[4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]-[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride

Base Information

• Chemical Name: [4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]-[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride
• CAS No.: 23313-68-0
• Molecular Formula: C27H39ClN2O4
• Molecular Weight: 491.071
• Hs Code.: 2926909090
• Mol file: 23313-68-0.mol

Synonyms:EINECS 245-579-2;(1)-(3-Cyano-3-(3,4-dimethoxyphenyl)hex-6-yl)(5,6-dimethoxyphenethyl)methylammonium chloride;[4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]-[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride;2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile;hydron;AKOS000280876;AKOS025116941;MCULE-4314350683

Chemical Property of [4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]-[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride

Chemical Property:

• Appearance/Colour: white to off-white powder
• Vapor Pressure: 1.01E-13mmHg at 25°C
• Melting Point: 142 °C (dec.)(lit.)
• Boiling Point: 586.1 °C at 760 mmHg
• Flash Point: 308.3 °C
• PSA: 63.95000
• LogP: 5.89508
• Storage Temp.: 0-6°C
• Solubility.: methanol: 50 mg/mL, clear, colorless
• Water Solubility.: soluble
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 13
• Exact Mass: 490.2598354
• Heavy Atom Count: 34
• Complexity: 606

Purity/Quality:

99%, ^*data from raw suppliers

Verapamil hydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,Xi
• Hazard Codes: T,Xi
• Statements: 23/24/25-36/37/38
• Safety Statements: 36/37-45-37/39-26

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)C(CCC[NH+](C)CCC1=CC(=C(C=C1)OC)OC)(C#N)C2=CC(=C(C=C2)OC)OC.[Cl-]
• Description: Verapamil hydrochloride (VRP) is a phenylalkylamine calcium ion influx inhibitor (calcium antagonist). Verapamil hydrochloride exerts its pharmacologic effects by modulating the influx of ionic through the slow channels of vascular smooth muscle and cardiac cell membranes. It is widely used for the treatment of hypertension, angina pectoris, supraventricular tachycardia, myocardial infraction, and vascular headaches. Verapamil has also been used in cell biology as an inhibitor of drug efflux pump proteins such as P-glycoprotein, which are often over-expressed in certain tumor cell lines The plasma half-life of verapamil hydrochloride is 2–7 hours, which necessitates multiple dosing. After oral administration of VRP to humans, the drug is rapidly absorbed and widely distributed. It is approximately 90% absorbed from the gastrointestinal tract but is subject to considerable first pass metabolism and its bioavailability is around 20–30%. The low bioavailability is owing to the rapid biotransformation in the liver with a biological half-life of 4.0±1.5 hours.
• Uses: A calcium channel blocker. Antihypertensive; antianginal; antiarrhythmic (class IV) Calcium antagonists
• Clinical Use: Calcium-channel blocker: Supraventricular arrhythmias Angina Hypertension Cluster headaches (unlicensed)
• Drug interactions: Potentially hazardous interactions with other drugs Aminophylline and theophylline: enhanced effect of aminophylline and theophylline. Anaesthetics: increased hypotensive effect. Anti-arrhythmics: increased risk of amiodaroneinduced bradycardia, AV block and myocardial depression; increased risk of myocardial depression and asystole with disopyramide and flecainide; increased risk of bradycardia and myocardial depression with dronedarone. Antibacterials: metabolism increased by rifampicin; metabolism possibly inhibited by erythromycin, clarithromycin and telithromycin (increased risk of toxicity). Anticoagulants: possibly increases dabigatran concentration - reduce dabigatran dose. Antidepressants: enhanced hypotensive effect with MAOIs; concentration of imipramine and possibly other trycyclics increased; concentration significantly reduced by St John’s wort. Antiepileptics: effect probably reduced by barbiturates, phenytoin and primidone; enhanced effect of carbamazepine. Antifungals: negative inotropic effect possibly increased with itraconazole. Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of postsynaptic alpha-blockers. Antipsychotics: possibly increases concentration of lurasidone. Antivirals: concentration possibly increased by atazanavir and ritonavir; use telaprevir with caution. Avanafil: concentration of avanafil increased. Beta-blockers: enhanced hypotensive effect; risk of asystole, severe hypotension and heart failure if coprescribed with beta-blockers. Cardiac glycosides: increased levels of digoxin. Increased AV block and bradycardia. Ciclosporin: variable reports of decreased nephrotoxicity and potentiated effect; may also increase ciclosporin levels. Colchicine: possibly increased risk of colchicine toxicity - suspend or reduce colchicine, avoid concomitant use in renal or hepatic failure. Cytotoxics: possibly increased bosutinib, doxorubicin, ibrutinib concentration - reduce dose of bosutinib and ibrutinib; possibly increased risk of bradycardia with crizotinib; concentration of both drugs may be increased in combination with everolimus - consider reducing everolimus dose; concentration of olaparib possibly increased - avoid or reduce olaparib dose. Fingolimod: increased risk of bradycardia. Grapefruit juice: concentration increased - avoid concomitant use. Ivabradine: concentration of ivabradine increased - avoid concomitant use. Lenalidomide: possibly increases lenalidomide concentration. Lipid-lowering agents: increased myopathy with atorvastatin and simvastatin - reduce dose of atorvastatin, do not exceed 20 mg of simvastatin1 , concentration of verapamil increased by atorvastatin; concentration of lomitapide increased - avoid. Sirolimus: concentration of both drugs increased. Tacrolimus: may increase tacrolimus levels.

