3222-49-9

Basic information

• Product Name: 5-Methylnicotinic acid
• Synonyms: 5-METHYLNICOTINIC ACID;5-METHYPYRIDINE-3-CARBOXYLIC ACID;5-METHYLPYRIDINE-3-CARBOXYLIC ACID;RARECHEM AL BO 2392;5-Methylnicotinicacid,97%;5-METHYL-3-PYRIDINECARBOXYLICACID;5-Methylnicotinic acid, tech;5-Methylnicotic acid
• CAS NO: 3222-49-9
• Molecular Formula: C₇H₇NO₂
• Molecular Weight: 137.14
• EINECS: -0
• Product Categories: Nitrogen cyclic compounds;Pyridine Series;pharmacetical;Building Blocks;Pyridine;Pyridines
• Mol File: 3222-49-9.mol
• Article Data: 9

Chemical Properties

• Melting Point: 210-212°C
• Boiling Point: 303.9 °C at 760 mmHg
• Flash Point: 137.6 °C
• Appearance: white crystalline powder
• Density: 1.23 g/cm³
• Vapor Pressure: 0.328Pa at 25℃
• Storage Temp.: Room temperature.
• Solubility: Sparingly soluble (0.083 g/L at 25°C).
• PKA: 2.27±0.10(Predicted)
• BRN: 112288
• CAS DataBase Reference: 5-Methylnicotinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Methylnicotinic acid(3222-49-9)
• EPA Substance Registry System: 5-Methylnicotinic acid(3222-49-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 3222-49-9(Hazardous Substances Data)

Usage

Chemical Properties

Solid

Uses

5-Methylnicotinic acid is an important raw material and intermediate used in organic synthesis, pharmaceuticals and agrochemicals.

Synthetic route

1-(5-methylpyridin-3-yl)ethanone (42972-46-3) → 5-methylnicotinic acid (3222-49-9)

Conditions	Yield
With sodium hydroxide; bromine In water Ambient temperature;	61%

3,5-Lutidine (591-22-0) → 5-methylnicotinic acid (3222-49-9)

Conditions	Yield
With potassium permanganate In water at 25 - 45℃; for 20h;	59.4%
With potassium permanganate In water at 45℃;	46%
With potassium permanganate at 45℃; for 20h;	41%
With potassium permanganate In water; acetone at 70℃; for 2h; Title compound not separated from byproducts;

3,5-Lutidine (591-22-0) → 5-methylnicotinic acid (3222-49-9) + 3,5-Pyridinedicarboxylic acid (499-81-0)

Conditions	Yield
With potassium permanganate In water 1.) from RT to 43 deg C, 5 h, 2.) 45 deg C, overnight;	A 27% B n/a

3-methylquinoline (612-58-8) → 5-methylnicotinic acid (3222-49-9)

Conditions	Yield
With potassium permanganate Erhitzen des Reaktionsprodukts im Hochvakuum;

3-methyl-5-pentyl-pyridine (112945-08-1) → 5-methylnicotinic acid (3222-49-9)

Conditions	Yield
With potassium permanganate

3-methyl-pyridine-dicarboxylic acid-(2.5) → 5-methylnicotinic acid (3222-49-9)

Conditions	Yield
With acetic anhydride; acetic acid at 225℃;

5-methyl-pyridine-dicarboxylic acid-(2.3) → 5-methylnicotinic acid (3222-49-9)

Conditions	Yield
With acetic anhydride; acetic acid at 225℃;

3-methylquinoline (612-58-8) + water (7732-18-5) + permanganate → 5-methylnicotinic acid (3222-49-9) + 5-methyl-pyridine-2,3-dicarboxylic acid (53636-65-0)

methanol (67-56-1) + 5-methylnicotinic acid (3222-49-9) → 5-methylnicotinic acid methyl ester (29681-45-6)

Conditions	Yield
With thionyl chloride at 20℃; for 4h; Concentration; Inert atmosphere; Reflux;	98.2%
With thionyl chloride at 60 - 65℃; Inert atmosphere;	96%
With thionyl chloride at 82℃; for 6.33333h; Temperature; Concentration;	96.5%

5-methylnicotinic acid (3222-49-9) + descarboethoxyloratadine (100643-71-8) → [4-(8-Chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-piperidin-1-yl]-(5-methyl-pyridin-3-yl)-methanone

Conditions	Yield
With boric acid In toluene Concentration; Reflux;	95%
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide for 18h; Ambient temperature;	44%

5-methylnicotinic acid (3222-49-9) + tert-butyl (S)-(1-(3-aminophenyl)ethyl)carbamate → tert-butyl (S)-(1-(3 -(5-methylnicotinamido)phenyl)ethyl)carbamate

