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Sposób wytwarzania perindoprilu i jego farmaceutycznie dopuszczalnych soli
专利权人:
LES LABORATOIRES SERVIER
发明人:
DUBUFFET THIERRY,LECOUVE JEAN-PIERRE
申请号:
PL38040804
公开号:
PL211161B1
申请日:
2004.06.28
申请国别(地区):
PL
年份:
2012
代理人:
摘要:
Industrial synthesis of perindopril (I) involves: (a) reacting N-((S)-ethoxycarbonyl-1-butyl)-(S)-alanine (II) with a sulfinyl chloride (III); (b) reacting the obtained ethyl (2S)-2-((4S)-4-methyl-2-oxido-5-oxo-1,2,3-oxathiazolidin-3-yl)-pentanoate (IV) with a (2S)-2,3,4,5,6,7-hexahydro-1H-indole-2-carboxylic acid compound (V); and (c) catalytically hydrogenating the obtained (2S)-1-((2S)-2-((1S)-1-(ethoxycarbonyl)-butylamino)-propionyl)-2,3,4,5,6,7-hexahydro-1H-indole-2-carboxylic acid compound (VI) under a pressure of 1-30 bars. Industrial synthesis of perindopril of formula (I) or its salts involves: (a) reacting N-((S)-ethoxycarbonyl-1-butyl)-(S)-alanine of formula (II) with a sulfinyl chloride of formula Cl-S(O)-R1 (III); (b) reacting the obtained ethyl (2S)-2-((4S)-4-methyl-2-oxido-5-oxo-1,2,3-oxathiazolidin-3-yl)-pentanoate of formula (IV) with (2S)-2,3,4,5,6,7-hexahydro-1H-indole-2-carboxylic acid or its ester of formula (V) (or its mineral or organic acid addition salt); (c) hydrogenating the obtained (2S)-1-((2S)-2-((1S)-1-(ethoxycarbonyl)-butylamino)-propionyl)-2,3,4,5,6,7-hexahydro-1H-indole-2-carboxylic acid or ester of formula (VI) in presence of a catalyst (e.g. palladium, platinum, rhodium or nickel) under a pressure of 1-30 (preferably 1-10) bars to give (I) (if necessary after deprotection of the acid function); and (d) optionally converting (I) into a salt (specifically the tert. butylamine salt). R1 = imidazolyl, benzimidazolyl or tetrazolyl; R2 = H, benzyl or 1-6C alkyl.
来源网站:
中国工程科技知识中心
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