107432-22-4Relevant articles and documents
Visible light-promoted copper catalyzed regioselective acetamidation of terminal alkynes by arylamines
Pampana, V. Kishore Kumar,Sagadevan, Arunachalam,Ragupathi, Ayyakkannu,Hwang, Kuo Chu
supporting information, p. 1164 - 1170 (2020/03/11)
Herein, we describe a copper photoredox catalyzed synthesis of acetamide via regioselective C-N coupling of arylamines with terminal alkynes using molecular oxygen (O2) as an oxidant at room temperature under visible light irradiation (47 examples). Unique simultaneous formation of both amide and ester functionalities occurs via intramolecular cyclization in a single-step reaction in the case of anthranilic acids using inexpensive copper as a catalyst and eco-friendly O2 as an oxidant and reagent. Different substrates undergo different reaction pathways to generate similar acetamide products, as evidenced by 18O2 labelling experiments. The current protocol was also applied for the rapid, few step preparation of biologically active inhibitors (BACE-1 and PDE4). This process can be readily scaled up to a gram scale, and calculations of green metrics suggest the economic feasibility and eco-friendly nature of the current photoredox approach.
Synthesis and X-ray crystallographic analysis of quinazolinone cholecystokinin/gastrin receptor ligands
Yu,McCowan,Mason,Deeter,Mendelsohn
, p. 2534 - 2542 (2007/10/02)
Compounds exemplified by 2-[2-(5-bromo-1H-indol-3-yl)ethyl]-3-[3-(1- methylethoxy)phenyl]-4(3H)-quinazolinone (3, IC50 = 0.0093 μM using mouse brain membranes) represent a structurally novel series of non-peptide cholecystokinin B receptor ligands. Since asperlicin, a selective CCK-A receptor antagonist, may be regarded as a conformationally constrained 2- substituted-3-phenyl-4(3H)-quinazolinone, the progenitor of compound 3 (compound 2, 2-[2-(1H-indol-3-yl)ethyl]-3-phenyl-4(3H)-quinazolinone) might therefore represent a conformationally flexible pharmacophore of the natural product. To probe possible conformational preferences for this class of receptor ligands, in particular the spatial relationship between the indole and quinazolinone rings, we prepared a series of analogues with methyl substituents on the ethylene bridge as well as congeners with different linkers. The X-ray crystal structure conformation for compound 22 (2-[2-(1H- indol-3-yl)ethyl]-3-]-3-(1-methylethoxy)phenyl]-4(3H)-quinazolinone, IC50 = 0.026 μM) is extended with the two heteroaromatic rings adopting an antiperiplanar arrangement around the central σ bond of the ethane linker, whereas the solid-state conformation for a less active analogue 19 (2-[2-(1H- indol-3-yl)-1-methylethyl]-3-[3-(1-methylethoxyphenyl]-4(3H)-quinazolinone, IC50 = 9.1 μM) is folded with the two heteroaromatic systems adopting a synclinal orientation. However, MM2 force field calculations (MacroModel, v 3.0) suggest that the energy difference between the folded and extended conformation is small. Thus, other factors such as unfavorable steric interactions may account for the difference in receptor affinity. For derivatives with one to three methylene units separating the indole and quinazolinone rings, maximal receptor binding activity was found when the distance separating the two heteroaromatic systems is defined by an ethyl group. Introducing unsaturation into the ethylene bridge of compound 3 limited the conformational flexibility of the molecule and decreased its receptor affinity greater than 2 orders of magnitude.
