Amiodarone hydrochloride

Base Information

• Chemical Name: Amiodarone hydrochloride
• CAS No.: 19774-82-4
• Molecular Formula: C25H30ClI2NO3
• Molecular Weight: 681.78
• Hs Code.: 29322090
• Mol file: 19774-82-4.mol

Synonyms:Ketone,2-butyl-3-benzofuranyl 4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl,hydrochloride (7CI,8CI);Methanone,(2-butyl-3-benzofuranyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]-,hydrochloride (9CI);2-Butyl-3-benzofuranyl4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl ketone hydrochloride;Amiodar;Amiodaronehydrochloride;Ancoron;Angiodarona;Cordarex;Cordarone;L 3428;Miocard;Ortacrone;Ritmocardyl;Trangorex;

Chemical Property of Amiodarone hydrochloride

Chemical Property:

• Appearance/Colour: white to cream crystalline powder
• Melting Point: 154-158°C
• Boiling Point: 635.1 °C at 760 mmHg
• PKA: pKa (25°C) 6.56 ±0.06
• Flash Point: 337.9 °C
• PSA: 42.68000
• Density: 1.58 g/cm3
• LogP: 7.73820
• Storage Temp.: 2-8°C
• Solubility.: Soluble in chloroform, methanol.
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 11
• Exact Mass: 681.00037
• Heavy Atom Count: 32
• Complexity: 547

Purity/Quality:

99% ^*data from raw suppliers

Amiodarone hydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn,T,F
• Statements: 20/21/22-39/23/24/25-23/24/25-11
• Safety Statements: 36-45-36/37-16-7

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: [H+].CCCCC1=C(C2=CC=CC=C2O1)C(=O)C3=CC(=C(C(=C3)I)OCCN(CC)CC)I.[Cl-]
• Description: Amiodarone HCl (19774-82-4) is a nonselective ion channel blocker. Class III antiarrhythmic.1 Induces cytochrome c release and induces apoptosis.2 An alkalizing agent which stimulates progranulin (GRN) production and prevents GRN-dependent neurodegeneration.3 Induces autophagy and suppresses hepatocellular carcinoma tumorigenesis via autophagy-mediated MIR224 degradation in vitro and in vivo.4
• Uses: Amiodarone induces an immediate influx of Ca2+ in Saccharomyces cerevisiae, followed by mitochondrial fragmentation and cell death. Antiarrhythmic;Na+ channel blocker A non-selective ion channel blocker. Antiarrhythmic (class III) Amiodarone hydrochloride is a non-selective ion channel blocker with broad fungicidal activity. Amiodarone induces an immediate influx of Ca2+ in Saccharomyces cerevisiae, followed by mitochondrial fragmentation and cell death. Amiodarone hydrochloride has also been used in a study to determine concentrations of thyroid disrupting substances in effluents from wastewater treatment plants.
• Therapeutic Function: Coronary vasodilator
• Clinical Use: Cardiac arrhythmias
• Drug interactions: Potentially hazardous interactions with other drugs Anti-arrhythmics: additive effect and increased risk of myocardial depression; increased risk of ventricular arrhythmias with disopyramide or dronedarone - avoid; increased flecainide concentration - halve flecainide dose; increased procainamide concentration - avoid. Antibacterials: increased risk of ventricular arrhythmias with parenteral erythromycin, cotrimoxazole levofloxacin and moxifloxacin - avoid; increased risk of ventricular arrhythmias with delamanid; avoid with fidaxomicin; possibly increased risk of ventricular arrhythmias with telithromycin. Anticoagulants: metabolism inhibited (increased anti-coagulant effect); increased dabigatran concentration (reduce dabigatran dose). Antidepressants: increased risk of ventricular arrhythmias with citalopram and escitalopram, tricyclic antidepressants and venlafaxine - avoid. Antiepileptics: phenytoin and fosphenytoin metabolism inhibited (increased concentration). Antifungals: avoid with fluconazole due to risk of QT prolongation. Antihistamines: increased risk of ventricular arrhythmias with mizolastine - avoid. Antimalarials: increased risk of ventricular arrhythmias with chloroquine, hydroxychloroquine, mefloquine and quinine and possibly with piperaquine with artenimol and artemether/ lumefantrine - avoid. Antimuscarinics: increased risk of ventricular arrhythmias with tolterodine. Antipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval; increased risk of ventricular arrhythmias with amisulpride, benperidol, droperidol, haloperidol, phenothiazines, pimozide or zuclopenthixol - avoid; increased risk of ventricular arrhythmias with sulpiride. Antivirals: increased risk of ventricular arrhythmias with fosamprenavir ritonavir, saquinavir and telaprevir - avoid; concentration possibly increased by atazanavir; possible increased risk of bradycardia with daclatasvir, ledipasvir, sofosbuvir and simeprevir; avoid with indinavir, reduce the dose of the others. Atomoxetine: increased risk of ventricular arrhythmias. Beta-blockers, diltiazem, and verapamil: increased risk of bradycardia, AV block and myocardial depression; increased risk of ventricular arrhythmias with sotalol - avoid. Ciclosporin: increased levels of ciclosporin possible. Cobicistat: concentration possibly increased by cobicistat - avoid. Colchicine: possibly increased colchicine toxicity. Cytotoxics: possibly increased afatinib concentration (separate administration by 6-12 hours); possibly increased risk of ventricular arrhythmias with panobinostat and vandetanib - avoid; concentration of ibrutinib possibly increased - reduce dose of ibrutinib; avoid with idelalisib; increased risk of ventricular arrhythmias with arsenic trioxide, bosutinib and ceritinib. Digoxin: increased concentration (halve digoxin maintenance dose). Fingolimod: possible increased risk of bradycardia. Grapefruit juice: may increase concentration of amiodarone - avoid. Ivabradine: increased risk of ventricular arrhythmias - avoid. Lipid-lowering drugs: give lomitapide 12 hours after amiodarone; increased risk of myopathy with simvastatin - do not exceed 20 mg of simvastatin.1 Lithium: increased risk of ventricular arrhythmias - avoid. Pentamidine: increased risk of ventricular arrhythmias - avoid.

