29082-92-6

Usage

Uses

A natural imino acid.

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

Synthetic route

5-hydroxypicolinic acid (15069-92-8) + methyl iodide (74-88-4) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
With silver(l) oxide In dimethyl sulfoxide for 2h; Ambient temperature;	48%

5-amino-pyridine-2-carboxylic acid (24242-20-4) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) conc. H2SO4, NaNO2; 2) conc. H2SO4 / 1) H2O, 0 deg C, 5 min; 2) reflux, H2O 2: 48 percent / Ag2O / dimethylsulfoxide / 2 h / Ambient temperature View Scheme

5-nitro-pyridin-2-ylamine (4214-76-0) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions

Yield

Multi-step reaction with 6 steps 1: 1.) 48 percent HBr, Br2; 2.) NaNO2 / 1) 30-40 deg C; 2) -5 deg C, H2O; 10-15 Deg C, 90 min.; 3) 40 deg C. 15 min 2: dimethylsulfoxide / 0.08 h / 180 °C 3: 54 percent / HCl / 1.5 h / Heating 4: 70 percent / H2S, 25 percent NH3 5: 1) conc. H2SO4, NaNO2; 2) conc. H2SO4 / 1) H2O, 0 deg C, 5 min; 2) reflux, H2O 6: 48 percent / Ag2O / dimethylsulfoxide / 2 h / Ambient temperature View Scheme

2-bromo-5-nitropyridine (4487-59-6) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: dimethylsulfoxide / 0.08 h / 180 °C 2: 54 percent / HCl / 1.5 h / Heating 3: 70 percent / H2S, 25 percent NH3 4: 1) conc. H2SO4, NaNO2; 2) conc. H2SO4 / 1) H2O, 0 deg C, 5 min; 2) reflux, H2O 5: 48 percent / Ag2O / dimethylsulfoxide / 2 h / Ambient temperature View Scheme

5-nitropyridine-2-carbonitrile (100367-55-3) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 54 percent / HCl / 1.5 h / Heating 2: 70 percent / H2S, 25 percent NH3 3: 1) conc. H2SO4, NaNO2; 2) conc. H2SO4 / 1) H2O, 0 deg C, 5 min; 2) reflux, H2O 4: 48 percent / Ag2O / dimethylsulfoxide / 2 h / Ambient temperature View Scheme

5-nitropicolinic acid (30651-24-2) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 70 percent / H2S, 25 percent NH3 2: 1) conc. H2SO4, NaNO2; 2) conc. H2SO4 / 1) H2O, 0 deg C, 5 min; 2) reflux, H2O 3: 48 percent / Ag2O / dimethylsulfoxide / 2 h / Ambient temperature View Scheme

5-methoxy-2-picoline (55270-47-8) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
With potassium permanganate In water; toluene
With potassium permanganate In water; toluene
With pyridine; selenium(IV) oxide for 62h; Heating / reflux;

5-methoxypyridine-2-carbonitrile (89809-63-2) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
With hydrogenchloride; water Heating / reflux;

2-bromo-5-methoxypyridine (105170-27-2) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; palladium diacetate; 1,3-bis-(diphenylphosphino)propane / N,N-dimethyl-formamide / 24 h / 100 °C / 37503.8 Torr 2: water; lithium hydroxide monohydrate / methanol / 12 h / 10 - 35 °C View Scheme

5-methoxypyridine-2-carboxylic acid methyl ester (29681-39-8) → 5-methoxypyridine-2-carboxylic acid (29082-92-6)

Conditions	Yield
With lithium hydroxide monohydrate; water In methanol at 10 - 35℃; for 12h;	2.4 g

5-methoxypyridine-2-carboxylic acid (29082-92-6) → 5-methoxypyridine-2-carbonyl chloride (88166-64-7)

Conditions	Yield
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane; toluene at 0 - 20℃; for 2h;	100%
With thionyl chloride at 50℃; for 3h;	100%
With thionyl chloride In tetrahydrofuran; N,N-dimethyl-formamide

5-methoxypyridine-2-carboxylic acid (29082-92-6) + (R)-Bornylamine (32511-34-5) → 5-methoxy-N-((1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)picolinamide

Conditions	Yield
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 20℃; for 16h; Inert atmosphere;	98%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + t-butoxycarbonylhydrazine (870-46-2) → tertbutyl 2-(5-methoxypicolinoyl)hydrazinecarboxylate

Conditions	Yield
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 at 20℃; for 16h;	93%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + 1-(2-(4-methoxyphenoxy)ethyl)piperazine (117132-44-2) → (4-(2-(4-methoxyphenoxy)ethyl)piperazin-1-yl)(5-methoxypyridin-2-yl)methanone

