Synthesis of 4‐Aryl‐4,6‐dihydropyrimido[4,5‐ d ]pyridazine‐2,5(1 H ,3 H )‐diones from Biginelli Compounds

Biginelli compounds 1 were first brominated at MeC(6) with 2,4,4,6‐tetrabromocyclohex‐2,5‐dien‐1‐one to give Br 2 CHC(6) derivatives 2 . The hydrolysis of the 6‐(dibromomethyl) group of 2c to give the 6‐formyl derivative 3c in the presence of an expensive Ag salt followed by reaction with N 2 H 4 ⋅H 2 O yielded tetrahydropyrimido[4,5‐ d ]pyridazine‐2,5(1 H ,3 H )‐dione ( 4c ; Scheme 1 ). However, treatment of the 6‐(dibromomethyl) derivatives 2 directly with N 2 H 4 ⋅H 2 O led to the fused heterocycles 4 in better overall yield ( Schemes 1 and 2 ; Table ).