| 摘要 |
#CMT# #/CMT# Preparing perindopril L-arginine salt (I) comprises reacting perindopril and L-arginine in a solvent system comprising a binary mixture of acetonitrile and dimethyl sulfoxide, a binary mixture of ethyl acetate and dimethyl sulfoxide, and a ternary mixture of acetonitrile, dimethyl sulfoxide and toluene, at a temperature of 10-100[deg] C; and isolating (I) by filtration. #CMT#ACTIVITY : #/CMT# Cardiovascular-Gen.; Hypotensive; Cardiant; Vasotropic. #CMT#MECHANISM OF ACTION : #/CMT# Angiotensin I converting enzyme inhibitor. #CMT#USE : #/CMT# The process is useful for preparing perindopril L-arginine salt (I) (claimed), which is useful for the treatment of cardiovascular diseases, preferably arterial hypertension, cardiac failure and the stable coronary disease. No biological data given. #CMT#ADVANTAGE : #/CMT# The process produces (I) in high yield with excellent purity and the obtained (I) can be easily isolated from the reaction mixture. #CMT#ORGANIC CHEMISTRY : #/CMT# Preferred Process: Perindopril is obtained by either reacting N-[1-(S)-ethoxycarbonyl-butyl]-(S)-alanine with an activation agent comprising carbonyl compounds of formula (X 2C(=O)) in an organic solvent or a system of organic solvents, at a temperature of -20[deg] C to 80[deg] C, and reacting (S)-2-((S)-4-methyl-2,5-dioxo-oxazolidin-3-yl)-pentanoic acid ethyl ester with (2S,3aS,7aS)-2-carboxyperhydroindole, at a temperature of 0-80[deg] C, or desaltificating perindopril tert-butylamine by the action of an acid. X : a leaving group. Preferred Components: The activation agent is N,N'-carbonyldiimidazole (preferred), phosgene, triphosgene, 1,1'-carbonyldi(1,2,4-triazole) or di(N-succinimidyl)carbonate. The amount of N,N'-carbonyldiimidazole and (2S,3aS,7aS)-2-carboxyperhydroindole is each 0.8-1.2 moles per mole of N-[1-(S)-ethoxycarbonyl-butyl]-(S)-alanine. #CMT#EXAMPLE : #/CMT# A mixture of perindopril (12.5 g) and L-arginine (5.32 g) was suspended in a mixture of acetonitrile (20 g) and dimethyl sulfoxide (61 g). The reaction mixture was heated at 50[deg] C overnight to obtain perindopril arginine salt, which was isolated by filtration. |
