103129-82-4

Basic information

• Product Name: (S)-Amlodipine
• Synonyms: 3,5-Pyridinedicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-, 3-ethyl 5-methyl ester, (4S)-;3,5-Pyridinedicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-, 3-ethyl 5-methyl ester, (S)-;l-Amlodipine;Levoamlodipine Besylate;(4S)-2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester;(S)-Amlodipine;Levamlodipine;Levamlodipine Besylate Tablets
• CAS NO: 103129-82-4
• Molecular Formula: C₂₀H₂₅ClN₂O₅
• Molecular Weight: 408.88
• EINECS: 1592732-453-0
• Product Categories: Pharmaceutical material and intermeidates;Amines;Chiral Reagents;Dihydropyridine;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;API
• Mol File: 103129-82-4.mol
• Article Data: 25

Chemical Properties

• Melting Point: 102-104°C
• Boiling Point: 527.2 °C at 760 mmHg
• Flash Point: 272.6 °C
• Appearance: white crystal powder
• Density: 1.227
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.546
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• PKA: 8.97±0.10(Predicted)
• CAS DataBase Reference: (S)-Amlodipine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-Amlodipine(103129-82-4)
• EPA Substance Registry System: (S)-Amlodipine(103129-82-4)

Safety Data

• Hazardous Substances Data: 103129-82-4(Hazardous Substances Data)

Usage

Description

(S)-Amlodipine, also known as the (S)-enantiomer of Amlodipine, is a dihydropyridine calcium channel blocker. It is a white to off-white solid and exhibits its primary activity in the (-)-isomer form. (S)-Amlodipine is a crucial component in the treatment of various cardiovascular conditions due to its ability to block calcium channels, thus relaxing the blood vessels and improving blood flow.

Uses

Used in Pharmaceutical Industry:
(S)-Amlodipine is used as a pharmaceutical agent for the treatment of hypertension (high blood pressure), angina pectoris (chest pain due to insufficient blood supply to the heart), and coronary artery spasm. It functions by blocking the calcium channels in the heart and blood vessel walls, leading to vasodilation and a reduction in blood pressure.
Additionally, (S)-Amlodipine is used as an anti-anginal agent to prevent and alleviate the symptoms of angina pectoris. Its vasodilatory effects help to increase the blood supply to the heart muscle, reducing the frequency and severity of anginal attacks.
Furthermore, (S)-Amlodipine is utilized in the management of chronic stable angina, a condition characterized by persistent chest pain due to reduced blood flow to the heart. By improving blood flow and reducing the workload on the heart, (S)-Amlodipine helps to alleviate the symptoms and improve the quality of life for patients with this condition.

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-/m0/s1

Synthetic route

S-(-)-amlodipine-hemi-D-tartrate mono-dimethylsulfoxide solvate → amlodipine (103129-82-4)

Conditions	Yield
With sodium hydroxide In dichloromethane; water at 20℃; for 0.666667h;	93.9%

2C20H25ClN2O5*C24H17NO10 → amlodipine (103129-82-4)

Conditions	Yield
With sodium hydroxide In dichloromethane; water at 20℃; for 0.5h;	93%

S(-) amlodipine-hemi L(+)-tartarate mono DMSO solvate → amlodipine (103129-82-4)

Conditions	Yield
With ammonia; water In dichloromethane for 0.5h; Product distribution / selectivity;	92%

2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9) → amlodipine (103129-82-4)

Conditions	Yield
Stage #1: 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine With D-(+)-camphoric acid In isopropyl alcohol at 20℃; for 12.5h; Stage #2: With sodium hydroxide In dichloromethane; water for 1h; Reagent/catalyst;	90.5%
With D-tartaric acid In dimethyl sulfoxide; acetone at 20 - 60℃; for 1.5h; Reagent/catalyst; Solvent;	45.2%
Stage #1: 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine With L-Tartaric acid In ISOPROPYLAMIDE at 5℃; for 2h; Resolution of racemate; Stage #2: With sodium hydroxide In dichloromethane; water for 0.666667h;	n/a
Multi-step reaction with 2 steps 1: water; iso-butanol / 1 h / 50 °C 2: sodium hydroxide / dichloromethane; water / pH 9 View Scheme

