Synthesis of 7‐(1‐pyrrolidinyl)‐1,2,4‐triazolo[4,3‐b]pyridazines

Abstract

AbstractThe reactions of secondary amines (pyrrolidine, piperidine and morpholine) with 3,4,5‐trichloropyridazine (4) was investigated. With 4 and excess amine, disubstitution occurred in good yield and selectively at positions 3 and 5. Treatment of 4 with 2 equivalents of the amine in ethanol afforded high yields of products resulting from monosubstitution at position 5. 3,4‐Dichloro‐5‐(1‐pyrrolidinyl)pyridazine (6a), resulting from 4 and 2 equivalents of pyrrolidine, was converted cleanly to 4‐chloro‐3‐hydrazino‐5‐(1‐pyrrolidinyl)pyridazine (8) with hydrazine hydrate. Pyridazine 8 was cyclized with formic acid to give a 1:1 complex (9) of formic acid and 8‐chloro‐7‐(1‐pyrrolidinyl)‐1,2,4‐triazolo[4,3‐b]pyridazine (13). Triazolopyridazine 13 also formed a monohydrate (12) and a monohydrochloride salt (14). Catalytic hydrogenation of 9 gave 7‐(1‐pyrrolidinyl)‐1,2,4‐triazolo[4,3‐b]pyridazine (3), which was a target compound of this investigation.