Development of a Water-Mediated and Catalyst-Free Green Protocol for Easy Access to a Huge Array of Diverse and Densely Functionalized Pyrido[2,3-<i>d</i>:6,5-<i>d</i>′]dipyrimidines via One-Pot Multicomponent Reaction under Ambient Conditions

A water-mediated and catalyst-free simple protocol for easily accessing a huge array of pharmaceutically interesting and diversely functionalized 5-alkyl/aryl/heteroaryl-10-alkyl/aryl-2,8-dioxo/dithioxo-9,10-dihydropyrido[2,3-d:6,5-d′]dipyrimidine-4,6(1H,3H,5H,7H)-dione derivatives 4 (4-1–4-42) and 5,5′-(1,4-phenylene)bis(10-alkyl/aryl-2,8-dioxo/dithioxo-9,10-dihydropyrido[2,3-d:6,5-d′]dipyrimidine-4,6(1H,3H,5H,7H)-dione) 4′ (4′-1–4′-8) has been developed based on a one-pot multicomponent reaction between barbituric/N,N-dimethylbarbituric/2-thiobarbituric acids (1), substituted amines (2), and aldehydes (3) under ambient conditions. The salient features of this protocol are the clean reaction profile, use of no added catalyst, water as reaction media, mild reaction conditions at room temperature, energy-efficiency, easy isolation of products, no need of column chromatographic purification, high atom-economy and low E-factor, good to excellent yields, and reusability of reaction media.

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