1965-54-4

Usage

Uses

Used in Pharmaceutical Industry:
2-[(4-NITROPHENYL)AMINO]ETHANOL is used as a key intermediate for the preparation of phenylpurinediamine derivatives, which are a class of reversible kinase inhibitors. These inhibitors target both EGFR-activating and resistance mutations of lung cancer, making them valuable in the development of anticancer drugs.
Additionally, 2-[(4-NITROPHENYL)AMINO]ETHANOL is used as a synthetic building block for the synthesis of benzannulated N-heterocycles. This application is achieved through palladium-catalyzed domino intermolecular alkylation/intramolecular amination of functionalized aryl iodides and bromoalkylamines. The resulting benzannulated N-heterocycles have potential applications in various fields, including the development of new pharmaceuticals and advanced materials.

Synthesis Reference(s)

Synthesis, p. 606, 1976 DOI: 10.1055/s-1976-24135

InChI:InChI=1/C8H10N2O3/c11-6-5-9-7-1-3-8(4-2-7)10(12)13/h1-4,9,11H,5-6H2

Upstream product

• 141-43-5 ethanolamine 
• 350-46-9 4-Fluoronitrobenzene 
• 52547-52-1 N-(2-hydroxyethyl)-2-(4-nitrophenoxy)acetamide 
• 100-00-5 4-chlorobenzonitrile 
• 100-01-6 4-nitro-aniline 
• 540-51-2 2-bromoethanol 
• 586-78-7 para-nitrophenyl bromide 
• 100-02-7 4-nitro-phenol 
• 636-98-6 p-nitrobenzene iodide 
• 103-84-4 Acetanilid 
• 98-74-8 4-Nitrobenzenesulfonyl chloride 
• 824-78-2 4-nitrophenol sodium salt 
• 16365-27-8 2-(4-nitrophenoxy)ethanol 
• 1798-11-4 4-nitrophenoxyacetic acid 

Downstream Products

• 75226-78-7 1-acetoxy-2-(N-acetyl-4-nitro-anilino)-ethane 
• 104741-03-9 1-acetoxy-2-(N-acetyl-4-amino-anilino)-ethane 
• 154576-85-9 N-allyl-N-(2-hydroxyethyl)-4-nitrobenzenamine 
• 1442460-04-9 1-ethyl 3-{2-[(4-nitrophenyl)amino]ethyl} 2-diazomalonate 
• 1442460-05-0 ethyl 4-(4-nitrophenyl)-2-oxomorpholine-3-carboxylate 
• 5198-52-7 3-(4-nitrophenyl)-2-oxazolidinone 
• 1311164-60-9 C₃₆H₃₈N₆O₂ 
• 1311164-58-5 C₃₆H₃₈N₆O₂ 
• 1363651-95-9 C₂₁H₂₅N₅ 
• 1363647-20-4 C₂₁H₂₅N₅ 
• 1363651-63-1 C₂₁H₂₃N₅O₂ 
• 1363644-43-2 C₂₁H₂₃N₅O₂ 
• 1159610-60-2 C₂₂H₂₇ClN₄O₆S 
• 1159610-59-9 C₁₇H₂₆N₄O₅ 

Relevant academic research and scientific papers

Binding abilities of polyaminocyclodextrins: Polarimetric investigations and biological assays

Three polyaminocyclodextrin materials, obtained by direct reaction between heptakis(6-deoxy-6-iodo)-β-cyclodextrin and the proper linear polyamines, were investigated for their binding properties, in order to assess their potential applications in biologi

“On Water” promoted N-arylation reactions using Cu (0)/myo-inositol catalytic system

Myo-inositol is originally applied as a cardiovascular medicine in clinic, which can be multi-ton manufactured via extraction from the byproducts in agricultural product processing such as defatted rice bran and corn-soaking water. Herein, the application of myo-inositol (MI) as a novel versatile tridentate O-donor ligand has been first described for promoting Cu-catalyzed amination reaction in aqueous medium.

Cu(II)-catalyzed C-N coupling of (hetero)aryl halides and N-Nucleophiles promoted by α-benzoin oxime

We first reported the new application of a translate metal chelating ligand α-benzoin oxime for improving Cu-catalyzed C-N coupling reactions. The system could catalyse coupling reactions of (hetero)aryl halides with a wide of nucleophiles (e.g., azoles, piperidine, pyrrolidine and amino acids) in moderate to excellent yields. The protocol allows rapid access to the most common scaαolds found in FDA-approved pharmaceuticals.

Copper(ii)-catalyzed c-n coupling of aryl halides and n-nucleophiles promoted by quebrachitol or diethylene glycol

Herein, we report the natural ligand quebrachitol (QCT) as a promoter for a Cu(II) catalyst, which is highly effective for N-Arylation of various amines and related aryl halides. A series of diarylamine derivatives were obtained in high yields by using diethylene glycol (DEG) as both ligand and solvent. The C-N coupling reactions proceed under mild conditions and exhibit good functional group tolerance.