S-(-)-amlodipine D-(-)-tartrate urea complex → amlodipine (103129-82-4)

Conditions	Yield
With sodium hydroxide In dichloromethane; water pH=9;	90%
With sodium hydroxide In dichloromethane; water pH=9;	90%

S(-) amlodipine-hemi-L-(+) tartarate monohydrate → amlodipine (103129-82-4)

Conditions	Yield
With ammonia; water In dichloromethane for 0.5h; Product distribution / selectivity;	82%

D-tartaric acid (147-71-7) + 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → (R)-amlodipine-D-hemitartrate dimethylformamide solvate + amlodipine (103129-82-4)

Conditions	Yield
In water at 20℃; for 4.5h; Product distribution / selectivity;	A 78.38% B n/a

(S)-(-)-amlodipine-hemi-L-tartrate → amlodipine (103129-82-4)

Conditions	Yield
With sodium hydrogencarbonate In dichloromethane; water at 5℃; for 0.333333h;	69%

(-)-2-<<2-<(tert-butoxycarbonyl)amino>ethoxy>-methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine (143191-87-1) → amlodipine (103129-82-4)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane; acetonitrile for 1h;	64%

2-<(2-azidoethoxy)methyl>-4(S)-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-1,4-dihydropyridine (125711-60-6) → amlodipine (103129-82-4)

Conditions	Yield
With hydrogen; Lindlar's catalyst In ethanol under 775.7 Torr; Yield given;
With sodium tetrahydroborate; nickel dichloride In ethanol Ambient temperature; Yield given;

(1R,3S)-camphoric acid salt of S-amlodipine → (R)-2-[(2-aminoethoxy)methyl]4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (103129-81-3) + amlodipine (103129-82-4)

Conditions	Yield
With sodium hydroxide; water In dichloromethane

S(-) amlodipine hemi D(-) tartarate → amlodipine (103129-82-4)

Conditions	Yield
With sodium hydroxide In tert-butyl methyl ether at 20 - 25℃; for 0.5h;

2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (103069-49-4) → amlodipine (103129-82-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) carbonyldiimidazole / 1.) CH2Cl2, reflux, 2.) THF, RT, 1 h 2: NaOEt / bis-(2-methoxy-ethyl) ether / 1 h / Heating 3: H2 / 5percent Pd/CaCO3 / ethanol / 775.7 Torr View Scheme
Multi-step reaction with 3 steps 1: 1.) carbonyldiimidazole 2: ethanol / 1 h / Heating 3: 6percent nickel chloride, sodium borohydride / ethanol / Ambient temperature View Scheme

(+)-2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-5-(methoxycarbonyl)-3-<(2(S)-methoxy-2-phenethoxy)carbonyl>-6-methyl-1,4-dihydropyridine (103094-34-4) → amlodipine (103129-82-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaOEt / bis-(2-methoxy-ethyl) ether / 1 h / Heating 2: H2 / 5percent Pd/CaCO3 / ethanol / 775.7 Torr View Scheme
Multi-step reaction with 2 steps 1: ethanol / 1 h / Heating 2: 6percent nickel chloride, sodium borohydride / ethanol / Ambient temperature View Scheme

2-cyanoethyl 4-(2-azidoethoxy)-3-oxobutanoate (103069-47-2) → amlodipine (103129-82-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 41 percent / ethanol / 2 h / Heating 2: 74 percent / aq. NaOH / bis-(2-methoxy-ethyl) ether / 2 h / Ambient temperature 3: 1.) carbonyldiimidazole / 1.) CH2Cl2, reflux, 2.) THF, RT, 1 h 4: NaOEt / bis-(2-methoxy-ethyl) ether / 1 h / Heating 5: H2 / 5percent Pd/CaCO3 / ethanol / 775.7 Torr View Scheme

2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-3-(2-cyanoethoxycarbonyl)-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (103069-48-3) → amlodipine (103129-82-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 74 percent / aq. NaOH / bis-(2-methoxy-ethyl) ether / 2 h / Ambient temperature 2: 1.) carbonyldiimidazole / 1.) CH2Cl2, reflux, 2.) THF, RT, 1 h 3: NaOEt / bis-(2-methoxy-ethyl) ether / 1 h / Heating 4: H2 / 5percent Pd/CaCO3 / ethanol / 775.7 Torr View Scheme

