56995-20-1

Basic information

• Product Name: Flupirtine
• Synonyms: CARBAMIC ACID;FLUPIRTINE;Ethyl N-[2-amino-6-[(4-fluorophenyl)methylamino]pyridin-3-yl]carbamate;FLUPIRITNE MALEATE;[2-Amino-6-[[(4-fluorophenyl)methyllaminol-3-pyridinyl]carbamic acid ethyl ester;D-9998;Katadolon;Carbamic acid, [2-amino-6-[[(4-fluorophenyl)methyl]amino]-3-pyridinyl]-, ethyl ester
• CAS NO: 56995-20-1
• Molecular Formula: C₁₅H₁₇FN₄O₂
• Molecular Weight: 304.32
• EINECS: 260-503-8
• Mol File: 56995-20-1.mol
• Article Data: 5

Chemical Properties

• Melting Point: 115-116°
• Boiling Point: 445.15°C (rough estimate)
• Flash Point: 216.8 °C
• Appearance: /
• Density: 1.35 g/cm³
• Vapor Pressure: 9.1E-08mmHg at 25°C
• Refractive Index: 1.661
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 12.19±0.70(Predicted)
• Water Solubility: 1g/L(temperature not stated)
• CAS DataBase Reference: Flupirtine(CAS DataBase Reference)
• NIST Chemistry Reference: Flupirtine(56995-20-1)
• EPA Substance Registry System: Flupirtine(56995-20-1)

Safety Data

• Hazardous Substances Data: 56995-20-1(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 56995-20-1 differently. You can refer to the following data:
1. Analgesic.
2. 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.

InChI:InChI=1/C15H17FN4O2/c1-2-22-15(21)19-12-7-8-13(20-14(12)17)18-9-10-3-5-11(16)6-4-10/h3-8H,2,9H2,1H3,(H,19,21)(H3,17,18,20)

Synthetic route

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

Conditions	Yield
In 1,4-dioxane at 20℃; Inert atmosphere; Darkness;	82%
In 1,4-dioxane at 20℃; for 1h;	75%
In tetrahydrofuran Ambient temperature; Yield given;

2,3-Diaminopyridine (452-58-4) → Flupirtine (56995-20-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 41.8 percent / propan-2-ol / 71 h / Heating 2: 52.8 percent / MnO2 / tetrahydrofuran / 18 h / Ambient temperature 3: Na2S2O4 / tetrahydrofuran; H2O / Ambient temperature 4: tetrahydrofuran / Ambient temperature View Scheme

spiropyridine> (76902-24-4) → Flupirtine (56995-20-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 52.8 percent / MnO2 / tetrahydrofuran / 18 h / Ambient temperature 2: Na2S2O4 / tetrahydrofuran; H2O / Ambient temperature 3: tetrahydrofuran / Ambient temperature View Scheme

5'-<(4-fluorobenzyl)amino>spiropyridine> (161263-86-1) → Flupirtine (56995-20-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: Na2S2O4 / tetrahydrofuran; H2O / Ambient temperature 2: tetrahydrofuran / Ambient temperature View Scheme

2,6-dicholoro-3-nitropyridine (16013-85-7) → Flupirtine (56995-20-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonia / methanol / 20 °C / Inert atmosphere 2: triethylamine / isopropyl alcohol / 3 h / Reflux; Inert atmosphere 3: hydrogenchloride; tin(II) chloride dihdyrate / water / 3 h / 70 °C / Inert atmosphere 4: 1,4-dioxane / 20 °C / Inert atmosphere; Darkness View Scheme

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

Conditions	Yield
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 View Scheme
Multi-step reaction with 3 steps 1: triethylamine / isopropyl alcohol / 0.5 h / 5 °C 2: palladium on activated charcoal; hydrogen / methanol / 5 h / 20 °C / 1551.49 Torr 3: 1,4-dioxane / 1 h / 20 °C View Scheme

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

Conditions	Yield
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 View Scheme
Multi-step reaction with 2 steps 1: palladium on activated charcoal; hydrogen / methanol / 5 h / 20 °C / 1551.49 Torr 2: 1,4-dioxane / 1 h / 20 °C View Scheme

para-fluorobenzylamine (140-75-0) → Flupirtine (56995-20-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / isopropyl alcohol / 0.5 h / 5 °C 2: palladium on activated charcoal; hydrogen / methanol / 5 h / 20 °C / 1551.49 Torr 3: 1,4-dioxane / 1 h / 20 °C View Scheme

