Modular Synthesis of 3,6-Disubstituted-1,2,4-triazines via the Cyclodehydration of β-Keto-N-acylsulfonamides with Hydrazine Salts

A straightforward method for preparing 3,6-disubstituted-1,2,4-triazines through a redox-efficient cyclodehydration of β-keto-N-acylsulfonamides with hydrazine salts is described. Two approaches for synthesizing the requisite β-keto-N-acylsulfonamides are presented, which allow for the late stage incorporation of either the C3 or C6 substituent in a flexible manner from acid chlorides or α-bromoketones, respectively. The scope of this methodology includes primary and secondary sp3-linked substituents at both the C3 and C6 positions, and the mild reaction conditions tolerate a variety of sensitive functionalities.