80876-01-3

Usage

Uses

Antihypertensive.

InChI:InChI=1/C24H34N2O5/c1-3-31-24(30)19(14-13-17-9-5-4-6-10-17)25-16(2)22(27)26-20-12-8-7-11-18(20)15-21(26)23(28)29/h4-6,9-10,16,18-21,25H,3,7-8,11-15H2,1-2H3,(H,28,29)/t16-,18-,19-,20-,21-/m0/s1

Upstream product

• 80876-04-6 (2R,3aR,7aR)-1-[(S)-2-((S)-1-Ethoxycarbonyl-3-phenyl-propylamino)-propionyl]-octahydro-indole-2-carboxylic acid tert-butyl ester 
• 79799-08-9 (2S,3aS,7aS)-Octahydro-indole-2-carboxylic acid ethyl ester 
• 108507-43-3 (2R,3aR,7aR)-Octahydro-indole-2-carboxylic acid tert-butyl ester 
• 80876-00-2 (2α,3aβ,7aβ)-octahydro-1H-indole-2-carboxylic acid 1,1-dimethylethyl ester 
• 80828-33-7 (2S,3aS,7aS)-1-[(S)-2-((R)-1-Ethoxycarbonyl-3-phenyl-propylamino)-propionyl]-octahydro-indole-2-carboxylic acid tert-butyl ester 
• 82717-96-2 [1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine 
• 80875-98-5 (2S,3aS,7aS)-perhydroindole-2-carboxylic acid 
• 80828-13-3 rac-trans-octahydroindole-2-carboxylic acid 
• 84793-24-8 N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride 
• 82717-90-6 cis,syn-octahydro-1H-indole-2(S)-carboxylic acid, phenylmethylester 
• 114192-42-6 N-[(S)-1-carbethoxy-3-phenyl-propyl]-S-alaninoyl chloride hydrochloride 
• 145438-94-4 (2S,3aR,7aS)-octahydroindolecarboxylic acid 
• 145641-35-6 phenylmethyl-(2S,3aR,7aS)-octahydroindole-2-carboxylate hydrochloride 
• 82717-97-3 octahydroindole-2-carboxylic acid benzyl ester hydrochloride 

Relevant academic research and scientific papers

A Stereoselective Synthesis of the ACE Inhibitor Trandolapril

A conceptually novel and stereoselective synthesis of the enantiopure octahydroindole building block and its conversion into the ACE inhibitor trandolapril was achieved. Key steps include the α-allylation of a protected l -pyroglutamic acid derivative, a highly diastereoselective Hosomi-Sakurai reaction and a Ru-catalyzed ring-closing metathesis of a 4,5-diallylated proline. This way, the synthesis of trandolapril was efficiently achieved in 25% overall yield (12 steps).

PROCESS FOR THE PREPARATION OF AMIDES OF N-[1-(S)-(ETHOXYCARBONYL)-3-PHENYLPROPYL]-L-ALANINE

A process for the production of amides of N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine is described. The process can be used for the production of key intermediates and finally the ACE inhibitors such as Ramipril, Enalapril, Quinapril, Trandolapril, Delapril and Moexipril starting from N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine by the reaction with the appropriate amines.

PROCESS FOR THE SYNTHESIS OF AN ACE INHIBITOR

A process for the synthesis of trandolapril which comprises condensing N-[I-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride with trans octahydro-1H- indole-2-carboxylic acid in a first organic solvent comprising a water immiscible inert organic solvent and in the presence of a base, and isolating trandolapril from a second organic solvent. N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride may also be condensed with (2S,3aR,7aS) octahydro-1H-indole-2-carboxyIic acid in a first organic solvent and in the presence of a base, and trandolapril isolated. There is also provided a process for the resolution of racemic trans octahydro-1H-indole-2-carboxylc acid.

