头孢洛扎的7-位侧链噻二唑衍生物TATD的制备方法

The method for preparing the 7-side chain thiadiazole derivative TATD of ceftolozane sulfate

首先将起始原料2-肟氰基乙酸乙酯与2-溴代异丁酸叔丁酯反应得到中间体1,中间体1再与氨水进行反应合成中间体2,接着依次与五氯化磷、氯化铵及氢氧化钠水溶液进行一锅法反应制备中间体3,最后中间体3与硫氰酸铵进行合环反应合成TATD。该工艺得到的TATD收率及纯度较高,原料易得,适合工业化生产。

The starting material ethyl cyanoglyoxylate-2-oxime was reacted with the t-Butyl 2-bromo isobutyrate to obtain intermediate 1.Subsequently,the intermediate 1 was reacted with ammonium hydroxide to synthesize intermediate 2 and intermediate 3 was prepared via the one-pot process which comprised reaction with phosphorus pentachloride,ammonium chloride and sodium hydroxide aqueous solution.Finally,intermediate 3 was combined with ammonium thiocyanate to synthesize TATD.TATD in high purity and yield was prepared via this process.Furthermore,the raw materials of this process were easy to obtain.The process could thus easily be scaled up to an industrial process.