16498-81-0

Basic information

• Product Name: 2-Methoxynicotinic acid
• Synonyms: 2-Methoxylnicotinicacid;RARECHEM AH CK 0125;TIMTEC-BB SBB005441;BUTTPARK 94\04-28;AKOS GLO-BB-364;2-METHOXYNICOTINIC ACID;2-METHOXY-3-PYRIDINECARBOXYLIC ACID;2-Methoxyniconitic acid
• CAS NO: 16498-81-0
• Molecular Formula: C₇H₇NO₃
• Molecular Weight: 153.14
• EINECS: 605-381-2
• Product Categories: blocks;Carboxes;Pyridines;Pyridine;Niacin;Organic acids;CHIRAL CHEMICALS
• Mol File: 16498-81-0.mol
• Article Data: 5

Chemical Properties

• Melting Point: 146-150 °C(lit.)
• Boiling Point: 285.5 °C at 760 mmHg
• Flash Point: 126.5 °C
• Appearance: /
• Density: 1.284 g/cm³
• Vapor Pressure: 0.0013mmHg at 25°C
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 3.36±0.10(Predicted)
• CAS DataBase Reference: 2-Methoxynicotinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methoxynicotinic acid(16498-81-0)
• EPA Substance Registry System: 2-Methoxynicotinic acid(16498-81-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36-36/37/38
• Safety Statements: 26-37/39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 16498-81-0(Hazardous Substances Data)

Usage

Chemical Properties

White solid

Uses

2-Methoxynicotinic Acid can be used as potenti antifungal agent.

InChI:InChI=1/C7H7NO3/c1-11-6-5(7(9)10)3-2-4-8-6/h2-4H,1H3,(H,9,10)/p-1

Synthetic route

2-chloronicotinic acid (2942-59-8) + sodium methylate (124-41-4) → 2-methoxynicotinic acid (16498-81-0)

Conditions	Yield
In methanol at 125℃; autoclave;	64%

2-chloronicotinic acid (2942-59-8) → 2-methoxynicotinic acid (16498-81-0)

Conditions	Yield
With sodium methylate In methanol; water

2-methoxynicotinic acid methyl ester (67367-26-4) → 2-methoxynicotinic acid (16498-81-0)

Conditions	Yield
Stage #1: 2-methoxynicotinic acid methyl ester With water; sodium hydroxide In methanol for 2h; Reflux; Stage #2: With hydrogenchloride In methanol; water pH=7;

2-methoxynicotinic acid (16498-81-0) → 2-methoxypyridine-3-carbonyl chloride (53750-65-5)

Conditions	Yield
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 27℃; for 2h; Inert atmosphere;	98%
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 27℃; for 2h; Inert atmosphere;	98%
With sulfuryl dichloride In dichloromethane for 2h; Heating;

2-methoxynicotinic acid (16498-81-0) + 1-bromo-2-(triisopropylsilyl)acetylene (111409-79-1) → methyl 2-methoxy-4-((triisopropylsilyl)ethynyl)nicotinate

Conditions	Yield
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; potassium carbonate at 90℃; for 14h;	92%

(±)-ethyl 2-(5-methoxy-1,2,3,4,5,6-hexahydro-7H-2,6-methanoazocino[5,4-b]indol-7-yl)acetate + 2-methoxynicotinic acid (16498-81-0) → (±)-ethyl 2-(5-methoxy-3-(2-methoxynicotinoyl)-1,2,3,4,5,6-hexahydro-7H-2,6-methanoazocino[5,4-b]indol-7-yl)acetate

Conditions	Yield
Stage #1: 2-methoxynicotinic acid With thionyl chloride In N,N-dimethyl-formamide; toluene for 1h; Reflux; Stage #2: (±)-ethyl 2-(5-methoxy-1,2,3,4,5,6-hexahydro-7H-2,6-methanoazocino[5,4-b]indol-7-yl)acetate With triethylamine In dichloromethane at 20℃;	92%

