54670-80-3Relevant academic research and scientific papers
Buchwald-Hartwig Amination of Coordinating Heterocycles Enabled by Large-but-Flexible Pd-BIAN-NHC Catalysts**
Li, Dong-Hui,Lan, Xiao-Bing,Song, A-Xiang,Rahman, Md. Mahbubur,Xu, Chang,Huang, Fei-Dong,Szostak, Roman,Szostak, Michal,Liu, Feng-Shou
supporting information, (2021/12/06)
A new class of large-but-flexible Pd-BIAN-NHC catalysts (BIAN=acenaphthoimidazolylidene, NHC=N-heterocyclic carbene) has been rationally designed to enable the challenging Buchwald-Hartwig amination of coordinating heterocycles. This robust class of BIAN-NHC catalysts permits cross-coupling under practical aerobic conditions of a variety of heterocycles with aryl, alkyl, and heteroarylamines, including historically challenging oxazoles and thiazoles as well as electron-deficient heterocycles containing multiple heteroatoms with BIAN-INon (N,N′-bis(2,6-di(4-heptyl)phenyl)-7H-acenaphtho[1,2-d]imidazol-8-ylidene) as the most effective ligand. Studies on the ligand structure and electronic properties of the carbene center are reported. The study should facilitate the discovery of even more active catalyst systems based on the unique BIAN-NHC scaffold.
Pd-Catalyzed Cross-Coupling Reactions Promoted by Biaryl Phosphorinane Ligands
Laffoon, Joshua D.,Chan, Vincent S.,Fickes, Michael G.,Kotecki, Brian,Ickes, Andrew R.,Henle, Jeremy,Napolitano, José G.,Franczyk, Thaddeus S.,Dunn, Travis B.,Barnes, David M.,Haight, Anthony R.,Henry, Rodger F.,Shekhar, Shashank
, p. 11691 - 11708 (2019/12/02)
We report the use of biaryl phosphorinanes as ligands for Pd-catalyzed cross-coupling reactions. A modular synthesis was developed that employs a double conjugate addition of primary biaryl phosphines into 1,1,5,5-tetraalkyl penta-1,4-diene-3-ones. Notably, this synthesis does not require the use of copper, a known contaminant in structurally related biaryl phosphane ligands. Using the synthetic strategy described above, we synthesized a library of biaryl phosphorinanes, varying their substitution about phosphorus and the steric and electronic nature of the biaryl motif. We then benchmarked their performance as ligands in Pd-catalyzed cross coupling reactions such as aryl sulfonamidation, aryl alkoxylation, and aryl amination in the presence of soluble organic bases. In each reaction studied, many ligands outperformed biaryl phosphanes known to promote the given transformation. Detailed substrate scopes were determined using high-throughput screening technology. Several biaryl phosphorinanes and their corresponding Pd(II) oxidative-addition complexes were extensively characterized using NMR spectroscopy and X-ray crystallography. General observations support that biaryl phosphorinanes promote reductive elimination and form robust catalysts with palladium. In many cases the use of these biaryl phosphorinanes may be advantageous over the use of biaryl phosphanes with respect to lower catalyst loadings, shorter reaction times, and robustness.
COMPOUNDS AND METHODS FOR MODULATING INTERLEUKIN-2-INDUCIBLE T-CELL KINASE
-
, (2018/05/27)
Provided herein, inter alia, are methods and compounds for modulating Interleukin-2-inducible T-cell kinase.
Breaking the Base Barrier: An Electron-Deficient Palladium Catalyst Enables the Use of a Common Soluble Base in C-N Coupling
Dennis, Joseph M.,White, Nicholas A.,Liu, Richard Y.,Buchwald, Stephen L.
supporting information, p. 4721 - 4725 (2018/04/11)
Due to the low intrinsic acidity of amines, palladium-catalyzed C-N cross-coupling has been plagued continuously by the necessity to employ strong, inorganic, or insoluble bases. To surmount the many practical obstacles associated with these reagents, we utilized a commercially available dialkyl triarylmonophosphine-supported palladium catalyst that facilitates a broad range of C-N coupling reactions in the presence of weak, soluble bases. The mild and general reaction conditions show extraordinary tolerance for even highly base-sensitive functional groups. Additionally, insightful heteronuclear NMR studies using 15N-labeled amine complexes provide evidence for the key acidifying effect of the cationic palladium center.
NOVEL HISTONE DEACETYLASE INHIBITORS AND THEIR USE IN THERAPY
-
Paragraph 74; 75, (2014/05/24)
A compound of the formula:(I) or a pharmaceutically acceptable salt thereof, wherein: L is a 5-membered nitrogen-containing heteroaryl which is optionally fused to a benzene; Y is a 5, 6 or 7-membered nitrogen-containing heteroaryl, which is optionally fused to a benzene; and W is a zinc-binding group. The compounds are HDAC inhibitors and therefore have potential utility in therapy.
Palladium-catalyzed n-arylation of 2-aminothiazoles
McGowan, Meredeth A.,Henderson, Jaclyn L.,Buchwald, Stephen L.
supporting information; experimental part, p. 1432 - 1435 (2012/05/05)
A method for the Pd-catalyzed coupling of 2-aminothiazole derivatives with aryl bromides and triflates is described. Significantly, for this class of nucleophiles, the coupling exhibits a broad substrate scope and proceeds with a reasonable catalyst loadi
THIAZOLYL COMPOUNDS USEFUL AS KINASE INHIBITORS
-
Page/Page column 14, (2010/03/31)
The invention provides compounds of formula I [INSERT CHEMICAL STRUCTURE HERE] (I) and pharmaceutically acceptable salts thereof. The formula I thiazolyl compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer's Disease.
Identification of 2-amino-5-(thioaryl)thiazoles as inhibitors of nerve growth factor receptor TrkA
Kim, Soong-Hoon,Tokarski, John S.,Leavitt, Kenneth J.,Fink, Brian E.,Salvati, Mark E.,Moquin, Robert,Obermeier, Mary T.,Trainor, George L.,Vite, Gregory G.,Stadnick, Linda K.,Lippy, Jonathan S.,You, Dan,Lorenzi, Matthew V.,Chen, Ping
, p. 634 - 639 (2008/09/18)
2-Amino-5-(thioaryl)thiazoles are potent inhibitors of TrkA (e.g., 20h, TrkA IC50 = 0.6 nM) that show anti-proliferative effect in cellular assays. A proposed inhibitor binding mode to TrkA active site is consistent with key SAR observations.
THIAZOLYL COMPOUNDS USEFUL AS KINASE INHIBITORS
-
Page/Page column 45, (2008/12/04)
The invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof. The formula I thiazolyl compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer's disease
Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors
Das, Jagabandhu,Furch, Joseph A.,Liu, Chunjian,Moquin, Robert V.,Lin, James,Spergel, Steven H.,McIntyre, Kim W.,Shuster, David J.,O'Day, Kathleen D.,Penhallow, Becky,Hung, Chen-Yi,Doweyko, Arthur M.,Kamath, Amrita,Zhang, Hongjian,Marathe, Punit,Kanner, Steven B.,Lin, Tai-An,Dodd, John H.,Barrish, Joel C.,Wityak, John
, p. 3706 - 3712 (2007/10/03)
A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.
