2247-88-3

Basic information

• Product Name: 4-Amino-3-fluoropyridine
• Synonyms: 4-AMINO-3-FLUOROPYRIDINE;3-FLUORO-4-AMINOPYRIDINE;3-FLUOROPYRIDIN-4-AMINE;4-AMINO-3-FLUOROPYRINE;4-Amino-3-fluoropyridine fluoropyridin-4-amine;3-Fluoro-4-pyridinamine;4-Amino-3-fluoropyridine ,98%
• CAS NO: 2247-88-3
• Molecular Formula: C₅H₅FN₂
• Molecular Weight: 112.11
• Product Categories: Pyridine;Heterocyclic Series;Pyridine series;Pyridines;Boronic Acid;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building BlocksHeterocyclic Building Blocks;New Products for Chemical Synthesis;Fluorine series
• Mol File: 2247-88-3.mol
• Article Data: 8

Chemical Properties

• Melting Point: 74-77
• Boiling Point: 217.1 °C at 760 mmHg
• Flash Point: 85.1 °C
• Appearance: Yellow to light yellow crystals
• Density: 1.257 g/cm³
• Vapor Pressure: 0.135mmHg at 25°C
• Refractive Index: 1.554
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: soluble in Methanol
• PKA: 7.19±0.12(Predicted)
• CAS DataBase Reference: 4-Amino-3-fluoropyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Amino-3-fluoropyridine(2247-88-3)
• EPA Substance Registry System: 4-Amino-3-fluoropyridine(2247-88-3)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22-36
• Safety Statements: 26
• WGK Germany: nwg
• HazardClass: IRRITANT
• Hazardous Substances Data: 2247-88-3(Hazardous Substances Data)

Usage

Chemical Properties

Yellow to light yellow crystals

Uses

4-Amino-3-fluoropyridine is an important intermediate in the synthesis of many new drugs, and it is an intermediate in the synthesis of transforming growth factor-β inhibitors and thrombin inhibitors.

InChI:InChI=1/C5H5FN2/c6-4-3-8-2-1-5(4)7/h1-3H,(H2,7,8)

Synthetic route

3-fluoro-4-nitropyridine N-oxide (769-54-0) → 3-fluoro-pyridin-4-ylamine (2247-88-3)

Conditions	Yield
titanium In tetrahydrofuran for 0.25h; Ambient temperature; Yield given;
With hydrogen; palladium on activated charcoal Yield given;
With palladium 10% on activated carbon; hydrogen In methanol for 0.166667h;
With palladium 10% on activated carbon; hydrogen In methanol at 25℃; under 760.051 Torr;

3-fluoropyridine-1-oxide (695-37-4) → 3-fluoro-pyridin-4-ylamine (2247-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 2: H2 / Pd/C View Scheme

FeSO4.H2O + 3-fluoro-4-nitropyridine N-oxide (769-54-0) → 3-fluoro-pyridin-4-ylamine (2247-88-3)

Conditions	Yield
With ammonium hydroxide In water

3-Bromo-4-nitropyridine N-oxide (1678-49-5) → 3-fluoro-pyridin-4-ylamine (2247-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrabutyl ammonium fluoride / tetrahydrofuran; dimethyl sulfoxide 2: palladium 10% on activated carbon; hydrogen / methanol / 0.17 h View Scheme
Multi-step reaction with 2 steps 1: tetrabutyl ammonium fluoride / dimethyl sulfoxide; tetrahydrofuran / 125 °C 2: hydrogen; palladium 10% on activated carbon / methanol / 25 °C / 760.05 Torr View Scheme

5-methoxymethylene-2,2-dimethyl-1,3-dioxane-4,6-dione (15568-85-1) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 5-[(3-fluoropyridin-4-ylamino)-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dione

Conditions	Yield
In isopropyl alcohol at 25℃; for 2h;	99%

potassium ethyl xanthogenate (140-89-6) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → thiazolo[5,4-c]pyridine-2-thiol

Conditions	Yield
In N,N-dimethyl-formamide at 130℃; for 24h;	98%

1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic chloride (874110-84-6) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → C20H13Cl2FN4O

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	97%

benzoyl chloride (98-88-4) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → N-(3-fluoropyridin-4-yl)benzamide (1315494-51-9)

Conditions	Yield
With triethylamine In tetrahydrofuran at -5 - 5℃; for 4h; Inert atmosphere; Large scale reaction;	92%
With pyridine; triethylamine In tetrahydrofuran at 3 - 15℃; for 4h;	74%

ethyl 4-phenoxy-2-(6-(trifluoromethyl)pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazine-5-carboxylate + 3-fluoro-pyridin-4-ylamine (2247-88-3) → ethyl 4-((3-fluoropyridin-4-yl)amino)-2-(6-(trifluoromethyl)pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazine-5-carboxylate

Conditions	Yield
Stage #1: 3-fluoro-pyridin-4-ylamine With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: ethyl 4-phenoxy-2-(6-(trifluoromethyl)pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazine-5-carboxylate at 20℃; for 3h;	90%

