1827-27-6

Basic information

• Product Name: 5-Amino-2-fluoropyridine
• Synonyms: 2-FLUORO-5-AMINO PYRIDINE;6-FLUORO-3-PYRIDINAMINE;6-FLUOROPYRIDIN-3-AMINE;6-FLUORO-PYRIDIN-3-YLAMINE;5-AMINO-2-FLUOROPYRIDINE;3-Amino-6-fluoropyridine;2-FLUOROPYRIDIN-5-AMINE;5-Amino-2-fluoropyridine 98%
• CAS NO: 1827-27-6
• Molecular Formula: C₅H₅FN₂
• Molecular Weight: 112.11
• EINECS: 1806241-263-5
• Product Categories: Fluorin-contained pyridine series;Pyridine;pharmacetical;Pyridine series;Pyridines;Boronic Acid;Building Blocks;C5;C5 to C6;Chemical Synthesis;Fluorinated Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Heterocyclic Fluorinated Building Blocks;Other Fluorinated Heterocycles;Fluorine series
• Mol File: 1827-27-6.mol
• Article Data: 11

Chemical Properties

• Melting Point: 86-87°C
• Boiling Point: 264 °C at 760 mmHg
• Flash Point: 113.5 °C
• Appearance: light yellow cryst
• Density: 1.257 g/cm³
• Vapor Pressure: 0.00168mmHg at 25°C
• Refractive Index: 1.557
• Storage Temp.: Room temperature.
• PKA: 2?+-.0.10(Predicted)
• CAS DataBase Reference: 5-Amino-2-fluoropyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Amino-2-fluoropyridine(1827-27-6)
• EPA Substance Registry System: 5-Amino-2-fluoropyridine(1827-27-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-41-37/38
• Safety Statements: 26-36/37/39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 1827-27-6(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow Cryst

InChI:InChI=1/C7H4F2O3/c8-4-2-1-3(7(11)12)6(10)5(4)9/h1-2,10H,(H,11,12)

Synthetic route

2-Fluoro-5-nitropyridine (456-24-6) → 2-fluoro-5-aminopyridine (1827-27-6)

Conditions	Yield
With hydrogen; sodium sulfate; palladium on activated charcoal In toluene	94%
With 5%-palladium/activated carbon; hydrogen; sodium sulfate In toluene for 15h;	75%
With hydrogen; nickel In ethyl acetate	70%

6-fluoronicotinamide (369-50-6) → 2-fluoro-5-aminopyridine (1827-27-6)

Conditions	Yield
With sodium hydroxide; bromine In tetrahydrofuran at 5 - 70℃; Hoffmann rearrangement;

2-chloro-5-nitropyridine (4548-45-2) → 2-fluoro-5-aminopyridine (1827-27-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / KF / dimethylsulfoxide / 18 h / 70 °C 2: 70 percent / H2 / Raney Ni / ethyl acetate View Scheme
Multi-step reaction with 2 steps 1: potassium fluoride / acetonitrile 2: palladium-carbon / ethanol View Scheme

2-chloro-5-nitropyridine (4548-45-2) + potassium-salt of/the/ 4-acetylamino-benzenesulfinic acid → 2-fluoro-5-aminopyridine (1827-27-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 83 percent / CsF / various solvent(s) / 18 h / 130 °C 2: 94 percent / H2, Na2SO4 / 5percent Pd/C / toluene View Scheme

2-fluoro-5-aminopyridine (1827-27-6) + diethyl 2-ethoxymethylenemalonate (87-13-8) → 2-(6-fluoro-3-pyridyl)-aminomethylene-malonic acid diethyl ester (1093114-31-8)

Conditions	Yield
at 120℃; for 3h;	100%

di-tert-butyl dicarbonate (24424-99-5) + 2-fluoro-5-aminopyridine (1827-27-6) → (6-fluoro-pyridin-3-yl)-carbamic acid, tert-butyl ester (171178-41-9)

