13362-28-2

Basic information

• Product Name: 2-Aminoisonicotinic acid
• Synonyms: CHEMBRDG-BB 4015121;2-AMINOISONICOTINIC ACID;2-AMINO-4-PYRIDINECARBOXYLIC ACID;2-AMINOPYRIDINE-4-CARBOXYLATE;2-AMINOPYRIDINE-4-CARBOXYLIC ACID;RARECHEM AL BO 2405;2-AMINO-4-PYRIDINECARBOXYLIC ACID AMIDE;4-Pyridinecarboxylicacid,2-amino-(9CI)
• CAS NO: 13362-28-2
• Molecular Formula: C₆H₆N₂O₂
• Molecular Weight: 138.12
• EINECS: -0
• Product Categories: AMINOACID;Amines;blocks;Carboxes;Pyridines;Pyridine series;pyridine derivative;pharmacetical;Carboxylic Acids;Pyridine;Organic acids;Carboxylic Acids
• Mol File: 13362-28-2.mol
• Article Data: 5

Chemical Properties

• Melting Point: 300-302°C
• Boiling Point: 498.5 °C at 760 mmHg
• Flash Point: 255.3 °C
• Appearance: Off-white to brown/Powder
• Density: 1.417 g/cm³
• Vapor Pressure: 9.33E-11mmHg at 25°C
• Refractive Index: 1.649
• Storage Temp.: Keep Cold
• PKA: 2.11±0.10(Predicted)
• BRN: 3156
• CAS DataBase Reference: 2-Aminoisonicotinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Aminoisonicotinic acid(13362-28-2)
• EPA Substance Registry System: 2-Aminoisonicotinic acid(13362-28-2)

Safety Data

• Hazard Codes: Xi,T,Xn
• Statements: 36/37/38-23/24/25-22
• Safety Statements: 26-36-45-36/37/39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 13362-28-2(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow Cryst

InChI:InChI=1/C6H6N2O2/c7-5-3-4(6(9)10)1-2-8-5/h1-3H,(H2,7,8)(H,9,10)

Synthetic route

2-chloroisonicotinic acid, (6313-54-8) → 2-aminoisonicotinic acid (13362-28-2)

Conditions	Yield
With ammonium hydroxide at 190℃;
With ammonia In water at 240℃; for 22h;

2-(acetylamino)isonicotinic acid (54221-95-3) → 2-aminoisonicotinic acid (13362-28-2)

Conditions	Yield
With sodium hydroxide
With sodium hydroxide

2-acetylamino-4-methylpyridine (5327-32-2) → 2-aminoisonicotinic acid (13362-28-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. KMnO4 / 10 h / 75 °C 2: 10percent NaOH View Scheme
Multi-step reaction with 2 steps 1: KMnO4; H2O 2: aqueous NaOH View Scheme
With potassium permanganate; cetyltrimethylammonium chloride; sodium carbonate In water at 55 - 60℃;

2-Amino-4-methylpyridine (695-34-1) → 2-aminoisonicotinic acid (13362-28-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfur / 20 h / 140 - 160 °C 2: sodium hydroxide / water / 50 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: acetyl chloride / 10 h / 115 - 120 °C 2: sodium carbonate; cetyltrimethylammonium chloride; potassium permanganate / water / 55 - 60 °C View Scheme

2-amino-thioisonicotinic acid dimethylamide → 2-aminoisonicotinic acid (13362-28-2)

Conditions	Yield
With sodium hydroxide In water for 50h; Reflux;

ethanol (64-17-5) + 2-aminoisonicotinic acid (13362-28-2) → 2-amino-4-ethoxycarbonyl-pyridine (13362-30-6)

Conditions	Yield
With oxygen In water at 20 - 80℃; for 2h; pH=9; Temperature; pH-value; Reflux;	95.1%
With sulfuric acid

methanol (67-56-1) + 2-aminoisonicotinic acid (13362-28-2) → methyl 2-aminoisonicotinate (6937-03-7)

Conditions	Yield
With thionyl chloride at 0 - 50℃; for 13h; Inert atmosphere;	89%
With sulfuric acid at 80℃; for 72h;	89%
With sulfuric acid at 80℃; for 72h;	86%

2-aminoisonicotinic acid (13362-28-2) → 2-amino-3,4,5,6-tetrahydropyridine-4-carboxylic acid hydrochloride