2-methoxynicotinic acid (16498-81-0) → 2-methoxy-5-iodonicotinic acid

Conditions	Yield
With N-iodo-succinimide; acetic acid at 35℃; for 16h;	90%

N1-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)benzene-1,4-diamine (1428155-03-6) + 2-methoxynicotinic acid (16498-81-0) → 2-methoxy-N-(4-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)phenyl)pyridine-3-carboxamide (1428155-13-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	89%

2-methoxynicotinic acid (16498-81-0) → 3-Bromo-2-methoxypyridine (13472-59-8)

Conditions	Yield
With potassium phosphate; tetrabuthylammonium tribromide In acetonitrile at 100℃;	88%

methyl 5-amino-6-(4-(2,4-difluorophenoxy)piperidin-1-yl)nicotinate + 2-methoxynicotinic acid (16498-81-0) → methyl 6-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5-(2-methoxynicotinamido)nicotinate

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one; ethyl acetate at 60℃;	88%

2-methoxynicotinic acid (16498-81-0) → 5-bromo-2-methoxy-nicotinic acid (54916-66-4)

Conditions	Yield
With N-Bromosuccinimide In water at 20 - 25℃; for 16h; Reagent/catalyst; Temperature;	87%
With bromine In water at 20℃;	82%
With bromine In water at 20℃;	82%

3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)aniline (1428155-06-9) + 2-methoxynicotinic acid (16498-81-0) → 2-methoxy-N-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)phenyl)pyridine-3-carboxamide (1428155-48-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	86%

methanol (67-56-1) + 2-methoxynicotinic acid (16498-81-0) → 2-methoxynicotinic acid methyl ester (67367-26-4)

Conditions	Yield
Stage #1: methanol; 2-methoxynicotinic acid With sulfuric acid for 6h; Reflux; Stage #2: With sodium hydrogencarbonate In water	85%
Stage #1: methanol; 2-methoxynicotinic acid With sulfuric acid for 6h; Reflux; Stage #2: With sodium hydrogencarbonate In water	85%
With sulfuric acid at 0 - 65℃; for 6h;

2-fluoro-N1-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)benzene-1,4-diamine (1428155-04-7) + 2-methoxynicotinic acid (16498-81-0) → N-(3-fluoro-4-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)phenyl)-2-methoxypyridine-3-carboxamide (1428155-20-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	83%

2-methoxynicotinic acid (16498-81-0) + 5-((((9H-fluoren-9-yl)methoxy)carbonylamino)methyl)thiophene-2-carboxylic acid (476362-75-1) → N-((5-(hydroxycarbamoyl)thiophen-2-yl)methyl)-2-methoxynicotinamide

Conditions	Yield
Stage #1: 5-((((9H-fluoren-9-yl)methoxy)carbonylamino)methyl)thiophene-2-carboxylic 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 N,N-dimethyl-formamide for 1h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.333333h; Stage #3: 2-methoxynicotinic acid Further stages;	80%

di(n-butyl)tin oxide (818-08-6) + 2-methoxynicotinic acid (16498-81-0) → C60H96N4O14Sn4

Conditions	Yield
In ethanol at 80 - 90℃; for 10h;	80%

N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) + 2-methoxynicotinic acid (16498-81-0) → N,2-dimethoxy-N-methylnicotinamide (926003-56-7)

Conditions	Yield
Stage #1: 2-methoxynicotinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With pyridine In dichloromethane at 0 - 20℃; for 18h;	78%
Stage #1: 2-methoxynicotinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 1h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With pyridine In dichloromethane at 0 - 20℃; for 18h;	61%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane for 18h; Cooling;	51%
Stage #1: N,O-dimethylhydroxylamine*hydrochloride; 2-methoxynicotinic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In chloroform for 6h; Cooling with ice; Stage #2: dmap at 20℃;