9-(4-methoxybenzyl)-6-phenoxy-2-(6-(trifluoromethyl)pyridin-2-yl)-9H-purine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → N-(3-fluoropyridin-4-yl)-9-(4-methoxybenzyl)-2-(6-(trifluoromethyl)pyridin-2-yl)-9H-purin-6-amine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil for 3h;	90%

ethyl 2-(6-(difluoromethyl)pyridin-2-yl)-4-phenoxypyrrolo[2,1-f][1,2,4]triazine-5-carboxylate + 3-fluoro-pyridin-4-ylamine (2247-88-3) → ethyl 2-(6-(difluoromethyl)pyridin-2-yl)-4-((3-fluoropyridin-4-yl)amino)pyrrolo[2,1-f][1,2,4]triazine-5-carboxylate

Conditions	Yield
Stage #1: 3-fluoro-pyridin-4-ylamine With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.0833333h; Stage #2: ethyl 2-(6-(difluoromethyl)pyridin-2-yl)-4-phenoxypyrrolo[2,1-f][1,2,4]triazine-5-carboxylate In N,N-dimethyl-formamide at 20℃; for 2h;	86%

9-(4-methoxybenzyl)-6-phenoxy-2-(pyridin-2-yl)-9H-purine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → N-(3-fluoropyridin-4-yl)-9-(4-methoxybenzyl)-2-(pyridin-2-yl)-9H-purin-6-amine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil for 3h;	84%

3-fluoro-pyridin-4-ylamine (2247-88-3) → 3-bromo-5-fluoropyridin-4-amine (1214326-89-2)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile at 20℃; for 16h;	83%

C17H18F2N2O3 + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 5-(4,4-difluoro-7-methyl-2,3-dihydro-chromen-6-yl)-N-(3-fluoro-pyridin-4-yl)-1-methyl-1H-pyrazole-3-carboxylic acid amide

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 60℃; for 2h;	80%

2,4-dichloro-6-nitropyrrolo[2,1-f][1,2,4]triazine (1160995-45-8) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 2-chloro-N-(3-fluoropyridin-4-yl)-6-nitropyrrolo[2,1-f][1,2,4]triazin-4-amine

Conditions	Yield
In tetrahydrofuran at 20℃; for 1h;	75%

2-(6-(difluoromethyl)pyridin-2-yl)-5-methyl-4-phenoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → C24H27F3N6OSi

Conditions	Yield
Stage #1: 3-fluoro-pyridin-4-ylamine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Stage #2: 2-(6-(difluoromethyl)pyridin-2-yl)-5-methyl-4-phenoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine In N,N-dimethyl-formamide; mineral oil at 20℃; for 16h;	75%

3-fluoro-pyridin-4-ylamine (2247-88-3) + 4-(chlorosulfonyl)benzenesulfonyl fluoride → C11H8F2N2O4S2

Conditions	Yield
With pyridine In chloroform at 20℃; for 48h; chemoselective reaction;	75%

di-tert-butyl dicarbonate (24424-99-5) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → tert-butyl (3-fluoropyridin-4-yl)carbamate (1260683-20-2)

Conditions	Yield
In Petroleum ether	75%
In acetonitrile at 45℃; for 2.25h; Inert atmosphere; Large scale;
In acetone at 5 - 25℃; for 20h; Inert atmosphere; Large scale; Green chemistry;

5-bromo-selenophene-2-carbonyl chloride (117961-93-0) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → C10H6BrFN2OSe (1366109-59-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; dmap In dichloromethane at 20℃; for 2h;	72%

C8H7ClINO + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 3-(3-fluoropyridin-4-yl)-1-(2-iodophenyl)-1-methylurea

Conditions	Yield
Stage #1: 3-fluoro-pyridin-4-ylamine With sodium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: C8H7ClINO In tetrahydrofuran at -78 - 20℃; for 2h;	68%

2-(5-fluoro-6-methylpyridin-2-yl)-9-(4-methoxybenzyl)-6-phenoxy-9H-purine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 2-(5-fluoro-6-methylpyridin-2-yl)-N-(3-fluoropyridin-4-yl)-9-(4-methoxybenzyl)-9H-purin-6-amine

Conditions	Yield
In N,N-dimethyl-formamide; mineral oil for 3h;	67.3%

2-(6-methylpyridin-2-yl)-4-phenoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → N-(3-fluoropyridin-4-yl)-2-(6-methylpyridin-2-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo [2,3-d]pyrimidin-4-amine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 12h;	66.9%

C14H10ClN3O2S (1616930-39-2) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 5-(2-chloro-5-thiazol-2-yl-phenyl)-N-(3-fluoro-pyridin-4-yl)-1-methyl-1H-pyrazole-3-carboxylic acid amide (1616929-84-0)

Conditions	Yield
Stage #1: C14H10ClN3O2S With thionyl chloride at 50℃; for 0.5h; Stage #2: 3-fluoro-pyridin-4-ylamine With triethylamine In dichloromethane at 20℃; for 1h;	64%

