21758-07-6

Upstream product

• 64-18-6 formic acid 
• 21133-98-2 ethyl 3-(4-chlorophenyl)-3-hydroxybutanoate 
• 858782-62-4 2-chloro-3-(4-chloro-phenyl)-butyric acid ethyl ester 
• 3095-95-2 diethylphosphonoacetic acid 
• 99-91-2 para-chloroacetophenone 
• 93404-35-4 E-methyl β-methyl-p-chlorocinnamate 
• 98272-71-0 γ-acetoxycrotonic acid methyl ester 
• 1679-18-1 4-Chlorophenylboronic acid 
• 902154-51-2 γ-acetoxycrotonic acid tert-butyl ester 
• 21757-98-2 ethyl (E)-3-(4-chlorophenyl)-2-butenoate 
• 106-47-8 4-chloro-aniline 
• 586354-80-5 C₁₄H₁₇ClO₂ 
• 81187-86-2 ethyl 3-(4-chlorophenyl)-2-butenoate 

Downstream Products

• 81187-86-2 ethyl 3-(4-chlorophenyl)-2-butenoate 
• 1712-70-5 1-chloro-4-(1-methylethenyl)-benzene 
• 1243130-08-6 ethyl 3-methyl-3-p-chlorophenylpropionate 
• 1259929-95-7 2,6-dimethylphenyl (E)-3-(4-chlorophenyl)-2-butenoate 
• 1259930-09-0 C₂₄H₂₃ClO₂ 
• 145949-81-1 1-[(1E)-1-bromoprop-1-en-2-yl]-4-chlorobenzene 
• 1332645-39-2 (R)-4-(4-chlorophenyl)-6-(trifluoromethyl)-6-(4-chlorophenyl)-5,6-dihydro-2H-pyran-2-one 
• 1332645-28-9 (R)-4-(4-chlorophenyl)-6-(trifluoromethyl)-6-phenyl-5,6-dihydro-2H-pyran-2-one 
• 1377848-23-1 (RS)-4-(4-chlorophenyl)-6-(trifluoromethyl)-6-phenyl-5,6-dihydro-2H-pyran-2-one 
• 1025403-22-8 (R)-3-(4-chlorophenyl)butanal 
• 1134201-77-6 (R)-3-(4-chlorophenyl)butan-1-ol 

Relevant academic research and scientific papers

N-Heterocyclic Carbene-Catalyzed Activation of Esters of N-Hydroxyphthalimide: A Highly Enantioselective Route to Chiral Dihydropyridinones Bearing an All Carbon Quaternary Stereogenic Center

An N-heterocyclic carbene-catalyzed highly enantioselective [3 + 3] annulation reaction of N-hydroxyphthalimide (NHPI) 3,3-disubstituted acrylates and N-Ts ketimines was developed. In most cases, the desired chiral dihydropyridinone products bearing an all carbon quaternary stereogenic center could be obtained in good yields with excellent enantioselectivities (>99% ee's), which demonstrated the NHPI acrylates as a kind of excellent substrate in NHC-catalysis.

Metal-Free Hydropyridylation of Thioester-Activated Alkenes via Electroreductive Radical Coupling

An electrochemical hydropyridylation of thioester-activated alkenes with 4-cyanopyridines has been developed. The reactions experience a tandem electroreduction of both substrates on the cathode surface, protonation, and radical cross-coupling process, resulting in a variety of valuable pyridine variants, which contain a tertiary and even a quaternary carbon at the α-position of pyridines, in high yields. The employment of thioesters to the conjugated alkenes enables no requirement of catalyst and high temperature, representing a highly sustainable synthetic method.

Synergistic N-Heterocyclic Carbene/Palladium-Catalyzed [3 + 2] Annulation of Vinyl Enolates with 1-Tosyl-2-vinylaziridine

The synergistic combination of N-heterocyclic carbene organocatalysis and transition-metal catalysis for a formal [3 + 2] annulation between 3-substituted but-2-enoates and 1-tosyl-2-vinylaziridine was developed. This cooperative strategy provides a facile and efficient access to various functionalized (E)-3-ethylidene-4-vinylpyrrolidin-2-ones in a regioselective and stereoselective manner. The preliminary asymmetric studies were also performed, which indicated a potential for enantioselective annulation of vinyl enolate intermediates with transition-metal-π-allyl species.

