An Expeditious and Metal‐Free Synthetic Route towards Quinolones, Naphthyridones and Benzonaphthyridones

Abstract

An efficient, two‐step synthetic strategy has been developed to access the quinolone, naphthyridone and benzonaphthyridone classes of chemotherapeutic agents from Baylis–Hillman adducts. The method involves tandem aza‐Michael addition, SNAr cyclisation followed by oxidation of the resulting 4‐hydroxy‐1,2,3,4‐tetrahydroquinoline or 4‐hydroxy‐1,2,3,4‐tetrahydro‐1,8‐naphthyridine derivative using IBX, and works well with substrates having a wide variety of substitution pattern.magnified image

Adenine Modification at C7 as a Viable Strategy to Potentiate the Antimalarial Activity of Quinolones

“…Syntheses of target quinolones was done through a convenient strategy that we have developed earlier, which involves the use of Baylis-Hillman adduct as the precursor (e. g. 2 a, Scheme 1). [30] For the current study, 2,4-dichloro-5-nitrobenzaldehyde (1 a) was reacted with methyl acrylate in presence of DABCO in THF to get 2 a in 84 % yield as a pale-yellow solid. Treatment of 2 a with appropriate amines in presence of Et 3 N in NMP gave the products 3 a-c arising through Michael addition followed by cyclization.…”

Accessing 1,8‐Naphthyridones by Metal‐Free Regioselective Amination of Pyridine N‐oxides/Acid‐Mediated Cyclization

“…Previous reports achieved the key C2À N bond formation of the 1,8-naphthyridone via nucleophilic aromatic substitution (S N Ar) between 2-halogen substituted pyridines (1 or 2) and amines (Scheme 2A & 2B). [5] However, few 1,8-naphthyridones have actually been prepared by either of these approaches as they each suffer from inherent limitations. The inclusion of the halogen atom requires additional steps and generates halide waste.…”