20826-04-4

Basic information

• Product Name: 5-Bromonicotinic acid
• Synonyms: RARECHEM AL BO 0841;TIMTEC-BB SBB003524;5-bromo-3-pyridinecarboxylicaci;5-bromo-nicotinicaci;AURORA KA-3027;IFLAB-BB F3095-3197;AKOS BBS-00007710;3-PYRIDINECARBOXYLIC ACID, 5-BROMO-
• CAS NO: 20826-04-4
• Molecular Formula: C₆H₄BrNO₂
• Molecular Weight: 202.01
• EINECS: 244-065-5
• Product Categories: blocks;Bromides;Carboxes;Pyridines;Pyridine;pyridine derivative;Acids and Derivatives;Heterocycles;Pyridines, Pyrimidines, Purines and Pteredines;pharmacetical;Pyridine series;Carboxylic Acids;Organic acids;Pyridines derivates;PROTECTED AMINO ACID & PEPTIDES;Bromopyridines;Halopyridines;Carboxylic Acids;NULL;alkyl bromide|carboxylic acid
• Mol File: 20826-04-4.mol
• Article Data: 8

Chemical Properties

• Melting Point: 178-180 °C(lit.)
• Boiling Point: 259.67°C (rough estimate)
• Flash Point: 152.5 °C
• Appearance: White to yellow-gray or light brown/Powder
• Density: 1.7477 (rough estimate)
• Vapor Pressure: 7.59E-05mmHg at 25°C
• Refractive Index: 1.6120 (estimate)
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.08±0.10(Predicted)
• BRN: 115854
• CAS DataBase Reference: 5-Bromonicotinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Bromonicotinic acid(20826-04-4)
• EPA Substance Registry System: 5-Bromonicotinic acid(20826-04-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-24/25
• WGK Germany: 3
• RTECS: QT0868000
• HazardClass: IRRITANT
• Hazardous Substances Data: 20826-04-4(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow Cryst

Uses

5-Bromopyridine-3-carboxylic acid (5-bromonicotinic acid) was used in the synthesis of 3-guanidinomethyl-5-iodopyridine.

Synthesis Reference(s)

Journal of the American Chemical Society, 70, p. 2381, 1948 DOI: 10.1021/ja01187a020

Purification Methods

The acid is recrystallised from H2O and then from EtOH using charcoal. The amide has m 219-219.5o (from aqueous EtOH), and the methyl ester, prepared by addition of ethereal diazomethane, can be purified by sublimation in a vacuum and has m 98-99o. The acid chloride also can be sublimed in vacuo and has m 74-75o and gives the methyl ester in MeOH. [Graf J Prakt Chem 138 244 1933, Bachman & Micucci J Am Chem Soc 70 2381 1948, Garcia et al. J Am Chem Soc 82 4430 1960, Misic-Vokovic et al. J Chem Soc 34 1978, Beilstein 22/2 V 181.]

InChI:InChI=1/C6H4BrNO2/c7-5-1-4(6(9)10)2-8-3-5/h1-3H,(H,9,10)/p-1

Synthetic route

5-bromonicotinamide (28733-43-9) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With acetic acid; isopentyl nitrite at 80℃; for 24h; Inert atmosphere;	98%

3-pyridinecarbonyl chloride (10400-19-8) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With bromine at 0 - 155℃; for 10h;	94%

5-bromo-3-pyridine carboxylic acid methyl ester (29681-44-5) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With potassium hydroxide In methanol; water for 12h; Ambient temperature;	91%
With water; sodium hydroxide In tetrahydrofuran at 20℃; for 0.166667h;	33%

nicergoline (27848-84-6, 28057-46-7, 58001-19-7, 58001-20-0, 58001-21-1, 140387-88-8) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4) + 1-Methyl-10alpha-methoxy-9,10-dihydrolysergol (35155-28-3)