2-<<2-<(tert-butoxycarbonyl)amino>ethoxy>-methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine (143290-24-8) → amlodipine (103129-82-4)

Conditions	Yield
Multi-step reaction with 2 steps 2: 64 percent / 6.7 M HCl / acetonitrile; dioxane / 1 h View Scheme

(S)-amlodipine-hemi-D-tartrate → amlodipine (103129-82-4)

Conditions	Yield
With sodium hydroxide In tert-butyl methyl ether; water; isopropyl alcohol
With sodium hydroxide In tert-butyl methyl ether; water at 20 - 25℃; for 0.333333 - 0.5h;
With sodium hydroxide In n-heptane; tert-butyl methyl ether; water at 20 - 40℃; for 2.5 - 3.5h;

L-(+)-tartaric acid + 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9) → amlodipine (103129-82-4)

Conditions	Yield
Stage #1: L-(+)-tartaric acid; 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine With sodium hydroxide In water; butanone at 20℃; for 1h; Stage #2: With sodium hydroxide In dichloromethane; water for 0.5h;	n/a
Stage #1: L-(+)-tartaric acid; 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine With sodium hydroxide In dichloromethane; butanone at 20℃; for 1h; Stage #2: With sodium hydroxide In dichloromethane; water for 0.5h;	n/a
Stage #1: L-(+)-tartaric acid; 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine With sodium hydroxide In ethyl acetate; butanone at 20℃; for 1h; Stage #2: With sodium hydroxide In dichloromethane; water for 0.5h;	n/a
Stage #1: L-(+)-tartaric acid; 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine With sodium hydroxide In ethanol; butanone at 20℃; for 1h; Stage #2: With sodium hydroxide In dichloromethane; water for 0.5h;	n/a
Stage #1: L-(+)-tartaric acid; 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine With sodium hydroxide In acetone; butanone at 20℃; for 1h; Stage #2: With sodium hydroxide In dichloromethane; water for 0.5h;	n/a

(S)-(-)-amlodipine L-(+)-tartrate → amlodipine (103129-82-4)

Conditions	Yield
With sodium hydroxide In dichloromethane; water for 0.5h;	n/a

2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9) → (R)-2-[(2-aminoethoxy)methyl]4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (103129-81-3) + amlodipine (103129-82-4)

Conditions	Yield
With chiral stationary phase including isopropyl-functionalized CF6 In methanol; acetic acid; triethylamine; acetonitrile at 0℃; Purification / work up;
With isopropylamine; trifluoroacetic acid In methanol; isopropyl alcohol at 35℃; under 103432 Torr; Resolution of racemate; Supercritical conditions;
With acetic acid; triethylamine In methanol at 5℃; Reagent/catalyst; Concentration; Temperature; Resolution of racemate;
With L-glutamate based immobilized chiral ionic liquid on SBA-15 In methanol Resolution of racemate;

(R)-2-[(2-aminoethoxy)methyl]4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (103129-81-3) → amlodipine (103129-82-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: calcium hypochlorite / ethyl acetate; water / 20 - 30 °C 2: acetic acid; sodium cyanoborohydride / 2 h / 15 - 25 °C 3: D-tartaric acid / dimethyl sulfoxide; acetone / 1.5 h / 20 - 60 °C View Scheme

(S)-Malic acid (97-67-6) + amlodipine (103129-82-4) → (S)-(-)-amlodipine L-malate salt

Conditions	Yield
In tert-butyl methyl ether; water; isopropyl alcohol at 0 - 50℃; for 4.5 - 5h;	98.1%
In tert-butyl methyl ether; water; isopropyl alcohol at 50℃; for 1h; Product distribution / selectivity;	98.1%
In tert-butyl methyl ether; water; isopropyl alcohol at 0 - 50℃; for 4h; Product distribution / selectivity;	98.1%

amlodipine (103129-82-4) + L-Pyroglutamic acid (98-79-3) → (S)-(-)-amlodipine pidolate salt (851447-24-0)

