25310-30-9Relevant academic research and scientific papers
Assembly of α-(Hetero)aryl Nitriles via Copper-Catalyzed Coupling Reactions with (Hetero)aryl Chlorides and Bromides
Chen, Ying,Xu, Lanting,Jiang, Yongwen,Ma, Dawei
supporting information, p. 7082 - 7086 (2021/02/26)
α-(Hetero)aryl nitriles are important structural motifs for pharmaceutical design. The known methods for direct synthesis of these compounds via coupling with (hetero)aryl halides suffer from narrow reaction scope. Herein, we report that the combination of copper salts and oxalic diamides enables the coupling of a variety of (hetero)aryl halides (Cl, Br) and ethyl cyanoacetate under mild conditions, affording α-(hetero)arylacetonitriles via one-pot decarboxylation. Additionally, the CuBr/oxalic diamide catalyzed coupling of (hetero)aryl bromides with α-alkyl-substituted ethyl cyanoacetates proceeds smoothly at 60 °C, leading to the formation of α-alkyl (hetero)arylacetonitriles after decarboxylation. The method features a general substrate scope and is compatible with various functionalities and heteroaryls.
Base-controlled chemoselectivity: direct coupling of alcohols and acetonitriles to synthesise α-alkylated arylacetonitriles or acetamides
Bai, Liang,Ge, Min-Tong,Li, Chen,Qiu, Yuan-Rui,Wang, Ying,Xia, Ai-Bao,Xu, Dan-Qian
supporting information, p. 15200 - 15204 (2021/09/06)
We achieved chemoselective synthesis of α-alkylated arylacetonitriles and acetamides by combining Ir complex-catalysed direct coupling of alcohols and nitriles by a simple adjustment of the base. Methanol and ethanol performed well as the alkylating reagents. This method of acetonitrile alkylation provided a novel approach for carbon chain extension.
Overcoming Selectivity Issues in Reversible Catalysis: A Transfer Hydrocyanation Exhibiting High Kinetic Control
Bhawal, Benjamin N.,Ehinger, Christian,Morandi, Bill,Reisenbauer, Julia C.
supporting information, p. 10914 - 10920 (2020/07/13)
Reversible catalytic reactions operate under thermodynamic control, and thus, establishing a selective catalytic system poses a considerable challenge. Herein, we report a reversible transfer hydrocyanation protocol that exhibits high selectivity for the thermodynamically less favorable branched isomer. Selectivity is achieved by exploiting the lower barrier for C-CN oxidative addition and reductive elimination at benzylic positions in the absence of a cocatalytic Lewis acid. Through the design of a novel type of HCN donor, a practical, branched-selective, HCN-free transfer hydrocyanation was realized. The synthetically useful resolution of a mixture of branched and linear nitrile isomers was also demonstrated to underline the value of reversible and selective transfer reactions. In a broader context, this work demonstrates that high kinetic selectivity can be achieved in reversible transfer reactions, thus opening new horizons for their synthetic applications.
Sustainable Alkylation of Nitriles with Alcohols by Manganese Catalysis
Borghs, Jannik C.,Tran, Mai Anh,Sklyaruk, Jan,Rueping, Magnus,El-Sepelgy, Osama
, p. 7927 - 7935 (2019/06/24)
A general and chemoselective catalytic alkylation of nitriles using a homogeneous nonprecious manganese catalyst is presented. This alkylation reaction uses naturally abundant alcohols and readily available nitriles as coupling partners. The reaction tolerates a wide range of functional groups and heterocyclic moieties, efficiently providing useful cyanoalkylated products with water as the only side product. Importantly, methanol can be used as a C1 source and the chemoselective C-methylation of nitriles is achieved. The mechanistic investigations support the multiple role of the metal-ligand manganese catalyst, the dehydrogenative activation of the alcohol, α-C-H activation of the nitrile, and hydrogenation of the in-situ-formed unsaturated intermediate.
