發(fā)布時(shí)間：2018-06-18 23:41

  本文選題：Entresto + sacubitril��； 參考：《中國(guó)醫(yī)藥工業(yè)雜志》2017年01期

【摘要】：以(2R,4S)-5-([1,1'-聯(lián)苯]-4-基)-4-[(叔丁氧羰基)氨基]-2-甲基戊酸為原料,經(jīng)乙醇/氯化亞砜一步法進(jìn)行酯化-脫保護(hù)反應(yīng)得(2R,4S)-5-([1,1'-聯(lián)苯]-4-基)-4-氨基-2-甲基戊酸乙酯鹽酸鹽,再與丁二酸酐經(jīng)�；磻�(yīng)得4-[[(2S,4R)-1-([1,1'-聯(lián)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與乙酸鈉成鈉鹽純化精制后,再與纈沙坦復(fù)合從而得到抗心衰藥Entresto,總收率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.
【作者單位】： 南陽醫(yī)學(xué)高等�？茖W(xué)校第一附屬醫(yī)院;
【分類號(hào)】：R914
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本文編號(hào)：2037309