新型抗心衰药物Entresto的合成

发布时间：2018-06-18 23:41

  本文选题：Entresto + sacubitril　； 参考：《中国医药工业杂志》2017年01期

【摘要】：以(2R,4S)-5-([1,1'-联苯]-4-基)-4-[(叔丁氧羰基)氨基]-2-甲基戊酸为原料,经乙醇/氯化亚砜一步法进行酯化-脱保护反应得(2R,4S)-5-([1,1'-联苯]-4-基)-4-氨基-2-甲基戊酸乙酯盐酸盐,再与丁二酸酐经酰化反应得4-[[(2S,4R)-1-([1,1'-联苯]-4-基)-5-乙氧基-4-甲基-5-氧代戊烷-2-基]氨基]-4-氧代丁酸(sacubitril,4),4与乙酸钠成钠盐纯化精制后,再与缬沙坦复合从而得到抗心衰药Entresto,总收率81%。
[Abstract]:The esterification and deprotection reaction of ~ (2) R ~ (2 +) ~ (2) R ~ (2 +) 4S ~ (-) -5 ([1H _ (1N) -biphenyl] -4 ~ (-4) -amino ~ (-2-methyl) pentanoic acid) was carried out by a one-step esterification and de-protection reaction of ethanol / sulfoxide to give ethyl ester ([11-biphenyl] -4- (4-yl) -4-amino-2-methylvalerate) ethyl valerate hydrochloride, which was prepared by a one-step esterification and de-protection reaction of ethanol / sulfoxide. After acylation with succinic anhydride, 4- [H2SN 4RN] -1-( [1H1ON-biphenyls] -4-ethoxy-5-methyl-5-oxopentane-2-yl] amino] -4-oxo-butyrate was purified from sacubitril44 and sodium acetate, and then combined with valsartan to obtain an anti-heart failure drug Entrestostov, with total yield of 81C.
【作者单位】： 南阳医学高等专科学校第一附属医院;
【分类号】：R914
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本文编号：2037309