113994-41-5

Basic information

• Product Name: Dehydro Amlodipine (Amlodipine Impurity D)
• Synonyms: 2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylic Acid 3-Ethyl 5-Methyl Ester;3-Ethyl 5-Methyl Ester 2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methylpyridine-3,5-dicarboxylate;Amlodipine Impurity D;Dehydro Amlodipine (Amlodipine Impurity D);2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylic Acid 3-Ethyl 5-Methyl Ester Oxalate;Dehydro Amlodipine Oxalate;3-Ethyl, 5-Methyl [2-(2-aMinoethoxyMethyl)-4-(2-chlorophenyl)-6-Methyl-3,5-pyridinedicarboxylate] fuMarate;AMlodipine USP Related CoMpound A
• CAS NO: 113994-41-5
• Molecular Formula: C₂₀H₂₃ClN₂O₅
• Molecular Weight: 406.86002
• Product Categories: Chemical Impurities;Impurities;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 113994-41-5.mol
• Article Data: 13

Chemical Properties

• Melting Point: 106-108°C
• Boiling Point: 517.9±50.0 °C(Predicted)
• Appearance: /
• Density: 1.241±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 8.42±0.10(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: Dehydro Amlodipine (Amlodipine Impurity D)(CAS DataBase Reference)
• NIST Chemistry Reference: Dehydro Amlodipine (Amlodipine Impurity D)(113994-41-5)
• EPA Substance Registry System: Dehydro Amlodipine (Amlodipine Impurity D)(113994-41-5)

Safety Data

• Hazardous Substances Data: 113994-41-5(Hazardous Substances Data)

Usage

Chemical Properties

White to Off-White Solid

Uses

Different sources of media describe the Uses of 113994-41-5 differently. You can refer to the following data:
1. Amlodipine impurity D
2. Dehydro Amlodipine is an Amlodipine (A633495) impurity.
3. Dehydro Amlodipine (Amlodipine Besylate EP Impurity D) is an Amlodipine (A633495) impurity.

Synthetic route

2-[2-(phthalimido)ethoxymethyl]-3-ethoxycarbonyl-4-(o-chlorophenyl)-5-methoxycarbonyl-6-methylpyridine → 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5)

Conditions	Yield
With hydrazine hydrate In ethanol at 20℃; for 20h;	98%
With hydrazine In methanol; toluene at 20℃; for 4h;	61%

(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) → 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5)

Conditions	Yield
With calcium hypochlorite In water; ethyl acetate at 20 - 30℃; Reagent/catalyst; Temperature; Solvent;	93.4%

2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9) → 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5)

Conditions	Yield
Stage #1: 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine With hydrogenchloride In water Stage #2: With nickel In water at 20℃; for 6h;	73.2%
With potassium permanganate In 1,4-dioxane; water for 16h; Ambient temperature;
With potassium superoxide In dimethyl sulfoxide at 37℃; for 5h; Kinetics;

2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9) + C4H9N2O2*ClH → 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5)

Conditions	Yield
With Britton-Robinson buffer In water; N,N-dimethyl-formamide at 37℃; pH=7.4; Kinetics;

4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-[2-phthalimidoethoxymethyl]-1,4-dihydropyridine (88150-62-3) → 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 97 percent / Pb(OAc)4 / CH2Cl2; acetic acid / 19 h / 20 °C 2: 98 percent / hydrazine monohydrate / aq. ethanol / 20 h / 20 °C View Scheme

amlodipine (103129-82-4) → 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5)

Conditions	Yield
With human P450 enzyme CYP3A4; NADPH In aq. phosphate buffer for 0.216667h; pH=7.4; Enzymatic reaction;

2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9) → 4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-2-(carboxymethoxy)methyl-6-methylpyridine + 4-(2-chlorophenyl)-5-carboxy-2-(carboxymethoxy)methyl-3-ethoxycarbonyl-6-methylpyridine + 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5)

Conditions	Yield
With sodium hypochlorite; octabromotetrakis(2,6-dichlorophenyl)porphyrin Fe(III)Cl; water In acetonitrile at 80℃; for 0.166667h; Microwave irradiation;

2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9) → C16H13NO4 + C17H16N2O5 + C20H22N2O5 + C19H20N2O5 + C18H19NO5 + C19H18N2O4 + C18H18N2O5 + C17H15NO4 + 4-(2-Chloro-phenyl)-2,6-dimethyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (130161-00-1) + 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5)

Conditions	Yield
In water at 10℃; Irradiation;

...Expand

2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5) + L-Pyroglutamic acid (98-79-3) → amlodipine (S)-(-)-pyroglutamate

Conditions	Yield
In ethyl acetate at 25℃; for 1h;	95.3%
In ethyl acetate at 25℃; for 1h;	95.3%

2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5) + Pyroglutamic acid (149-87-1) → amlodipine pyroglutamate (racemate)

Conditions	Yield
	95.2%

2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5) + D-pyrrolidone-5-carboxylic acid (4042-36-8) → amlodipine (R)-(+)-pyroglutamate

