82586-56-9

Upstream product

• 77497-74-6 (S)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, 1,1-dimethylethyl ester 
• 80828-26-8 N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine hydrochloride 
• 74163-81-8 L-Tic-OH 
• 84793-24-8 N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride 
• 82586-60-5 (S)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, 1,1-dimethylethyl ester, hydrochloride 

Downstream Products

• 82586-55-8 quinapril hydrochloride 
• 115-11-7 isobutene 
• 103733-45-5 (S)-2-{(S)-2-[((S)-1-Ethoxycarbonyl-3-phenyl-propyl)-methyl-amino]-propionyl}-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid 
• 103733-49-9 <3S-<2(R*),3α,11aβ>>-1,3,4,6,11,11a-hexahydro-3-methyl-1,4-dioxo-α-(2-phenylethyl)-2H-pyrazino<1,2-b>isoquinoline-2-acetic acid, ethyl ester 
• 103733-46-6 <3S-<2>,3R*>-2-<2-<<1-(ethoxycarbonyl)-3-phenylpropyl>methylamino>-1-oxopropyl>-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, 1,1-dimethylethyl ester 
• 103775-08-2 (S)-2-[(S)-2-((S)-1-Carboxy-3-phenyl-propylamino)-propionyl]-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid tert-butyl ester 
• 85441-61-8 quinapril 

Relevant academic research and scientific papers

Continuous Flow Synthesis of ACE Inhibitors From N-Substituted l-Alanine Derivatives

A strategy for the continuous flow synthesis of angiotensin converting enzyme (ACE) inhibitors is described. An optimization effort guided by in situ IR analysis resulted in a general amide coupling approach facilitated by N-carboxyanhydride (NCA) activation that was further characterized by reaction kinetics analysis in batch. The three-step continuous process was demonstrated by synthesizing 8 different ACE inhibitors in up to 88 % yield with throughputs in the range of ≈0.5 g h?1, all while avoiding both isolation of reactive intermediates and process intensive reaction conditions. The process was further developed by preparing enalapril, a World Health Organization (WHO) essential medicine, in an industrially relevant flow platform that scaled throughput to ≈1 g h?1.

PREPARATION OF QUINAPRIL HYDROCHLORIDE

Methods and materials for preparing quinapril, its pharmaceutically acceptable salts, including quinapril hydrochloride, are disclosed. The method includes reacting (2S,4S)-2-(4-methyl-2,5-dioxo-oxazolidin-3-yl)-4-phenyl-butyric acid ethyl ester with (3S)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid tert-butyl ester to yield quinapril tert-butyl ester, which is subsequently reacted with an acid to yield quinapril or an acid addition salt of quinapril.