764588-50-3

Usage

Chemical class

Amines

Derivative

Cyclohexanamine with a phenethyl group attached at the first carbon position

Common usage

Research chemical

Potential medical applications

neurology and psychiatry

Function

Monoamine oxidase inhibitor

Effect on brain

Affects levels of neurotransmitters such as serotonin, dopamine, and norepinephrine

Research status

Ongoing to better understand its properties and potential uses

Upstream product

• 108-94-1 cyclohexanone 
• 100-42-5 styrene 
• 108-91-8 cyclohexylamine 
• 1940-18-7 1-ethylcyclohexanol 
• 591-50-4 iodobenzene 
• 2626-60-0 1-ethylcyclohexan-1-amine 

Relevant academic research and scientific papers

Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines

Catalytic, intermolecular hydroaminoalkylation (HAA) of styrenes provides a powerful disconnection for pharmacologically relevant γ-arylamines, but current methods cannot utilize unprotected primary alkylamines as feedstocks. Metal-catalyzed HAA protocols are also highly sensitive to α-substitution on the amine partner, and no catalytic solutions exist for α-tertiary γ-arylamine synthesis via this approach. We report a solution to these problems using organophotoredox catalysis, enabling a direct, modular, and sustainable preparation of α-(di)substituted γ-arylamines, including challenging electron-neutral and moderately electron-rich aryl groups. A broad range of functionalities are tolerated, and the reactions can be run on multigram scale in continuous flow. The method is applied to a concise, protecting-group-free synthesis of the blockbuster drug Fingolimod, as well as a phosphonate mimic of itsin vivoactive form (by iterative α-C-H functionalization of ethanolamine). The reaction can also be sequenced with an intramolecularN-arylation to provide a general and modular access to valuable (spirocyclic) 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydronaphthyridines. Mechanistic and kinetic studies support an irreversible hydrogen atom transfer activation of the alkylamine by the azidyl radical and some contribution from a radical chain. The reaction is photon-limited and exhibits a zero-order dependence on amine, azide, and photocatalyst, with a first-order dependence on styrene.

Native amine-directed site-selective C(sp3)-H arylation of primary aliphatic amines with aryl iodides

Direct C(sp3)-H functionalization of N-unprotected aliphatic amines represents one of the most efficient and straightforward strategies for amine synthesis. Despite some recent progress in this field, the NH2-directed γ-C(sp3)-H arylation of primary aliphatic amines except α-amino esters remained an unmet challenge. In this report, we established a simple and efficient method for site-selective C(sp3)-H arylation of primary aliphatic amines by aryl iodides. In the presence of only 5 mol% Pd(OAc)2, a wide range of aliphatic amines including O-benzyl and O-silyl amino alcohols were arylated at γ- or δ-positions by aryl iodides containing a broad scope of functional groups. The synthetic application of this method had also been demonstrated by large-scale synthesis, the synthesis of a fingolimod analogue, and the conjugation with natural D-menthol and fluorescent 1,8-naphthalimide.

Photocatalysed eosin Y mediated C(sp3)-H alkylation of amine substrates via direct HAT

A visible light promoted, photoredox catalysed, green one-pot approach for the alkylation of amine substrates with sp2 carbon has been developed. This eosin Y based organic transformations, can behave as an effective direct hydrogen-atom transfer catalyst for coupling reaction. The proposed strategy includes simple procedure which can make adduct product with sp2 carbon. This eosin Y based photocatalytic hydrogen-atom transfer strategy may hold great potential for diverse functionalization of a wide range of native C[sbnd]H bonds in an economical and sustainable manner.

Carbon Dioxide as a Directing Group for C-H Functionalization Reactions Involving Lewis Basic Amines, Alcohols, Thiols, and Phosphines for the Synthesis of Compounds

Methods of synthesizing compounds using CO2 as a directing group for C—H functionalization, and compounds made thereby, are described.

Palladium-Catalyzed C(sp3)?H Arylation of Primary Amines Using a Catalytic Alkyl Acetal to Form a Transient Directing Group

C?H Functionalization of amines is a prominent challenge due to the strong complexation of amines to transition metal catalysts, and therefore typically requires derivatization at nitrogen with a directing group. Transient directing groups (TDGs) permit C?H functionalization in a single operation, without needing these additional steps for directing group installation and removal. Here we report a palladium catalyzed γ-C?H arylation of amines using catalytic amounts of alkyl acetals as transient activators (e.g. commercially available (2,2-dimethoxyethoxy)benzene). This simple additive enables arylation of amines with a wide range of aryl iodides. Key structural features of the novel TDG are examined, demonstrating an important role for the masked carbonyl and ether functionalities. Detailed kinetic (RPKA) and mechanistic investigations determine the order in all reagents, and identify cyclopalladation as the turnover limiting step. Finally, the discovery of an unprecedented off-cycle free-amine directed ?-cyclopalladation of the arylation product is reported.

Carbon Dioxide-Mediated C(sp3)-H Arylation of Amine Substrates

Elaborating amines via C-H functionalization has been an important area of research over the past decade but has generally relied on an added directing group or sterically hindered amine approach. Since free-amine-directed C(sp3)-H activation is still primarily limited to cyclization reactions and to improve the sustainability and reaction scope of amine-based C-H activation, we present a strategy using CO2 in the form of dry ice that facilitates intermolecular C-H arylation. This methodology has been used to enable an operationally simple procedure whereby 1° and 2° aliphatic amines can be arylated selectively at their γ-C-H positions. In addition to potentially serving as a directing group, CO2 has also been demonstrated to curtail the oxidation of sensitive amine substrates.

Site-selective C-H arylation of primary aliphatic amines enabled by a catalytic transient directing group

Transition-metal-catalysed direct C-H bond functionalization of aliphatic amines is of great importance in organic and medicinal chemistry research. Several methods have been developed for the direct sp 3 C-H functionalization of secondary and tertiary aliphatic amines, but site-selective functionalization of primary aliphatic amines in remote positions remains a challenge. Here, we report the direct, highly site-selective γ-arylation of primary alkylamines via a palladium-catalysed C-H bond functionalization process on unactivated sp 3 carbons. Using glyoxylic acid as an inexpensive, catalytic and transient directing group, a wide array of γ-arylated primary alkylamines were prepared without any protection or deprotection steps. This approach provides straightforward access to important structural motifs in organic and medicinal chemistry without the need for pre-functionalized substrates or stoichiometric directing groups and is demonstrated here in the synthesis of analogues of the immunomodulatory drug fingolimod directly from commercially available 2-amino-2-propylpropane-1,3-diol.