Application of Ylideneketonitriles: A Facile Approach to Novel 1,8‐Naphthyridin‐2‐ones via a Sequential One‐Pot Two‐Step Synthesis

ABSTRACT In the present article, a novel, efficient synthesis of structurally diverse 1,8‐naphthyridin‐2‐ones ( 5a‐v ) from ylideneketonitriles is reported in good to decent yield, that is, 47%–60%. The two‐step sequential addition method begins with ylideneketonitriles (R 1 = –CF 3 , –CHF 2 ) reacting with primary amines (R 2 = –Bn, –CH 2 Py, –CyPr) in acetonitrile at 80°C for 1 h, forming 2‐aminopyridine derivatives ( 3a‐f ). Subsequent cyclization using acid chloride or ester with potassium carbonate in acetonitrile at 80°C for 2 h yields the target compounds. Acid chloride‐mediated cyclization provides 15%–20% higher yields compared to ester. Notably, in a one‐pot two‐step synthesis, the yields were 10%–30% lower than the sequential two‐step approach. Additionally, the multicomponent reaction (MCR) approach using ester in propionitrile as solvent and potassium carbonate as base affords the desired products in 19%–35% yield. This methodology allows facile introduction of various substituents at R 1 , R 2 , and R 3 positions, enabling the generation of a novel 1,8‐naphthyridin‐2‐ones library. This methodology offers several advantages, including the use of readily available reagents, moderate reaction temperatures, and relatively short reaction times.