2-methoxynicotinic acid (16498-81-0) + acetone (67-64-1) → 4-bromo-1,1-dimethyl-1H-furo[3,4-c]pyridin-3-one

Conditions	Yield
Stage #1: 2-methoxynicotinic acid With 2,2,6,6-tetramethyl-piperidine; n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: acetone In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #3: With hydrogen bromide; acetic acid In ethanol for 3h; Heating;	76%

2-methoxynicotinic acid (16498-81-0) → 5-chloro-2-methoxypyridine-3-carboxylic acid (54916-65-3)

Conditions	Yield
With sodium hypochlorite Ambient temperature;	75%
With sodium hypochlorite Ambient temperature;	75%
In chloroform; water
With hydrogenchloride In aqueous sodium hypochlorite	195 mg. (52%)
In chloroform; water

2-methoxynicotinic acid (16498-81-0) + propionaldehyde (123-38-6) → 1-ethyl-4-methoxyfuro[3,4-c]pyridin-3(1H)-one (1357194-87-6)

Conditions	Yield
Stage #1: 2-methoxynicotinic acid With n-butyllithium In tetrahydrofuran; hexane at -65℃; for 1h; Inert atmosphere; Stage #2: propionaldehyde In tetrahydrofuran; hexane at 20℃; for 3h; Inert atmosphere;	75%

rac-6-(4-(2,2-difluorocyclobutyl)-4H-1,2,4-triazol-3-yl)pyridin-2-amine + 2-methoxynicotinic acid (16498-81-0) → rac-N-(6-(4-(2,2-difluorocyclobutyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-methoxynicotinamide

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 110℃; for 1h; Microwave irradiation;	75%

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + 2-methoxynicotinic acid (16498-81-0) → 2-Methoxynicotinic acid N-succinimide ester (76988-05-1)

Conditions	Yield
With dicyclohexyldicarboimide In 1,4-dioxane at 20℃; for 6.5h;	74%

4-nitro-phenol (100-02-7) + 2-methoxynicotinic acid (16498-81-0) → 2-Methoxy-nicotinic acid 4-nitro-phenyl ester

Conditions	Yield
With dicyclohexyldicarboimide In pyridine	74%

2,2'-dipyridyldisulphide (2127-03-9) + 2-methoxynicotinic acid (16498-81-0) → S-pyridin-2-yl 2-methoxypyridine-3-carbothioate

Conditions	Yield
With triphenylphosphine In tetrahydrofuran at 20℃; for 6h; Inert atmosphere;	74%
With triphenylphosphine In tetrahydrofuran at 25℃; for 12h; Inert atmosphere;	72%

4-(4-(2,4-difluorophenoxy)piperidin-1-yl)-6-methoxypyridin-3-amine + 2-methoxynicotinic acid (16498-81-0) → N-(4-(4-(2,4-difluorophenoxy)piperidin-1-yl)-6-methoxypyridin-3-yl)-2-methoxynicotinamide

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one; ethyl acetate at 50℃; for 7h;	73.2%

C10H8BrN3O + 2-methoxynicotinic acid (16498-81-0) → N-(5-(4-bromophenyl)-1H-pyrazol-3-yl)-2-methoxynicotinamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;	73%

(+)-10-amino-2-pyrimidin-4-yl-7,8,9,10-tetrahydropyrimido[1,2-a]azepin-4(6H)-one + 2-methoxynicotinic acid (16498-81-0) → (+)-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydro-pyrimido[1,2-a]azepin-10-yl)-nicotinamide

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	70%

rac-6-[4-(2,2-difluoro-1-methyl-ethyl)-1,2,4-triazol-3-yl]pyridin-2-amine + 2-methoxynicotinic acid (16498-81-0) → rac-N-(6-(4-(1,1-difluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-methoxynicotinamide