Diphenyl-aminopyrimidine compound for inhibiting kinase activity
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Paragraph 0310; 0311; 0312; 0313; 0314; 0315, (2019/05/04)
The invention relates to a diphenyl-aminopyrimidine compound with an inhibiting function on protein tyrosine kinase, a pharmaceutical composition containing the diphenyl-aminopyrimidine compound, andpreparation and application of the diphenyl-aminopyrimidine compound, in particular to a compound shown as the formula (I) and pharmaceutically acceptable salt or crystal forms or prodrugs or metabolin or aquo-complex or solvate or isotope derivatives thereof, wherein R1, R2, R5, R6, R7, R8 and W are defined as the description. The compound can be used for treating ALK-mediated cancer related symptoms, such as non-small cell lung cancer or breast cancer or neural tumors or esophagus cancer or soft tissue cancer or lymphoma or leukemia. The formula is shown in the specification.
Cooperative Palladium/Lewis Acid-Catalyzed Transfer Hydrocyanation of Alkenes and Alkynes Using 1-Methylcyclohexa-2,5-diene-1-carbonitrile
Bhunia, Anup,Bergander, Klaus,Studer, Armido
supporting information, p. 16353 - 16359 (2018/11/25)
Catalytic transfer hydrocyanation represents a clean and safe alternative to hydrocyanation processes using toxic HCN gas. Such reactions provide access to pharmaceutically important nitrile derivatives starting with alkenes and alkynes. Herein, an efficient and practical cooperative palladium/Lewis acid-catalyzed transfer hydrocyanation of alkenes and alkynes is presented using 1-methylcyclohexa-2,5-diene-1-carbonitrile as a benign and readily available HCN source. A large set of nitrile derivatives (>50 examples) are prepared from both aliphatic and aromatic alkenes with good to excellent anti-Markovnikov selectivity. A range of aliphatic alkenes engage in selective hydrocyanation to provide the corresponding nitriles. The introduced method is useful for chain walking hydrocyanation of internal alkenes to afford terminal nitriles in good regioselectivities. This protocol is also applicable to late-stage modification of bioactive molecules.
Selective α-Monomethylation by an Amine-Borane/N,N-Dimethylformamide System as the Methyl Source
Xia, Hui-Min,Zhang, Feng-Lian,Ye, Tian,Wang, Yi-Feng
supporting information, p. 11770 - 11775 (2018/09/10)
A new and practical α-monomethylation strategy using an amine-borane/N,N-dimethylformamide (R3N-BH3/DMF) system as the methyl source was developed. This protocol has been found to be effective in the α-monomethylation of arylacetonitriles and arylacetamides. Mechanistic studies revealed that the formyl group of DMF delivered the carbon and one hydrogen atoms of the methyl group, and R3N-BH3 donated the remaining two hydrogen atoms. Such a unique reaction pathway enabled controllable assemblies of CDH2-, CD2H-, and CD3- units using Me2NH-BH3/d7-DMF, Me3N-BD3/DMF and Me3N-BD3/d7-DMF systems, respectively. Further application of this method to the facile synthesis of anti-inflammatory flurbiprofen and its varied deuterium-labeled derivatives was demonstrated.
Catalytic asymmetric protonation of silyl ketene imines
Guin, Joyram,Varseev, Georgy,List, Benjamin
supporting information, p. 2100 - 2103 (2013/03/28)
An efficient catalytic and highly enantioselective protonation of silyl ketene imines is described. The reaction is catalyzed by the chiral phosphoric acids TRIP or STRIP in the presence of a stoichiometric amount of methanol as the proton source and silyl acceptor. A variety of substituted racemic silyl ketene imines have been transformed into highly enantioenriched nitriles.
CYCLIC DIARYL ETHER COMPOUNDS AS ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
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Page/Page column 108, (2009/10/09)
Described herein are compounds that are antagonists of PGD2 receptors. Also described are pharmaceutical compositions and medicaments that include the antagonists of PGD2 receptors described herein, as well as methods of using such antagonists of PGD2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2-mediated conditions or diseases.
Tetrahydroisoquinoline LXR modulators
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Page/Page column 56, (2010/11/26)
A compound of formula I wherein X, R1, R2a, R3a, R3b, R4a, R4b, R4c and R5 are defined herein.