Conditions	Yield
	95.1%

2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5) → 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-42-9)

Conditions	Yield
With sodium cyanoborohydride; acetic acid at 15 - 25℃; for 2h; Reagent/catalyst; Temperature;	93.1%

(2E)-but-2-enedioic acid (110-17-8) + 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5) → 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester; compound with (E)-but-2-enedioic acid

Conditions	Yield
In ethanol Heating;	8.4 g

toluene-4-sulfonic acid (104-15-4) + 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5) → amlodipine para-toluenesulfonate

Conditions	Yield
In methanol at 23℃; for 3h;

2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (113994-41-5) → amlodipine hydrochloride

Conditions	Yield
With hydrogenchloride In methanol at 23℃; for 3h;

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 
• 103129-82-4 amlodipine 
• 88150-62-3 4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-[2-phthalimidoethoxymethyl]-1,4-dihydropyridine 

Downstream Products

• 88150-42-9 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 2138811-33-1 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester; compound with (E)-but-2-enedioic acid 

Relevant articles and documents

A simple sonochemical assisted synthesis of NiMoO4/chitosan nanocomposite for electrochemical sensing of amlodipine in pharmaceutical and serum samples

In this investigation, a facile sonochemical route has been developed for the preparation of porous nickel molybdate nanosheets/chitosan nanocomposite (NiMoO4/CHIT) by using ammonium molybdate and nickel(II) acetate tetrahydrate and as nickel and molybdate precursor, respectively (ultrasonic power 60 W/cm2 and frequency 20 kHz). The ultrasonic based materials preparation as a fast, convenient and economical approach has been widely used to generate novel nanomaterials. Herein, we report an efficient voltammetric sensor for amlodipine drug by using porous nickel molybdate nanosheets/chitosan nanocomposite (NiMoO4/CHIT). Its structure and properties were characterized by x-ray diffraction pattern, scanning electron microscope, transmission electron microscope, elemental analysis and mapping. The electrochemical studies are indicated the NiMoO4/CHIT modified glassy carbon electrode (GCE) exhibited the good performance towards electrocatalytic sensing of amlodipine drug. Consequently, a linear correlation between the anodic peak current with sensor concentration 0.025–373.6 μM with a detection limit and sensitivity of 4.62 nM and 4.753 μA·μM?1·cm?2, respectively. A voltammetry based drug analysis was found to be high sensitive and reproducible, which able to detect nanomolar concentration. Furthermore, the fabricated electrochemical sensor was applied in drug and biological samples.

Measurement of Intracellular Nitric Oxide with a Quantitative Mass Spectrometry Probe Approach

Nitric oxide (NO) is a molecule of physiological importance, and the function of NO depends on its concentration in biological systems, particularly in cells. Concentration-based analysis of intracellular NO can provide insight into its precise role in health and disease. However, current methods for detecting intracellular NO are still inadequate for quantitative analysis. In this study, we report a quantitative mass spectrometry probe approach to measure NO levels in cells. The probe, Amlodipine (AML), comprises a Hantzsch ester group that reacts with NO to form a pyridine, Dehydro Amlodipine (DAM). Quantification of DAM by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) allows specific measurement of intracellular NO levels. Notably, the AML/NO reaction proceeds rapidly (within 1 s), which is favorable for NO detection considering its large diffusivity and short half-life. Meanwhile, studies under simulated physiological conditions revealed that the AML response to NO is proportional and selective. The presented UPLC-MS/MS method showed high sensitivity (LLOQ = 0.24 nM) and low matrix interference (less than 15%) in DAM quantification. Furthermore, the mass spectrometry probe approach was demonstrated by enabling the measurement of endogenous and exogenous NO in cells. Hence, the quantitative UPLC-MS/MS method developed using AML as a probe is expected to be a new method for intracellular NO analysis.

Dihydropyridine compound dehydrogenation aromatization method and in use in the drug detection (by machine translation)

Relates to dihydropyridine compound dehydrogenation aromatization method and in use in the drug detection, compounds such as nifedipine, amlodipine, Cini horizontal, Lacidipine, felodipine, NIKA of amlodipine, nitrendipine, nimodipine and BANI to equal, the method in acidic aqueous solution in the presence of a nickel-containing catalyst in the oxidation reaction of the then purified to realize. The method can be used for preparing this kind of drug detection and quality monitoring of the impurity reference substance, also can be used for quality detection process is used in the instrument of the instrument such as the dissolution of the design reference, drug synthesis process and the design of the manufacturing process of the preparation of the reference, in order to avoid impurities introduced by the process channels, in addition can also be dihydropyridine compound of related synthetic process route provides design provides a reference. The reaction can be in the acidic aqueous solution, to a suitable oxidant (such as air) as the oxidizing agent, in the presence of nickel, at normal temperature to carry out dehydrogenation aromatization reaction, mild reaction conditions, the target compound of high conversion rate, the operation is simple, by-product little small pollution to the environment, is a completely environment-friendly preparation process. (by machine translation)