One-Pot Synthesis of Novel Functionalized Fused Pyridine Derivatives via Consecutive Pyrrolidine Ring-Closure/Ring-Opening/Formal Aza-Diels–Alder Reactions

Abstract

In this article, we report a highly regioselective method for the synthesis of new fused pyridine derivatives�2,3disubstituted quinolines and 1,2-dihydro-3H-pyrazolo[3,4-b]pyridin-3-one derivatives. The method is based on the reaction of 1,1-diethoxybutane derivatives with aromatic and heterocyclic nucleophiles. The isolated compounds are similar to the products formed as a result of the Debner−Miller reaction. However, we have shown that the interaction of 1,1-diethoxybutane derivatives with (hetero)aromatic amines proceeds according to a mechanism different from that of the Doebner−Miller reaction. The proposed method is distinguished by the possibility of obtaining a wide range of substituted quinolines and 1,2-dihydro-3H-pyrazolo[3,4-b]pyridin-3-one derivatives in one step, the absence of the need to use expensive metal-containing catalysts, and a high product yield.

One-Step Synthesis of Functionalized Pyrazolo[3,4-b]pyridines via Ring Opening of the Pyrrolinium Ion

“…Besides this, there are also examples of the reactions of azomethynes, which involve a CN bond and result in pyrazolidin-3-one derivatives. , The next stage involves opening of the pyrrolidine ring with the formation of dihydropyridine I . The possibility of such cleavage of the C–N bond in pyrrolidine derivatives was previously described by us . Finally, it is oxidized by air oxygen to the final product 3 .…”

“…The possibility of such cleavage of the C−N bond in pyrrolidine derivatives was previously described by us. 18 Finally, it is oxidized by air oxygen to the final product 3. It should be noted that the mechanism of our reaction is different from the mechanism suggested by Jana et al, 21 where the first stage of the reaction is the attack of the lone pair of Scheme 2.…”

“…We previously reported on a highly regioselective method for the synthesis of new derivatives of 1,2-dihydro-3 H -pyrazolo­[3,4- b ]­pyridin-3-one. This method is based on the reaction of N -(4,4-diethoxybutyl)­sulfonamides with 1-phenyl-4-aminopyrazol-5-one (Scheme c) …”

“…This method is based on the reaction of N- (4,4-diethoxybutyl)sulfonamides with 1-phenyl-4-aminopyrazol-5-one (Scheme 1c). 18 Derivatives of 1-pyrroline are of particular interest for the synthesis of diverse heterocyclic compounds due to the ability to undergo various transformations. 19 The ability of ring catalyst, which makes the suggested approach simple to operate and provides wide opportunities for the preparation of functionalized pyrazolo [3,4-b]pyridines (Scheme 1e).…”

Recent Advances in Pyridine Scaffold: Focus on Chemistry, Synthesis, and Antibacterial Activities

“…Very recently, Rizbayeva et al [ 51 ] used aza-Diels-Alder reaction to synthesize functionalized new benzo[ b ]pyridine (quinoline) 72 and pyrazolo-pyridine 75 in a single step ( Scheme 18 ). Reflux of a mixture of anilines 70 and 4-chloro-1,1-diethoxybutane 71 (3 : 2) in dioxane furnished 2,3-disubstituted quinoline 72 (~75%).…”