849937-96-8

Basic information

• Product Name: 5-BROMO-2,4-DICHLORO-PYRIDINE
• Synonyms: Pyridine, 5-bromo-2,4-dichloro-;2,4-dichloro-5-bromopyridine
• CAS NO: 849937-96-8
• Molecular Formula: C₅H₂BrCl₂N
• Molecular Weight: 226.89
• EINECS: 214-589-6
• Product Categories: Variety of halogenated heterocyclic series;Heterocycle-Pyridine series
• Mol File: 849937-96-8.mol
• Article Data: 1

Chemical Properties

• Melting Point: 21-22℃
• Boiling Point: 60-62℃ (0.9 Torr)
• Flash Point: 100.8oC
• Appearance: /
• Density: 1.848g/cm3
• Vapor Pressure: 0.0512mmHg at 25°C
• Refractive Index: 1.597
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -1.31±0.10(Predicted)
• CAS DataBase Reference: 5-BROMO-2,4-DICHLORO-PYRIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 5-BROMO-2,4-DICHLORO-PYRIDINE(849937-96-8)
• EPA Substance Registry System: 5-BROMO-2,4-DICHLORO-PYRIDINE(849937-96-8)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 849937-96-8(Hazardous Substances Data)

Usage

General Description

5-Bromo-2,4-Dichloro-Pyridine is an organic compound that belongs to the class of halopyridines. It contains a pyridine ring – a basic aromatic ring with five carbon atoms and one nitrogen atom, that is substituted at positions 2, 4, and 5 by bromine and chlorine atoms. Its molecular formula is C5H2BrCl2N. This chemical is typically used as an intermediate in pharmaceutical manufacturing and also finds use in the synthesis of various chemical compounds. As a laboratory reagent, it is used within scientific research and development settings. Proper care and handling are required when working with this compound due to its potential for harmful impacts.

InChI:InChI=1/C5H2BrCl2N/c6-3-2-9-5(8)1-4(3)7/h1-2H

Synthetic route

5-bromo-2-chloropyridine (53939-30-3) → 5-bromo-2,4,-dichloropyridine (849937-96-8)

Conditions	Yield
Stage #1: 5-bromo-2-chloropyridine With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -100℃; for 0.75h; Stage #2: With 1,1,2-Trichloro-1,2,2-trifluoroethane In tetrahydrofuran; hexane at -75℃; for 0.75h;	83%

5-bromo-pyridine-2,4-diol (80791-79-3) → 5-bromo-2,4,-dichloropyridine (849937-96-8)

Conditions	Yield
With trichlorophosphate at 130℃;

5-bromo-2,4,-dichloropyridine (849937-96-8) + triethylsilyl chloride (994-30-9) → 2,4-dichloro-5-(triethylsilyl)pyridine (837364-99-5)

Conditions	Yield
Stage #1: 5-bromo-2,4,-dichloropyridine With n-butyllithium In diethyl ether; hexane at -75℃; for 0.75h; Stage #2: triethylsilyl chloride In diethyl ether; hexane	89%

5-bromo-2,4,-dichloropyridine (849937-96-8) + aniline (62-53-3) → 5-bromo-4-chloro-N-phenylpyridin-2-amine

Conditions	Yield
With 1,1'-bis[bis(dimethylamino)phosphino]ferrocene; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In 1,4-dioxane at 70℃; for 15h; Sealed tube; Inert atmosphere;	86%

5-bromo-2,4,-dichloropyridine (849937-96-8) + ethylene glycol (107-21-1) → 2-((5-bromo-2-chloropyridin-4-yl)oxy)ethan-1-ol

Conditions	Yield
Stage #1: ethylene glycol With sodium hydride In dimethyl sulfoxide at 20℃; for 0.5h; Stage #2: 5-bromo-2,4,-dichloropyridine In dimethyl sulfoxide at 50℃; for 1h;	82%

5-bromo-2,4,-dichloropyridine (849937-96-8) + 1-Amino-2-methyl-propan-2-ol (2854-16-2) → 1-((5-bromo-2-chloropyridin-4-yl)amino)-2-methylpropan-2-ol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 100℃; for 2h;	79%

oxetan-3-one (6704-31-0) + 5-bromo-2,4,-dichloropyridine (849937-96-8) → 3-(4,6-dichloropyridin-3-yl)oxetan-3-ol (1613239-16-9)

Conditions	Yield
Stage #1: 5-bromo-2,4,-dichloropyridine With TurboGrignard In tetrahydrofuran at -15℃; for 1h; Inert atmosphere; Stage #2: oxetan-3-one In tetrahydrofuran at -15 - 20℃;	72%
Stage #1: 5-bromo-2,4,-dichloropyridine With TurboGrignard In tetrahydrofuran at -15℃; for 1h; Inert atmosphere; Stage #2: oxetan-3-one In tetrahydrofuran at -15 - 20℃;

5-bromo-2,4,-dichloropyridine (849937-96-8) + cyclopropylboronic acid (411235-57-9) → 2,4-dichloro-5-cyclopropyl-pyridine (1613239-40-9)

