103129-81-3

Basic information

• Product Name: d-Amlodipine
• Synonyms: (R)-(+)-Amlodipine;(R)-Amlodipine;3,5-Pyridinedicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-, 3-ethyl 5-methyl ester, (4R)-;3,5-Pyridinedicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-, 3-ethyl 5-methyl ester, (R)-;d-Amlodipine;(4R)-2-[(2-AMinoethoxy)Methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-Methyl-3,5-pyridinedicarboxylic Acid 3-Ethyl 5-Methyl Ester;Amlodipine (R)-Isomer
• CAS NO: 103129-81-3
• Molecular Formula: C₂₀H₂₅ClN₂O₅
• Molecular Weight: 408.88
• Product Categories: Amines;Chiral Reagents;Dihydropyridine;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 103129-81-3.mol

Chemical Properties

• Melting Point: 101-103°C
• Boiling Point: 527.161°C at 760 mmHg
• Flash Point: 272.617°C
• Appearance: /
• Density: 1.228g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.546
• Storage Temp.: -20°C Freezer
• Solubility: Acetonitrile (Slightly), Chloroform (Slightly), Methanol (Slightly)
• PKA: 8.97±0.10(Predicted)
• CAS DataBase Reference: d-Amlodipine(CAS DataBase Reference)
• NIST Chemistry Reference: d-Amlodipine(103129-81-3)
• EPA Substance Registry System: d-Amlodipine(103129-81-3)

Safety Data

• Hazardous Substances Data: 103129-81-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
d-Amlodipine is used as a calcium channel blocker for treating various cardiovascular conditions. It works by blocking the movement of calcium ions into heart and blood vessel cells, which helps to relax the blood vessels and reduce the workload on the heart. This can be particularly beneficial for patients with hypertension, angina, and certain heart rhythm disorders.
Used in Cardiovascular Treatment:
d-Amlodipine is used as a therapeutic agent for managing high blood pressure and preventing angina (chest pain). By blocking calcium channels, it helps to dilate the blood vessels, allowing for better blood flow and reduced pressure on the heart.
Used in Hypertension Management:
d-Amlodipine is used as an antihypertensive medication to lower blood pressure in patients with hypertension. Its calcium channel blocking action helps to reduce the force of heart contractions and the resistance of blood vessels, leading to a decrease in blood pressure.
Used in Angina Prophylaxis:
d-Amlodipine is used as a prophylactic agent for angina, a condition characterized by chest pain due to insufficient blood flow to the heart. By relaxing the blood vessels and improving blood flow, d-Amlodipine can help prevent the onset of angina attacks.
Used in Heart Rhythm Disorders:
d-Amlodipine is used as a treatment for certain heart rhythm disorders, such as supraventricular tachycardia and atrial fibrillation. Its calcium channel blocking properties can help regulate the heart's electrical activity, restoring a more normal rhythm.

InChI:InChI=1/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3/t17-/m1/s1

Upstream product

• 125639-89-6 2-<(2-azidoethoxy)methyl>-4(R)-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-1,4-dihydropyridine 
• 103069-49-4 2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 103094-33-3 (-)-2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-5-(methoxycarbonyl)-3-<(2(S)-methoxy-2-phenethoxy)carbonyl>-6-methyl-1,4-dihydropyridine 
• 103069-47-2 2-cyanoethyl 4-(2-azidoethoxy)-3-oxobutanoate 
• 103069-48-3 2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-3-(2-cyanoethoxycarbonyl)-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 87-69-4 L-Tartaric acid 
• 88150-42-9 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 1029898-76-7 ramipril-amlodipine salt 
• 103129-82-4 amlodipine 
• 88150-42-9 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 113994-41-5 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester 

Relevant articles and documents

Enantioseparation of racemic amlodipine using immobilized ionic liquid by solid-phase extraction

In this paper, a novel l-glutamate based immobilized chiral ionic liquid (SBA-IL (Glu)) was prepared by chemical bonding method and applied as a solid sorbent for chiral separation of amlodipine. The performance of SBA-IL (Glu) was investigated for the absorption of (S)-amlodipine and separation of amlodipine enantiomer. The static experiment showed that equilibrium adsorption was achieved within 80 minutes, and the saturation adsorptions capacity was 12 mg/g. The complex was then packed in a glass chromatographic column for the separation of amlodipine and the enantiomeric excess (%ee) of (S)-amlodipine reached 24.67%. The immobilized ionic liquids exhibit good reusability, and the separation efficiency remains 18.24% after reused five times, which allows potential scale-up for the chiral separation of amlodipine.

Enantiomeric separation of racemic amlodipine by sequential fractional crystallization through formation of diastereomeric salt solvates and co-crystals of solvate-like compounds with specific structure — A tandem resolution

A new resolution method of racemic amlodipine has been developed. The racemic compound is reacted in a suitable solvent with 0.25-mol equivalent of (R,R)-tartaric acid. After the decomposition of the diastereomeric salt, the remaining racemic fraction is precipitated with half-equivalent of fumaric acid, and the pure amlodipine enantiomer is obtained. A quarter equivalent of the same resolving agent, (R,R)-tartaric acid has been also added to the mother liquor to obtain the other enantiomer. The advantage of this method is that both of the enantiomers of amlodipine could be obtained with high enantiomeric excess with the same resolving agent. The racemic excess can also be isolated and re-resolved. Achiral reagents (urea and thiourea) have been added to the resolving agent. These neutral additives are incorporated as co-crystals in the structure of the diastereomeric salts. The used solvate-former solvents and achiral additives are structurally similar, and their presence can enable the fractional separation of the diastereomers. In addition, the racemate, the enantiomers, and some intermediate salts with high diastereomeric excess obtained in the resolution process of amlodipine have been also subjected to thermal (DSC, TG/DTA-EGA-MS, and -FTIR), analytical (FTIR spectroscopic), and structural (XRD) comparisons, which indicate that the key-intermediate crystalline diastereomeric salts—as solvates and co-crystals—inherit a kind of structural similarity from their related additives—solvents (DMF, DMAA, and DMSO) or (thio)ureas, respectively.

