[(1-Phenyl-ethylcarbamoyl)-methyl]-carbamic acid tert-butyl ester | 1023370-35-5

• 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: [(1-Phenyl-ethylcarbamoyl)-methyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[2-oxo-2-(1-phenylethylamino)ethyl]carbamate
• CAS: 1023370-35-5
• 化学式: C₁₅H₂₂N₂O₃
• mdl: MFCD11855516
• 分子量: 278.351
• InChiKey: QGUJTKWZZPWQFY-UHFFFAOYSA-N

物化性质

• 沸点：
  468.2±38.0 °C(Predicted)
• 密度：
  1.083±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [(1-Phenyl-ethylcarbamoyl)-methyl]-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以1.6 g的产率得到2-amino-N-(α-methylbenzyl)acetamide hydrochloride
  参考文献：
  名称：

  Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores

  摘要：

  Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha -methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl-2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha -methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg(-1), TD50 = 36.4 mg kg(-1), PI = 6.3). Replacement of the piperidine ring of I by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)01206-x
• 作为产物：
  描述：

  2-(叔丁氧羰基氧亚氨基)-2-苯乙腈 在 N-甲基吗啉 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 1.08h， 生成 [(1-Phenyl-ethylcarbamoyl)-methyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores

  摘要：

  Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha -methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl-2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha -methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg(-1), TD50 = 36.4 mg kg(-1), PI = 6.3). Replacement of the piperidine ring of I by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)01206-x

文献信息

• Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines Using Aerobic Copper/Nitroxyl Catalysis
  作者：Paige E. Piszel、Aristidis Vasilopoulos、Shannon S. Stahl

  DOI：10.1002/anie.201906130

  日期：2019.8.26

  The aerobic Cu/ABNO catalyzed oxidative coupling of alcohols and amines is highlighted in the synthesis of amide bonds in diverse drug-like molecules (ABNO=9-azabicyclo[3.3.1]nonane N-oxyl). The robust method leverages the privileged reactivity of alcohols bearing electronegative hetero- atoms (O, F, N, Cl) in the β-position. The reaction tolerates over 20 unique functional groups and is demonstrated

  醇和胺的需氧Cu / ABNO催化的醇和胺的氧化偶联在不同药物样分子（ABNO = 9-氮杂双环[3.3.1]壬烷N-氧基）中酰胺键的合成中得到了强调。稳健的方法利用了在β位带有负电性杂原子（O，F，N，Cl）的醇的特权反应性。该反应可耐受20多个独特的官能团，并在空气中以15 mmol的规模进行了证明。催化剂的立体约束使得在仲胺存在下伯胺的化学选择性酰胺化成为可能。所有催化剂组分都是可商购的，并且反应在温和的条件下进行，并且在两个反应伙伴中都保留了立构中心，而仅产生副产物水。
• SERINE RACEMASE INHIBITOR
  申请人：National University Corporation University Of Toyama

  公开号：EP2808014A1

  公开（公告）日：2014-12-03

  A novel serine racemase inhibitor exhibits sufficient activity and specificity. The serine racemase inhibitor includes one or more compounds selected from compounds respectively represented by the following general formulas [MM_1], [DR_1], [DR'_1], [LW_1], and [ED_1] as an active ingredient.

  一种新型丝氨酸消旋酶抑制剂具有足够的活性和特异性。丝氨酸消旋酶抑制剂包括一种或多种选自分别由下列通式[MM_1]、[DR_1]、[DR'_1]、[LW_1]和[ED_1]表示的化合物作为活性成分的化合物。