Conditions	Yield
In tert-butyl alcohol at 40℃; for 4h;	96%
In hexane; tert-butyl alcohol at -15 - 40℃; for 22h;	96%
In tert-butyl alcohol at -18 - 40℃; for 22h;	96%

4-(2-((tert-butoxycarbonyl)amino)cyclopropyl)benzoic acid + 2-fluoro-5-aminopyridine (1827-27-6) → C20H22FN3O3

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 18h;	96%

[ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 (52462-29-0) + 2-fluoro-5-aminopyridine (1827-27-6) → (η6-p-cymene)RuCl2(2-fluoro-5-aminopyridine)

Conditions	Yield
In diethyl ether for 10h; Reflux; Inert atmosphere;	95%
In methanol at 60℃; Inert atmosphere;	90%

2-fluoro-5-aminopyridine (1827-27-6) + 2,2,2-Trichloroethyl chloroformate (17341-93-4) → 2,2,2-trichloroethyl (6-fluoropyridin-3-yl)carbamate (1143578-58-8)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0℃; for 1h;	92%
With pyridine In acetonitrile at 0 - 20℃; for 1h;	83%

ammonium thiocyanate (1147550-11-5) + 2-fluoro-5-aminopyridine (1827-27-6) → 1-(6-fluoropyridin-3-yl)thiourea

Conditions	Yield
Stage #1: ammonium thiocyanate With benzoyl chloride In acetone for 0.25h; Reflux; Stage #2: 2-fluoro-5-aminopyridine In acetone at 40℃; for 1.5h; Stage #3: With sodium hydroxide at 60℃; for 2.5h;	91%

2-fluoro-5-aminopyridine (1827-27-6) + Cyclobutanecarbonyl chloride (5006-22-4) → N-(6-fluoropyridin-3-yl)cyclobutanecarboxamide (1421785-53-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	86%

6-bromo-4-chloroquinozoline (38267-96-8) + 2-fluoro-5-aminopyridine (1827-27-6) → 6-bromo-N-(6-fluoropyridin-3-yl)quinazolin-4-amine

Conditions	Yield
In isopropyl alcohol at 90℃; for 4h;	85.2%

2-fluoro-5-aminopyridine (1827-27-6) → 2-fluoro-5-hydrazinylpyridine (940958-93-0)

Conditions	Yield
With hydrogenchloride; tin(ll) chloride; sodium nitrite	85%
Stage #1: 2-fluoro-5-aminopyridine With hydrogenchloride; sodium nitrite In water at -20 - 10℃; for 0.5h; Stage #2: With tin(ll) chloride In water at -20 - 10℃; for 1h; Stage #3: With potassium hydroxide In water	68%
Stage #1: 2-fluoro-5-aminopyridine With hydrogenchloride; sodium nitrite In water at 0℃; for 1.5h; Stage #2: With hydrogenchloride; tin(II) chloride dihdyrate In water at 0℃; for 1h;	40%
Stage #1: 2-fluoro-5-aminopyridine With hydrogenchloride; tin(ll) chloride; sodium nitrite In water at 0 - 5℃; for 4h; Stage #2: With potassium hydroxide In water pH=14;	39%
Stage #1: 2-fluoro-5-aminopyridine With hydrogenchloride; sodium nitrite In water at -20 - 20℃; for 0.5h; Stage #2: With tin(II) chloride dihdyrate In water at -20℃; for 1h;

N-(tert-butoxycarbonyl)-4-aminobutanoic acid (57294-38-9) + 2-fluoro-5-aminopyridine (1827-27-6) → tert-butyl 4-(6-fluoropyridin-3-ylamino)-4-oxobutylcarbamate (1323277-18-4)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 3h;	83%

4-trifluoromethyl-phenyl acetyl chloride (329-15-7) + 2-fluoro-5-aminopyridine (1827-27-6) → C13H8F4N2O

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 8h; Cooling with ice;	83%

C15H11ClN2O + 2-fluoro-5-aminopyridine (1827-27-6) → 1-benzyl-3,4-dihydro-3-(6-fluoropyridin-3-yl)-4-iminoquinazolin-2(1H)-one

