33252-30-1

Basic information

• Product Name: 2-Chloro-4-cyanopyridine
• Synonyms: BUTTPARK 43\57-01;4-CYANO-2-CHLORO PYRIDINE;2-CHLORO-4-CYANOPYRIDINE;2-CHLORO-4-PYRIDINECARBONITRILE;2-CHLOROPYRIDINE-4-CARBONITRILE;2-CHLOROISONICOTINONITRILE;2-CHLORO-4-CYANOPYRIDINE 99+%;2-CHLORO-4-CYANOPYRIDINE 2-CHLORO-ISONICOTINONITRILE
• CAS NO: 33252-30-1
• Molecular Formula: C₆H₃ClN₂
• Molecular Weight: 138.55
• EINECS: -0
• Product Categories: blocks;Carboxes;Pyridines;Boron, Nitrile, Thio,& TM-Cpds;Heterocycles;Pyridines, Pyrimidines, Purines and Pteredines;Halides;Pyridine;Chloropyridines;Halopyridines
• Mol File: 33252-30-1.mol
• Article Data: 7

Chemical Properties

• Melting Point: 69-73 °C(lit.)
• Boiling Point: 104-106°C 15mm
• Flash Point: 104-106°C/15mm
• Appearance: white or light yellow crystal
• Density: 1.33 g/cm³
• Vapor Pressure: 0.307mmHg at 25°C
• Refractive Index: 1.525
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• PKA: -1.60±0.10(Predicted)
• BRN: 113927
• CAS DataBase Reference: 2-Chloro-4-cyanopyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-4-cyanopyridine(33252-30-1)
• EPA Substance Registry System: 2-Chloro-4-cyanopyridine(33252-30-1)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 26-36-36/37/39-36/37
• RIDADR: 3276
• WGK Germany: 3
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 33252-30-1(Hazardous Substances Data)

Usage

Chemical Properties

White to off-white solid

Uses

2-Chloro-4-cyanopyridine is an intermediate used to prepare pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). It is also used to synthesize pyridinyl-tetrazoles as scaffold to identify matrix MMP-13 inhibitors for treatment of osteoarthritis.

InChI:InChI=1/C7H5Cl2F/c8-4-5-1-2-6(9)3-7(5)10/h1-3H,4H2

Synthetic route

2-chloro-4-cyanopyridine 1-oxide → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
With ammonium formate; silica gel; zinc In methanol at 20℃; for 0.166667h; chemoselective reaction;	89%

4-cyanopyridine N-oxide (14906-59-3) → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
With trichlorophosphate at 100℃; for 24h;	69%
With triethylamine; trichlorophosphate In 1,2-dichloro-ethane for 4h;	117.5 g

4-Amino-2-chloropyridine (14432-12-3) + potassium cyanide (151-50-8) → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
With sulfuric acid; copper(II) sulfate; sodium nitrite Diazotization.weitere Reagentien: Kupfer-Pulver, wss. Na2CO3;

4-pyridine carboxamide 1-oxide (38557-82-3) → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate

4-pyridine carboxamide 1-oxide (38557-82-3) + phosphorus pentachloride (10026-13-8, 874483-75-7) + trichlorophosphate (10025-87-3, 12599-09-6, 63736-95-8) → 2-chloro-4-pyridinenitrile (33252-30-1)

2-chloropyridine-N-oxide (2402-95-1) → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: concentrated sulfuric acid; nitric acid 2: acetic acid; iron-powder / anschliessend mit Zink-Pulver unter Zusatz von wenig wss. HgCl2 3: NaNO2; aqueous H2SO4; CuSO4 / Diazotization.weitere Reagentien: Kupfer-Pulver, wss. Na2CO3 View Scheme

2-chloro-4-nitropyridine-N-oxide (14432-16-7) → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; iron-powder / anschliessend mit Zink-Pulver unter Zusatz von wenig wss. HgCl2 2: NaNO2; aqueous H2SO4; CuSO4 / Diazotization.weitere Reagentien: Kupfer-Pulver, wss. Na2CO3 View Scheme

isonicotinamide (1453-82-3) → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous H2O2; acetic acid 2: POCl3; PCl5 View Scheme

4-cyanopyridine N-oxide (14906-59-3) + pyrographite (7440-44-0) → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
With sodium hydroxide; trichlorophosphate In n-heptane

4-cyanopyridine N-oxide (14906-59-3) + phosphorus pentachloride (10026-13-8, 874483-75-7) → 2-chloro-4-pyridinenitrile (33252-30-1)

Conditions	Yield
With trichlorophosphate	8.4 g (24%)

