Flupirtine

Base Information

• Chemical Name: Flupirtine
• CAS No.: 56995-20-1
• Molecular Formula: C15H17FN4O2
• Molecular Weight: 304.324
• European Community (EC) Number: 260-503-8
• UNII: MOH3ET196H
• DSSTox Substance ID: DTXSID4048436
• Nikkaji Number: J11.728E
• Wikipedia: Flupirtine
• Wikidata: Q415403
• NCI Thesaurus Code: C72116
• Pharos Ligand ID: FDHQVB1C8LH3
• Metabolomics Workbench ID: 149865
• ChEMBL ID: CHEMBL255044
• Mol file: 56995-20-1.mol

Synonyms:D 9998;D-9998;ethyl 2-amino-6-((p-fluorobenzyl)amino)-3-pyridinecarbamate;flupirtin maleate;flupirtine;flupirtine maleate (1:1);Katadolon

Chemical Property of Flupirtine

Chemical Property:

• Vapor Pressure: 9.1E-08mmHg at 25°C
• Melting Point: 115-116°
• Refractive Index: 1.661
• Boiling Point: 434.9 °C at 760 mmHg
• PKA: 12.19±0.70(Predicted)
• Flash Point: 216.8 °C
• PSA: 89.27000
• Density: 1.35 g/cm³
• LogP: 3.71060
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Water Solubility.: 1g/L(temperature not stated)
• XLogP3: 2.4
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 6
• Exact Mass: 304.13355396
• Heavy Atom Count: 22
• Complexity: 350

Purity/Quality:

99% ^*data from raw suppliers

Carbamic acid [2-oxo-2-(2-propynylamino)ethoxy]-1,1-dimethylethyl ester95% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOC(=O)NC1=C(N=C(C=C1)NCC2=CC=C(C=C2)F)N
• Recent ClinicalTrials: Flupirtine as Oral Treatment in Multiple Sclerosis
• Recent EU Clinical Trials: Flupirtin as Oral Treatment in MS
• Uses: Analgesic. Therapeutic use of Flupirtine was discontinued due to drug induced liver injury (DILI). Since the mechanism of action is not related to its adverse effects, it is important to focus on chemical modifications.

Technology Process of Flupirtine

There total 9 articles about Flupirtine 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: 82.0%

chloroformic acid ethyl ester (541-41-3) + N6-(4-fluorobenzyl)pyridine-2,3,6-triamine (112523-78-1) → Flupirtine (56995-20-1)

Guidance literature:

In 1,4-dioxane; at 20 ℃; Inert atmosphere; Darkness;

DOI:10.1021/acs.jmedchem.7b01199

Reference yield:

2-amino-6-chloro-3-nitropyridine (27048-04-0) → Flupirtine (56995-20-1)

Guidance literature:

Multi-step reaction with 3 steps

1: triethylamine / isopropyl alcohol / 3 h / Reflux; Inert atmosphere

2: hydrogenchloride; tin(II) chloride dihdyrate / water / 3 h / 70 °C / Inert atmosphere

3: 1,4-dioxane / 20 °C / Inert atmosphere; Darkness

With hydrogenchloride; tin(II) chloride dihdyrate; triethylamine; In 1,4-dioxane; water; isopropyl alcohol;

DOI:10.1021/acs.jmedchem.7b01199

Reference yield:

2-amino-3-nitro-6-(p-fluoro-benzylamino)-pyridine (33400-49-6) → Flupirtine (56995-20-1)

Guidance literature:

Multi-step reaction with 2 steps

1: hydrogenchloride; tin(II) chloride dihdyrate / water / 3 h / 70 °C / Inert atmosphere

2: 1,4-dioxane / 20 °C / Inert atmosphere; Darkness

With hydrogenchloride; tin(II) chloride dihdyrate; In 1,4-dioxane; water;

DOI:10.1021/acs.jmedchem.7b01199

upstream raw materials:

chloroformic acid ethyl ester

N⁶-(4-fluorobenzyl)pyridine-2,3,6-triamine

2,3-Diaminopyridine

spiropyridine>

Downstream raw materials:

flupirtine maleate

2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine acetate

2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine propionate

2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine tosilate

Refernces

• 1、 Kinarivala, Nihar,Patel, Ronak,Boustany, Rose-Mary,Al-Ahmad, Abraham,Trippier, Paul C.. "Discovery of Aromatic Carbamates that Confer Neuroprotective Activity by Enhancing Autophagy and Inducing the Anti-Apoptotic Protein B-Cell Lymphoma 2 (Bcl-2)". . p. 9739 - 9756. Retrieved 2017/12/26.
• 2、 Schwoch,Kramer,Neidlein,Suschitzky. "2,3-Dihydrospiro[1H-4- and 5-azabenzimidazole-2,1'-cyclohexane] (= spiro[cyclohexane-1,2'(3'H)-1'H-imidazo[4,5-b]pyridine] and spiro[cyclohexane-1,2'(3'H)-1'H-imidazo[4,5-c]pyridine]): Reactions with nucleophiles". . p. 2175 - 2190. Retrieved 2007/10/02.