Chen Xue-xi
2012
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Journal
Fine chemicals
Abstract
Imidazo [1,2-b] pyridazine is the C-3 side chain of the fourth-generation cephalosporins:cefozopran.In this paper,maleic anhydride was used as the starting material to synthesize imidazo [1,2-b] pyridazine through hydrazinolysis,halogenation,ammonolysis,cyclization and dehalogenation.Strong acids were applied as the reaction medium of the first step,and the yield of maleic hydrazide could reach 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 h to 0.5 h.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,and 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.