Conditions	Yield
With potassium hydroxide In methanol Heating;	A 12% B 91%

3,5-dibromopyridine (625-92-3) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With n-butyllithium; diethyl ether at -30℃; Behandeln der Reaktionsloesung mit festem CO2;

nicotinic acid (59-67-6) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With thionyl chloride Erhitzen des Reaktionsprodukts mit Brom auf 150-170grad und Behandeln des Reaktionsgemisches mit H2O bei pH 3;

3-bromoquinoline (5332-24-1) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With nitric acid at 150℃;

5-Bromo-pyridine-2,3-dicarboxylic acid (98555-51-2) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With acetic acid
beim Schmelzen;

para-bromophenacyl bromide (99-73-0) + <5-3H>-sesbanine → 5-bromo-3-pyridinecarboxylic acid (20826-04-4) + <5-3H>-nicotinic acid (109440-03-1) + 5-Bromo-nicotinic acid 2-(4-bromo-phenyl)-2-oxo-ethyl ester

Conditions	Yield
With pyridine; potassium hydroxide; potassium permanganate; thionyl chloride; bromine; benzoyl chloride multistepreaction to study the origin of the carbon skeleton;

3.bz.bz-tribromo-6-methoxy-quinoline → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With nitric acid

5-bromo-quinolinic acid → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

diazotized 5-amino-nicotinic acid → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With copper(I) bromide

5-bromo-3-picoline (3430-16-8) → 5-bromo-3-pyridinecarboxylic acid (20826-04-4)

Conditions	Yield
With potassium permanganate Heating;

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (144222-22-0) → tert-butyl 4-((5-bromonicotinamido)methyl)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 80℃; for 2h; Microwave irradiation;	100%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → tert-butyl-4-(5-bromonicotinoyl)piperazine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 80℃; for 2h; Microwave irradiation;	100%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + ethanol (64-17-5) → ethyl 5-bromo-3-pyridinecarboxylate (20986-40-7)

Conditions	Yield
Stage #1: 5-bromo-3-pyridinecarboxylic acid With thionyl chloride Reflux; Stage #2: ethanol for 2h; Reflux; Stage #3: With sodium hydrogencarbonate In dichloromethane; water pH=8;	99%
With sulfuric acid for 18h; Heating;	94%
With sulfuric acid for 18h; Inert atmosphere; Reflux; Cooling with ice;	89%

5-((1S,2S)-2-Hydroxy-1-methyl-5-oxo-cyclopentyl)-pentanoic acid methyl ester (915285-91-5) + 5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-Bromo-nicotinic acid (1S,2S)-2-(4-methoxycarbonyl-butyl)-2-methyl-3-oxo-cyclopentyl ester

Conditions	Yield
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 20h;	99%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + 3-methyl-4-isopropylaniline hydrochloride (4534-11-6) → 5-bromo-N-(4-isopropyl-3-methylphenyl)pyridine-3-carboxamide

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℃;	98.2%

diazomethane (186581-53-3, 908094-01-9) + 5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-bromo-3-pyridine carboxylic acid methyl ester (29681-44-5)

Conditions	Yield
In tetrahydrofuran; diethyl ether for 2h; Ambient temperature;	97%
In diethyl ether for 0.25h;

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + 1-methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5,6,7,8-tetrahydro-isoquinoline (872175-75-2) → 5-(1-methoxy-5,6,7,8-tetrahydro-isoquinolin-4-yl)-nicotinic acid (872175-89-8)

Conditions	Yield
With potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In DMF (N,N-dimethyl-formamide) at 110℃; for 18h; Suzuki Coupling;	97%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + (S)-tert-butyl(dimethyl)[3-(S-phenylsulfonimidoyl)propoxy]silane → (S)-5-bromo-N-[(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)(oxido)phenyl-λ4-sulfanylidene]nicotinamide

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.25h;	97%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + pivaloyl chloride (3282-30-2) → tert-butylcarbonyl-5-bromonicotinic acid (133343-68-7)

