(Benzyl-ethyl-amino)-acetonitrile | 127780-68-1

• 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: (Benzyl-ethyl-amino)-acetonitrile
• 英文别名: 2-[Benzyl(ethyl)amino]acetonitrile
• CAS: 127780-68-1
• 化学式: C₁₁H₁₄N₂
• mdl: MFCD09906888
• 分子量: 174.246
• InChiKey: QFXYUVPTRNJNHV-UHFFFAOYSA-N

物化性质

• 沸点：
  284.8±15.0 °C(Predicted)
• 密度：
  1.010±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (Benzyl-ethyl-amino)-acetonitrile 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 (Benzyl-ethyl-amino)-trimethylsilanyl-acetonitrile
  参考文献：
  名称：

  Synthesis of 1-(Trimethylsilyl)aikylamines

  摘要：

  通过格氏试剂与（二烷基氨基）乙腈 1 的硅烷化反应制备的 2-二烷基氨基-2-（三甲基硅基）乙腈 3 反应，合成了多种 N,N-二烷基[1-（三甲基硅基）烷基]胺 4。

  DOI：

  10.1055/s-1990-26780
• 作为产物：
  描述：

  N-乙基苄胺 、 氯乙腈 在 TEA 作用下， 以 甲苯 为溶剂， 生成 (Benzyl-ethyl-amino)-acetonitrile
  参考文献：
  名称：

  5-(2-Aminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones:  Variation of N-Alkyl Substituents Modulates Sensitivity to Efflux Transporters Associated with Multidrug Resistance

  摘要：

  5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo [c, h]-[1,6]naphthyridin-6-one (ARC-111) has potent TOP1-targeting activity and pronounced antitumor activity. Several analogues of ARC-111 were synthesized with NH2, N-alkyl, N,N-dialkyl, pyrrolidinyl, piperidinyl, and piperazinyl substituents at the 2-position of the 5-ethyl group. The relative TOP1-targeting activity and cytotoxicity of these structural analogues were assessed in RPMI8402 and P388 tumor cells and their camptothecin-resistant variants CPT-K5 and P388/CPT45, respectively. Potent TOP1-targeting activity was retained within a series of mono N-alkyl analogues that included NHCH2CH3, NHCH(CH3)(2), and NHC(CH3)(3). TOP1-targeting activity was diminished by the presence of a N-benzyl moiety. In a comparison of a series of N-alkyl-N-isopropyl analogues, activity decreased in the order CH3 > CH2CH3 > CH(CH3)(2). Cytotoxicity in RPMI8402 and P388 did correlate with TOP1-targeting activity. Cytotoxic activity was also determined in KB3-1 cells and its variants KB/V-1 and KBH5.0. As KB/V-1 cells overexpress MDR1 and KBH5.0 cells overexpress BCRP, decreased cytotoxicity in these cell lines relative to the parent cell line is indicative of compounds that are substrates for these efflux transporters. In view of their diminished cytotoxicity in KB/V-1 cells, it appears that the likely demethylated metabolites of ARC-111, i.e., where NH2 or NHCH3 replaces the N(CH3)(2) at the 2-position of the 5-ethyl substituent, are substrates for MDR1. In contrast, no significant difference in cytotoxicity among these three cell lines was observed with other N-alkyl analogues, including NHC2H5, NHCH(CH3)(2), NHC(CH3)(3), N(CH3)(2), N(CH2CH3)(2), NCH3(CH(CH)(3))(2)), and either the pyrrolidinyl or the piperidinyl analogues. The 2-(piperazinyl) analogues were associated with diminished cytotoxicity in KB/V-1 cells, suggesting that the second basic amino substituent is associated with their recognition as substrates by MDR1. Comparative studies on the antitumor activity of ARC-111 and its N-demethylated derivatives (the NHCH3 and NH2 analogues) against SJ-BT45 medulloblastoma xenografts in scid mice revealed that the secondary amine metabolite is at least as active as ARC-111 in vivo, although the primary amine derivative was significantly less potent.