A process for the preparation method of the compound aromatic amines (by machine translation)

The invention discloses a method for preparing aromatic amine compounds, comprising the following steps: under protection of inert gas, with the ratio of the phenolic compound amine according to mole 1:2 - 40 are mixed and dissolved in the solvent, 50 - 140 °C reaction 6 - 15 hours, corresponding to preparing polymerizable aromatic amine compound, and then after treatment to obtain a pure aromatic amine compound. Raw materials of this invention generally are easy, simple operation, substrate and wide range of application, in the absence of catalyst under catalytic conditions of the phenolic compound can be obtained by nucleophilic addition reaction of the corresponding aromatic amine compound, and is suitable for industrial production. The present invention allows the presence of water in the reaction system, can be ammonia or hydrazine hydrate as the substrate, in order to ammonium chloride as a catalyst and a cosolvent, the success of the preparation to obtain a level from phenol hydroxy aromatic primary amino compound. The invention to phenol hydroxy has better selectivity, even if the presence of halogen atoms in the substrate does not affect the occurrence of the reaction. (by machine translation)

Room-Temperature Practical Copper-Catalyzed Amination of Aryl Iodides

An efficient and highly practical procedure is reported for the Ullmann-Goldberg-type copper-catalyzed amination of aryl iodides. By using a combination of copper iodide and proline in the presence of an excess of an amine, a wide range of aryl iodides can be readily aminated at room temperature. The reaction proceeds well regardless of the electronic properties of the starting aryl iodide and the amination products can be obtained without the need for purification by column chromatography in most cases. Owing to its efficiency and the mildness of the reaction conditions, this amination could also be extended to the amination of complex aryl iodides at room temperature.

Highly Efficient Mechanochemical N-Arylation of Amino Alcohols and Diamines with Cu0 Powder

Cu0-catalysed arylations have rightly acquired great importance over the last decade. This paper reports the N-arylation of amino alcohols and diamines with iodobenzene derivatives in a planetary ball mill and an investigation into the procedure. This newly developed solvent-free protocol is fast, efficient and occurs under the mechanochemical activation of metallic copper powder. It does not require additional ligands and gives excellent yields. This paper aims to broaden the scope of mechanochemical Cu0-activation and so a new one-pot, two-step synthesis that combines CuAAC and N-arylation has been successfully performed and reported herein.

Studies towards the synthesis of alkyl N-(4-nitrophenyl)-3/2-oxomorpholine- 2/3-carboxylates

The syntheses of methyl 4-(4-nitrophenyl)-3-oxomorpholine-2-carboxylate (3a) and ethyl 4-(4-nitrophenyl)-2-oxomorpholine-3-carboxylate (5b), important building blocks for the synthesis of factor Xa inhibitor rivaroxaban analogs with potential dual antithrombotic activity, via Rh2(OAc) 4-catalyzed O-H and N-H carbene insertion reactions are described.

Copper-catalyzed C-N cross-coupling reactions for the preparation of aryl diamines applying mild conditions

In this work, aryl diamines were prepared by C-N cross-coupling reactions between aryl halides and ethylenediamine. These reactions were successfully catalyzed by low quantities of Cu2O or CuO (1 mol %) employing low reflux temperature and low diamine excess. Products were afforded in good yields (up to 95%).

Structural optimization and structure-activity relationships of N 2-(4-(4-methylpiperazin-1-yl)phenyl)- N 8-phenyl-9 H -purine-2,8-diamine derivatives, a new class of reversible kinase inhibitors targeting both EGFR-activating and resistance mutations

This paper describe the structural optimization of a hit compound, N 2-(4-(4-methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine- 2,8-diamine (1), which is a reversible kinase inhibitor targeting both EGFR-activating and drug-resistance (T790M) mutations but has poor binding affinity. Structure-activity relationship studies led to the identification of 9-cyclopentyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)-N 8-phenyl-9H-purine-2,8-diamine (9e) that exhibits significant in vitro antitumor potency against the non-small-cell lung cancer (NSCLC) cell lines HCC827 and H1975, which harbor EGFR-activating and drug-resistance mutations, respectively. Compound 9e was further assessed for potency and selectivity in enzymatic assays and in vivo anti-NSCLC studies. The results indicated that compound 9e is a highly potent kinase inhibitor against both EGFR-activating and resistance mutations and has good kinase spectrum selectivity across the kinome. In vivo, oral administration of compound 9e at a dose of 5 mg/kg caused rapid and complete tumor regression in a HCC827 xenograft model, and an oral dose of 50 mg/kg initiated a considerable antitumor effect in an H1975 xenograft model.