Enantioselective epoxidation of β,β-disubstituted enamides with a manganese catalyst and aqueous hydrogen peroxide

Enantioselective epoxidation of β,β-disubstituted enamides with aqueous hydrogen peroxide and a novel manganese catalyst is described. Epoxidation is stereospecific and proceeds fast under mild conditions. Amides are disclosed as key functional groups to enable high enantioselectivity.

Construction of Multi-Substituted Benzenes via NHC-Catalyzed Reactions of Carboxylic Esters

A carbene-catalyzed ester activation reaction for the synthesis of multi-substituted benzenes is developed. Tetra-substituted benzene compounds are efficiently synthesized through this methodology. Compared with aldehyde substrates used in previous reports, the ester substrates used here are much more readily available and inexpensive. In addition, the TEMPO oxidant used here is more inexpensive than the quinones commonly used in related carbene-catalyzed reactions.

Determination of the absolute configuration of two αvβ6 integrin inhibitors for the treatment of idiopathic pulmonary fibrosis and investigations on the asymmetric 1,4-addition of arylboronic acids to crotonate esters bearing a C4-oxygen substituent

The absolute configuration of two novel αvβ6 integrin inhibitors was established via degradation to the corresponding C3-aryl substituted butyrolactone. The configuration of the resulting lactones was established by asymmetric synthesis using 1,4-addition of arylboronic acids to butenolide, catalysed by bis(norbornadiene)rhodium (I) tetrafluoroborate in the presence of (R)-BINAP, and confirmed by X-ray crystallography. Studies on arylboronic acid conjugate additions to acyclic crotonate esters bearing a γ-oxygen substituent are also reported. Three Rh catalysts were investigated and the one giving the highest enantioselectivity was bis(norbornadiene)rhodium (I) tetrafluoroborate.

DMAP-Catalyzed [4 + 2] Cycloaddition of α,β-Unsaturated Carboxylic Acids with Ketones for Synthesis of α,β-Unsaturated δ-Lactones

The DMAP-catalyzed [4 + 2] cycloaddition of α,β-unsaturated carboxylic acids with ketones furnishing α,β-unsaturated δ-lactones in good yields (up to 80%) is described, which is the first example of remote γ-C(sp3)-H activation of α,β-unsaturated carboxylic acids facilitated by DMAP, a pyridine-based catalyst. Copyright

Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1) Antagonists Demonstrating Potent in Vivo Activity

There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo target coverage has been challenging. Here we describe the optimization of a potent, selective series of quinazolinone-based TRPA1 antagonists. High-throughput screening identified 4, which possessed promising potency and selectivity. A strategy focused on optimizing potency while increasing polarity in order to improve intrinisic clearance culminated with the discovery of purinone 27 (AM-0902), which is a potent, selective antagonist of TRPA1 with pharmacokinetic properties allowing for >30-fold coverage of the rat TRPA1 IC50 in vivo. Compound 27 demonstrated dose-dependent inhibition of AITC-induced flinching in rats, validating its utility as a tool for interrogating the role of TRPA1 in in vivo pain models.

Enantioselective Hydrogenation of β,β-Disubstituted Unsaturated Carboxylic Acids under Base-Free Conditions

An additive-free enantioselective hydrogenation of β,β-disubstituted unsaturated carboxylic acids catalyzed by the Rh-(R,R)-f-spiroPhos complex has been developed. Under mild conditions, a wide scope of β,β-disubstituted unsaturated carboxylic acids were hydrogenated to the corresponding chiral carboxylic acids with excellent enantioselectivities (up to 99.3% ee). This methodology was also successfully applied to the synthesis of the pharmaceutical molecule indatraline.

Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: Part 2

Melanin concentrating hormone receptor 1 (MCHR1) antagonists have potential for the treatment of obesity and several CNS disorders. In the preceding article, we have described a novel series of quinazolines as MCHR1 antagonists and demonstrated in vivo proof of principle with an early lead. Herein we describe the detailed SAR and SPR studies to identify an optimized lead candidate having good efficacy in a sub-chronic DIO model with a good cardiovascular safety window.