66265-34-7

Upstream product

• 104-20-1 4-(4-methoxyphenyl)-2-butanone 
• 594-39-8 2-methyl-2-butylamine 
• 696-62-8 para-iodoanisole 
• 877-99-6 1-methoxy-4-(2-methyl-1-propenyl)benzene 
• 52214-79-6 1-(p-methoxyphenyl)-2,2-dichloro-3,3-dimethylcyclopropane 
• 623-26-7 terephthalonitrile 
• 90433-31-1 1-(p-methoxyphenyl)-2,2-dimethylcyclopropane 
• 14305-29-4 3-hydroxy-1-(4-methoxyphenyl)-3-methylbutane 
• 123-11-5 4-methoxy-benzaldehyde 
• 943-88-4 4-(p-methoxyphenyl)-3-butene-2-one 
• 637-69-4 4-Methoxystyrene 
• 75-31-0 isopropylamine 

Downstream Products

• 79798-13-3 1-[3-(4-Methoxy-phenyl)-1,1-dimethyl-propylamino]-3-{2-[(E)-2-(3-methyl-isoxazol-5-yl)-vinyl]-phenoxy}-propan-2-ol 
• 66265-81-4 1-(4-Hydroxy-3-methanesulfonyl-phenyl)-2-[3-(4-methoxy-phenyl)-1,1-dimethyl-propylamino]-ethanone 

Relevant academic research and scientific papers

8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study

β2-Agonists that bind to plasmalemmal β2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50 2-agonists among the compounds tested. They behaved as partial β2-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β2-agonists with potential applicability in chronic respiratory diseases.

Design, synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists

A series of β2-adrenoceptor agonists with an 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one moiety is presented. The stimulatory effects of the compounds on human β2-adrenoceptor and β1-adrenoceptor were characterized by a cell-based assay. Their smooth muscle relaxant activities were tested on isolated guinea pig trachea. Most of the compounds were found to be potent and selective agonists of the β2-adrenoceptor. One of the compounds, (R)-18c, possessed a strong β2-adrenoceptor agonistic effect with an EC50 value of 24 pM. It produced a full and potent airway smooth muscle relaxant effect same as olodaterol. Its onset of action was 3.5 min and its duration of action was more than 12 h in an in vitro guinea pig trachea model of bronchodilation. These results suggest that (R)-18c is a potential candidate for long-acting β2-AR agonists.

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.

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.

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-Driven Palladium-Catalyzed C-H Activation of Amines: A Unified Approach for the Arylation of Aliphatic and Aromatic Primary and Secondary Amines

Amines are an important class of compounds in organic chemistry and serve as an important motif in various industries, including pharmaceuticals, agrochemicals, and biotechnology. Several methods have been developed for the C-H functionalization of amines

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.

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.

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.

Redox-photosensitized aminations of 1,2-benzo-1,3-cycloalkadienes, arylcyclopropanes, and quadricyclane with ammonia

1,2,4-Triphenylbenzene and 2,2′-methylenedioxy-1,1′ -binaphthalene successfully photosensitized the aminations of 1,2-benzo-1,3-cycloalkadienes, arylcyclopropanes, and quadricyclane with ammonia and primary amines in the presence of m- or p-dicyanobenzene, which gave the 4-amino-1,2-benzocycloalkenes, 3-amino-1-arylpropanes, and 7-amino-5-(p-cyanophenyl)bicyclo[2.2.1]hept-2-ene, respectively. A key pathway for the photosensitized amination is the hole transfer from the cation radicals of the sensitizers that were generated by photoinduced electron transfer to the electron acceptors to the substrates. Therefore, it was found that the relationships in oxidation potentials between the sensitizers and the substrates and the positive charge distribution of the cation radicals of the substrates were important factors for the efficient amination.