Conditions	Yield
Stage #1: 2-fluoro-5-aminopyridine With sodium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: C15H11ClN2O In tetrahydrofuran at -78 - 20℃; for 2h;	82%

2-chloro-N-(2-(cyclohexylamino)-2-oxo-1-(o-tolyl)ethyl)-N-(3-fluorophenyl)acetamide (1355324-97-8) + 2-fluoro-5-aminopyridine (1827-27-6) → N-cyclohexyl-2-(N-(3-fluorophenyl)-2-((6-fluoropyridin-3-yl)amino)acetamido)-2-(o-tolyl)acetamide (1355326-85-0)

Conditions	Yield
In ethanol for 16h; Reflux;	81%

2-fluoro-5-aminopyridine (1827-27-6) + N-<(phenylmethoxy)carbonyl>-4(S)-methoxy-(S)-proline methyl ester (75176-19-1) → (2S,4S)-benzyl 2-(6-fluoropyridin-3-ylcarbamoyl)-4-methoxypyrrolidine-1-carboxylate (1109790-64-8)

Conditions	Yield
Stage #1: 2-fluoro-5-aminopyridine With isopropylmagnesium chloride In tetrahydrofuran at 0 - 20℃; Stage #2: N-<(phenylmethoxy)carbonyl>-4(S)-methoxy-(S)-proline methyl ester In tetrahydrofuran at 20℃; for 14h;	80%

(1-cyclopentyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-D-alanine + 2-fluoro-5-aminopyridine (1827-27-6) → (R)-2-((1-cyclopentyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-N-(6-fluoropyridin-3-yl)propanamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 2h;	80%

2-fluoro-5-aminopyridine (1827-27-6) + 6-phenylimidazo<2,1-b>thiazole-3-acetic acid (68347-91-1) → N-(6-fluoropyridin-3-yl)-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide (1388831-91-1)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	77%

4-fluorobenzaldehyde (459-57-4) + 2-fluoro-5-aminopyridine (1827-27-6) → N-(4-fluorobenzyl)-2-fluoro-5-aminopyridine

Conditions	Yield
Stage #1: 4-fluorobenzaldehyde; 2-fluoro-5-aminopyridine With acetic acid at 20℃; for 1h; Stage #2: With sodium cyanoborohydride at 10 - 15℃; for 0.5h;	75.6%

2-fluoro-5-aminopyridine (1827-27-6) + 6-(4'-chlorophenyl)imidazo<2,1-b>thiazole-3-acetic acid (68347-92-2) → 2-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl)-N-(6-fluoropyridin-3-yl)acetamide (1388831-93-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	74%

2-fluoro-5-aminopyridine (1827-27-6) → 5-azido-2-fluoropyridine (864866-13-7)

Conditions	Yield
With tert.-butylnitrite; trimethylsilylazide In acetonitrile at 0 - 20℃; for 5h;	72.1%
Stage #1: 2-fluoro-5-aminopyridine With hydrogenchloride; sodium nitrite In water at -15 - -10℃; for 0.166667h; Stage #2: With sodium azide In water at 0℃; for 0.166667h;	62%

cyclopropanecarboxylic acid chloride (4023-34-1) + 2-fluoro-5-aminopyridine (1827-27-6) → N-(2-fluoro-5-pyridyl)cyclopropane carboxamide (112959-64-5)

Conditions	Yield
With pyridine In dichloromethane	72%

2-chloro-4,6-dimethoxy-1 ,3,5-triazine (3140-73-6) + 2-fluoro-5-aminopyridine (1827-27-6) → N-(6-fluoropyridin-3-yl)-4,6-dimethoxy-1,3,5-triazin-2-amine

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 70℃; for 4h;	72%

3-(tert-butyloxycarbonylamino)propionic acid (3303-84-2) + 2-fluoro-5-aminopyridine (1827-27-6) → tert-Butyl 3-(6-fluoropyridin-3-ylamino)-3-oxopropylcarbamate (1037411-75-8)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 4h;	70.6%