Enantioseparation of chiral pharmaceuticals by vancomycin-bonded stationary phase and analysis of chiral recognition mechanism

The drug chirality is attracting increasing attention because of different biological activities, metabolic pathways, and toxicities of chiral enantiomers. The chiral separation has been a great challenge. Optimized high-performance liquid chromatography (HPLC) methods based on vancomycin chiral stationary phase (CSP) were developed for the enantioseparation of propranolol, atenolol, metoprolol, venlafaxine, fluoxetine, and amlodipine. The retention and enantioseparation properties of these analytes were investigated in the variety of mobile phase additives, flow rate, and column temperature. As a result, the optimal chromatographic condition was achieved using methanol as a main mobile phase with triethylamine (TEA) and glacial acetic acid (HOAc) added as modifiers in a volume ratio of 0.01% at a flow rate of 0.3?mL/minute and at a column temperature of 5°C. The thermodynamic parameters (eg, ΔH, ΔΔH, and ΔΔS) from linear van 't Hoff plots revealed that the retention of investigated pharmaceuticals on vancomycin CSP was an exothermic process. The nonlinear behavior of lnk′ against 1/T for propranolol, atenolol, and metoprolol suggested the presence of multiple binding mechanisms for these analytes on CSP with variation of temperature. The simulated interaction processes between vancomycin and pharmaceutical enantiomers using molecular docking technique and binding energy calculations indicated that the calculated magnitudes of steady combination energy (ΔG) coincided with experimental elution order for most of these enantiomers.

Enantioselective potential of polysaccharide-based chiral stationary phases in supercritical fluid chromatography

The enantioselective potential of two polysaccharide-based chiral stationary phases for analysis of chiral structurally diverse biologically active compounds was evaluated in supercritical fluid chromatography using a set of 52 analytes. The chiral selectors immobilized on 2.5?μm silica particles were tris-(3,5-dimethylphenylcarmabate) derivatives of cellulose or amylose. The influence of the polysaccharide backbone, different organic modifiers, and different mobile phase additives on retention and enantioseparation was monitored. Conditions for fast baseline enantioseparation were found for the majority of the compounds. The success rate of baseline and partial enantioseparation with cellulose-based chiral stationary phase was 51.9% and 15.4%, respectively. Using amylose-based chiral stationary phase we obtained 76.9% of baseline enantioseparations and 9.6% of partial enantioseparations of the tested compounds. The best results on cellulose-based chiral stationary phase were achieved particularly with propane-2-ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO2, respectively. Methanol and basic additive isopropylamine were preferred on amylose-based chiral stationary phase. The complementary enantioselectivity of the cellulose- and amylose-based chiral stationary phases allows separation of the majority of the tested structurally different compounds. Separation systems were found to be directly applicable for analyses of biologically active compounds of interest.

COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS

The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.

Process for Producing Enantiomer of Amlodipine in High Optical Purity

The present invention relates to a process for preparation of optically pure (S)-amlodipine-L-hemitartrate DMF solvate comprising the steps of treating (R,S) amlodipine base with L-tartaric acid in the presence of dimethyl formamide and a co-solvent. The invention also relates to a process for converting (R) or (S)-amlopidine-L-hemitartrate DMF solvate into their besylates without isolating free chiral amlopidine base after solution.

Method for the enantiomoeric separation of optical active amlodipine

The present invention relates to the preparation of the (S)-(?)-amlodipine and (R)-(+)-amlodipine by means of enantiomoeric separation of racemic amlodipine mixture, in which, L- or D-tartaric acid is used as resolution agent, and organic solvent containing 2-butone is used as solvent. The 2-butone used in the present invention has the advantage of low boiling point, low toxicity, litter pollution, and the method is suitable for large-scaled production.

Resolution of the enantiomers of amlodipine

The invitation provides an efficient method for the resolution of (R)-(+)-(formula (I)) and (S)-(?)(formula (II))-enantiomers of amlodipine, where the chiral reagent for resolution is tartaric acid and the chiral auxiliary reagent for resolution is deuterated dimethyl sulphoxide (DMSO-d6).

Separation of the enantiomers of amlodipine via their diastereomeric tartrates

A method for the separation of R-(+)- and S-(-)-isomers of amlodipine (I) from mixtures thereof, which comprises the reaction of the mixture of isomers with either L- or D-tartaric acid in an organic solvent containing sufficient dimethyl sulphoxide (DMSO) for the precipitation of, respectively, a DMSO solvate of an L-tartrate salt of R-(+)-amlodipine, or a DMSO solvate of a D-tartrate salt of S-(-)-amlodipine. STR1