Flupirtine (56995-20-1) + maleic acid (110-16-7) → flupirtine maleate

Conditions	Yield
In Isopropyl acetate; dimethyl sulfoxide at 55℃; for 1h; Temperature; Solvent; Inert atmosphere;	96%

Flupirtine (56995-20-1) → 5-(4-fluorobenzylamino)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-one

Conditions	Yield
at 200℃; for 0.5h;	88%

4-fluorobenzaldehyde (459-57-4) + Flupirtine (56995-20-1) → C37H37F3N8O4

Conditions	Yield
With triethylamine In ethanol for 16h; Reflux;	70%

[2-(2,6-dichloroanilino)phenyl]acetic acid (15307-86-5) + Flupirtine (56995-20-1) → C15H17FN4O2*C14H11Cl2NO2

Conditions	Yield
In toluene at 60℃; Inert atmosphere;	66%

Flupirtine (56995-20-1) + methyl iodide (74-88-4) → ethyl [2-amino-6-(4-fluorobenzylamino)pyridine-3-yl](methyl)carbamate

Conditions	Yield
Stage #1: Flupirtine With sodium hydride In tetrahydrofuran; hexane at 0℃; for 0.5h; Inert atmosphere; Darkness; Stage #2: methyl iodide In tetrahydrofuran; hexane Inert atmosphere;	40%

Flupirtine (56995-20-1) + trifluoroacetic acid (76-05-1) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine triflutate

Conditions	Yield
In isopropyl alcohol at -5 - 30℃;
In isopropyl alcohol at 30℃;

Flupirtine (56995-20-1) + maleic acid (110-16-7) → flupirtine maleate

Conditions	Yield
In isopropyl alcohol at 17 - 60℃; Product distribution / selectivity;
In isopropyl alcohol at 20 - 60℃; Product distribution / selectivity;
In isopropyl alcohol at 20 - 60℃; Product distribution / selectivity;
In isopropyl alcohol at 60℃;

Flupirtine (56995-20-1) + acetic acid (64-19-7) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine acetate (1198579-27-9)

Conditions	Yield
In ethanol at -15 - 60℃; Inert atmosphere;
In ethanol at 40 - 60℃; Inert atmosphere;

Flupirtine (56995-20-1) + propionic acid (802294-64-0) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine propionate (1198579-28-0)

Conditions	Yield
In isopropyl alcohol at -5 - 60℃; Inert atmosphere;
In isopropyl alcohol at 50 - 60℃; Inert atmosphere;

toluene-4-sulfonic acid (104-15-4) + Flupirtine (56995-20-1) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine tosilate (1200119-41-0)

Conditions	Yield
In isopropyl alcohol at 20 - 50℃;
In isopropyl alcohol at 20 - 40℃;

methanesulfonic acid (75-75-2) + Flupirtine (56995-20-1) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine mesilate (1200119-31-8)

Conditions	Yield
In isopropyl alcohol at 20 - 60℃; for 0.5h; Inert atmosphere;
In isopropyl alcohol at 20 - 60℃; Inert atmosphere;

Flupirtine (56995-20-1) + benzenesulfonic acid (98-11-3) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine besilate (1200119-39-6)

Conditions	Yield
In isopropyl alcohol at 20 - 60℃; for 0.5h; Inert atmosphere;
In isopropyl alcohol at 20 - 60℃; Inert atmosphere;

toluene-4-sulfonic acid (104-15-4) + Flupirtine (56995-20-1) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)pyridine tosilate

Conditions	Yield
In isopropyl alcohol at 20 - 40℃;

Flupirtine (56995-20-1) + trifluoroacetic acid (76-05-1) → (x)C2HF3O2*C15H17FN4O2

Conditions	Yield
In isopropyl alcohol at 30℃; for 0.5h;

methanesulfonic acid (75-75-2) + Flupirtine (56995-20-1) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)pyridine mesylate

