2-(4-chlorobenzylamino)acetaldehyde dimethyl acetal | 54879-87-7

• 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: 2-(4-chlorobenzylamino)acetaldehyde dimethyl acetal
• 英文别名: N-(4-chlorobenzyl)-2,2-dimethoxyethan-1-amine；N-[(4-chlorophenyl)methyl]-2,2-dimethoxyethanamine
• CAS: 54879-87-7
• 化学式: C₁₁H₁₆ClNO₂
• mdl: MFCD12148382
• 分子量: 229.707
• InChiKey: KYYVJZGZJOQVCZ-UHFFFAOYSA-N

物化性质

• 沸点：
  93-97 °C(Press: 0.12 Torr)
• 密度：
  1.117±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-chlorobenzylamino)acetaldehyde dimethyl acetal 在 cerium(III) chloride heptahydrate 、 硫酸 作用下， 以 水 、 乙腈 为溶剂， 反应 48.0h， 生成 1-(4-chlorobenzyl)benzo[f]indole-4,9-dione
  参考文献：
  名称：

  Ultrasound assisted one-pot synthesis of benzo-fused indole-4,9-dinones from 1,4-naphthoquinone and α-aminoacetals

  摘要：

  A one-pot synthesis of benzo[f]indole-4,9-diones from 1,4-naphthoquinone with alpha-aminoacetals has been developed. This method provides a straightforward synthesis of benzo[f]indole-4,9-diones via intramolecular nucleophilic attack of aminoquinones to aldehydes under mild reaction conditions. The detailed mechanism was also investigated. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2016.04.031
• 作为产物：
  描述：

  4-氯苯甲醛 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 24.33h， 生成 2-(4-chlorobenzylamino)acetaldehyde dimethyl acetal
  参考文献：
  名称：

  Multisubstrate inhibitors of dopamine .beta.-hydroxylase. 2. Structure-activity relationships at the phenethylamine binding site

  摘要：

  1-Aralkylimidazole-2-thiones have been shown to be potent multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1). In the present study, a series of 1-benzylimidazole-2-thiones was prepared to explore the effects of substitution in the benzyl ring on the inhibition of DBH. A detailed structure-activity relationship for in vitro activity was discovered and this was shown by a modified Hansch analysis to correlate (r = 0.91) with four key structural features of the benzyl ring: the presence of a hydroxyl at the 4-position, molar refractivity at the 3-, 4-, and 5-positions, inductive effects of the substituents at the 3-, 4-, and 5-positions, and pi-electron density. The affinity (Kis) of eight substituted inhibitors for DBH was shown to correlate (r = 0.75) with the affinity (KD) of comparably substituted tyramines for the ternary DBH-oxygen-tyramine complex. This correlate is used to support the hypothesis that binding of inhibitor to DBH occurs in a fashion that mimics the binding of tyramine substrates. The most potent inhibitors were selected for study in vivo in the spontaneously hypertensive rat model of hypertension. The changes in vascular dopamine and norepinephrine levels that resulted from oral administration of the inhibitors corresponded to the observed reduction in mean arterial blood pressure. A divergence between in vitro potency and in vivo efficacy upon oral dosing was noted and is suggested to result from an in vivo metabolic conjugation of the phenolic group of inhibitor.

  DOI：

  10.1021/jm00386a008

文献信息

• Design, Synthesis, and Biological Evaluation of Imidazopyrazinone Derivatives as Antagonists of <scp>Inhibitor of Apoptosis Proteins</scp> (IAPs)
  作者：Jisook Kim、Inhwan Bae、Jiyoung Song、Younghoon Kim、Younggil Ahn、Hyun‐Ju Park、Ha Hyung Kim、Dae Kyong Kim

  DOI：10.1002/bkcs.12271

  日期：2021.6

  proteins are overexpressed in many cancers and implicated in tumor growth, so the development of antagonist that disrupts with the binding of IAP to their partner protein is a promising therapeutic strategy. In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized monovalent analogues based on imidazopyrazinone structure of 9. Optimization

