14277-03-3

Upstream product

• 106-47-8 4-chloro-aniline 
• 75-05-8 acetonitrile 
• 106-39-8 bromochlorobenzene 
• 124-42-5 acetamidine hydrochloride 
• 917-64-6 methyl magnesium iodide 
• 13463-94-0 N-(4-chlorophenyl)cyanamide 

Downstream Products

• 80306-53-2 3-(4-chlorophenyl)-2-methyl-6-phenylpyrimidin-4(3H)-one 
• 1002107-32-5 1-(4-chlorophenyl)-2-methyl-1H-imidazole-5-carbaldehyde 
• 87356-79-4 3-(4-Chloro-phenyl)-6-phenyl-2-((Z)-styryl)-3H-pyrimidin-4-one 
• 87356-56-7 3-(4-chloro-phenyl)-2-methyl-pyrimid-4(3H)-one 

Relevant academic research and scientific papers

Discovery of 6-[(3 S,4 S)-4-Amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methyl-3,4-dihydropyrimidin-4-one (IACS-15414), a Potent and Orally Bioavailable SHP2 Inhibitor

Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) plays a role in receptor tyrosine kinase (RTK), neurofibromin-1 (NF-1), and Kirsten rat sarcoma virus (KRAS) mutant-driven cancers, as well as in RTK-mediated resistance, making the identification of small-molecule therapeutics that interfere with its function of high interest. Our quest to identify potent, orally bioavailable, and safe SHP2 inhibitors led to the discovery of a promising series of pyrazolopyrimidinones that displayed excellent potency but had a suboptimal in vivo pharmacokinetic (PK) profile. Hypothesis-driven scaffold optimization led us to a series of pyrazolopyrazines with excellent PK properties across species but a narrow human Ether-à-go-go-Related Gene (hERG) window. Subsequent optimization of properties led to the discovery of the pyrimidinone series, in which multiple members possessed excellent potency, optimal in vivo PK across species, and no off-target activities including no hERG liability up to 100 μM. Importantly, compound 30 (IACS-15414) potently suppressed the mitogen-activated protein kinase (MAPK) pathway signaling and tumor growth in RTK-activated and KRASmut xenograft models in vivo.

Practical Synthesis of Benzimidazo[1,2- A[quinolines via Rh(III)-Catalyzed C-H Activation Cascade Reaction from Imidamides and Anthranils

We report a novel and practical one-pot Rh(III)-catalyzed strategy to construct benzimidazo[1,2-a]quinolines from readily available imidamides and anthranils. The cascade reaction proceeds via a C-H amination-cyclization-cyclization process in ionic liquid without any additives and possesses simple operation, moderate-to-high yield, and broad substrate scope features, which will provide the reference for the construction of biologically active fused benzimidazoles.

Synthesis of indoles and quinazolines via additive-controlled selective C-H activation/annulation of N -arylamidines and sulfoxonium ylides

Selective synthesis of indole and quinazoline products was achieved through a precise control of the C-H activation/annulation by changing the additives from NaOAc to CuF2/CsOAc. This strategy constructs indole and quinazoline scaffolds efficie

Unaromatized Tetrahydrobenzimidazole Synthesis from p-Benzoquinone and N-Arylamidines and their Cytotoxic Potential

A diverse set of unaromatized and densely functionalized tetrahydrobenzimidazole adducts were obtained in good yields by simple mixing p-benzoquinone 1 with N-arylamidines 2 under mild conditions. The main features of these adducts include a hemi N,O-acet

Synthesis of 2-Substituted Quinolines via Rhodium(III)-Catalyzed C–H Activation of Imidamides and Coupling with Cyclopropanols

An efficient synthesis of 2-substituted quinolines from readily available cyclopropanols and imidamides has been developed, where the cyclopropanol acts as a C3 synthon. With the assistance of a bifunctional imidamide directing group, the reaction occurred via sequential C–H/C–C cleavage and C–C/C–N bond formation. (Figure presented.).

Palladium-catalyzed N-monoarylation of amidines and a one-pot synthesis of quinazoline derivatives

A method for the Pd-catalyzed N-arylation of both aryl and alkyl amidines with a wide range of aryl bromides, chlorides, and triflates is described. The reactions proceed in short reaction times and with excellent selectivity for monoarylation. A one-pot synthesis of quinazoline derivatives, via addition of an aldehyde to the crude reaction mixture following Pd-catalyzed N-arylation, is also demonstrated.

Synthesis and evaluation of new difluoromethyl azoles as antileishmanial agents

Several compounds of great pharmacological interest contain the triazole and imidazole rings. In order to find new drugs with antileishmanial activity we have synthesized and evaluated new imidazole and triazole compounds carrying either the carbaldehyde or the difluoromethylene functionalities against promastigote forms of Leishmania amazonensis. Among the compounds tested difluoromethylene azoles 4b and 8f have inhibited the parasite growth significantly. Our results show that the introduction of the difluoromethylene moieties has turned the inactive carbaldehydes into active antileishmanial compounds.

Synthesis and Biological Evaluation of 6-Substituted 3-Aryl-2-methyl-4(3H)-pyrimidones

6-Substituted 3-aryl-2-methyl-4(3H)-pyrimidones (III) have been prepared by the reaction of N-arylacetamidines (II) with various diplorophiles like ethyl propiolate, ethyl tetrolate and ethyl phenylpropiolate.The structure of the products has been confirm