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目的:为加强对阿塞那平药物的质量控制,合成了阿塞那平的4个杂质,其中杂质C和杂质D的合成为首次报道。方法:以11-氯-2,3-二氢-2-甲基-1H-二苯并[2,3:6,7]氧杂并[4,5-c]吡咯-1-酮(6)为起始原料,经还原反应合成杂质A,对A继续还原得到杂质B,利用氧气氧化杂质B可以得到杂质C;同样以6为起始物,经过二氧化锰氧化得到杂质D。结果与结论:目标化合物结构经1H-NMR,MS确证,HPLC检测纯度也都达到98%以上,合成的4种杂质可以作为阿塞那平药物质量控制的杂质对照品。该合成方法路线短,反应条件温和,原料易得,操作简单。
OBJECTIVE: To improve the quality control of asenapine, four impurities of asenapine were synthesized. The synthesis of impurity C and impurity D was reported for the first time. Method: A solution of 11-chloro-2,3-dihydro-2-methyl-1H-dibenz [2,3: 6,7] oxazolo [4,5-c] ) As the starting material, the synthesis of impurities by reduction A, continue to restore A to give impurities B, the use of oxygen to oxidize impurities B can be impurities C; the same 6 as starting material, after manganese dioxide oxidation to give impurities D. RESULTS AND CONCLUSION: The structure of the target compound was confirmed by 1H-NMR and MS. The purity of the target compound was over 98%. The four impurities synthesized could be used as reference substance for quality control of asenapine. The synthetic route is short, the reaction conditions are mild, the raw materials are easy to obtain and the operation is simple.