甲氧苄啶中相关杂质的合成

Synthesis of the related impurities of Trimethoprim

目的设计合成甲氧苄啶(TMP)的2个重要杂质TMP-A和TMP-F。方法以3,4,5-三甲氧基苯甲醛为原料,经过缩合、重排、加成、环合、氯代及亲核取代制得TMP-A。以香兰素为原料,经过缩合、重排、加成和环合制得TMP-F。结果与结论成功制备了TMP-A,收率较文献提高。首次合成TMP-F,所设计路线的反应条件温和,试剂廉价易得,操作简单。

OBJECTIVE To synthesize two important impurities in Trimethoprim（TMP- A and TMP- F）. METHODS TMP- A was synthesized from 3,4,5 - trimethoxybenzaldehyde by the method of condensation, rearrangement, addition, cyclization, chloration and substitution. TMP- F was synthesized from vanillin by the method of condensation, rearrangement, addition and cyclization. RESULTS and CONCLUSION TMP - A was successfully synthesized which had a higher yield than literature. At the same time,TMP - F was synthesized for the first time. The designed route has mild reaction conditions, cheap and easy reagents, simple operation.