13621-30-2Relevant articles and documents
Enantioselective C-H Amination Catalyzed by Nickel Iminyl Complexes Supported by Anionic Bisoxazoline (BOX) Ligands
Dong, Yuyang,Lund, Colton J.,Porter, Gerard J.,Clarke, Ryan M.,Zheng, Shao-Liang,Cundari, Thomas R.,Betley, Theodore A.
supporting information, p. 817 - 829 (2021/02/03)
The trityl-substituted bisoxazoline (TrHBOX) was prepared as a chiral analogue to a previously reported nickel dipyrrin system capable of ring-closing amination catalysis. Ligand metalation with divalent NiI2(py)4 followed by potassium graphite reduction afforded the monovalent (TrHBOX)Ni(py) (4). Slow addition of 1.4 equiv of a benzene solution of 1-adamantylazide to 4 generated the tetrazido (TrHBOX)Ni(κ2-N4Ad2) (5) and terminal iminyl adduct (TrHBOX)Ni(NAd) (6). Investigation of 6 via single-crystal X-ray crystallography, NMR and EPR spectroscopies, and computations revealed a Ni(II)-iminyl radical formulation, similar to its dipyrrinato congener. Complex 4 exhibits enantioselective intramolecular C-H bond amination to afford N-heterocyclic products from 4-aryl-2-methyl-2-azidopentanes. Catalytic C-H amination occurs under mild conditions (5 mol % catalyst, 60 °C) and provides pyrrolidine products in decent yield (29%-87%) with moderate ee (up to 73%). Substrates with a 3,5-dialkyl substitution on the 4-aryl position maximized the observed enantioselectivity. Kinetic studies to probe the reaction mechanism were conducted using 1H and 19F NMR spectroscopies. A small, intermolecular kinetic isotope effect (1.35 ± 0.03) suggests an H-atom abstraction step with an asymmetric transition state while the reaction rate is measured to be first order in catalyst and zeroth order in substrate concentrations. Enantiospecific deuterium labeling studies show that the enantioselectivity is dictated by both the H-atom abstraction and radical recombination steps due to the comparable rate between radical rotation and C-N bond formation. Furthermore, the competing elements of the two-step reaction where H-removal from the pro-R configuration is preferred while the preferential radical capture occurs with the Si face of the carboradical likely lead to the diminished ee observed, as corroborated by theoretical calculations. Based on these enantio-determining steps, catalytic enantioselective synthesis of 2,5-bis-tertiary pyrrolidines is demonstrated with good yield (50-78%) and moderate ee (up to 79%).
HISTONE DEMETHYLASE INHIBITORS
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Paragraph 00549, (2014/07/08)
The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted amidopyridine or amidopyridazine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.
AMINO ALCOHOL COMPOUND
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Page/Page column 55, (2010/11/25)
A pharmaceutical composition is provided that has a low toxicity, demonstrates superior physicochemical properties and pharmacokinetics, and has superior peripheral blood lymphocyte count lowering activity. The pharmaceutical composition contains a compound having general formula (I): (wherein R 1 represents a methyl group or an ethyl group, R 2 represents a methyl group or an ethyl group, and R 3 represents a phenyl group substituted with 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a cycloalkyl group, a lower alkoxy group, a halogeno lower alkyl group, a lower aliphatic acyl group and a cyano group), a pharmacologically acceptable salt thereof or a pharmacologically acceptable ester thereof.
