比阿培南关键中间体的合成工艺改进

Improved synthesis of the key intermediate of biapenem

目的改进比阿培南的关键中间体 6 ,7 二氢 6 巯基 5H 吡唑 [1,2 α][1,2 ,4 ]三唑内氯化物合成工艺。方法以水合肼为起始原料经缩合 ,再经烯丙基化、脱保护、溴化、环合、硫代乙酰化、醇解、氧化、去甲酰化、环合、还原得到目标化合物 ,对原工艺中 10步反应进行了改进。结果目标化合物经核磁共振氢谱、质谱确证其化学结构。结论总收率为 12 .1%。本方法反应条件温和 ,操作简单。

Aim To synthesize 6,7-dihydro-6-mercapto-5H-pyrazolo[1,2-α][1,2,4]-triazolium chloride,the key intermediate of biapenem and to improve the synthetic procedure.Methods 6,7-Dihydro-6-mercapto-5H-pyrazolo[1,2-α][1,2,4]-triazolium chloride was synthesized from hydrazine via condensation,allylation,deprotection of ketimine,bromination,cyclization,thioacetylation,methanolysis,oxidation,deformylation,cyclization and reduction.Results The chemical structure of the target compound was confirmed by 1H-NMR and FAB-MS.Conclusion The total yield was 12.1%.This procedure has advantages of mild reaction conditions and convenient operations.