Conditions	Yield
Stage #1: 5-methoxypyridine-2-carboxylic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: 1-(2-(4-methoxyphenoxy)ethyl)piperazine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	93%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → N,5‐dimethoxy‐N-methylpicolinamide (858599-72-1)

Conditions	Yield
Stage #1: 5-methoxypyridine-2-carboxylic acid With 1,1'-carbonyldiimidazole In dichloromethane at 30℃; for 3h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In dichloromethane for 2h;	90%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 14.5h;

5-methoxypyridine-2-carboxylic acid (29082-92-6) → 5-methoxy-6-nitropyridine-2-carboxylic acid (324028-85-5)

Conditions	Yield
With Vilsmeier reagent; potassium nitrate In neat (no solvent) at 100℃; under 1500.15 Torr; Reagent/catalyst; Temperature; Microwave irradiation;	89%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + aniline (62-53-3) → 5-methoxy-N-phenylpicolinamide (1575754-48-1)

Conditions	Yield
Stage #1: 5-methoxypyridine-2-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; Inert atmosphere; Stage #2: aniline With triethylamine In dichloromethane at 0 - 20℃;	85%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	79%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + N-[(4aR,6S,8aR)-8a-(4-amino-1,3-thiazol-2-yl)-6-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide → N-(2-((4aR,6S,8aR)-2-benzamido-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl)thiazol-4-yl)-5-methoxypicolinamide

Conditions

Yield

Stage #1: 5-methoxypyridine-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 at 15℃; for 0.5h; Inert atmosphere; Stage #2: N-[(4aR,6S,8aR)-8a-(4-amino-1,3-thiazol-2-yl)-6-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide In N,N-dimethyl-formamide at 20℃; for 32h; Inert atmosphere;

85%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + (1-methylcyclohexyl)methanamine (3913-98-2) → 5-methoxy-N-((1-methylcyclohexyl)methyl)picolinamide

Conditions	Yield
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 20℃; for 16h; Inert atmosphere;	85%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + 1-(2-amino-4-ethynylphenyl)propan-1-one → N-(5-ethynyl-2-propionylphenyl)-5-methoxypicolinamide

Conditions	Yield
Stage #1: 5-methoxypyridine-2-carboxylic acid With N-ethyl-N,N-diisopropylamine; O‐(1H‐benzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: 1-(2-amino-4-ethynylphenyl)propan-1-one In N,N-dimethyl-formamide at 150 - 154℃; for 0.5h; Microwave irradiation;	83%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + 1,1-Dimethyl-3-phenyl-propylamin (43052-72-8) → C18H22N2O2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 12h;	82%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + bis[2-(2,4-difluorophenyl)pyridinato-N,C6']iridium(III) chloride dimer → (2,4-difluorophenylpyridine(1-))2Ir(5-methoxypicolinate(1-)) (1392214-65-1)

Conditions	Yield
With Na2CO3 In 2-ethoxy-ethanol soln. Ir complex, ligand and Na2CO3 in 2-ethoxyethanol was refluxed for 24 h; solvent was roto-evapd., residue was chromed. on silica (CH2Cl2 - n-hexane);	80%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + 2-((2-aminoethyl)amino)-5,7-dimethylquinoline-3-carbonitrile (604754-35-0) → N-(2-((3-cyano-5,7-dimethylquinolin-2-yl)amino)ethyl)-5-methoxypicolinamide (1356485-87-4)

Conditions	Yield
Stage #1: 5-methoxypyridine-2-carboxylic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 0.5h; Stage #2: 2-((2-aminoethyl)amino)-5,7-dimethylquinoline-3-carbonitrile In dichloromethane for 18h;	78%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + 2-Methylbutylamine (96-15-1) → 5-methoxy-N-(2-methylbutyl)picolinamide

Conditions	Yield
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 20℃; for 16h; Inert atmosphere;	76%

5-methoxypyridine-2-carboxylic acid (29082-92-6) → 5-methoxypicolinic acid N-oxide (672957-93-6)

Conditions	Yield
With urea hydrogen peroxide adduct; trifluoroacetic anhydride In dichloromethane at 0 - 20℃; for 1.5h;	75%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 60℃; for 12h;	36%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 60℃; for 12h;	36%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + 2,6-dichlorobenzenesulfonamide (10290-98-9) → N-[(2,6-Dichlorophenyl)sulfonyl]-5-methoxy-2-pyridinecarboxamide (204378-24-5)

Conditions	Yield
	63.7%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + benzene (71-43-2) → 5-methoxyl-2-phenylpyridine (53698-54-7)