  凋亡抑制剂 (IAP) 蛋白在许多癌症中过度表达并与肿瘤生长有关，因此开发可破坏 IAP 与其伙伴蛋白结合的拮抗剂是一种很有前景的治疗策略。为了增加细胞活性并改善有利的类药物特性，我们新设计并合成了基于9咪唑并吡嗪酮结构的单价类似物。细胞效力的优化导致17的鉴定，这表 明亚微摩尔活性 (GI 50 = 234 nM) 和 Caspase-3 激活（6.3 倍）在 MDA-MB-231 乳腺癌细胞中增加。这些发现清楚地表明了17 作为开发有效抗癌治疗的有前途的单价拮抗剂。
• Synthesis of tetrahydroisoquinolines through TiCl4-mediated cyclization and Et3SiH reduction
  作者：Zeyu Shi、Qiong Xiao、Dali Yin

  DOI：10.1016/j.cclet.2019.09.023

  日期：2020.3

  Abstract A versatile and efficient telescoped reaction sequence for the synthesis of tetrahydroisoquinolines (THIQs) is reported that uses TiCl4 to promote cyclization of a benzylaminoacetal derivative and Et3SiH for reduction of the intermediate 4-hydroxy-THIQ. This method is complimentary to the classical Pomeranz-Fritsch and related reactions since it tolerates electron-withdrawing substituents

  摘要报道了一种通用且有效的伸缩反应序列，用于合成四氢异喹啉（THIQs），该序列使用TiCl4促进苄氨基缩醛衍生物的环化反应，并使用Et3SiH还原中间体4-羟基-THIQ。此方法是对经典Pomeranz-Fritsch和相关反应的补充，因为它可以耐受吸电子取代基并允许使用8位取代的THIQ。
• Cu(II)-Catalyzed Construction of Heterobiaryls using 1-Diazonaphthoquinones: A General Strategy for the Synthesis of QUINOX and Related P,N Ligands
  作者：Aniruddha Biswas、Subarna Pan、Rajarshi Samanta

  DOI：10.1021/acs.orglett.2c00127

  日期：2022.3.4

  was developed for the synthesis of heterobiaryls using easily available N-oxides and diazonaphthoquinones under cheap Cu(II) catalysis. The developed method offered QUINOX and related congeners in a simple manner. A wide scope of important heterobiaryls was achieved with high site selectivity. The synthesized naphthols were transformed into the privileged related P,N ligands. Suitable resolution methods

  开发了一种有效且直接的方法，用于在廉价的 Cu(II) 催化下使用容易获得的N-氧化物和重氮萘醌合成杂二芳基化合物。所开发的方法以简单的方式提供了 QUINOX 和相关同类物。以高位点选择性实现了范围广泛的重要杂二芳基化合物。合成的萘酚被转化为特权相关的 P,N 配体。合适的拆分方法可以直接提供相应的轴向手性杂二芳基化合物。
• Ag-Catalyzed Cyanomethylation of Amines Using Nitromethane as a C₁ Source
  作者：Takuya Takashima、Hamdiye Ece、Taiga Yurino、Takeshi Ohkuma

  DOI：10.1021/acs.orglett.3c02256

  日期：2023.8.18

  A new methodology to afford α-amino nitriles through oxidative cyanomethylation of amines using nitromethane as the methylene source in the presence of Me3SiCN without the addition of an external oxidant was developed. A catalytic amount of AgCN and a stoichiometric amount of LiBF4 cooperatively promoted the transformation. A wide variety of the amines, including both aromatic compounds and aliphatic

  开发了一种在 Me 3 SiCN存在下，在不添加外部氧化剂的情况下，使用硝基甲烷作为亚甲基源，通过胺的氧化氰甲基化来提供 α-氨基腈的新方法。催化量的AgCN和化学计量量的LiBF 4协同促进转化。多种胺，包括芳香族化合物和脂肪族胺，在氧化条件下不稳定，适用于该反应。
• Ultrasound assisted one-pot synthesis of benzo-fused indole-4,9-dinones from 1,4-naphthoquinone and α-aminoacetals
  作者：Quang H. Luu、Jorge D. Guerra、Cecilio M. Castañeda、Manuel A. Martinez、Jong Saunders、Benjamin A. Garcia、Brenda V. Gonzales、Anushritha R. Aidunuthula、Shizue Mito

  DOI：10.1016/j.tetlet.2016.04.031

  日期：2016.5

  A one-pot synthesis of benzo[f]indole-4,9-diones from 1,4-naphthoquinone with alpha-aminoacetals has been developed. This method provides a straightforward synthesis of benzo[f]indole-4,9-diones via intramolecular nucleophilic attack of aminoquinones to aldehydes under mild reaction conditions. The detailed mechanism was also investigated. (C) 2016 Elsevier Ltd. All rights reserved.