Terbinafine

Base Information

• Chemical Name: Terbinafine
• CAS No.: 91161-71-6
• Molecular Formula: C21H25N
• Molecular Weight: 291.436
• Hs Code.: 2921499090
• European Community (EC) Number: 618-706-8
• UNII: G7RIW8S0XP
• DSSTox Substance ID: DTXSID2023640
• Nikkaji Number: J1.406.049I,J126.310B
• Wikipedia: Terbinafine
• Wikidata: Q415259
• NCI Thesaurus Code: C48019
• RXCUI: 37801
• Pharos Ligand ID: 31CWQ1ANWQ83
• ChEMBL ID: CHEMBL822
• Mol file: 91161-71-6.mol

Synonyms:(E)-N-(6,6-dimethyl-2-heptenynyl)-N-methyl-1-naphthalenementhamin hydrochloride;DA 5505;Lamisil;SF 86 327;SF 86-327;SF 86327;SF-86-327;SF86327;TDT 067;TDT-067;TDT067;terbinafine;terbinafine hydrochloride;Terbinafine, (Z)-;terbinafine, (Z)-isomer

Chemical Property of Terbinafine

Chemical Property:

• Appearance/Colour: white to off-white crystalline powder
• Vapor Pressure: 0Pa at 25℃
• Melting Point: 203-205 °C
• Boiling Point: 417.9 °C at 760 mmHg
• PKA: 6.92±0.50(Predicted)
• Flash Point: 183.7 °C
• PSA: 3.24000
• Density: 1.007g/cm³
• LogP: 4.87730
• Storage Temp.: 2-8°C
• Solubility.: soluble in Methanol
• XLogP3: 5.6
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 5
• Exact Mass: 291.198699802
• Heavy Atom Count: 22
• Complexity: 428

Purity/Quality:

99% ^*data from raw suppliers

Terbinafine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antifungal Agents
• Canonical SMILES: CC(C)(C)C#CC=CCN(C)CC1=CC=CC2=CC=CC=C21
• Isomeric SMILES: CC(C)(C)C#C/C=C/CN(C)CC1=CC=CC2=CC=CC=C21
• Recent ClinicalTrials: Comparative Study Between Pulse Therapy With Oral Itraconazole Versus Continuous Oral Terbinafine Therapy for Treatment of Onychomycosis
• Recent EU Clinical Trials: From fungus to virus, a phase 2a clinical trial investigating the safety and efficacy of terbinafine in chronic hepatitis B patients
• Uses: Terbinafine (Lamisil) is a second-generation allylamine that is related to naftifine; however, it is 10 to 100 times more potent in vitro. It is fungicidal, whereas griseofulvin, ketoconazole, itraconazole, and other azole derivatives are all fungistatic. Because it is fungicidal, duration of therapy is shorter, and relapse rates are less than with other oral or topical therapies. Terbinafine acts by inhibiting squalene epoxidase and thereby decreasing synthesis of ergosterol, an essential component of fungal cell membranes. It is highly lipophilic and concentrates in the stratum corneum, sebum, and hair follicles. Slightly better cure rates are attained with b.i.d. than with daily dosing.
• Indications: Terbinafine (Lamisil) is a second-generation allylamine that is related to naftifine; however, it is 10 to 100 times more potent in vitro. It is fungicidal, whereas griseofulvin, ketoconazole, itraconazole, and other azole derivatives are all fungistatic. Because it is fungicidal, duration of therapy is shorter, and relapse rates are less than with other oral or topical therapies. Terbinafine acts by inhibiting squalene epoxidase and thereby decreasing synthesis of ergosterol, an essential component of fungal cell membranes. It is highly lipophilic and concentrates in the stratum corneum, sebum, and hair follicles. Slightly better cure rates are attained with b.i.d. than with daily dosing.
• Therapeutic Function: Antifungal
• Clinical Use: Terbinafine hydrochloride can be used in Tinea pedis, tinea corporis, tinea cruris, tinea capitis, Onychomycosis caused by dermatophytes.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration reduced by rifampicin.

Technology Process of Terbinafine

There total 31 articles about Terbinafine 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%

tert-butyl-2-chloro-acetylene (16865-61-5) + (2E)-3-chloro-N-methyl-N-(naphthalen-1-ylmethyl)prop-2-en-1-amine (134865-58-0) → terbinafin (91161-71-6)

Guidance literature:

tert-butyl-2-chloro-acetylene; With n-butyllithium; In n-heptane; toluene; at 80 ℃; for 2.5h;

(2E)-3-chloro-N-methyl-N-(naphthalen-1-ylmethyl)prop-2-en-1-amine; nickel dichloride; In tetrahydrofuran; toluene; at 50 - 95 ℃; for 1h; Product distribution / selectivity;

Reference yield: 100.0%

1,1-dichloro-3,3-dimethyl-1-butene (32363-94-3) + (2E)-3-chloro-N-methyl-N-(naphthalen-1-ylmethyl)prop-2-en-1-amine (134865-58-0) → terbinafin (91161-71-6)

Guidance literature:

1,1-dichloro-3,3-dimethyl-1-butene; With n-butyllithium; In n-heptane; toluene; at 80 - 90 ℃; for 2.75h;

(2E)-3-chloro-N-methyl-N-(naphthalen-1-ylmethyl)prop-2-en-1-amine; bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; at 90 - 95 ℃; for 4h; Product distribution / selectivity;

Reference yield: 98.0%

((E)-3-Bromo-allyl)-methyl-naphthalen-1-ylmethyl-amine + lithium tert-butylethynyl(triisopropoxy)borate → terbinafin (91161-71-6)

Guidance literature:

copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; In N,N-dimethyl-formamide; at 60 ℃; for 36h;

DOI:10.1016/s0040-4039(00)01543-4

upstream raw materials:

N-methyl-1-naphthalenemethylamine

3-hydroxy-6,6-dimethylhept-1-ene-4-yne

tributyl(3,3-dimethyl-1-butyn-1-yl)stannane

((E)-3-Iodo-allyl)-methyl-naphthalen-1-ylmethyl-amine

Downstream raw materials:

1-naphthaldehyde

formaldehyd

Demethylterbinafine

N-methyl-1-naphthalenemethylamine

Refernces

• 1、 -. "Synthesis method of terbinafine". Paragraph 0027-0029. . Retrieved 2020/05/19.
• 2、 Hadi, Victor,Yoo, Kyung Soo,Jeong, Min,Jung, Kyung Woon. "Expeditious enyne construction from alkynes via oxidative Pd(II)-catalyzed Heck-type coupling". scheme or table. p. 2370 - 2373. Retrieved 2009/07/19.