O-Alkylation Redirected Condensation of 5-Hydroxy-1,2-oxazine-6-ones with Primary Amines for Synthesis of 5-Hydroxyiminopyridine-2,6(1H,3H)-diones

Herein we report a short and general protocol for synthesis of potentially biologically active pyridine-2,6-diones. The approach is based on the redirection of the condensation of the intermediates of Dornow reaction - 5-hydroxy-1,2-oxazine-6-ones with primary amines by their prior O-alkylation. Such manipulation blocks their transformation into isoxazoles and allows one to obtain a library of 30+ previously undescribed 5-alkoxy-3-(hydroxyimino)-4-aryl-pyridine-2,6(1H,3H)-dione derivatives in 37-89 % yields.

Automated summary

A short and general protocol for synthesizing potentially biologically active pyridine-2,6-diones is reported, involving O-alkylation of 5-hydroxy-1,2-oxazine-6-ones to redirect their condensation with primary amines. This manipulation allows the synthesis of a library of over 30 previously undescribed derivatives in yields ranging from 37% to 89%.