Conditions	Yield
With triethylamine In benzene for 16h; Ambient temperature; 1.) C6H6, RT, 1 h, 2.) C6H6, 16 h;	96%
With triethylamine In benzene	95%
Stage #1: 5-bromo-3-pyridinecarboxylic acid With triethylamine In toluene at 0 - 20℃; for 1h; Inert atmosphere; Schlenk technique; Stage #2: pivaloyl chloride In toluene at 0 - 20℃; Inert atmosphere; Schlenk technique;	77%

methanol (67-56-1) + 5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-bromo-3-pyridine carboxylic acid methyl ester (29681-44-5)

Conditions	Yield
Stage #1: 5-bromo-3-pyridinecarboxylic acid With boron trichloride Stage #2: methanol	96%
sulfuric acid for 3h; Heating / reflux;	90%
With sulfuric acid at 65℃;	88%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + 4-fluoroboronic acid (1765-93-1) + C20H19NO4 → (S)-1-[5-(4-Fluoro-phenyl)-pyridine-3-carbonyl]-pyrrolidine-2-carboxylic acid

Conditions	Yield
Multistep reaction;	96%

4-((1S,2S)-2-Hydroxy-1-methyl-5-oxo-cyclopentyl)-butyric acid methyl ester (915285-93-7) + 5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-Bromo-nicotinic acid (1S,2S)-2-(3-methoxycarbonyl-propyl)-2-methyl-3-oxo-cyclopentyl ester

Conditions	Yield
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 20h;	96%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 5-bromopyridine-3-carboxylate (263270-02-6)

Conditions	Yield
With dmap In tetrahydrofuran Reflux;	96%
With 4-pyrrolidin-1-ylpyridine; triethylamine In tetrahydrofuran at 20℃; for 48h;	91%
With dmap In tetrahydrofuran at 20℃; for 1.5h; Cooling with ice;	82%
With dmap In tetrahydrofuran for 1h; Reflux;	79%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + 3-iodo-4-methylaniline (35944-64-0) → C13H10BrIN2O

Conditions	Yield
Stage #1: 5-bromo-3-pyridinecarboxylic acid With thionyl chloride In toluene at 82℃; for 2h; Stage #2: 3-iodo-4-methylaniline With triethylamine In toluene at 20℃;	96%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-bromonicotinoyl chloride (39620-02-5)

Conditions	Yield
With thionyl chloride for 12h; Reflux;	95%
With thionyl chloride In dichloromethane for 2h; Reflux;	64%
With thionyl chloride

5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-bromonicotinic acid chloride hydrochloride

Conditions	Yield
With thionyl chloride; N,N-dimethyl-formamide In 1,2-dichloro-ethane Reflux;	95%
With thionyl chloride for 4h;	92%
With oxalyl dichloride
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide 0 deg C, 1 h; RT, 30 min;

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + Tocopherol (59-02-9) → (R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyltridecyl)chroman-6-yl 5-bromonicotinate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran Inert atmosphere;	95%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-bromo-3-pyridine carboxylic acid methyl ester (29681-44-5)

Conditions	Yield
In methanol	94%
Multi-step reaction with 2 steps 1: SOCl2 View Scheme

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + (R)-S-methyl-S-phenylsulfoximine (60933-65-5) → (R)-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (1027725-42-3)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 2.66667h;	94%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + [{Mo(O)(5,10,15,20-meso-tetrakis(4-bromophenyl)porphyrin)}2O] → [Mo(O)(5,10,15,20-meso-tetrakis(4-bromophenyl)porphyrin)(5-bromonicotinate)]

Conditions	Yield
In methanol; chloroform for 0.5h;	94%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-aminonicotinic acid (24242-19-1)

