42142-17-6

Usage

Uses

Used in Pharmaceutical Industry:
1-o-Tolylethylamine is used as a key intermediate in the synthesis of macamides analogs for its role as a TNF-α inhibitor. This application is significant in the development of anti-inflammatory drugs, as TNF-α is a cytokine involved in systemic inflammation and a target for various therapeutic interventions.
Used in Chemical Research:
1-o-Tolylethylamine serves as a valuable compound for the synthesis and screening of macamides analogs, which are essential in advancing the understanding of their structure-activity relationships and potential therapeutic effects. This application is crucial for the discovery and optimization of new drug candidates with improved efficacy and safety profiles.

InChI:InChI=1/C9H13N/c1-7-5-3-4-6-9(7)8(2)10/h3-6,8H,10H2,1-2H3

Upstream product

• 91854-81-8 1-(2-methylphenyl)ethan-1-imine 
• 27810-08-8 1-(2-methylphenyl)ethanone oxime 
• 577-16-2 2-Methylacetophenone 
• 59961-18-1 2-isothiochroman-4-one oxime 
• 64-17-5 ethanol 
• 74-88-4 methyl iodide 
• 35106-85-5 4-methyl-1,4-dihydro-benzo[d][1,2]oxazine-3-carboxylic acid ethyl ester 
• 35106-84-4 1-bromomethyl-2-(α-bromoethyl)benzene 
• 35106-83-3 o-(α-Bromoethyl)benzylalkoholacetat 
• 35050-24-9 2-(vinyl)benzyl acetate 
• 60-29-7 diethyl ether 
• 1307727-86-1 1-phenyl-N-(1-(o-tolyl)ethylidene)methanamine 
• 194024-39-0 N-benzyl-1-(o-tolyl)ethan-1-amine 
• 35106-87-7 1-o-tolylethanamine hydrochloride 

Downstream Products

• 42071-03-4 N-(1-(o-tolyl)ethyl)formamide 
• 76279-30-6 (-)-(S)-1-(2-methylphenyl)ethylamine 
• 105615-45-0 [(1R)-1-(2-methylphenyl)ethyl]amine 
• 105290-97-9 (R)-N-(1-o-tolylethyl)benzamide 
• 1256602-12-6 N⁽¹⁾-1'-(2''-tolyl)ethyl-2,7-dihydro-1H-azepine 
• 1332827-98-1 (S)-2,2,2-trifluoro-N-(1-(2-(methyl)phenyl)ethyl)acetamide 
• 856562-88-4 (R)-1-o-tolylethanamine hydrochloride 
• 1332832-16-2 (S)-1-(2-methylphenyl)ethanamine hydrochloride 
• 35106-87-7 1-o-tolylethanamine hydrochloride 
• 1207166-30-0 (R)-2,2,2-trifluoro-N-(1-(2-(methyl)phenyl)ethyl)acetamide 
• 1350639-69-8 6-(4-methoxyphenyl)-N-(1-o-tolylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1350639-85-8 4-(4-((1-(o-tolyl)ethyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)phenol hydrobromide 

Relevant academic research and scientific papers

The Synthesis of Primary Amines through Reductive Amination Employing an Iron Catalyst

The reductive amination of ketones and aldehydes by ammonia is a highly attractive method for the synthesis of primary amines. The use of catalysts, especially reusable catalysts, based on earth-abundant metals is similarly appealing. Here, the iron-catalyzed synthesis of primary amines through reductive amination was realized. A broad scope and a very good tolerance of functional groups were observed. Ketones, including purely aliphatic ones, aryl–alkyl, dialkyl, and heterocyclic, as well as aldehydes could be converted smoothly into their corresponding primary amines. In addition, the amination of pharmaceuticals, bioactive compounds, and natural products was demonstrated. Many functional groups, such as hydroxy, methoxy, dioxol, sulfonyl, and boronate ester substituents, were tolerated. The catalyst is easy to handle, selective, and reusable and ammonia dissolved in water could be employed as the nitrogen source. The key is the use of a specific Fe complex for the catalyst synthesis and an N-doped SiC material as catalyst support.

Substituent effects on chiral resolutions of derivatized 1-phenylalkylamines by heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin GC stationary phase

Chiral resolutions of trifluoroacetyl-derivatized 1-phenylalkylamines with different type and position of substituent were investigated by capillary gas chromatography by using heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin diluted in OV-1701 as a chiral stationary phase. The influence of column temperature on retention and enantioselectivity was examined. All enantiomers of meta-substituted analytes as well as fluoro-substituted analytes could be resolved. Temperature had a favorable influence on enantioselectivity for small amines with substituents at the ortho-position. The type of substituent at the stereogenic center of amines also had a crucial effect as the ethyl group led to poor enantioseparation. Among all analytes studied, trifluoroacetyl-derivatized 1-(2′-fluorophenyl)ethylamine exhibited baseline resolution with the shortest analysis time.

Stereoselective amination of racemic sec-alcohols through sequential application of laccases and transaminases

A one-pot/two-step bienzymatic asymmetric amination of secondary alcohols is disclosed. The approach is based on a sequential strategy involving the use of a laccase/TEMPO catalytic system for the oxidation of alcohols into ketone intermediates, and their following transformation into optically enriched amines by using transaminases. Individual optimizations of the oxidation and biotransamination reactions have been carried out, studying later their applicability in a concurrent process. Therefore, 17 racemic (hetero) aromatic sec-alcohols with different substitutions in the aromatic ring have been converted into enantioenriched amines with good to excellent selectivities (90-99% ee) and conversion values (67-99%). The scalability of the process was also demonstrated when two different amine donors were used in the transamination step, such as isopropylamine and cis-2-buten-1,4-diamine. Satisfyingly, both sacrificial amine donors can shift the equilibrium toward the amine formation, leading to the corresponding isolated enantioenriched amines with good to excellent results.

