Efficient Synthesis of Functionalized Benzo[b][1,8]naphthyridine Derivatives via Three-Component Reaction Catalyzed by l-Proline

Abstract

A facile and efficient one-pot procedure for the preparation of functionalized benzo[b][1,8]naphthyridine derivatives by three-component reaction of 2-chloroquinoline-3-carbaldehyde, 1,3-dicarbonyl compounds, and enaminones catalyzed by l-proline is described. This new protocol has the advantages of environmental friendliness, good yields, and convenient operation.

Recent advances in the chemistry of 2-chloroquinoline-3-carbaldehyde and related analogs

“…It was noticed that the best yields were obtained using l -proline as a catalyst in refluxing ethanol rather than using catalysts such as cesium carbonate or sodium hydroxide or piperidine, etc … and solvents such as water or DMF or chloroform or toluene or acetonitrile. 83 …”

“…Knoevenagel condensation of 76 with the reactive iminium ion (intermediate A) produces intermediate (B). Elimination of L-proline led to the formation of intermediate (C) which reacted with enaminone 113 to produce the intermediate D. Finally, intramolecular cyclization of intermediate D gave tetrahydrodibenzo[b,g][1,8]naphthyridin-1(2H)-ones 114a-n 83. A series of tetrahydrodibenzo[b,g][1,8]naphthyridin-1(2H)ones 116a-h were prepared through multicomponent reactions of substituted 2-chloro-3-formylquinolines 16 with 5-methyl-2,4-dihydro-3H-pyrazol-3-one (115) and 5,5-dimethyl-3-(phenylamino)cyclohex-2-en-1-one 113 by heating in ethanol in the presence of catalytic L-proline (Scheme 36).…”

Design, Synthesis and Biological Evaluation of Tetrahydrodibenzo[b,g][1,8]napthyridinones as Potential Anticancer Agents and Novel Aurora Kinases Inhibitors

“…The 2-Chloroquinoline-3-carbaldehydes, are key moieties used for the formation of various heterocyclic molecules. The treatment of dimedone with aryl amines generated amine3 (a-h) via nucleophilic substitution of dimedone within the presence of variedphenylamine, [31] afterward, the reaction of 2-chloroquinoline-3-carbaldehydes 1 (ac), phenyl pyrazolone (2) compounds with the 3 (a-h) afforded tetrahydrodibenzo[b,g] [1,8]naphthyridinone derivatives withLproline as a organocatalyst in ethanolbelow reflux condition. Initially 2-Chloroquinoline-3-carbaldehyde (1 a), phenyl pyrazolone (2), and enaminone (3 a) were designated as model substrates and evaluated belowvaried conditions (Scheme 2).…”

2-Chloroquinoline-3-carbaldehydes: synthesis and reactions (2012-2017)

“…The crystalline solids were collected and purified by recrystallization from DMF and water to give pure products 36{7,1,5} (Scheme 21). 34 In an extended work at the same context, the synthesis of diverse naphthyridinone derivatives 68a-h was presented. When 2-chloroquinoline-3-carbaldehydes I, 3-methyl-1H-pyrazol-5(4H)-one 67, enaminone 35, L-proline was stirred and refluxed in ethanol (Scheme 22).…”