Conditions	Yield
In ethanol at 20℃; for 1h;	97%

malonic acid (141-82-2) + amlodipine (103129-82-4) → (S)-(-)-amlodipine malonate salt (851447-25-1)

Conditions	Yield
In ethanol at 20℃; for 1h;	96%

2,2-dimethylglutaric acid (681-57-2) + amlodipine (103129-82-4) → (S)-(-)-amlodipin 2,2-dimethylglutarate salt

Conditions	Yield
In ethanol at 20℃; for 1h;	96%

succinic acid (110-15-6) + amlodipine (103129-82-4) → S(-) amlodipine succinate

Conditions	Yield
In ethanol; water	93%

amlodipine (103129-82-4) + maleic acid (110-16-7) → (-)-Amlodipine maleate (135969-53-8)

Conditions	Yield
In ethanol at 25℃; for 2h; Product distribution / selectivity;	91%
In water at 25℃; for 2h; Product distribution / selectivity;	89%
In ethanol; water	82.88%

Adipic acid (124-04-9) + amlodipine (103129-82-4) → S-(-)-amlodipine adipic acid salt

Conditions	Yield
In ethanol; isopropyl alcohol at 25℃; for 2h; Product distribution / selectivity;	91%
In ethanol; isopropyl alcohol at 25℃; for 2h; Product distribution / selectivity;	91%
In water for 5h; Product distribution / selectivity;	89%

oxalic acid (144-62-7) + amlodipine (103129-82-4) → S(-) amlodipine oxalate

Conditions	Yield
In ethanol; water	89.2%

amlodipine (103129-82-4) + benzenesulfonic acid (98-11-3) → (-)-Amlodipine besylate (150566-71-5)

Conditions	Yield
In water; isopropyl alcohol at 20℃; for 0.5h; Product distribution / selectivity;	89%
In ethanol; water at 0 - 20℃;	85%
In ethanol; water Product distribution / selectivity;	82.88%
In ethanol; water at 20℃; for 24h;	80.2%

(1S)-10-camphorsulfonic acid (3144-16-9) + amlodipine (103129-82-4) → (S)-amlodipine (1S)-(+)-10-camsylate hydrate

Conditions	Yield
With water In isopropyl alcohol at 20℃; for 1h;	88%

(1S)-10-camphorsulfonic acid (3144-16-9) + amlodipine (103129-82-4) → S-(-)-amlodipine (1S)-(+)-camphorsulfonate

Conditions	Yield
In water; isopropyl alcohol at 40℃; Product distribution / selectivity;	88%
In tert-butyl methyl ether; isopropyl alcohol at 25℃; for 2h; Product distribution / selectivity;	84%
In water at 25℃; for 2h; Product distribution / selectivity;	83%
In hexane; tert-butyl methyl ether; isopropyl alcohol at 20℃; for 2h;	81.5%

(1S)-10-camphorsulfonic acid (3144-16-9) + amlodipine (103129-82-4) → S-(-)-amlodipine (1S)-(+)-10-camphorsulfonate

Conditions	Yield
In water; isopropyl alcohol at 40℃;	88%

camphor-10-sulfonic acid (76-26-6, 3144-16-9, 5872-08-2, 35963-20-3) + amlodipine (103129-82-4) → (S)-amlodipine (+/-)-10-camsylate hydrate

Conditions	Yield
With water In isopropyl alcohol at 15 - 20℃; for 5h;	87.4%

orotic acid (65-86-1) + amlodipine (103129-82-4) → S-(-)-amlodipine orotate (1040924-28-4)

Conditions	Yield
In methanol at 25℃; for 2h; Product distribution / selectivity;	85%
In water at 20 - 25℃; for 2h; Product distribution / selectivity;	85%

(R)-10-camphorsulfonic acid (35963-20-3) + amlodipine (103129-82-4) → S-(-)-amlopidine (1R)-(-)-10-camsylate

Conditions	Yield
In tert-butyl methyl ether; isopropyl alcohol at 25℃; for 2h; Product distribution / selectivity;	84%
In water at 25℃; for 2h; Product distribution / selectivity;	83%
In water; isopropyl alcohol at 15 - 20℃;	62.3%