(S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-2-methylpyrrolidine-2-carboxylic acid (1001353-78-1) + 2-fluoro-5-aminopyridine (1827-27-6) → BMS-754807

Conditions	Yield
Stage #1: (S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-2-methylpyrrolidine-2-carboxylic acid With thionyl chloride In N,N-dimethyl-formamide at 5 - 20℃; for 1h; Stage #2: 2-fluoro-5-aminopyridine In N,N-dimethyl-d6-formamide for 24h;	70%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 45℃; for 18h;	18%

potassium thioacyanate (333-20-0) + 2-fluoro-5-aminopyridine (1827-27-6) → 5-fluorothiazolo[5,4-b]pyridin-2-amine (865663-86-1)

Conditions	Yield
With bromine; acetic acid at 0 - 20℃; for 16.5h;	69.2%
With bromine; acetic acid at 0℃; for 0.5h;	69.2%
With bromine; acetic acid at 20℃; for 4h;	61.8%

4-bromo-6-acetamido-1H-indole-2-carboxylic acid ethyl ester + 2-fluoro-5-aminopyridine (1827-27-6) → 4-((6-fluoropyridin-3-yl)amino)-6-acetylamino-1H-indole-2-carboxylic acid ethyl ester

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos In 1,4-dioxane at 90℃; for 1h; Microwave irradiation; Inert atmosphere;	68.9%
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos In 1,4-dioxane at 100℃; Inert atmosphere; Microwave irradiation;	68.9%

2-fluoro-5-aminopyridine (1827-27-6) + 1-benzyl-pyrrolidine-2-carboxylic acid (60169-72-4) → 1-benzyl-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide

Conditions	Yield
Stage #1: 2-fluoro-5-aminopyridine With trimethylaluminum In toluene at 20℃; for 0.5h; Inert atmosphere; Stage #2: 1-benzyl-pyrrolidine-2-carboxylic acid In toluene at 80℃; for 18h; Inert atmosphere;	68.1%

(S)-methyl 1-(4-(5-cyano-1H-pyrazol-3-ylamino)pyrrolo[1,2-f][1,2,4]triazin-2-yl)-2-methylpyrrolidine-2-carboxylate (1001353-08-7) + 2-fluoro-5-aminopyridine (1827-27-6) → (S)-1-(4-(5-cyano-1H-pyrazol-3-ylamino)pyrrolo[1,2-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide

Conditions	Yield
With isopropylmagnesium chloride In tetrahydrofuran at 20℃; for 21h;	68%

2-mesitylenesulphonyl chloride (773-64-8) + 2-fluoro-5-aminopyridine (1827-27-6) → N-(6-fluoro-pyridin-3-yl)-2,4,6-trimethyl-benzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 16h;	68%

Upstream product

• 456-24-6 2-Fluoro-5-nitropyridine 
• 369-50-6 6-fluoronicotinamide 
• 4548-45-2 2-chloro-5-nitropyridine 

Downstream Products

• 171197-80-1 2-fluoro-5-iodopyridine 
• 1109790-64-8 (2S,4S)-benzyl 2-(6-fluoropyridin-3-ylcarbamoyl)-4-methoxypyrrolidine-1-carboxylate 
• 1355326-85-0 N-cyclohexyl-2-(N-(3-fluorophenyl)-2-((6-fluoropyridin-3-yl)amino)acetamido)-2-(o-tolyl)acetamide 
• 171178-41-9 (6-fluoro-pyridin-3-yl)-carbamic acid, tert-butyl ester 
• 171178-42-0 5-[N-(tert-Butoxycarbonyl)-amino]-2-fluoropyridine-4-carboxylic acid 
• 2135696-72-7 (E)-N-(4-((3-bromo-4-chlorophenyl)amino)pyrido[3,4-d]pyrimidin-6-yl)-4-(dimethylamino)but-2-enamide 
• 175357-98-9 4-chloro-6-fluoro-pyrido[3,4-d]pyrimidine 
• 55758-32-2 6-fluoropyridin-3-ol 

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