Conditions	Yield
With potassium phosphate; palladium diacetate; tricyclohexylphosphine In water; toluene at 25 - 100℃; for 12h; Inert atmosphere;	61%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 100℃; for 3h; Suzuki Coupling; Inert atmosphere;	700 mg

5-bromo-2,4,-dichloropyridine (849937-96-8) + tert-butyl 4-(hydroxymethyl)piperidin-1-carboxylate (123855-51-6) → tert-butyl 4-(((5-bromo-2-chloropyridin-4-yl)oxy)methyl)piperidine-1-carboxylate

Conditions	Yield
Stage #1: tert-butyl 4-(hydroxymethyl)piperidin-1-carboxylate With potassium tert-butylate at 20℃; for 0.333333h; Stage #2: 5-bromo-2,4,-dichloropyridine at 0 - 20℃; for 16h;	50%

5-bromo-2,4,-dichloropyridine (849937-96-8) + potassium cyclopropyltrifluoroborate (1065010-87-8) → 2,4-dichloro-5-cyclopropyl-pyridine (1613239-40-9)

Conditions	Yield
With palladium diacetate; caesium carbonate; catacxium A In water; toluene at 110℃;	40%

5-bromo-2,4,-dichloropyridine (849937-96-8) + Cyclopropylamine (765-30-0) → 5-bromo-2-chloro-N-cyclopropylpyridin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 100℃; for 17h;	39%

5-bromo-2,4,-dichloropyridine (849937-96-8) + isopropylamine (75-31-0) → 5-bromo-2-chloro-N-isopropylpyridin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 120℃; for 4h;	37%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 120℃; for 4h;	37%

5-bromo-2,4,-dichloropyridine (849937-96-8) + 1-(2,2-difluoroethyl)-1H-pyrazol-4-ylamine (1006333-08-9) → 5-bromo-2-chloro-N-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)pyridin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 120℃; for 14h;	35%

5-bromo-2,4,-dichloropyridine (849937-96-8) + trans-4-aminocyclohexan-1-ol (27489-62-9) → trans-4-((5-bromo-2-chloropyridin-4-yl)amino)cyclohexan-1-ol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 0 - 120℃; for 24h;	32%

5-bromo-2,4,-dichloropyridine (849937-96-8) → 5-bromo-2-chloropyridin-4-amine (857730-21-3)

Conditions	Yield
With ammonium hydroxide at 160℃;

5-bromo-2,4,-dichloropyridine (849937-96-8) → 4-chloro-2-(dimethylamino)-5-(triethylsilyl)pyridine (849937-97-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: BuLi / diethyl ether; hexane / 0.75 h / -75 °C 1.2: 89 percent / diethyl ether; hexane 2.1: H2O / 60 h / 50 °C View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 4-chloro-2-hydrazino-5-(triethylsilyl)pyridine (837365-02-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: BuLi / diethyl ether; hexane / 0.75 h / -75 °C 1.2: 89 percent / diethyl ether; hexane 2.1: H2NNH2 / tetrahydrofuran / 120 h / Heating View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 4-chloro-3-(triethylsilyl)pyridine (123506-94-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: BuLi / diethyl ether; hexane / 0.75 h / -75 °C 1.2: 89 percent / diethyl ether; hexane 2.1: H2NNH2 / tetrahydrofuran / 120 h / Heating 3.1: 3.68 g / CuSO4*5H2O / H2O / 0.75 h / Heating View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 4-chloro-N,N-dimethylpyridin-2-amine (735255-56-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: BuLi / diethyl ether; hexane / 0.75 h / -75 °C 1.2: 89 percent / diethyl ether; hexane 2.1: H2O / 60 h / 50 °C 3.1: 3.37 g / tetrabutylammonium fluoride trihydrate / tetrahydrofuran / 2 h / 25 °C View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 5-bromo-2,3-dichloro-[4]pyridylamine

