Imidazo [1,2-b] pyridazine is the C-3 side chain of the fourth-generation cephalosporins: Cefozopran. This paper used maleic anhydride as the starting material, synthesized imidazo [1, 2-b] pyridazine through hydrazinolysis, halogenation, ammonolysis, cyclization and dehalogenation. Strong acids were applied as the reaction medium of the first step, the yield of maleic hydrazide can be reached up to 96%. 3, 6-dichloro-pyridazine was synthesized by a new one-pot method which increased the yield from 74.4% to 88%. 3-amino-6-chloro pyridazine was synthesized by microwave-assisted ammonolysis, which could shorten the reaction time from 17 hours to 0.5 hours. During the formation of the imidazole ring, with ethanol as the solvent, the use of low-cost chloroacetaldehyde could simplify the reaction process. In the hydrogenation of the 6-chloro-imidazo [1,2-b] pyridazine, palladium carbon was used as the catalyst, the reaction could be accomplished at atmospheric pressure. Since each single-step yield was higher than 80%, this synthetic route was considered to be practical in industry.