921630-23-1

Upstream product

• 21739-92-4 5-bromo-2-chlorobenzoic acid 
• 1206625-85-5 2-chloro-5-(2-methoxyethyl)benzoic acid 
• 1206625-83-3 2-chloro-5-(2-methoxyvinyl)benzoic acid 
• 1206625-81-1 2-chloro-5-formylbenzoic acid 
• 1206625-87-7 2-chloro-N-cyclopropyl-5-(2-methoxyethyl)benzamide 

Downstream Products

• 948558-88-1 (rac)-N-[2-chloro-5-(2-methoxy-ethyl)-benzyl]-2-cyano-N-cyclopropyl-3-{6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-pyridin-3-yl}-propionamide 
• 1206625-73-1 (3'R,4'S)-3'-{[2-chloro-5-(2-methoxy-ethyl)-benzyl]cyclopropylcarbamoyl}-6-[2-(2,6-dichloro-4-methyl-phenoxy)ethoxy]-3',4',5',6'-tetrahydro-2'H-[3,4']bipyridinyl-1'-carboxylic acid tert-butyl ester 
• 1206625-79-7 (3'R,4'S)-6-[2-(2,6-dichloro-4-methyl-phenoxy)ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)benzyl]cyclopropylamide acetate 
• 1007392-69-9 MK-1597 
• 946003-68-5 C₄₀H₄₉Cl₃N₄O₅ 
• 949152-13-0 (rac)-3-{[2-chloro-5-(2-methoxyethyl)benzyl]cyclopropylcarbamoyl}-4-oxopiperidine-1-carboxylic acid tert-butyl ester 
• 949152-22-1 benzyl-(2-{[2-chloro-5-(2-methoxyethyl)benzyl]cyclopropylcarbamoyl}ethyl)carbamic acid tert-butyl ester 
• 1007393-31-8 (3R,4S)-3-{[2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-carbamoyl}-4-{4-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester 
• 1056555-53-3 N-[2-chloro-5-(2-methoxyethyl)benzyl]-N-cyclopropyl-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-hydroxybutanamide 

Relevant academic research and scientific papers

A practical synthesis of renin inhibitor MK-1597 (ACT-178882) via catalytic enantioselective hydrogenation and epimerization of piperidine intermediate

A practical enantioselective synthesis of renin inhibitor MK-1597 (ACT-178882), a potential new treatment for hypertension, is described. The synthetic route provided MK-1597 in nine steps and 29% overall yield from commercially available p-cresol (7). The key features of this sequence include a catalytic asymmetric hydrogenation of a tetrasubstituted ene-ester, a highly efficient epimerization/saponification sequence of 4 which sets both stereocenters of the molecule, and a short synthesis of amine fragment 2.

PROCESS FOR MAKING A RENIN INHIBITOR

A salt of the compound (3'R,4'S)-6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-amide selected from the group consisting of monoacetate salt and bis-D-tartrate salt. In one embodiment of the invention, the salt is (3',4'S)-6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-amide monoacetate. In one embodiment of the invention, the salt is (3'R, 4'S)-6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-amide bis-D-tartrate. The invention also describes a asymmetric synthesis of (3'R, 4'S)-6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-3'-carboxylic acid [2-chloro-5-(2-methoxy-ethyl)-benzyl]-cyclopropyl-amide as a monoacetate salt or as a bis-D-tartrate salt

RENIN INHIBITORS

The present invention relates to novel renin inhibitors of the general Formula (I), and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds. These novel renin inhibitors are used in treating cardiovascular events and renal insufficiency.