2-(Substituted amino)-8-azachromones from 4,6-Diaryl-2-pyridones: A Synthetic Strategy toward Compounds of Broad Structural Diversity

Abstract

3-Acetoacetyl-4,6-diaryl-2-pyridones are synthesized in three steps from chalcones and then condense with carbon disulfide to afford 8-azachromones containing a methylthio group at C2. This leaving group offers an entry point for the insertion of more complex moieties via nucleophilic substitution. For this purpose, N-nucleophiles are explored according to their positions in the Mayr's nucleophilicity scale (N parameter), and three main classes are distinguished depending on whether the substitution takes place from their neutral forms, from their deprotonated anionic forms, or under nucleophilic catalysis. A broad range of primary and secondary amines may be inserted by this method, including enantiomerically pure amino acids, enabling us to explore structural diversity.

Second‐Generation CD73 Inhibitors Based on a 4,6‐Biaryl‐2‐thiopyridine Scaffold

“…Therefore, we explored the second strategy B leveraging our recent work, [13b] related to the preparation of the desired 4,6‐disubstituted 3‐cyano‐2‐chloro‐pyridines (Scheme 1, 5 ). Thus, when refluxing the crude 3‐cyano‐2‐pyridone 3 c and 3 d obtained beforehand (Scheme 2) in phosphorus oxychloride, the corresponding 4,6‐diaryl 3‐cyano‐2‐chloropyridines 5 a and 5 b (Scheme 4) were isolated in good yields.…”

Accessing 7‐Azaaurones of Controllable E and Z Configurations from 8‐Azaflavones via a Rearrangement‐Acylation‐Photoisomerization Sequence

“…Application of this methodology to 8‐azaflavones relies on the availability of 3‐acetyl‐2‐pyridones. It has recently been shown that such compounds can be conveniently prepared by methylation of 3‐cyano‐2‐pyridones with dimethylmagnesium, [16] which is generated in situ from methylmagnesium bromide by the dioxane precipitation method [17] . By generating Me 2 Mg from MeMgCl (instead of MeMgBr), and by performing the imine hydrolysis in the presence of one equivalent of hydrogen chloride (instead of the reported neutral conditions), we obtained the 3‐acetyl‐2‐pyridones 2 a – d from the corresponding cyanopyridones with higher yields and purities (Scheme 2).…”