Axial stereocontrol in: Tropos dibenz [c, e] azepines: The individual and cooperative effects of alkyl substituents

6,7-Dihydro-5H-dibenz[c,e]azepines, a class of secondary amine incorporating a centre-axis chirality relay, can be prepared from N-(2-bromobenzyl)-N-(1-arylalkyl)methanesulfonamides via Pd-catalysed intramolecular direct arylation, and methylated at C(7)

Liquid chromatographic resolution of fendiline and its analogues on a chiral stationary phase based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid

Fendiline, an effective anti-anginal drug for the treatment of coronary heart diseases, and its sixteen analogues were resolved on a CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. Fendiline was resolved quite well with the separation factor (α) of 1.25 and resolution (RS ) of 1.55 when a mobile phase consisting of methanol-acetonitrile-trifluoroacetic acid-triethylamine at a ratio of 80/20/0.1/0.5 (v/v/v/v) was used. The comparison of the chromatographic behaviors for the resolution of fendiline and its analogues indicated that the 3,3-diphenylpropyl group bonded to the secondary amino group of fendiline is important in the chiral recognition and the difference in the steric bulkiness between the phenyl group and the methyl group at the chiral center of fendiline is also important in the chiral recognition.

Microwave-Enhanced Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)imines

Microwave irradiation has considerably enhanced the efficiency of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in isopropyl alcohol catalyzed by a ruthenium complex bearing the achiral ligand 2-amino-2-methylpropan-1-ol. In addition to shortening reaction times for the transfer hydrogenation processes to only 30 min, the amounts of ruthenium catalyst and isopropyl alcohol can be considerably reduced in comparison with our previous procedure assisted by conventional heating, which diminishes the environmental impact of this new protocol. This methodology can be applied to aromatic, heteroaromatic and aliphatic N-(tert-butylsulfinyl)ketimines, leading, after desulfinylation, to the expected primary amines in excellent yields and with enantiomeric excesses of up to 96 %. Microwave irradiation promotes the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)imines in 2-propanol catalysed by a ruthenium complex bearing an achiral β-amino alcohol as ligand. After desulfinylation, α-branched primary amines containing aromatic, heteroaromatic and aliphatic substituents are obtained in excellent yields and with enantiomeric excesses of up to 96 %.

Synthesis and in vitro EGFR (ErbB1) tyrosine kinase inhibitory activity of 4-N-substituted 6-aryl-7H-pyrrolo[2,3-d]pyrimidine-4-amines

A series of 4-N-substituted 6-aryl-7H-pyrrolo[2,3-d]pyrimidine-4-amines have been synthesised, characterised and tested for their in vitro EGFR (ErbB1) tyrosine kinase inhibitory activity. The compounds were prepared from ethyl cyanoacetate and α-bromoacetophenones via the 2-amino-3-ethoxycarbonyl-5- aryl-pyrroles and 4-chloro-6-arylpyrrolopyrimidines. Aromatic substitution with benzylic amines was performed by conventional thermal substitution, and palladium catalysed coupling. The two methods resulted in similar yields, but the palladium coupling had the benefit of lower chemical consumption and reduced reaction times. Eight of the new compounds had IC50 values in the range of 2.8-9.0 nM. Four of these have a fluorine atom positioned at sites otherwise potentially susceptible to oxidative metabolism. Structural variation of the 6-aryl group indicated that the inhibitory action was only moderately sensitive to modifications in this fragment. However, the potency depended strongly on the structure of the aromatic part of the 4-amino group, and any aromatic substitution except fluorine reduced the in vitro activity. The cellular EGFR internalization response of selected compounds was evaluated using HeLa cells. Three fluorinated derivatives had a pronounced effect in inhibiting EGFR internalization.

Sequential reductive amination-hydrogenolysis: A one-pot synthesis of challenging chiral primary amines

Difficult-to-access chiral primary amines were formed in good to high yield and ee using a rare example of a one-pot synthesis from prochiral ketones (sequential reductive amination-hydrogenloysis). As a highlight we also demonstrate a one-pot reductive amination-hydrogenolysis-reductive amination (five reactions) of ortho-methoxyacetophenone resulting in the chiral diamine 1-(2-methoxyphenyl)ethyl-(2-pyridylmethyl)-amine (4) (58% overall yield, >99% ee), a new organocatalyst for aqueous enantioselective aldol reactions. Copyright

SELECTIVE SPLITTING OF SUBSTITUTED BISBENZYLAMIDES AND BISBENZYLAMINES

The invention relates to a method for the area-selective splitting of secondary amines or amides.

Synthesis and chiral recognition ability of O-phenyl ethylphosphonothioic acid with a conformationally flexible phenoxy group for CH/π interaction

Enantiopure O-phenyl ethylphosphonothioic acid 1 was easily obtained by the enantioseparation of racemic 1, which was prepared from commercially available phosphorothioic trichloride in four steps. Enantiopure 1 was found to show an excellent chiral recognition ability for various 1-arylethylamine derivatives during the diastereomeric salt formation. In particular, enantiopure 1 was able to recognize the chirality of o- and m-substituted 1-arylethylamine derivatives, of which the chirality is generally difficult to establish by conventional resolving agents. X-ray crystallographic analyses of the less-soluble diastereomeric salts revealed that the conformation of the phenoxy group in enantiopure 1 could change in the diastereomeric salt crystals and that the excellent chiral recognition ability of enantiopure 1 resulted from the effective CH/π interaction of the phenoxy phenyl group.