Technology Process of [4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]-[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride

There total 7 articles about [4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl]-[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride 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: 84.6%

2-(3,4-dimethoxyphenyl)-3-methylbutyronitrile (20850-49-1) + 1-chloro-3-propane oxalate (85226-25-1) → verapamil hydrochloride (23313-68-0,152-11-4)

Guidance literature:

1-chloro-3-propane oxalate; With sodium hydroxide; In water; toluene; at 20 - 25 ℃; pH=13 - 14;

2-(3,4-dimethoxyphenyl)-3-methylbutyronitrile; With sodium amide; In toluene; at 20 - 110 ℃; Inert atmosphere;

With hydrogenchloride; In methanol; water; ethyl acetate; toluene; at 20 - 30 ℃; for 4h;

Reference yield: 67.7%

N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine (36770-74-8) → verapamil hydrochloride (23313-68-0,152-11-4)

Guidance literature:

N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine; 2-(3,4-dimethoxyphenyl)-3-methylbutyronitrile; With sodium amide; In toluene; at 20 - 110 ℃; Inert atmosphere;

With hydrogenchloride; In water; at 20 - 25 ℃; pH=1;

Reference yield:

2-(3,4-dimethoxyphenyl)-2-(3-oxopropyl)-2-isopropylacetonitrile (27339-25-9) + <2-(3,4-dimethoxyphenyl)ethyl>methylamine hydrochloride (13078-76-7) → verapamil hydrochloride (23313-68-0,152-11-4)

Guidance literature:

2-(3,4-dimethoxyphenyl)-2-(3-oxopropyl)-2-isopropylacetonitrile; <2-(3,4-dimethoxyphenyl)ethyl>methylamine hydrochloride; With hydrogen; palladium 10% on activated carbon; In ethanol; at 40 - 45 ℃;

With sodium hydroxide; In water;

With hydrogenchloride; In isopropyl alcohol;

upstream raw materials:

N-methylhomoveratrylamine

2-(3,4-dimethoxyphenyl)-2-(3-oxopropyl)-2-isopropylacetonitrile

<2-(3,4-dimethoxyphenyl)ethyl>methylamine hydrochloride

Verapamil

Downstream raw materials:

(+/-)-5-<(3,4-dimethoxyphenethyl)methylamino>-2-(3,4-dimethoxyphenyl)-2-isopropylpentyl isothiocyanate

(+/-)-5-<(3,4-dimethoxyphenethyl)methylamino>-2-(3,4-dimethoxyphenyl)-2-isopropylpentylamine

Refernces

• 1、 -. "A PROCESS FOR THE PREPARATION OF VERAPAMIL HYDROCHLORIDE". . . Retrieved 2016/12/01.
• 2、 -. "Compound and process". . . Retrieved 2008/06/13.