2-chloro-4-pyridinenitrile (33252-30-1) + tri-n-butyl(vinyl)tin (7486-35-3) → 2-vinylpyrimidine-4-carbonitrile

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In toluene for 2h; Reflux; Inert atmosphere;	100%

2-chloro-4-pyridinenitrile (33252-30-1) + 4-trifluoromethylphenylboronic acid (128796-39-4) → 2-[4-(trifluoromethyl)phenyl]pyridine 4-carbonitrile (1257437-26-5)

Conditions	Yield
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); sodium carbonate In 1,4-dioxane; water at 120℃; for 0.333333h; Microwave irradiation;	99%
With caesium carbonate; palladium diacetate; XPhos In 1,4-dioxane at 100℃; for 4h; Sealed tube;	78%
Stage #1: 2-chloro-4-pyridinenitrile; 4-trifluoromethylphenylboronic acid With sodium hydrogencarbonate In 1,2-dimethoxyethane; water at 20℃; for 5h; Stage #2: With tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane; water at 100℃;	47%
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,2-dimethoxyethane; water at 100℃; Inert atmosphere;	47%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; Inert atmosphere;

2-chloro-4-pyridinenitrile (33252-30-1) → 2-chloro-4-pyridine carboxamide (100859-84-5)

Conditions	Yield
With manganese(IV) oxide; water In isopropyl alcohol at 60℃; under 5171.62 Torr; for 0.2h;	98%
With water at 110℃; for 20h;	95%
With ammonium hydroxide; cesiumhydroxide monohydrate at 100℃; for 1h; Schlenk technique; Sealed tube;	89%
With cesium hydroxide; water; dimethyl sulfoxide at 30℃; for 24h; Temperature; Schlenk technique; Green chemistry;	88%
Stage #1: 2-chloro-4-pyridinenitrile With caesium carbonate In 2-pyrrolidinon at 130℃; for 2h; Sealed vessel; Stage #2: With methanol In 2-pyrrolidinon; dichloromethane at 20℃; Filtering through Celite pad;	72%

2-chloro-4-pyridinenitrile (33252-30-1) → 2-chloro-4-(1H-tetrazole-5-yl)pyridine (1196152-14-3)

Conditions	Yield
With sodium azide; ammonium cerium (IV) nitrate In N,N-dimethyl-formamide at 110℃; for 6h; Inert atmosphere; Green chemistry;	98%
With sodium azide In N,N-dimethyl-formamide at 100℃; for 4h; Reagent/catalyst; Temperature;	97%
With sodium azide; gold In N,N-dimethyl-formamide at 80℃; for 1h; Reagent/catalyst; Inert atmosphere;	96%

2-chloro-4-pyridinenitrile (33252-30-1) + 2-Amino-2-methyl-1-propanol (124-68-5) → 2-(2-chloropyridin-4-yl)-4,5-dihydro-4,4-dimethyloxazole (93639-38-4)

Conditions	Yield
With sodium carbonate In methanol at 80℃; for 15h; Inert atmosphere; Schlenk technique;	98%

2-chloro-4-pyridinenitrile (33252-30-1) + 4-Chlorophenylboronic acid (1679-18-1) → 2-(4-chlorophenyl)isonicotinonitrile (1415250-86-0)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; acetonitrile at 80℃; for 1h; Inert atmosphere;	98%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; acetonitrile for 1h; Suzuki-Miyaura Coupling; Inert atmosphere; Reflux;	96%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; Inert atmosphere;

2-chloro-4-pyridinenitrile (33252-30-1) + trimethylsilylacetylene (1066-54-2) → 4-cyano-2-[2-(trimethylsilyl)ethynyl]pyridine

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at 60℃; for 3h; Inert atmosphere;	98%

2-chloro-4-pyridinenitrile (33252-30-1) → 2-chloropyridine-4-carbothioamide (91447-89-1)

Conditions	Yield
With triethanolamine; hydrogen sulfide In ethanol	97%
With triethanolamine; ethanol; hydrogen sulfide

2-chloro-4-pyridinenitrile (33252-30-1) + ethanolamine (141-43-5) → 2-(2-chloropyridin-4-yl)-4,5-dihydrooxazole

Conditions	Yield
With sodium carbonate In methanol at 80℃; for 15h; Inert atmosphere; Schlenk technique;	97%

