106860-19-9

Upstream product

• 88767-98-0 ethyl (R)-4-phenyl-2-<<(trifluoromethyl)sulfonyl>oxy>butyrate 
• 106860-20-2 9-amino-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1-(S)carboxylic acid t-butyl ester 
• 90315-82-5 ethyl (R)-2-hydroxy-4-phenylbutyrate 
• 603-35-0 triphenylphosphine 
• 88767-16-2 (S)-4-Chlorocarbonyl-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyric acid benzyl ester 
• 109010-59-5 (R)-2-<(4-nitrobenzolsulfonyl)oxy>-4-phenylbuttersaeure-ethylester 
• 88784-33-2 (2S)-4-benzyloxicarbonyl-2-phthalimidobutanoic acid 
• 106928-72-7 (1S,9S)-t-butyl 1,2,3,4,7,8,9,10-octahydro-6,10-dioxo-9-phthalimidopyridazino<1,2-a><1,2>diazepine-1-carboxylate 
• 106927-97-3 (1S,9S)-t-butyl octahydro-10-oxo-9-phthalimido-6H-pyridazino<1,2-a><1,2>diazepine-1-carboxylate 
• 72064-51-8 (3S)-N¹-benzyloxycarbonyl-piperazic acid tert-butyl ester 
• 106860-13-3 (S)-2-[(S)-4-Benzyloxycarbonyl-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyryl]-tetrahydro-pyridazine-1,3-dicarboxylic acid 1-benzyl ester 3-tert-butyl ester 
• 88767-18-4 (S,S)-5-(6-(tert-butoxycarbonyl)tetrahydropyridazin-1(2H)-yl)-4-(1,3-dioxoisoindolin-2-yl)-5-oxopentanoic acid 
• 29678-81-7 (R)-2-hydroxy4-phenylbutanoic acid 

Downstream Products

• 88768-40-5 cilazapril 

Relevant academic research and scientific papers

Synthesis method of cilazapril containing hexahydropyridazine acid structure

The invention discloses a simple synthesis method of cilazapril containing a hexahydropyridazine acid structure. (1S,9S)-9-amino-10-oxo-6H-pyridazine[1,2-a][1,2]diazepine-1-carboxylic acid tert-butylester(II) and (R)-2-hydroxy phenyl butyrate ethyl ester(III) are subjected to a Mitsunobu condensation reaction at 0-60 DEG C and under the action of triphenylphosphine and azodicarboxylate to form amixture of (1S,9S)-9-[(1S)-ethoxycarbonyl-3-phenylpropylamino]octahydro-10-oxo-6H-pyridazine[1,2-a][1,2]diazepine-1-carboxylic acid tert-butyl ester(IV) and (1S,9S)-9-[[(1S)-ethoxycarbonyl-3-phenylpropyl]amino]octahydro-10-oxo-6H-pyridazine[1,2-a][1,2]diazepine-1-carboxylic acid tert-butyl ester triphenylphosphine salt(V), crude cilazapril is prepared from the mixture under the action of an aqueous hydrochloric acid solution, and then the crude cilazapril is recrystallized to obtain cilazapril (I). By adopting the synthesis method provided by the invention, a step of purification operation isreduced, the operation is simple, the use of expensive trifluoromethanesulfonic anhydride and pyridine with an unpleasant odor is avoided, and the method is suitable for industrial production.

PROCESS FOR THE PREPARATION OF AN INTERMEDIATE OF CILAZAPRIL

The present invention relates to a process for the preparation of optically pure (S,S)-6-t-butoxycarbonyl-hexahydro-1-pyridazinylcarbonyl-1,3-dioxo-2-isoindolebutyric acid, an intermediate for the preparation of cilazapril.

A NOVEL PROCESS FOR THE PREPARATION OF CILAZAPRIL

Cilazapril is prepared in good yield using ethyl R-2-(nitro or halo substituted benzene sulfonyloxy)-4-phenyl butyrate. Thus, (1S,9S)-t-butyl octahydro-10-oxo-9-amino-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate is reacted with ethyl R-2-(4-nitro benz

The Design and Synthesis of the Angiotensin Converting Enzyme Inhibitor Cilazapril and Related Bicyclic Compounds

The postulated binding functions for the active site of Angiotensin Converting Enzyme (A.C.E.), derived in an earlier study, have made possible the design of improved inhibitors.Consequently, (1S,9S)-9-octahydro-10-oxo-6H-pyridazodiazepine-1-carboxylic acid (Cilazapril), and related compounds, have been synthesized.They are very active inhibitors of A.C.E. and are highly potent antihypertensives in vivo.