C13H14ClN3O2 + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 5-(5-chloro-2-methyl-pyridin-3-yl)-N-(3-fluoro-pyridin-4-yl)-1-methyl-1H-pyrazole-3-carboxylic acid amide

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran; hexane at 60℃; for 1h;	63%

2-(6-(difluoromethyl)pyridin-2-yl)-9-(4-methoxybenzyl)-6-phenoxy-9H-purine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 2-(6-(difluoromethyl)pyridin-2-yl)-N-(3-fluoropyridin-4-yl)-9-(4-methoxybenzyl)-9H-purin-6-amine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil for 3h;	57.7%

3-fluoro-pyridin-4-ylamine (2247-88-3) + benzyl alcohol (100-51-6) → N-benzyl-3-fluoropyridin-4-amine

Conditions	Yield
With C34H38Cl4N6Ni2; potassium 2-methylbutan-2-olate In toluene at 140℃; for 12h; Inert atmosphere;	57%

C10H4Cl2F3N3O + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 1-(3-chloropyridin-2-yl)-N-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃; for 12h;	55%

9-(4-methoxybenzyl)-2-(6-methylpyridin-2-yl)-6-phenoxy-9H-purine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → N-(3-fluoropyridin-4-yl)-9-(4-methoxybenzyl)-2-(6-methylpyridin-2-yl)-9H-purin-6-amine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil for 3h;	53.7%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 3h;	53.7%

6'-bromo-8'-chloro-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 8'-chloro-6'-((3-fluoropyridin-4-yl)amino)-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 130℃; for 0.5h; Microwave irradiation;	52%

2-(6’-dibocaminopyridyl-2-yl)-4-phenoxy-pyrrolotriazine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → tert-butyl (6-(4-((3-fluoropyridin-4-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-2-yl)carbamate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h; Inert atmosphere;	50.8%

trans-(R)-4-(1-(tert-butoxycarbonylamino)ethyl)cyclohexanecarboxylic acid (671815-99-9) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → C19H28FN3O3 (1318865-32-5)

Conditions	Yield
With 2-chloro-1-methyl-pyridinium iodide; triethylamine In dichloromethane at 20℃; for 48h; Mukaiyama reaction; Inert atmosphere;	50%

2-(6-methylpyridin-2-yl)-4-phenoxypyrrolo[2,1-f][1,2,4]triazine + 3-fluoro-pyridin-4-ylamine (2247-88-3) → 3-fluoro-N-[2-(6-methylpyridin-2-yl)pyrrolo[2,1-f] [1 ,2,4]triazin-4-yl]pyridin-4-amine

Conditions	Yield
In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h;	50%

C15H13N3O3S (1616930-35-8) + 3-fluoro-pyridin-4-ylamine (2247-88-3) → N-(3-fluoro-pyridin-4-yl)-5-(2-methoxy-5-thiazol-2-yl-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid amide (1616929-82-8)

Conditions	Yield
Stage #1: C15H13N3O3S With thionyl chloride at 50℃; for 0.5h; Stage #2: 3-fluoro-pyridin-4-ylamine With triethylamine In dichloromethane at 20℃; for 2h;	46%

ethyl 4-phenoxy-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazine-5-carboxylate + 3-fluoro-pyridin-4-ylamine (2247-88-3) → ethyl 4-((3-fluoropyridin-4-yl)amino)-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazine-5-carboxylate

Conditions	Yield
Stage #1: 3-fluoro-pyridin-4-ylamine With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: ethyl 4-phenoxy-2-(pyridin-2-yl)pyrrolo[2,1-f][1,2,4]triazine-5-carboxylate In N,N-dimethyl-formamide at 20℃; for 1h;	42.4%

Upstream product

• 769-54-0 3-fluoro-4-nitropyridine N-oxide 
• 13505-01-6 3-fluoro-4-nitropyridine 
• 5720-07-0 4-methoxyphenylboronic acid 
• 1678-49-5 3-Bromo-4-nitropyridine N-oxide 
• 695-37-4 3-fluoropyridine-1-oxide 

Downstream Products

• 1318865-32-5 C₁₉H₂₈FN₃O₃ 
• 1315494-51-9 N-(3-fluoropyridin-4-yl)benzamide 
• 945127-72-0 C₁₄H₂₀N₂O 
• 1315494-52-0 4-benzamido-1-ethyl-3-fluoropyridinium iodide 
• 1315494-53-1 N-(1-ethyl-3-fluoro-1,2,5,6-tetrahydropyridin-4-yl)benzamide 
• 1315494-54-2 N-[(3S,4R)-1-ethyl-3-fluoropiperidin-4-yl]benzamide 
• 1434126-99-4 tert-butyl N-[(3R,4S)-3-fluoropiperidin-4-yl]carbamate 
• 73889-19-7 tert-butyl (1-benzylpiperidin-4-yl)carbamate 

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