沙库巴曲内酰胺类杂质的合成

Synthesis of Lactam Impurities in Sacubitril

制备了沙库巴曲3个工艺杂质:(3R,5S)-5-([1,1′-联苯]-4-甲基)-3-甲基吡咯烷-2-酮(杂质Ⅰ),4-((3R,5S)-5-([1,1′-联苯基]-4-亚甲基)-3-甲基-2-氧代吡咯烷-1-基)-4-氧代丁酸(杂质‖),4-((3R,5S)-5-([1,1′-联苯基]-4-基甲基)-3-甲基-2-氧代吡咯烷-1-基)-4-氧代丁酸异丙酯(杂质Ⅲ),并对其结构进行质谱以及核磁鉴定,为药物质量研究提供对照品。

The impurities(3R,5S)-5-([1,1′-biphenyl]-4-ylmethyl)-3-methylpyrrolidin-2-one,4-((3R,5S)-5-([1,1′-biphenyl]-4-ylmethyl)-3-methyl-2-oxopyrrolidin-1-yl)-4-oxobutanoic acid and isopropyl 4-((3R,5S)-5-([1,1′-biphenyl]-4-ylmethyl)-3-methyl-2-oxopyrrolidin-1-yl)-4-oxobutanoate were prepared.Their structures were confirmed by 1H NMR 13 C NMR and MS.