瑞德西韦制备工艺中手性杂质的合成

Synthesis of Chiral Impurities in Production Process of Remdesivir

为了增强对瑞德西韦的质量控制,设计合成了其工艺路线中易产生的重要手性杂质,包括(S)-2-[[(S)-[[(2R,3S,4R,5S)-5-(4-氨基吡咯并[2,1-f][1,2,4]三嗪-7-基)-5-氰基-3,4-二羟基四氢呋喃-2-基]甲氧基](苯氧基)磷酰基]氨基]丙酸-2-乙基丁基酯,以及其(S)-2-[(R)-(2R,3S,4R,5R)]-型和(S)-2-[(R)-(2R,3S,4R,5S)]-型光学异构体,这些化合物的结构通过MS和NMR确证。本工艺条件温和、收率高、无需手性分离,适合实验室规模制备。

To improve quality control of remdesivir,the key chiral impurities easily generated in the production process of remdesivir were designed and synthesized.The structures of these compounds included(S)-2-ethylbutyl 2-[[(S)-[[(2R,3S,4R,5S)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl]-methoxy](phenoxy)phosphoryl]amino]propanoate,(S)-2-[(R)-(2R,3S,4R,5R)]-type and(S)-2-[(R)-(2R,3S,4R,5S)]-type optical isomers were confirmed by MS and NMR.This method was suitable for laboratory synthesis due to its mild reaction conditions,high yield and no need for chiral separation.