2-chloro-4-pyridinenitrile (33252-30-1) + 4-trifluoromethoxyphenylboronic acid (139301-27-2) → 2-[4-(trifluoromethoxy)phenyl]pyridine-4-carbonitrile (1257437-27-6)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,2-dimethoxyethane; water at 100℃; for 12h; Inert atmosphere;	96%
With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate In 1,2-dimethoxyethane; water at 100℃; for 12h; Inert atmosphere;	96%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; Inert atmosphere;

2-chloro-4-pyridinenitrile (33252-30-1) + meta-phenoxyphenol (713-68-8) → 2-chloro-6-(3-phenoxyphenoxy)isonicotinonitrile

Conditions	Yield
With caesium carbonate; N,N-dimethylethylenediamine at 20℃; for 16h;	96%

2-chloro-4-pyridinenitrile (33252-30-1) + phenol (108-95-2) → 2-phenoxyisonicotinonitrile (81249-44-7)

Conditions	Yield
Stage #1: phenol With caesium carbonate; N,N-dimethylethylenediamine at 20℃; for 0.5h; Stage #2: 2-chloro-4-pyridinenitrile at 80℃; for 2h;	95%
Stage #1: phenol With caesium carbonate In N,N-dimethyl acetamide at 20℃; for 0.5h; Stage #2: 2-chloro-4-pyridinenitrile In N,N-dimethyl acetamide at 80℃; for 20h;	95%
With caesium carbonate In 1-methyl-pyrrolidin-2-one at 80℃; for 16h;	57.95%
Stage #1: 2-chloro-4-pyridinenitrile; phenol With potassium carbonate In N,N-dimethyl-formamide at 120℃; Stage #2: With hydrogenchloride In water Cooling;

2-chloro-4-pyridinenitrile (33252-30-1) → 2-chloropyridine-4-carboximidamide hydrochloride (82019-89-4)

Conditions	Yield
With trimethylaluminum; ammonium chloride In toluene at 90℃;	95%

3-methoxyazetidine hydrochloride + 2-chloro-4-pyridinenitrile (33252-30-1) → 2-(3-methoxyazetidin-1-yl)isonicotinonitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 120℃; for 2h; Microwave irradiation; Inert atmosphere;	95%

2-chloro-4-pyridinenitrile (33252-30-1) + 1,1-dimethylethyl (2S)-2-methyl-4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperazinecarboxylate (1177559-74-8) → 1,1-dimethylethyl (2S)-4-{[3-(4-cyano-2-pyridinyl)phenyl]methyl}-2-methyl-1-piperazinecarboxylate (1177559-73-7)

Conditions	Yield
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 140℃; for 0.5h;	94%
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 140℃; for 0.5h; Microwave irradiation;	94%

2-chloro-4-pyridinenitrile (33252-30-1) + methylamine (74-89-5) → 2-(methylamino)isonicotinonitrile (137225-13-9)

Conditions	Yield
In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 120℃; for 2h; Microwave irradiation;	93%
With sodium hydrogencarbonate In pyridine at 120℃; for 40h;
With sodium hydrogencarbonate In tetrahydrofuran; pyridine at 120℃; for 40h;
In tetrahydrofuran; water at 20℃; for 18h;
In tetrahydrofuran at 80℃; for 16h; Sealed tube;

2-chloro-4-pyridinenitrile (33252-30-1) + methyl N-[6-(4-hydroxyphenyl)pyrimidin-4-yl]phenylalaninate (693792-82-4) → methyl N-(6-{4-[(4-cyanopyridin-2-yl)-oxy]phenyl}pyrimidin-4-yl)phenylalaninate (693792-97-1)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 60℃;	93%

2-chloro-4-pyridinenitrile (33252-30-1) + aniline (62-53-3) → 2-(phenylamino)isonicotinonitrile (137225-05-9)

Conditions	Yield
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,4-dioxane at 80℃; for 4h; Buchwald-Hartwig Coupling; Sealed tube; Inert atmosphere;	93%

2-chloro-4-pyridinenitrile (33252-30-1) → 2-chloroisonicotinic acid, (6313-54-8)

Conditions	Yield
With 1-butyl-3-methylimidazolium hydrogen sulfate; water at 60 - 65℃; for 2.4h; Green chemistry;	92%
With hydrogenchloride

2-chloro-4-pyridinenitrile (33252-30-1) + 1-cyclopentylpiperazine (21043-40-3) → 2-(4-cyclopentyl-piperazin-1-yl)-isonicotinonitrile (892867-16-2)

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 16h;	92%

2-chloro-4-pyridinenitrile (33252-30-1) + 4-methylphenylboronic acid (5720-05-8) → 2-(p-tolyl)isonicotinonitrile (1039775-36-4)