2-methylglutaric acid (18069-17-5) + amlodipine (103129-82-4) → (S)-(-)-amlodipine hemi-2-methylglutarate salt

Conditions	Yield
In ethanol at 20℃; for 1h;	84%

toluene-4-sulfonic acid (104-15-4) + amlodipine (103129-82-4) → S(-) amlodipine tosylate

Conditions	Yield
In ethanol; water	82.88%

nicotinic acid (59-67-6) + amlodipine (103129-82-4) → (S)-(-)-amlodipine nicotinate (675605-61-5)

Conditions	Yield
In Petroleum ether for 5h; Heating / reflux;	79.3%

atorvastatin lactone (125995-03-1) + amlodipine (103129-82-4) → (S)-3-ethyl-5-methyl-2-{[2-({7-[(3-anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoyl}amino)ethoxy]methyl}-4-(2-chlorophenyl)-6-methyl-1,4-dihydro-3,5-pyridinedicarboxylate

Conditions	Yield
In ethanol for 18h; Heating / reflux;	64%

(1S)-(-)-camphanic chloride (39637-74-6) + amlodipine (103129-82-4) → (-)-2-<<2-(camphanoylamino)ethoxy>methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine (143191-86-0)

Conditions	Yield
With pyridine In dichloromethane for 2h; Ambient temperature; Yields of byproduct given;

Upstream product

• 103129-81-3 (R)-2-[(2-aminoethoxy)methyl]4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester 
• 88150-42-9 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 147-71-7 D-tartaric acid 
• 68-12-2 N,N-dimethyl-formamide 
• 138508-61-9 L-(+)-tartaric acid 
• 143290-24-8 2-<<2-<(tert-butoxycarbonyl)amino>ethoxy>-methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine 
• 103069-48-3 2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-3-(2-cyanoethoxycarbonyl)-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 103069-47-2 2-cyanoethyl 4-(2-azidoethoxy)-3-oxobutanoate 
• 103094-34-4 (+)-2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-5-(methoxycarbonyl)-3-<(2(S)-methoxy-2-phenethoxy)carbonyl>-6-methyl-1,4-dihydropyridine 
• 103069-49-4 2-<(2-azidoethoxy)methyl>-4-(2-chlorophenyl)-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 143191-87-1 (-)-2-<<2-<(tert-butoxycarbonyl)amino>ethoxy>-methyl>-4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydropyridine 
• 125711-60-6 2-<(2-azidoethoxy)methyl>-4(S)-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-1,4-dihydropyridine 

Downstream Products

• 675605-61-5 (S)-(-)-amlodipine nicotinate 
• 150566-71-5 (-)-Amlodipine besylate 
• 1040924-28-4 S-(-)-amlodipine orotate 
• 1357024-06-6 0.5C₄H₄O₄*C₂₀H₂₅ClN₂O₅*(x)H₂O 
• 113994-41-5 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester 
• 1029898-78-9 ramipril-amlodipine salt 
• 851447-24-0 (S)-(-)-amlodipine pidolate salt 
• 851447-25-1 (S)-(-)-amlodipine malonate salt 
• 135969-53-8 (-)-Amlodipine maleate 

Relevant articles and documents

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.

Method for preparing levamlodipine

The invention provides a method for preparing levamlodipine and belongs to the technical field of medicine synthesis. The method provided by the invention comprises the following steps: concentratingamlodipine resolution mother liquor to be dry, then mixing with an oxidizing agent and a first solvent, and carrying out an oxidation reaction to obtain 2-((2-aminoethoxy)methyl)-4-(2-chlorphenyl)-6-methyl-3,5-pyridine ethyl methyl diformate, wherein the oxidizing agent is an achiral reagent; mixing the 2-((2-aminoethoxy)methyl)-4-(2-chlorphenyl)-6-methyl-3,5-pyridine ethyl methyl diformate, a reducing agent and a second solvent, and carrying out a reduction reaction to obtain an amlodipine racemate; and mixing the amlodipine racemate, a resolution reagent and a third solvent, and carrying outresolution treatment to obtain levamlodipine. According to the method provided by the invention, the amlodipine in the amlodipine resolution mother liquor can be effectively recycled and converted into high-value levamlodipine.

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.