Conditions	Yield
Stage #1: 5-methylnicotinic acid With 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: tert-butyl (S)-(1-(3-aminophenyl)ethyl)carbamate With N-ethyl-N,N-diisopropylamine at 20℃; for 16h;	92%

5-methylnicotinic acid (3222-49-9) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → N-methoxy-N,5-dimethylnicotinamide (342602-12-4)

Conditions	Yield
Stage #1: 5-methylnicotinic 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 0.5h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In N,N-dimethyl-formamide at 20℃; for 16h;	91%
Stage #1: 5-methylnicotinic 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;	87%

5-methylnicotinic acid (3222-49-9) + dihydroartemisinin (71939-50-9) → C22H29NO6

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 9.5h;	86%

5-methylnicotinic acid (3222-49-9) + (S)-5-((1-(3-aminophenyl)ethyl)amino)-1-(4-methoxybenzyl)-3-methyl-1.3-dihydro-2H-imidazo[4.5-b]pyrazin-2-one → (S)-N-(3-(1-((1-(4-methoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)amino)ethyl)phenyl)-5-methylnicotinamide

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 2h;	86%

5-methylnicotinic acid (3222-49-9) + N-(4-methyl-3-(piperidin-4-yloxy)phenyl)-4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzoamide trihydrochloride → N-(4-methyl-3-((1-(5-methylnicotinoyl)piperidin-4-yl)oxy)-phenyl)-4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)-benzamide

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 0 - 20℃; for 2h;	76%

5-methylnicotinic acid (3222-49-9) → 5-methyl-2-pyridinecarboxamide (20970-77-8) + 5-methylpyridinylcarboxamide (70-57-5)

Conditions	Yield
With ammonium chloride In methanol; thionyl chloride; 1,1-dichloroethane	A 73% B n/a

5-methylnicotinic acid (3222-49-9) + tert-butyl (S)-5-((1-(3-aminophenyl)ethyl)amino)-3-methyl-1H-pyrazolo[3,4-b]pyrazine-1-carboxylate → tert-butyl (S)-3-methyl-5-((1-(3-(5-methylnicotinamido)phenyl)ethyl)amino)-1H-pyrazolo[3,4-b]pyrazine-1-carboxylate

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 2h;	73%

5-methylnicotinic acid (3222-49-9) + (S)-N-(1-(3-aminophenyl)ethyl)-6-methylfuro[2,3-b]pyrazin-3-amine → (S)-5-methyl-N-(3-(1-((6-methylfuro[2,3-b]pyrazin-3-yl)amino)ethyl)phenyl)nicotinamide hydrochloride salt

Conditions	Yield
Stage #1: 5-methylnicotinic acid; (S)-N-(1-(3-aminophenyl)ethyl)-6-methylfuro[2,3-b]pyrazin-3-amine 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 2h; Stage #2: With hydrogenchloride In methanol; water	72%

5-methylnicotinic acid (3222-49-9) + thiosemicarbazide (79-19-6) → 5-(5-methylpyridin-3-yl)-1,3,4-thiadiazol-2-amine

Conditions	Yield
With polyphosphoric acid at 140℃; for 1h;	71%

5-methylnicotinic acid (3222-49-9) + C12H16N2O2 (1035211-30-3) → C19H21N3O3

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 70℃;	70%
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 70℃;	70%

5-methylnicotinic acid (3222-49-9) + 2-(1-phenyl-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazole → (2-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)(5-methylpyridin-3-yl)methanone

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 4.5h;	70%

5-methylnicotinic acid (3222-49-9) + tert-butyl alcohol (75-65-0) → tert-butyl N-(5-methylpyridin-3-yl)carbamate (631910-23-1)

Conditions	Yield
With diphenyl phosphoryl azide; N-ethyl-N,N-diisopropylamine at 80℃;	67%

5-methylnicotinic acid (3222-49-9) + N-ethyl-N,N-diisopropylamine (7087-68-5) → tert-butyl N-(5-methylpyridin-3-yl)carbamate (631910-23-1)

Conditions	Yield
With diphenylphosphoranyl azide In ethyl acetate; tert-butyl alcohol	67%

5-methylnicotinic acid (3222-49-9) + 3-aminophenylboronic acid pinacolate (210907-84-9) → 5-methyl-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)nicotinamide

Conditions	Yield
Stage #1: 5-methylnicotinic acid; 3-aminophenylboronic acid pinacolate With HATU In N,N-dimethyl-formamide at 30℃; for 0.0833333h; Stage #2: With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 30℃; for 16h;	67%

4-amino-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (331281-25-5) + 5-methylnicotinic acid (3222-49-9) → 4-cyano-4-[(5-methyl-pyridine-3-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (1084926-72-6)

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 40℃;	65%
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 40℃;	65%

5-methylnicotinic acid (3222-49-9) + C23H15F3N4 → (5-methylpyridin-3-yl)(2-(1-phenyl-3-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)methanone