Conditions	Yield
With tert-butylhypochlorite; potassium carbonate at 80℃; for 20h;	63%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + (2S,4R)-4-hydroxy-α,α-diphenyl-2-pyrrolidinemethanol (176747-44-7) → ((2S,4R)-4-hydroxy-2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)(5-methoxypyridin-2-yl)methanone (1217168-93-8)

Conditions	Yield
Stage #1: 5-methoxypyridine-2-carboxylic acid With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at 0℃; for 1.25h; Stage #2: (2S,4R)-4-hydroxy-α,α-diphenyl-2-pyrrolidinemethanol In tetrahydrofuran at 0 - 20℃;	61%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + 5-(4-(4-aminophenyl)piperazin-1-yl)picolinonitrile → N-(4-(4-(6-cyanopyridin-3-yl)piperazin-1-yl)phenyl)-5-methoxypicolinamide

Conditions	Yield
Stage #1: 5-methoxypyridine-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 at 20℃; for 0.333333h; Stage #2: 5-(4-(4-aminophenyl)piperazin-1-yl)picolinonitrile In N,N-dimethyl-formamide at 20℃;	35%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + 2-amino-4-bromo-benzoic acid methyl ester (135484-83-2) → methyl 4-bromo-2-(5-methoxypicolinamido)benzoate

Conditions	Yield
Stage #1: 5-methoxypyridine-2-carboxylic acid With N-ethyl-N,N-diisopropylamine; O‐(1H‐benzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: 2-amino-4-bromo-benzoic acid methyl ester In N,N-dimethyl-formamide at 80℃; for 0.5h; Microwave irradiation;	29%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + (R)-4-(5-amino-2-fluorophenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (1310350-45-8) → C18H17F3N4O3 (1432512-05-4)

Conditions	Yield
Stage #1: 5-methoxypyridine-2-carboxylic acid With 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In methanol at 0℃; for 0.5h; Stage #2: (R)-4-(5-amino-2-fluorophenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine In methanol at 0 - 22℃; for 20h;	26%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + o-hydroxyacetophenone (118-93-4) → C15H13NO4 (884501-85-3)

Conditions	Yield
With pyridine; trichlorophosphate at 20℃; for 24h;	24%

5-methoxypyridine-2-carboxylic acid (29082-92-6) + methyl 2-(aminosulfonyl)benzoate (57683-71-3) → 2-[[[(5-Methoxypyridin-2-yl)carbonyl]amino]-sulfonyl]benzoic Acid Methyl Ester (204378-16-5)

Conditions	Yield
	16.5%

5-methoxypyridine-2-carboxylic acid (29082-92-6) → 5-hydroxypicolinic acid (15069-92-8)

Conditions	Yield
With hydrogen iodide

Upstream product

• 15069-92-8 5-hydroxypicolinic acid 
• 74-88-4 methyl iodide 
• 100367-55-3 5-nitropyridine-2-carbonitrile 
• 30651-24-2 5-nitropicolinic acid 
• 29681-39-8 5-methoxypyridine-2-carboxylic acid methyl ester 
• 105170-27-2 2-bromo-5-methoxypyridine 
• 89809-63-2 5-methoxypyridine-2-carbonitrile 
• 55270-47-8 5-methoxy-2-picoline 
• 4487-59-6 2-bromo-5-nitropyridine 
• 4214-76-0 5-nitro-pyridin-2-ylamine 
• 24242-20-4 5-amino-pyridine-2-carboxylic acid 

Downstream Products

• 15069-92-8 5-hydroxypicolinic acid 
• 30766-12-2 methyl 5-hydroxypicolinate 
• 204378-24-5 N-[(2,6-Dichlorophenyl)sulfonyl]-5-methoxy-2-pyridinecarboxamide 
• 88166-64-7 5-methoxypyridine-2-carboxylic acid chloride 
• 884501-85-3 C₁₅H₁₃NO₄ 
• 1217168-93-8 ((2S,4R)-4-hydroxy-2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)(5-methoxypyridin-2-yl)methanone 
• 1624605-00-0 N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-methoxypicolinamide 
• 1624605-08-8 N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-chloro-4-fluorophenyl)-5-methoxypicolinamide 
• 1624605-28-2 N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluoro-5-methylphenyl)-5-methoxypicolinamide 
• 1448793-24-5 N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-methoxypicolinamide 
• 1624604-45-0 N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)phenyl)-5-methoxypicolinamide 
• 1624604-56-3 N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-methoxypicolinamide 
• 325796-84-7 1‐(5‐methoxypyridin‐2‐yl)ethan‐1‐one 
• 67310-56-9 1-(5-hydroxy-pyridin-2-yl)-ethanone 

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