Entacapone

Base Information

• Chemical Name: Entacapone
• CAS No.: 130929-57-6
• Molecular Formula: C14H15N3O5
• Molecular Weight: 305.29
• Hs Code.: 2926900005
• Mol file: 130929-57-6.mol

Synonyms:Entacom;OR 611;2-Propenamide,2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-, (E)-;(E)-Entacapone;Comtan;

Chemical Property of Entacapone

Chemical Property:

• Appearance/Colour: Yellow crystalline solid
• Vapor Pressure: 1.05E-11mmHg at 25°C
• Melting Point: 162-163 °C
• Refractive Index: 1.641
• Boiling Point: 526.6 °C at 760 mmHg
• PKA: pKa ~4.5(at 25℃)
• Flash Point: 272.3 °C
• PSA: 130.38000
• Density: 1.392 g/cm³
• LogP: 2.30458
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: soluble20mg/mL, clear

Purity/Quality:

99% ^*data from raw suppliers

Entacapone ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,T,F
• Hazard Codes: Xn,T,F

MSDS Files:

SDS file from LookChem

Useful:

• Uses: As COMT inhibitors, it is used to treat Parkinson's disease. (E)-Isomer of Entacapone polymorphic form A. Peripherally acting inhibitor of catechol-O-methyl transferase (COMT), an enzyme involved in the metabolism of catecholamine neurotransmitters and related drugs. Antiparkinsonian antiparkinsinian;catechol-O-methyl transferase inhibitor This compound belongs to the cinnamic acid amides. These are amides of cinnamic acids. Used as an adjunct to levodopa / carbidopa in the symptomatic treatment of patients with idiopathic Parkinson's Disease who experience the signs and symptoms of end-of-
• Production method: 1.83 g 3,4-dihydroxy-5-nitrobenzaldehyde and 1.5g N, N-diethyl-cyanoacetamide and a catalytic amount of piperidine acetate are dissolved in 40ml of dry ethanol , followed by stirring overnight , 2.23 g crude product is obtained, yield 73%, melting point 153~156 ℃. Heated at 90 ℃, the 3.0 kg crude product is dissolved in 8.0kg acetic acid (or formic acid) containing 80 g HBr (or 40gHCl).It is slowly cooled to 20 ℃, and stirred at this temperature for 20h, then at 15 ℃ stirred for 6h. The precipitated crystals were collected by filtration, carefully washed with cool (4 ℃) 1L toluene-acetic acid (1: l v/v) mixed solution, and washed with 1L cold toluene. It is dried at 45 ℃under vacuum and 2.4kg crystalline pure Entacapone is obtained, yield 80%, melting point 162-163 ℃.
• Description: Entacapone was introduced in Finland, Germany and Sweden as an adjunctive treatment with L-dopa in Parkinson’s disease. Entacapone is the second drug in its class to reach the market; it can be obtained by basecatalyzed condensation of the corresponding benzaldehyde with a cyanoacetamide. Entacapone is a highly selective and orally-active catechol-0- methyltransferase (COMT) inhibitor ; by inhibiting metabolism of L-dopa when given as an adjuvant in patients with Parkinson’s disease, Entacapone markedly prolongs the effects of L-dopa and improves its bioavailability. Results from clinical studies showed that 200mglday Entacapone coadministered with L-dopa lowered the dose of the latter required to reduce fluctuations in motor performance.
• Therapeutic Function: Antiparkinsonian
• Clinical Use: #N/A
• Drug interactions: Potentially hazardous interactions with other drugs Anticoagulants: enhances anticoagulant effect of warfarinAntidepressants: use with caution in combination with moclobemide, tricyclics and venlafaxine; avoid with MAOIs. Dopaminergics: possibly enhances effects of apomorphine; possibly reduces concentration of rasagiline; max dose of selegiline is 10 mg in combination.

Technology Process of Entacapone

There total 34 articles about Entacapone 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: 100.0%

(E)-2-cyano-N,N-diethyl-3-(3-pivaloyloxy-4-hydroxy-5-nitrophenyl)propenamide (345317-61-5) → entacapone (130929-57-6)

Guidance literature:

With phosphate buffer; at 37 ℃; pH=7.4; Kinetics;

DOI:10.1211/0022357011778025

Reference yield: 100.0%

(E)-2-cyano-N,N-diethyl-3-[3-t-butyloxycarbonyloxy-4-hydroxy-5-nitrophenyl]propenamide (404860-98-6) → entacapone (130929-57-6)

Guidance literature:

With phosphate buffer; at 37 ℃; pH=7.4; Kinetics;

DOI:10.1211/0022357011778025

Reference yield: 98.0%

(2E)-2-cyano-3-(3-methoxy-4-hydroxy-5-nitro-phenyl)-N,Ndiethylprop-2-enamide (857629-78-8) → entacapone (130929-57-6)

Guidance literature:

(2E)-2-cyano-3-(3-methoxy-4-hydroxy-5-nitro-phenyl)-N,Ndiethylprop-2-enamide; With aluminum (III) chloride; triethylamine; In dichloromethane; at 0 - 5 ℃; for 3 - 4h; Heating / reflux;

With hydrogenchloride; In dichloromethane; at 0 - 20 ℃; for 0.5h;

upstream raw materials:

(E)-2-cyano-N,N-diethyl-3-(3-pivaloyloxy-4-hydroxy-5-nitrophenyl)propenamide

(E)-2-cyano-N,N-diethyl-3-[3-t-butyloxycarbonyloxy-4-hydroxy-5-nitrophenyl]propenamide

(E)-2-cyano-N,N-diethyl-3-[3,4-bis(pivaloyloxymethoxy)-5-nitrophenyl]propenamide

(2Z)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide

Downstream raw materials:

entacapone; piperidine salt

entacapone; sodium salt

Refernces

• 1、 -. "Method for producing entacapone". Paragraph 0059-0073. . Retrieved 2021/04/10.
• 2、 Harisha, Attimogae Shivamurthy,Nayak, Suresh Parameshwar,Nagarajan, Kuppuswamy,Guru Row, Tayur Narasingarow,Hosamani, Amar A.. "Novel triethylamine mediated thermal reactions of 3-aryl-2-cyanoprop-2-enoic acid derivatives - Demethylation, reduction and vinylogation". supporting information. p. 1427 - 1431. Retrieved 2015/03/04.