  DOI：

  10.1021/jm049447z

文献信息

• A Widely Applicable Regioselective Aerobic α-Cyanation of Tertiary Amines Heterogeneously Catalyzed by Manganese Oxides
  作者：Kazuya Yamaguchi、Ye Wang、Noritaka Mizuno

  DOI：10.1002/cctc.201300477

  日期：2013.10

  A fit catalyst for some aerobic exercise: A manganese oxide‐based octahedral molecular sieve, OMS‐2, could act as an efficient heterogeneous catalyst for the regioselective α‐cyanation of various tertiary amines, including trialkyl, benzylic, and N,N‐dialkylaniline derivatives using trimethylsilyl cyanide (TMSCN) as the cyano source and molecular oxygen as the terminal oxidant.

  适合进行有氧运动的催化剂：基于氧化锰的八面体分子筛OMS-2可作为有效的非均相催化剂，用于多种叔胺的区域选择性α-氰化，包括三烷基，苄基和N，N-二烷基苯胺衍生物，使用三甲基甲硅烷基氰化物（TMSCN）作为氰基源，使用分子氧作为末端氧化剂。
• Florea, Cristina; Stavarache, Cristina; Petride, Horia, Revue Roumaine de Chimie, 2016, vol. 61, # 4-5, p. 319 - 325
  作者：Florea, Cristina、Stavarache, Cristina、Petride, Horia

  DOI：——

  日期：——
• Synthesis and neuroleptic activity of benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds
  作者：Sumio Iwanami、Mutsuo Takashima、Yasufumi Hirata、Osamu Hasegawa、Shinji Usuda

  DOI：10.1021/jm00142a019

  日期：1981.10

  Three series of benzamides of N,N-disubstituted ethylenediamines (linear alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 1-substituted 3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed and synthesized as potential neuroleptics. All target compounds were evaluated for their inhibitory effects on apomorphine-induced stereotyped behavior in rats, and a good correlation between structure and activity was found throughout the series. In the linear series (analogues of metoclopramide), introduction of a benzyl group on the terminal nitrogen, rather than an ethyl group, and a methyl group on the p-amino group of metoclopramide both enhanced the activity. The resulting N-[2-(N-benzyl-N-methylamino)ethyl]-5-chloro-2-methoxy-4-(methylamino) benzamide(23) was about 15 times more active than metoclopramide. In the cyclic series, particularly among the benzamides of 1-benzyl-3-aminopyrrolidine, most of the compounds tested were more active than the corresponding linear benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino) benzamide (YM-09151-2, 55) was the most active among all of the compounds tested, being 13 and 408 times more potent than haloperidol and metoclopramide, respectively. Moreover, compound 55 exhibited a fairly high ratio of antistereotypic activity to cataleptogenicity compared with haloperidol and metoclopramide. It is expected that compound 55 may be used as a potent drug with few side effects in the treatment of psychosis.
• Ti(II)-Mediated Conversion of α-Heterosubstituted (O, N, S) Nitriles to Functionalized Cyclopropylamines. Effect of Chelation on the Cyclopropanation Step
  作者：Philippe Bertus、Jan Szymoniak

  DOI：10.1021/jo025634y

  日期：2002.5.1

  alpha-Alkoxy, amino-, and thio nitriles under-go a Ti(II)-mediated coupling with Grignard reagents to afford heterofunctionalized cyclopropylamines. A chelation effect appears to be generally responsible for the spontaneous contraction of the intermediate azatitanacycle leading to cyclopropane. By using the described reaction, 1-amino-cyclopropanecarboxylic acids were prepared in four steps, in good overall yields, from the readily available benzyloxy-acetonitrile.
• RuO4 – mediated oxidation of tertiary amines. Stereoelectronic effects
  作者：Horia PETRIDE、Cristina FLOREA、Anca HÎRTOPEANU、Cristina STAVARACHE

  DOI：10.33224/rrch/2020.65.1.10

  日期：——