Conditions	Yield
Stage #1: 5-bromo-3-pyridinecarboxylic acid With copper(ll) sulfate pentahydrate; ammonia In water at 170 - 180℃; for 19h; Autoclave; Stage #2: In water pH=4 - 5; Acidic aq. solution;	93%
With copper(I) sulfate; ammonia In water at 120℃; for 16h; Acidic aqueous solution;	74%
With ammonia; copper(II) sulfate In water at 180℃; for 15h;	64%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + Fmoc-Leu-OH (35661-60-0) + 4-fluoroboronic acid (1765-93-1) → (S)-2-{[5-(4-Fluoro-phenyl)-pyridine-3-carbonyl]-amino}-4-methyl-pentanoic acid

Conditions	Yield
Multistep reaction;	93%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → N-methyl-N-methoxy-5-bromopyridine-3-carboxamide (183608-47-1)

Conditions	Yield
With oxalyl dichloride; triethylamine In tetrahydrofuran at 0 - 20℃; for 4h;	93%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; Inert atmosphere;	86%
Stage #1: 5-bromo-3-pyridinecarboxylic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 4h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride With triethylamine In dichloromethane at 20℃; for 3.5h;	73%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1-methyl-pyrrolidin-2-one; dichloromethane at 0 - 20℃;	51.1%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1-methyl-pyrrolidin-2-one; dichloromethane at 0 - 20℃;	51.1%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + phenylboronic acid (98-80-6) → 5-phenylnicotinic acid (10177-12-5)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 70℃; for 1.66667h; Suzuki Coupling;	93%
With meso-tetrakis[4-(methoxycarbonyl)phenyl]porphyrinatopalladium(II); potassium carbonate In water at 80℃; for 4.66667h; Suzuki Coupling; Green chemistry;	91%
With potassium carbonate In water; N,N-dimethyl-formamide at 80℃; for 0.333333h; Catalytic behavior; Suzuki-Miyaura Coupling;	82%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + descarboethoxyloratadine (100643-71-8) → (5-Bromo-pyridin-3-yl)-[4-(8-chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-piperidin-1-yl]-methanone

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide for 18h; Ambient temperature;	92%

5-bromo-3-pyridinecarboxylic acid (20826-04-4) + (S)-S-methyl-S-phenylsulfoximine (4381-25-3, 33903-50-3, 60933-65-5, 81162-81-4) → (S)-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (1027729-52-7)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 2.16667h;	92%

4-aminopyridine (504-24-5) + 5-bromo-3-pyridinecarboxylic acid (20826-04-4) → 5-bromo-N-(pyridin-4-yl)nicotinamide (634173-90-3)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	92%

Upstream product

• 59-67-6 nicotinic acid 
• 98555-51-2 5-Bromo-pyridine-2,3-dicarboxylic acid 
• 27848-84-6 nicergoline 
• 28733-43-9 5-bromonicotinamide 
• 10400-19-8 3-pyridinecarbonyl chloride 
• 3430-16-8 5-bromo-3-picoline 
• 99-73-0 para-bromophenacyl bromide 
• 29681-44-5 5-bromo-3-pyridine carboxylic acid methyl ester 
• 5332-24-1 3-bromoquinoline 
• 625-92-3 3,5-dibromopyridine 

Downstream Products

• 29681-44-5 5-bromo-3-pyridine carboxylic acid methyl ester 
• 59-67-6 nicotinic acid 
• 209915-44-6 5-ethenylnicotinic acid 
• 10177-12-5 5-phenylnicotinic acid 
• 90325-36-3 5-bromopyridine-3,4-dicarboxylic acid 
• 491588-98-8 5-bromo-4-iodonicotinic acid 
• 183608-47-1 N-methyl-N-methoxy-5-bromopyridine-3-carboxamide 
• 342013-81-4 4-[(5-bromopyridin-3-yl)carbonyl]morpholine 
• 91702-86-2 methyl 5-(methylamino)pyridine-3-carboxylate 
• 91702-88-4 5-(methylamino)nicotinic acid 
• 361550-43-8 (5-bromo-pyridin-3-yl)-carbamic acid tert-butyl ester 

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