Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(1H,3H)-diones via Annulation of Anthranilic Esters with N-pyridyl Ureas

Abstract

A new route for the synthesis of quinazolin-2,4(1H,3H)-diones and thieno [2,3-d]pyrimidine-2,4(1H,3H)-diones substituted by pyridyl/quinolinyl moiety in position 3 has been developed. The proposed method concluded in an annulation of substituted anthranilic esters or 2-aminothiophene-3-carboxylates with 1,1-dimethyl-3-(pyridin-2-yl) ureas. The process consists of the formation of N-aryl-N′-pyridyl ureas followed by their cyclocondensation into the corresponding fused heterocycles. The reaction does not require the use of metal catalysts and proceeds with moderate to good yields (up to 89%). The scope of the method is more than 30 examples, including compounds with both electron-withdrawing and electron-donating groups, as well as diverse functionalities. At the same time, strong electron-acceptor substituents in the pyridine ring of the starting ureas reduce the product yield or even prevent the cyclocondensation step. The reaction can be easily scaled to gram quantities.

N‐Pyridylureas as Masked Isocyanates Fort the Late‐Stage Diversification of Pyridine‐N‐Oxides

“…[75,76] Moreover, it has found that such ureas are able to react with N-and O-nucleophiles acted like masked hetaryl isocyanates. [77][78][79][80] We hypothesized that involving N-oxides of these ureas into similar transformations can be a good "late-stage modification" approach to rise the diversity of azine-N-oxides. The results of this study are presented in this paper.…”