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咪唑并[1,2-b]哒嗪是第四代头孢类抗生素——头孢唑兰的3位侧链。以马来酸酐为起始原料,通过肼解、卤代、氨解、成环、脱卤合成了咪唑并[1,2-b]哒嗪。采用强酸为反应介质,可使马来酰肼的收率达到96%。采取一锅法合成中间体3,6-二氯哒嗪,产品收率由两步法的74.4%提高至88%。采用微波辅助合成3-氨基-6-氯哒嗪,反应时间从17 h缩短到0.5 h。在咪唑环形成过程中,以乙醇为溶剂,采用价格低廉的氯乙醛,简化了反应后处理过程。在6-氯咪唑并[1,2-b]哒嗪脱氯过程中,使用钯碳作催化剂,在常压下通入氢气即可完成反应。各单步收率均高于80%。
Imidazo [1,2-b] pyridazine is the third generation cephalosporin antibiotic cephrazola 3 side chain. Starting from maleic anhydride, imidazo [1,2-b] pyridazine was synthesized via hydrazinolysis, halogenation, aminolysis, cyclization and dehalogenation. Using strong acid as reaction medium, the yield of maleic hydrazide can reach 96%. The one-pot synthesis of 3,6-dichloropyridazine was used as the intermediate and the yield of the product was increased from 74.4% to 88% in the two-step method. Using microwave assisted synthesis of 3-amino-6-chloropyridazine, the reaction time was shortened from 17 h to 0.5 h. In the formation of imidazole ring, ethanol as a solvent, the use of inexpensive acetaldehyde, simplifying the post-reaction process. In the process of dechlorination of 6-chloroimidazo [1,2-b] pyridazine, the reaction can be completed by using palladium on carbon as a catalyst and introducing hydrogen gas under atmospheric pressure. The single-step yields were higher than 80%.