Novel syntheses of 2, 3, 8-trisubstituted pyrido [2, 3-d] pyridazines and 2, 3, 5-trisubstituted pyrazino [2, 3-d] pyridazines are described. Two complementary routes to pyrido [2, 3-d] pyridazines were developed, the first of which began by constructing the pyridine ring, and the second of which started by constructing the pyridazine ring. Pyrazino [2, 3-d] pyridazines were prepared in a route employing an aza-Wadsworth–Emmons cyclization as the key ...