Conditions	Yield
In isopropyl alcohol at 20 - 60℃; Inert atmosphere;

Flupirtine (56995-20-1) + acetic acid (64-19-7) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)pyridine acetate

Conditions	Yield
In ethanol at 40 - 60℃; Inert atmosphere;

Flupirtine (56995-20-1) + propionic acid (802294-64-0) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)pyridine propionate

Conditions	Yield
In isopropyl alcohol at 60℃; Inert atmosphere;

Flupirtine (56995-20-1) + benzenesulfonic acid (98-11-3) → 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)pyridine besilate

Conditions	Yield
In isopropyl alcohol at 20 - 60℃; Inert atmosphere;

Flupirtine (56995-20-1) → ethyl 5-(4-fluorobenzylamino)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate

Conditions	Yield
Multi-step reaction with 2 steps 1: 0.5 h / 200 °C 2: acetonitrile; N,N-dimethyl-formamide / 75 °C View Scheme

Flupirtine (56995-20-1) → ethyl 5-[(ethoxycarbonyl)(4-fluorobenzyl)amino]-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate

Conditions	Yield
Multi-step reaction with 2 steps 1: 0.5 h / 200 °C 2: acetonitrile; N,N-dimethyl-formamide / 75 °C View Scheme

Upstream product

• 541-41-3 chloroformic acid ethyl ester 
• 112523-78-1 N⁶-(4-fluorobenzyl)pyridine-2,3,6-triamine 
• 452-58-4 2,3-Diaminopyridine 
• 76902-24-4 spiropyridine> 
• 161263-86-1 5'-<(4-fluorobenzyl)amino>spiropyridine> 
• 16013-85-7 2,6-dicholoro-3-nitropyridine 
• 27048-04-0 2-amino-6-chloro-3-nitropyridine 
• 33400-49-6 2-amino-3-nitro-6-(p-fluoro-benzylamino)-pyridine 
• 140-75-0 para-fluorobenzylamine 

Downstream Products

• 75507-68-5 flupirtine maleate 
• 1198579-27-9 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine acetate 
• 1198579-28-0 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine propionate 
• 1200119-41-0 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine tosilate 
• 1200119-31-8 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine mesilate 
• 1200119-39-6 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine besilate 
• 951624-49-0 5-(4-fluorobenzylamino)-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-one 

Relevant articles and documents

A flupirtin derivative and its inorganic acid salt preparation method (by machine translation)

The invention relates to a kind of flupirtine derivative and its inorganic acid salt of the preparation method, the [...] derivatives by the following chemical formula 1 that: The [...] derivative is maleic acid flupirtin synthesis process and/or storage of produced in the process of an important impurity. The preparation method according to this application, and may be the above-mentioned yield of flupirtine derivative and its inorganic acid salt, each step of the reaction yield can be up to 55% or more. (by machine translation)

Use of a combination of active substances containing bioquinones for the production of cosmetic or dermatological preparations

The invention relates to the use of a compound or several compounds from the group of bioquinones a) in combination with a compound or several compounds from the group of potassium channel openers and/or b) in combination with a compound or several compounds from the group of 5-alpha-reductase inhibitors, for the production of cosmetic or dermatological preparations for treatment of the scalp and for hair in order to prolong the anagenic phase and/or for the treatment and prophylaxis of seborrhoeic symptoms, optionally by additionally using one or several compounds from the group formed from carnitine, arginine, succinic acid, folic acid, conjugated fatty acids and respectively the derivatives thereof, in addition to antioxidants.

2-Amino-3-acylamino-6-benzylamino-pyridine-derivative having antiepileptic action

Compounds of the formula STR1 where R is a C1 -C4 alkyl group, a C1 -C4 alkoxy group, a phenoxy group or a phenyl-C1 -C2 -alkoxy group, R1 is hydrogen or a C1 -C4 -alkyl group and R5 is hydrogen or a C1 -C4 -alkyl group and the groups R2, R3, and R4 are the same or different and are hydrogen, halogen atoms, C1 -C4 alkyl groups, C1 -C4 -alkylcarbonyl group, the aminosulfonyl group, the trifluoromethyl group and their acid addition salts are effective as antiepileptics.