Conditions	Yield
With hydrogenchloride; hydrogen; platinum(IV) oxide In ethanol under 1499.7 Torr; for 2h; Ambient temperature;	88%

zinc(II) nitrate hexahydrate + N,N-dimethyl acetamide (127-19-5) + 2-aminoisonicotinic acid (13362-28-2) → Zn(2-aminoisonicotinate)2*(N,N-dimethylacetamide)

Conditions	Yield
In N,N-dimethyl acetamide High Pressure; mixt. sealed in vial, heated at 120°C for 3 d; cooled to room temp.; elem. anal.;	88%

zinc(II) nitrate hexahydrate + 2-aminoisonicotinic acid (13362-28-2) + adenine (73-24-5) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → [Zn(adenine(1-))(2-aminoisonicotinate)]*(N,N-dimethylformamide) (1415717-01-9)

Conditions	Yield
at 120℃; for 72h; Autoclave;	88%

zinc(II) nitrate hexahydrate + 2-aminoisonicotinic acid (13362-28-2) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → Zn(2-aminoisonicotinate)2*(N,N-dimethylformamide)

Conditions	Yield
In N,N-dimethyl acetamide High Pressure; mixt. sealed in vial, heated at 120°C for 3 d; cooled to room temp.; elem. anal.;	84.5%

2-aminoisonicotinic acid (13362-28-2) + 4-methoxy-aniline (104-94-9) → 2-amino-N-(4-methoxyphenyl)isonicotinamide

Conditions	Yield
Stage #1: 2-aminoisonicotinic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 4-methoxy-aniline With pyridine; ethylenediamine In ethanol; dichloromethane; N,N-dimethyl-formamide at 20℃; for 2.5h; Reflux; Further stages;	75.5%

2-aminoisonicotinic acid (13362-28-2) + 2-methyl-[1,1′-biphenyl]-3-amine (172975-98-3) → 2-bromo-N-(2-methyl-[1,1'-biphenyl]-3-yl)isonicotinamide

Conditions	Yield
Stage #1: 2-aminoisonicotinic acid 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 dichloromethane for 1h; Stage #2: 2-methyl-[1,1′-biphenyl]-3-amine In dichloromethane	67.9%

5-aminotetrazole (4418-61-5) + 2-aminoisonicotinic acid (13362-28-2) + zinc diacetate (557-34-6) → C6H5N2O2(1-)*CH2N5(1-)*Zn(2+)

Conditions	Yield
In methanol; water at 150℃; for 12h;	65%

(-)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethanamine hydrochloride + 2-aminoisonicotinic acid (13362-28-2) → 2-amino-N-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)isonicotinamide

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 1h;	63%

2-aminoisonicotinic acid (13362-28-2) + acetic anhydride (108-24-7) → 2-(acetylamino)isonicotinic acid (54221-95-3)

Conditions	Yield
With sulfuric acid In water at 90℃;	60%

2-aminoisonicotinic acid (13362-28-2) + N,N-dimethylammonium chloride (506-59-2) → C8H11N3O

Conditions	Yield
Stage #1: 2-aminoisonicotinic acid; N,N-dimethylammonium chloride With triethylamine In N,N-dimethyl-formamide at 10℃; for 0.166667h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	55.2%

2-methoxy-ethanol (109-86-4) + 2-aminoisonicotinic acid (13362-28-2) → (2-methoxyethyl)-2-aminoisonicotinoate

Conditions	Yield
With sulfuric acid at 120 - 140℃; for 48h;	49%

6-benzyloxy-1-[(E)-2-(5-benzyloxy-4-methoxy-2-methyl-phenyl)vinyl]-7-methoxy-1,2,3,4-tetrahydroisoquinoline + 2-aminoisonicotinic acid (13362-28-2) → (2-amino-4-pyridyl)-[6-benzyloxy-1-[(E)-2-(5-benzyloxy-4-methoxy-2-methyl-phenyl)vinyl]-7-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]methanone

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 1h;	46%

4-[3-amino-1-(4-fluoro-phenyl)-propyl]-N-methyl-benzamide (914386-75-7) + 2-aminoisonicotinic acid (13362-28-2) → 2-Amino-N-[3-(4-fluoro-phenyl)-3-(4-methylcarbamoyl-phenyl)-propyl]-isonicotinamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide	44.2%