Method for producing {n-[1-(s)-carbalkoxy-3-phenylpropyl]-s-alanyl-2s, 3ar, 7as-octahydroindole-2-carboxylic acid} compounds

A method for preparing optionally substituted {N-[1-(S)-carbalkoxy-3-phenylpropyl]-S-alanyl-2S,3aR,7aS-octahydroindole-2-carboxylic acid} and pharmaceutically acceptable salts thereof, wherein a racemic mixture of optionally substituted trans-octahydroindole-2-carboxylic acid is reacted with the N-carboxyanhydride of {N-[1-(S)-alkoxycarbonyl-3-phenylpropyl]-L-alanine}, which is optionally substituted on the phenyl ring, in a suitable inert solvent, and subsequently the resulting optionally substituted {N-[1-S-carbalkoxy-3-phenylpropyl]-S-alanyl-2S,3aR,7aS-octahydroindole-2-carboxylic acid}, preferably trandolapril, is isolated, and polymorphic forms A and B of trandolapril.

PREPARATION OF TRANDOLAPRIL

A process for preparing trandolapril, (2S,3aR,7aS)-1-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester, and intermediates that are useful in the process.

Process for the synthesis of ?2S, 3aR, 7aS|-octahydroindole-2-carboxylic acid and its conversion to trandolapril

The present invention describes a novel method for the synthesis of (2S,3aR,7aS)-octahydroindole-2-carboxylic acid of formula III using a new intermediate of formula II and conversion of the product of formula-III to trandolapril of formula I

Process for the preparation of intermediates of trandolapril and use thereof for the preparation of trandolapril

A process for the preparation of an intermediate of trandolapril, (2S,3aR,7aS)-perhydroindole-2-carboxylic acid of Formula II is provided. Also provided are processes for preparing trandolapril.

2′-Benzothiazolylthioesters of N-substituted alpha amino acids: Versatile intermediates for synthesis of ACE inhibitors

ACE inhibitors have been synthesized from novel active esters using simple reaction conditions in high diastereomeric selectivity. The active esters may be obtained from the corresponding carboxylic acids or their acid chlorides.

A METHOD FOR THE PREPARATION OF (2S, 3AR, 7AS)-OCTAHYDRO-1H-INDOLE-2-CARBOXYLIC ACID AS KEY INTERMEDIATE IN THE PREPARATION OF TRANDOLAPRIL BY REACTING A CYCLOHEXYL AZIRIDINE WITH A DIALKYL MALONATE

A method for the synthesis of a compound of formula (I) as a mixture of enantiomers, formula (I) (wherein R1 is H or an acid protective group and H+A- indicates an optional acid with which the compound of formula (I) may form an ammonium salt) said method comprising; A) reacting a cyclohexyl aziridine with a dialkyl malonate, whereby to provide a trans-fused 3-alkylcarbonyl-octahydro-indol-2-one; B) decarbonylation at the 3-position, conversion of the ketone of the resulting trans-octahydro-indol-2-one to an optionally protected carboxylic acid group; and C) optionally removing any N-substitution if necessary.

METHOD FOR PRODUCING {N-[1-(S)-CARBALKOXY-3-PHENYLPROPYL]-S-ALANYL-2S, 3AR, 7AS-OCTAHYDROINDOL-2-CARBOXYLIC ACID} COMPOUNDS

The invention relates to a method for producing optionally substituted {N-[1-(S)-carbalkoxy-3-phenylpropyl]-S-alanyl-2S, 3aR, 7aS-octahydroindol-2-carboxylic acid} and the pharmaceutically acceptable salts thereof. To this end, a racemic mixture of optionally substituted trans-octahydroindol-2-carboxylic acid is reacted with the N-carboxyanhydride of {N-[1-(S)-alkoxycarbonyl-3-phenylpropyl]-L-alanine}, which is optionally substituted on the phenyl ring, in an appropriate inert solvent, and the obtained optionally substituted {N-[1-(S)-carbalkoxy-3-phenylpropyl]-S-alanyl-2S, 3aR, 7aS-octahydroindol-2-carboxylic acid}, preferably trandolapril, is subsequently isolated, as well as polymorphous forms A and B of trandolapril.