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous NH3 / 160 °C 2: concentrated aqueous HCl; aqueous H2O2 View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 4-chloro-5-(3-hydroxyoxetan-3-yl)pyridine-2-carbonitrile (1613239-17-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: TurboGrignard / tetrahydrofuran / 1 h / -15 °C / Inert atmosphere 1.2: -15 - 20 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: TurboGrignard / tetrahydrofuran / 1 h / -15 °C / Inert atmosphere 1.2: -15 - 20 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 5-(3-hydroxyoxetan-3-yl)-4-(2,2,2-trifluoroethoxy)pyridine-2-carbonitrile (1613239-18-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: TurboGrignard / tetrahydrofuran / 1 h / -15 °C / Inert atmosphere 1.2: -15 - 20 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere 3.1: potassium tert-butylate / N,N-dimethyl-formamide / 2.17 h / 0 - 80 °C / Inert atmosphere View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 5-(3-hydroxyoxetan-3-yl)-4-(2,2,2-trifluoroethoxy)pyridine-2-carboxylic acid (1613239-19-2)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: TurboGrignard / tetrahydrofuran / 1 h / -15 °C / Inert atmosphere 1.2: -15 - 20 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere 3.1: potassium tert-butylate / N,N-dimethyl-formamide / 2.17 h / 0 - 80 °C / Inert atmosphere 4.1: potassium hydroxide / ethanol / 1 h / 100 °C / Microwave irradiation View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 4-chloro-5-(3-fluorooxetan-3-yl)pyridine-2-carbonitrile (1613239-33-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: TurboGrignard / tetrahydrofuran / 1 h / -15 °C / Inert atmosphere 1.2: -15 - 20 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere 3.1: diethylamino-sulfur trifluoride / dichloromethane / 1.25 h / -75 - 0 °C View Scheme
Multi-step reaction with 3 steps 1.1: TurboGrignard / tetrahydrofuran / 1 h / -15 °C / Inert atmosphere 1.2: -15 - 20 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere 3.1: diethylamino-sulfur trifluoride / dichloromethane / 1.25 h / -78 - 0 °C View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 5-(3-fluorooxetan-3-yl)-4-(2,2,2-trifluoroethoxy)pyridine-2-carboxylic acid (1613239-34-1)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: TurboGrignard / tetrahydrofuran / 1 h / -15 °C / Inert atmosphere 1.2: -15 - 20 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere 3.1: diethylamino-sulfur trifluoride / dichloromethane / 1.25 h / -75 - 0 °C 4.1: water; potassium hydroxide / 1 h / 100 °C / Microwave irradiation View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 4-chloro-5-cyclopropyl-pyridine-2-carbonitrile (1613239-41-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium diacetate; potassium phosphate; tricyclohexylphosphine / toluene; water / 12 h / 25 - 100 °C / Inert atmosphere 2: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 1.17 h / 25 - 100 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: catacxium A; palladium diacetate; caesium carbonate / toluene; water / 110 °C 2: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 4-chloro-5-cyclopropyl-N'-hydroxypicolinimidamide

Conditions	Yield
Multi-step reaction with 3 steps 1: catacxium A; palladium diacetate; caesium carbonate / toluene; water / 110 °C 2: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C 3: hydroxylamine hydrochloride; triethylamine / ethanol / 90 °C View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 5-tert-butyl-3-(4-chloro-5-cyclopropylpyridin-2-yl)-1,2,4-oxadiazole

Conditions	Yield
Multi-step reaction with 4 steps 1: catacxium A; palladium diacetate; caesium carbonate / toluene; water / 110 °C 2: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C 3: hydroxylamine hydrochloride; triethylamine / ethanol / 90 °C 4: triethylamine / N,N-dimethyl-formamide / 20 - 110 °C View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 5-tert-butyl-3-[5-cyclopropyl-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridin-2-yl]-1,2,4-oxadiazole

Conditions

Yield

Multi-step reaction with 5 steps 1.1: catacxium A; palladium diacetate; caesium carbonate / toluene; water / 110 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C 3.1: hydroxylamine hydrochloride; triethylamine / ethanol / 90 °C 4.1: triethylamine / N,N-dimethyl-formamide / 20 - 110 °C 5.1: sodium hydride / N,N-dimethyl-formamide / 0.25 h / 20 °C 5.2: 0.5 h / 100 °C / Microwave irradiation View Scheme

5-bromo-2,4,-dichloropyridine (849937-96-8) → 1-[2-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-cyclopropylpyridin-4-yl]pyrrolidin-3-ol

Conditions

Yield

Multi-step reaction with 5 steps 1.1: catacxium A; palladium diacetate; caesium carbonate / toluene; water / 110 °C 2.1: 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 100 °C 3.1: hydroxylamine hydrochloride; triethylamine / ethanol / 90 °C 4.1: triethylamine / N,N-dimethyl-formamide / 20 - 110 °C 5.1: potassium carbonate / 1-methyl-pyrrolidin-2-one / 0.25 h / 20 °C 5.2: 1.5 h / 200 °C / Microwave irradiation View Scheme

Upstream product

• 80791-79-3 5-bromo-pyridine-2,4-diol 
• 53939-30-3 5-bromo-2-chloropyridine 

Downstream Products

• 857730-21-3 5-bromo-2-chloropyridin-4-amine 
• 880870-13-3 5-bromo-2-chloro-4-methoxypyridine 
• 1622217-00-8 2,4-dichloro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine 
• 123506-94-5 4-chloro-3-(triethylsilyl)pyridine 

Relevant articles and documents

Regiochemically flexible substitutions of di-, tri-, and tetrahalopyridines: The trialkylsilyl trick

(Chemical Equation Presented) 2,4-Difluoropyridine, 2,4-dichloropyridine, 2,4,6-trifluoropyridine, 2,4,6-trichloropyridine and 2,3,4,6-tetrafluoropyridine react with standard nucleophiles exclusively at the 4-position under halogen displacement. However, the regioselectivity can be completely reversed if a trialkylsilyl group is introduced in the 5-position of the 2,4-dihalopyridines or in the 3-position of the 2,4,6-trihalopyridines or 2,3,4,6-tetrahalopyridine. Then only the halogen most remote from the bulky silyl unit (at the 2-position in the case of the 2,4-halopyridines, at the 6-position with the other substrates) gets involved in the exchange process. After removal of the silyl protective group the nucleophile is invariably found to occupy the nitrogen-neighboring position.