2-aminoisonicotinic acid (13362-28-2) → (E)-2,2'-(diazene-1,2-diyl)diisonicotinic acid

Conditions	Yield
With sodium hypochlorite; sodium hydroxide In water at 0 - 5℃; for 4.25h;	44%

2-aminoisonicotinic acid (13362-28-2) + benzylamine (100-46-9) → 2-amino-N-benzylisonicotinamide (301542-44-9)

Conditions	Yield
Stage #1: 2-aminoisonicotinic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: benzylamine With benzotriazol-1-ol In N,N-dimethyl-formamide at 20℃; for 72h;	43%

7-methoxy-8-[3-(morpholin-4-yl)propoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine (1032570-74-3) + 2-aminoisonicotinic acid (13362-28-2) → 2-amino-N-{7-methoxy-8-[3-(morpholin-4-yl)propoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}isonicotinamide (1032568-46-9)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	37%
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	37%

2-amino-3-hydroxypyridine (16867-03-1) + 2-aminoisonicotinic acid (13362-28-2) → 4-(oxazolo[4,5-b]pyridin-2-yl)pyridin-2-amine (925438-78-4)

Conditions	Yield
With polyphosphoric acid at 220℃; for 4h;	36%

N-(3-amino-4-methylphenyl)-3-(trifluoromethyl)benzamide (30069-31-9) + 2-aminoisonicotinic acid (13362-28-2) → 2-amino-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)isonicotinamide (1186206-76-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 12h;	35%

chloro-trimethyl-silane (75-77-4) + 2-aminoisonicotinic acid (13362-28-2) + (2S,4S)-4-Acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-carboxypyrrolidine → (2S,4S)-1-(4-nitrobenzyloxycarbonyl)-2-(4-carboxy-2-pyridylcarbamoyl)pyrrolidin-4-ylthioacetate

Conditions	Yield
With thionyl chloride; N-ethyl-N,N-diisopropylamine; N,N-dimethyl-formamide In dichloromethane	32.5%

Upstream product

• 695-34-1 2-Amino-4-methylpyridine 
• 5327-32-2 2-acetylamino-4-methylpyridine 
• 6313-54-8 2-chloroisonicotinic acid, 
• 54221-95-3 2-(acetylamino)isonicotinic acid 

Downstream Products

• 54221-95-3 2-(acetylamino)isonicotinic acid 
• 75279-39-9 N-(4-aminopyridin-2-yl)acetamide 
• 639091-75-1 methyl 2-[(tert-butoxycarbonyl)amino]isonicotinate 

Relevant articles and documents

Preparation method of 2-aminopyridine-4-methanol medical intermediate

The invention discloses a preparation method of a 2-aminopyridine-4-methanol medical intermediate. By virtue of the preparation method, the 2-aminopyridine-4-methanol medical intermediate is prepared from 2-aminopyridine-4-methyl sequentially through acet

Discovery of an N-(2-aminopyridin-4-ylmethyl)nicotinamide derivative: A potent and orally bioavailable NCX inhibitor

Ca2+ overload in myocardial cells is responsible for arrhythmia. Sodium-calcium exchanger (NCX) inhibitors are more effective than sodium-hydrogen exchanger (NHE) inhibitors with regard to modulation of Ca 2+ overload, because NCX inhibitors can directly inhibit the influx of Ca2+ into cells. NCX is an attractive target for the treatment of heart failure and ischemia-reperfusion. We have designed and synthesized a series of N-(2-aminopyridin-4-ylmethyl)nicotinamide derivatives, based on compound 5. We have discovered a novel NCX inhibitor (23h) with an IC 50 value of 0.12 μM against reverse NCX. The inhibitory activities of our NCX inhibitors against cytochrome P450 were also evaluated. The effects on heart failure and the pharmacokinetic profile of compound 23h are discussed.

Substituent Effects on the Isomer Ratios in the Rearrangement of Some 2- and 4-Nitraminopyridines

The preparation, and rearrangement in 92percent sulfuric acid, of 4-X-2-nitramino- (1), 2-X-4-nitramino- (2), and 6-X-2-nitramino-pyridines (3) is reported (X=H,Me,MeO,Br,Cl,CO2H).The product isomer ratios can be explained by differential electronic stabilization of the appropriate ? complexes for aromatic nitration and steric effects seem relatively unimportant.Deuteration had no effect on the product distribution