104195-90-6

Basic information

• Product Name: (1R)-epi-RaMipril
• Synonyms: (1R)-epi-RaMipril;(2S,3aS,6aS)-1-[(1S)-2-[[(1R)-1-(Ethoxycarbonyl)-3-phenylpropyl]aMino]- 1-oxopropyl]octahydrocyclopenta[b]pyrrole-2-carboxylic Acid;[2S-[1[R*(S*)],2α,3aβ,6aβ]]-1-[2-[[1-(Ethoxycarbonyl)-3-phenylpropyl]aMino]-1-oxopropyl]octahydrocyclopenta[b]pyrrole-2-carboxylic Acid;1-epi-RaMipril;RaMipril IMpurity-H(EP)
• CAS NO: 104195-90-6
• Molecular Formula: C23H32N2O5
• Molecular Weight: 416.51058
• Product Categories: Aromatics;Heterocycles;Impurities;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 104195-90-6.mol

Chemical Properties

• Appearance: /
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Acetonitrile (Slightly), Aqueous Base (Slightly), Methanol (Slightly)
• CAS DataBase Reference: (1R)-epi-RaMipril(CAS DataBase Reference)
• NIST Chemistry Reference: (1R)-epi-RaMipril(104195-90-6)
• EPA Substance Registry System: (1R)-epi-RaMipril(104195-90-6)

Safety Data

• Hazardous Substances Data: 104195-90-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(1R)-epi-RaMipril is used as an active pharmaceutical ingredient (API) for the treatment of hypertension. It functions by inhibiting the angiotensin-converting enzyme (ACE), which in turn reduces the production of angiotensin II, a potent vasoconstrictor. This leads to vasodilation and a decrease in blood pressure.
Additionally, as an impurity in the production of Ramipril, (1R)-epi-RaMipril may be used for quality control and assurance purposes to ensure the purity and efficacy of the final drug product.

Upstream product

• 87269-86-1 (1RS,3RS,5RS)-2-Azabicyclo<3.3.0>octan-3-carbonsaeure-hydrochlorid 
• 84793-24-8 N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride 
• 87269-87-2 benzyl (2S,3AS,6AS)-octahydrocyclopenta[b]pyrrole-2-carboxylate hydrochloride 
• 87679-46-7 C₃₀H₃₈N₂O₅ 
• 1356847-95-4 C₃₀H₃₈N₂O₅ 
• 82717-96-2 [1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine 
• 765857-50-9 (2S)-2,3,3a,4,5,6-hexahydrocyclopenta[b]pyrrole-2-carboxylic acid 
• 109428-53-7 (2S,3aS,6aS)-1-(tert-butoxycarbonyl)octahydrocyclopenta[b]pyrrole-2-carboxylic acid 
• 87269-85-0 (±)-methyl 2-(acetylamino)-3-(2-oxocyclopentyl)-propionate 
• 87269-86-1 (S,S,S)-2-azabicyclo<3.3.0>octane-3-carboxylic acid hydrochloride 
• 93779-31-8 benzyl (1S,3S,5S)-2-azabicyclo<3.3.0>octane-3-carboxylate 
• 114192-42-6 N-[(S)-1-carbethoxy-3-phenyl-propyl]-S-alaninoyl chloride hydrochloride 
• 87269-99-6 N-[(1S)-1-ethoxycarbonyl-3-phenyl-3-oxopropyl]-L-alanine 
• 87269-98-5 (1'S,2S)-2-(1'-Methyl-2'-oxo-2'-phenylmethoxy-ethylamino)-4-oxo-4-phenyl-buttersaeure-ethylester 

Relevant articles and documents

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.

Drug intermediate in ACE- inhibitor synthesis and application thereof

Compound (I) of Formula, wherein R1 is aryl or alkyl ;R2 represents alkyl ;R3 represents alkyl or aralkyl, is a valuable pharmacological intermediate, which may be prepared by reacting a compound of Formula (IV) above (with thionyl chloride as defined above R1 in particular by reacting a compound of Formula R2 with thionyl chloride), especially for use in the preparation, inhibitor, such as for example for (VI) eperindopril or ramipril 2. ((I). The compound X of Formula . R3 is as defined (I) above). wherein (II) and (are defined above ACE. R1 and R2 wherein R is. a compound, of formula,).

PROCESS FOR THE PREPARATION OF RAMIPRIL

An enantioselective process for the production of (2S,3aS,6aS)-cyclopenta[b]pyrrole-2-carboxylic acid and its conversion into Ramipril is provided.

A METHOD FOR PREPARING RAMIPRIL

Enantio-specific synthesis of optically pure (2S)-acetylamino-3-(2-oxo-cyclopentyl)- propionic acid (I) comprising converting enantiomeric mixture of (1 -4C alkyl)-2- acetylamino-3-(2-oxocyclopentyl) propionoate (II) (+ and -) under the influence of an Alkaline serine endopeptidase is disclosed. The invention further describes use of optically pure (2S)-acetylamino-3-(2-oxocyclopentyl)-propionic acid (I) formed by the process of present invention, in the preparation of Ramipril.

COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE

To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.

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.

METHOD FOR THE SYNTHESIS OF A RAMIPRIL INTERMEDIATE

The present invention relates to a process for the preparation of octahydrocyclopenta[b]pyrrole-2-carboxylic acid and esters thereof of general formula (1) in the presence of a cobalt and/or nickel comprising catalyst and to the use of compounds of general formula (1) in the synthesis of ramipril.

IMPROVED RAMIPRIL SYNTHESIS

The present invention relates to the preparation of ramipril (formula [1]) from unprotected (2S,3S,6S)-octahydrocyclopenta[b]pyrrole-2-carboxylic acid and to a method for preparing unprotected (2S,3S,6S)-octahydrocyclopenta[b]pyrrole-2- carboxylic acid.

METHOD FOR THE PRODUCTION OF RAMIPRIL

An improved method for preparing ramipril is disclosed, and also an intermediate for use in the method.

A PROCESS FOR PREPARATION OF RAMIPRIL

Disclosed herein is a process for preparation of Ramipril; which comprises; reacting salts of (S,S,S)-azabicyclo[3.3.0]-octane-3-carboxylate with N-[l-(S)-ethoxy carbonyl)-3- phenyl propyl] -L-alanine in presence of dicyclohexylcarbodimide (DCC) and 1- hydroxybenzotriazole (HOBT) in a suitable solvent medium.