Technology Process of Amiodarone hydrochloride

There total 16 articles about Amiodarone hydrochloride which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 88.6%

2-butyl-3-[3,5-diiodo-4-(2-chloroethoxy)benzoyl]benzofuran + diethylamine (109-89-7) → amiodarone hydrochloride (19774-82-4)

Guidance literature:

2-butyl-3-[3,5-diiodo-4-(2-chloroethoxy)benzoyl]benzofuran; diethylamine; In methanol; toluene; at 75 ℃; for 7h;

With hydrogenchloride; In water; toluene; at 40 - 75 ℃;

Reference yield: 88.0%

2-chloro-N,N-diethylethylamine hydrochloride (869-24-9) + 2-n-butyl-3-(3',5'-diiodo-4'-hydroxybenzoyl)benzofuran (1951-26-4) → amiodarone hydrochloride (19774-82-4)

Guidance literature:

With potassium carbonate; In water; toluene; for 10h; Solvent; Reagent/catalyst; Reflux;

Reference yield:

2-n-butylbenzo[b]furan (4265-27-4) → amiodarone hydrochloride (19774-82-4)

Guidance literature:

Multi-step reaction with 3 steps

1.1: aluminum (III) chloride / dichloromethane / 10 h / -20 - -15 °C / Reflux

2.1: potassium carbonate; iodine / methanol; water / 40 - 65 °C

2.2: 2 h / 20 - 30 °C / pH 1 - 2

3.1: potassium carbonate / toluene; water / 4 h

With aluminum (III) chloride; iodine; potassium carbonate; In methanol; dichloromethane; water; toluene;

upstream raw materials:

2-chloro-N,N-diethylethylamine hydrochloride

2-n-butyl-3-(3',5'-diiodo-4'-hydroxybenzoyl)benzofuran

2-n-butylbenzo[b]furan

methyl 2-(2-formylphenoxy)hexanoate

Downstream raw materials:

4-Hydroxyamiodarone

(+/-)-{4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl}[2-(3-hydroxybutyl)benzofuran-3-yl]methanone hydrochloride

Refernces

• 1、 -. "Preparation method of amiodarone hydrochloride". Paragraph 0017. . Retrieved 2019/08/12.
• 2、 -. "Amiodarone hydrochloride preparation method". Paragraph 0098-0100. . Retrieved 2018/03/13.