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 80℃; for 3h;	70%

2-aminomethyl-1-methyl-1H-[4,4']bipyrimidinyl-6-one (1083006-42-1) + 2-methoxynicotinic acid (16498-81-0) → 2-Methoxy-N-(1-methyl-6-oxo-1,6-dihydro-[4,4']bipyrimidinyl-2-ylmethyl)-nicotinamide (1083006-12-5)

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 1h;	68%

C10H9N3O + 2-methoxynicotinic acid (16498-81-0) → 2-methoxy-N-(5-phenyl-1H-pyrazol-3-yl)nicotinamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;	68%

2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5-(methoxymethyl)pyridin-3-amine + 2-methoxynicotinic acid (16498-81-0) → N-(2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5-(methoxymethyl)pyridin-3-yl)-2-methoxynicotinamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl acetamide at 80℃; for 2h;	64%

3-amino-4-(4-((4-fluorophenyl)(methoxy)methyl)piperidin-1-yl)benzonitrile + 2-methoxynicotinic acid (16498-81-0) → N-(5-cyano-2-(4-((4-fluorophenyl)(methoxy)methyl)piperidin-1-yl)phenyl)-2-methoxynicotinamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 80℃; for 12h;	63.5%

Upstream product

• 2942-59-8 2-chloronicotinic acid 
• 124-41-4 sodium methylate 
• 67367-26-4 2-methoxynicotinic acid methyl ester 

Downstream Products

• 1381759-77-8 C₂₉H₃₂ClN₃O₆ 
• 1365997-30-3 C₂₀H₂₀ClN₃O₃ 
• 13472-59-8 3-Bromo-2-methoxypyridine 
• 893440-50-1 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine 
• 1407521-93-0 2-methoxy-5-iodonicotinic acid 
• 131674-40-3 1-(2-methoxypyridin-3-yl)ethanone 
• 1204535-60-3 (2S)-2-Methyl-1-{[2-(methyloxy)-3-pyridinyl]carbonyl}-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine 
• 1195760-39-4 N-(2-aminophenyl)-6-(2-((2-methoxy-pyridin-3-ylcarbonyl)amino)ethyl-amino)nicotinamide 
• 884502-25-4 1-(2-methoxypyridin-3-yl)-3-(4-nitrophenyl)propane-1,3-dione 
• 1128191-18-3 N-[4-chloro-3-(1,5-dimethylimidazol-2-yl)phenyl]-2-methoxy-pyridine-3-carboxamide 
• 82060-51-3 methyl 5-Chloro-2-methoxypyridine-3-carboxylate 
• 122433-46-9 5-chloro-2-methoxy-3-acetylpyridine 
• 122433-49-2 6-chloro-2,3-dihydro-4H-pyrano<2,3-b>pyridin-4-one 
• 76980-28-4 N-2-Methoxynicotinoylglutamic acid 

Relevant articles and documents

FLAVIN DERIVATIVES

The present invention relates novel flavin derivatives and other flavin derivatives, their use and compositions for use as riboswitch ligands and/or anti-infectives. The invention also provides method of making novel flavin derivatives.

AN IMPROVED METHOD OF CHLORINATING 2-ALKOXYNICOTINIC ACIDS

A novel chlorination process for preparing 5-chloro-2-alkoxynicotinic acids has been developed using commercial 5.25percent sodium hypochlorite (Clorox) as a chlorinating agent.

4-Substituted-1-piperidinesulfonamides

A series of novel 1-piperidinesulfonylurea compounds derived from a nitrogen-containing monocarboxylic acid have been prepared by reacting an appropriate sulfamide with an organic isocyanate or a trisubstituted urea equivalent thereof. The sulfamylureas so obtained are useful in therapy as oral hypoglycemic agents. Typical members include those compounds derived from 2-methoxynicotinic acid, of which 1-(bicyclo[2.2.1]hept-5-en-2-yl-endomethyl)-3-{4-[2-(2-methoxynicotinamido)ethyl]-1-piperidinesulfonyl}urea is a most preferred embodiment.