMPOUNDS<br/>[FR] COMPOSÉS ANTAGONISTES DU PCSK9
  申请人：MERCK SHARP & DOHME

  公开号：WO2021041770A1

  公开（公告）日：2021-03-04

  Disclosed are compounds of Formula (A), or a pharmaceutically acceptable salt thereof: where A, X, R1, and R2 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula (I) or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

  本公开了化合物的结构式（A），或其药学上可接受的盐：其中A，X，R1和R2如本文所定义，这些化合物具有拮抗PCSK9的特性。还描述了包含化合物的药物配方（I）或其盐，并且治疗心血管疾病和与PCSK9活性相关的疾病的方法，例如动脉粥样硬化，高胆固醇血症，冠心病，代谢综合征，急性冠状综合征或相关心血管疾病和心脏代谢状况。
• Mechanistic approach of the difference in non-enzymatic hydrolysis rate between the L and D enantiomers of no-carrier added 2-[18F]fluoromethyl-phenylalanine
  作者：Ken Kersemans、John Mertens、Frank De Proft、Paul Geerlings

  DOI：10.1002/jlcr.1811

  日期：——

  No-carrier added (n.c.a.) 2-[18F]fluoromethyl-l-phenylalanine was found to be very sensitive to hydrolysis in aqueous solutions. This problem was solved partially by the addition of calcium ions (0.04 M), increasing the shelf-life to at least 6 h. In this paper the defluorination reaction was studied in detail to elucidate its mechanism. Therefore, L and D enantiomers of 2-[18F]FMP and 4-[18F]FMP were synthesized, as well as 2-[18F]fluoromethyl-phenethylamine and 4-[18F]fluoromethyl-phenethylamine, both decarboxylated ‘mimetic’ molecules of the amino acid analogues. Radiosynthesis, using a customized Scintomics automatic synthesis hotboxthree module, resulted in a high overall yield and a radiochemical purity of >99%. The defluorination rates of all compounds were studied by HPLC. The L enantiomer of n.c.a 2-[18F]FMP defluorinated seven times faster than the D enantiomer and 2-[18F]fluoromethyl-phenethylamine. Both enantiomers of 4-[18F]FMP and 4-[18F]fluoromethyl-phenethylamine were stable. From these data, the reaction mechanism, involving two distinct intramolecular interactions, was derived. First, the interaction between the amine and the benzylic fluorine weakens the carbon–fluorine bond. Secondly, the formation of a second hydrogen bridge between the carboxyl group and one of the benzylic hydrogen atoms renders the fluorine atom even more susceptible to hydrolysis. The latter interaction induces an additional chiral center. The probability of its formation differs considerably between L and D enantiomers of n.c.a. 2-[18F]FMP, which explains the difference in hydrolysis rate. Copyright © 2010 John Wiley & Sons, Ltd.

  无载体添加的(n.c.a.) 2-[18F]氟甲基-l-苯丙氨酸在水溶液中对水解非常敏感。通过添加钙离子 (0.04 M)，该问题部分得到解决，使其货架期延长至至少6小时。本文详细研究了去氟反应，以阐明其机制。因此，合成了2-[18F]FMP和4-[18F]FMP的L和D对映体，以及2-[18F]氟甲基-苯乙胺和4-[18F]氟甲基-苯乙胺，这两者都是氨基酸类的去羧基‘模拟’分子。使用定制的Scintomics自动合成热盒三模块进行的放射合成，获得了高的总体产率和>99%的放射化学纯度。通过高效液相色谱(HPLC)研究了所有化合物的去氟速率。n.c.a 2-[18F]FMP的L对映体去氟速率是D对映体和2-[18F]氟甲基-苯乙胺的七倍。4-[18F]FMP和4-[18F]氟甲基-苯乙胺的两个对映体均表现出稳定性。根据这些数据，得出了反应机制，涉及两种不同的分子内相互作用。首先，胺与苯基氟之间的相互作用削弱了碳-氟键。其次，羧基与其中一个苯基氢原子形成的第二个氢桥使氟原子对水解的敏感性进一步增强。后者的相互作用引入了额外的手性中心。这种手性中心的形成概率在n.c.a. 2-[18F]FMP的L和D对映体之间存在显著差异，这解释了水解速率的差异。版权所有 © 2010 John Wiley & Sons, Ltd.
• Mechanistic approach of the difference in hydrolysis rate between the 2- and 4-isomers of no-carrier-added [18F]fluoromethyl-L-phenylalanine
  作者：Ken Kersemans、John Mertens、Frank De Proft、Paul Geerlings

  DOI：10.1002/jlcr.1852

  日期：2011.4

  No-carrier-added (n.c.a.) 2-[18F]fluoromethyl-l-phenylalanine (2-[18F]FMP) was found to be very sensitive to hydrolysis in aqueous solutions. In this paper, the defluorination reaction was studied in detail to elucidate its mechanism. Therefore, besides 2-[18F]FMP and 4-[18F]FMP, 2-[18F]fluoromethyl-phenethylamine (2-[18F]FMPAM) and 4-[18F]FMPAM were synthesized, both ‘mimetic’ molecules of the decarboxylated amino acid analogues. Radiosynthesis, using a customized Scintomics automatic synthesis hotboxthree module, resulted in a high overall yield and a radiochemical purity of >99%. The defluorination rates of all compounds were studied by HPLC. The defluorination rate of 2-[18F]FMLP at 50°C was approximately 300 times faster than that of n.c.a. 4-[18F]FMLP. The defluorination rate of 2-[18F]FMPAM is somewhat lower than of 2-[18F]FMP but still very high in comparison with 4-[18F]FMPAM, which is virtually stable. It allowed to elucidate the reaction mechanism ruled by two distinct intramolecular interactions. First, the hydrogen bond interaction between the amine and the benzylic fluorine weakening the carbon–fluorine bond. Secondly, the formation of a second hydrogen bond between the carboxyl oxygen atom and one of the benzylic hydrogen atoms rendering the benzyl fluoride group even more susceptible to hydrolysis. Copyright © 2010 John Wiley & Sons, Ltd.

  无载体添加（n.c.a.）的2-[18F]氟甲基-L-苯丙氨酸（2-[18F]FMP）在水溶液中对水解非常敏感。本文对去氟反应进行了详细研究，以阐明其机制。因此，除了合成2-[18F]FMP和4-[18F]FMP之外，还合成了2-[18F]氟甲基-苯乙胺（2-[18F]FMPAM）和4-[18F]FMPAM，这两者均为去羧化氨基酸类似物的“模拟”分子。使用定制的Scintomics自动合成热盒三模块进行的放射合成，得到了高的整体产率和>99%的放射化学纯度。通过高效液相色谱（HPLC）研究了所有化合物的去氟速率。2-[18F]FMLP在50°C的去氟速率大约是n.c.a. 4-[18F]FMLP的300倍。2-[18F]FMPAM的去氟速率略低于2-[18F]FMP，但与几乎稳定的4-[18F]FMPAM相比，仍然非常高。这有助于阐明由两种不同的分子内相互作用主导的反应机制。首先，是胺和苄基氟之间的氢键相互作用，削弱了碳-氟键。其次，羧氧原子与一个苄基氢原子之间形成第二个氢键，使得苄基氟烷基团更易于水解。版权 © 2010 John Wiley & Sons, Ltd.