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 4.5h;	65%

diazomethane (186581-53-3, 908094-01-9) + 5-methylnicotinic acid (3222-49-9) → 5-methylnicotinic acid methyl ester (29681-45-6)

Conditions	Yield
In methanol; diethyl ether	63%

5-methylnicotinic acid (3222-49-9) + N-[(1S)-1-(3-aminophenyl)ethyl]-6-bromopyridin-2-amine (1027256-71-8) → N-(3-{(1S)-1-[(6-bromopyridin-2-yl)amino]ethyl}phenyl)-5-methylnicotinamide (1027253-76-4)

Conditions	Yield
With 4-pyrrolidin-1-ylpyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 17h;	63%

5-methylnicotinic acid (3222-49-9) + (4-cyclobutyl-1,4-diazepan-1-yl)(7-azaspiro[3.5]nonan-2-yl)-methanone (1227610-25-4) → (4-cyclobutyl-1,4-diazepan-1-yl)(7-(5-methylnicotinoyl)-7-azaspiro[3.5]nonan-2-yl)methanone (1227609-95-1)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 72h;	62%

5-methylnicotinic acid (3222-49-9) + 2-(1-phenyl-3-(4-methylphenyl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazole → C30H23N5O

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 4.5h;	61%

5-methylnicotinic acid (3222-49-9) + NADP (53-59-8) → 5-methyl-NAADP

Conditions	Yield
With Aplysia californica ADP-ribosyl cyclase; sodium hydroxide In water at 37℃; for 2.5h; pH=4;	59%

5-methylnicotinic acid (3222-49-9) + (S)-N-(1-(3-aminophenyl)ethyl)-2-ethyl-2H-pyrazolo[3,4-b]pyrazin-6-amine → (S)-N-(3-(1-((2-ethyl-2H-pyrazolo[3.4-b]pyrazin-6-yl)amino)ethyl)phenyl)-5-methylnicotinamide hydrochloride salt

Conditions	Yield
Stage #1: 5-methylnicotinic acid; (S)-N-(1-(3-aminophenyl)ethyl)-2-ethyl-2H-pyrazolo[3,4-b]pyrazin-6-amine 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 3h; Stage #2: With hydrogenchloride In 1,4-dioxane	57%

5-methylnicotinic acid (3222-49-9) + lead(II) acetate trihydrate (6080-56-4) → [Pb(5-methylnicotinate)2]n

Conditions	Yield
With sodium hydroxide In acetonitrile at 125℃; for 48h; High pressure;	56%

5-methylnicotinic acid (3222-49-9) + lead(II) nitrate → [Pb(5-methylnicotinate)(NO3)]n

Conditions	Yield
With sodium hydroxide In acetonitrile at 125℃; for 48h; High pressure;	51%

5-methylnicotinic acid (3222-49-9) + (4-cyclobutylpiperazin-1-yl)(7-azaspiro[3.5]nonan-2-yl)methanone (1227610-21-0) → (4-cyclobutylpiperazin-1-yl)(7-(5-methylnicotinoyl)-7-azaspiro[3.5]nonan-2-yl)methanone (1227609-74-6)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide	49.2%

5-methylnicotinic acid (3222-49-9) + C14H12ClF3N4O → N-[(7S)-5-[3-chloro-4-(trifluoromethyl)phenyl]-7-methyl-4-oxo-6,7-dihydropyrazolo[1,5-a]pyrazin-3-yl]-5-methylpyridine-3-carboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h;	47%

Upstream product

• 612-58-8 3-methylquinoline 
• 7732-18-5 water 
• 591-22-0 3,5-Lutidine 
• 42972-46-3 1-(5-methylpyridin-3-yl)ethanone 
• 112945-08-1 3-methyl-5-pentyl-pyridine 

Downstream Products

• 29681-45-6 5-methylnicotinic acid methyl ester 
• 631910-23-1 tert-butyl N-(5-methylpyridin-3-yl)carbamate 
• 20826-02-2 ethyl 5-methyl-3-pyridinecarboxylate 
• 884494-95-5 5-methyl-nicotinic acid chloride 
• 158876-82-5 rupatadine 
• 1155662-43-3 methyl (3R*,5R*)-5-methylpiperidine-3-carboxylate 
• 1155662-43-3 methyl (3R*,5S*)-5-methylpiperidine-3-carboxylate 
• 1365887-45-1 1-(tert-butoxycarbonyl)-5-methylpiperidine-3-carboxylic acid 
• 1365887-44-0 1-(tert-butyl) 3-methyl 5-methylpiperidine-1,3-dicarboxylate 
• 66909-33-9 2-chloro-5-cyano-3-methylpyridine 
• 66909-34-0 2-chloro-5-methylpyridine-3-carbonitrile 

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