737745-17-4Relevant academic research and scientific papers
Experimental and Computational Development of a Conformationally Flexible Template for the meta-C-H Functionalization of Benzoic Acids
Fang, Lizhen,Saint-Denis, Tyler G.,Taylor, Buck L. H.,Ahlquist, Seth,Hong, Kai,Liu, Saisai,Han, Lili,Houk,Yu, Jin-Quan
, p. 10702 - 10714 (2017)
A conformationally flexible template for the meta-C-H olefination of benzoic acids was designed through both experimental and computational efforts. The newly designed template favors a silver-palladium heterodimer low barrier transition state, and demonstrates that it is feasible to lengthen templates so as to achieve meta-selectivity when the distance between the functional handle of the native substrate and target C-H bond decreases. Analysis of the ortho-, meta-, and para-C-H cleavage transition states determined that the new template conformation optimizes the interaction between the nitrile and palladium-silver dimer in the meta-transition state, enabling palladium to cleave meta-C-H bonds with moderate-to-good yields and generally high regioselectivity. Regioselectivity is governed exclusively by the template, and kinetic experiments reveal that there is a 4-fold increase in rate in the presence of monoprotected amino acid ligands. Using a Boltzmann distribution of all accessible C-H activation transition states, it is possible to computationally predict meta-selectivity in a number of investigated templates with reasonable accuracy. Structural and distortion energies reported may be used for the further development of templates for meta-C-H activation of hitherto unexplored arene substrates.
Pharmaceutical Product Comprising a P38 Kinase Inhibitor and a Second Active Ingredient
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, (2012/02/06)
The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is N-Cyclopropyl-3-fluoro-4-methyl-5[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide or a salt thereo