Conditions	Yield
With sodium tetrachloropalladate(II); dicyclohexyl {2-sulfo-9-[3-(4-sulfophenyl)propyl]-9H-fluoren-9-yl}phosphonium hydrogen sulfate; potassium carbonate In water; butan-1-ol at 100℃; for 12h; Suzuki coupling; Inert atmosphere;	92%

2-chloro-4-pyridinenitrile (33252-30-1) + 1-Naphthylboronic acid (13922-41-3) → C16H10N2 (1039775-44-4)

Conditions	Yield
With sodium tetrachloropalladate(II); dicyclohexyl {2-sulfo-9-[3-(4-sulfophenyl)propyl]-9H-fluoren-9-yl}phosphonium hydrogen sulfate; potassium carbonate In water; butan-1-ol at 100℃; for 12h; Suzuki coupling; Inert atmosphere;	91%

2-chloro-4-pyridinenitrile (33252-30-1) + (S)-N-((S)-1-(2-chlorophenyl)-2- ((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide → (2S)-N-{(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl}-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide (1448347-49-6)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl In acetic acid methyl ester; toluene Solvent; Reflux; Inert atmosphere;	91%
Stage #1: 2-chloro-4-pyridinenitrile; (S)-N-((S)-1-(2-chlorophenyl)-2- ((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene Inert atmosphere; Reflux; Stage #2: With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; Reagent/catalyst; Temperature;

2-chloro-4-pyridinenitrile (33252-30-1) → 1-(2-chloropyridin-4-yl)methanamine

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran	90%
With fac-1,2-bis(dipropylphosphaneyl)ethane tricarbonyl manganese(I) bromide; potassium tert-butylate; hydrogen In toluene at 100℃; under 37503.8 Torr; for 18h; Autoclave;	72 %Chromat.

2-chloro-4-pyridinenitrile (33252-30-1) + 1-(3-aminophenyl)ethanone (99-03-6) → 2-((3-acetylphenyl)amino)isonicotinonitrile (1438416-83-1)

Conditions	Yield
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,4-dioxane at 80℃; for 4h; Buchwald-Hartwig Coupling; Sealed tube; Inert atmosphere;	90%

2-chloro-4-pyridinenitrile (33252-30-1) + 4-nitro-aniline (100-01-6) → 2-((4-nitrophenyl)amino)isonicotinonitrile (58408-94-9)

Conditions	Yield
With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,4-dioxane at 80℃; for 4h; Buchwald-Hartwig Coupling; Sealed tube; Inert atmosphere;	90%

2-chloro-4-pyridinenitrile (33252-30-1) + tetrafluoroboric acid + C59H48Cl2O2OsP3 → C65H50Cl2N2O2OsP3(1+)*BF4(1-)

Conditions	Yield
With dihydrogen peroxide In dichloromethane; water at 20℃; for 3h;	90%

2-chloro-4-pyridinenitrile (33252-30-1) + isoniazid (54-85-3) → C12H8ClN5

Conditions	Yield
With sodium methylate In methanol at 25℃; for 14h;	90%

2-chloro-4-pyridinenitrile (33252-30-1) + 3-ethyl-4-hydroxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2(3H)-one → 2-((3-ethyl-2-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)oxy)isonicotinonitrile

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 18h; Inert atmosphere; Schlenk technique;	90%

2-chloro-4-pyridinenitrile (33252-30-1) + iodobenzene (591-50-4) → (2-chloropyridin-4-yl)(phenyl)methanone (80099-88-3)

Conditions	Yield
Stage #1: iodobenzene With n-butyllithium In diethyl ether; hexane at -78 - 0℃; for 0.75h; Inert atmosphere; Stage #2: 2-chloro-4-pyridinenitrile In diethyl ether; hexane at -78℃; for 1h; Stage #3: With hydrogenchloride In diethyl ether; hexane at -30℃; for 1h;	90%

Upstream product

• 14432-12-3 4-Amino-2-chloropyridine 
• 151-50-8 potassium cyanide 
• 38557-82-3 4-pyridine carboxamide 1-oxide 
• 10026-13-8 phosphorus pentachloride 
• 10025-87-3 trichlorophosphate 
• 14906-59-3 4-cyanopyridine N-oxide 
• 7440-44-0 pyrographite 
• 1453-82-3 isonicotinamide 
• 14432-16-7 2-chloro-4-nitropyridine-N-oxide 
• 2402-95-1 2-chloropyridine-N-oxide 

Downstream Products

• 383426-39-9 2-{[(1S)-1-phenylethyl]amino}-isonicotinonitrile 
• 101066-61-9 2-chloropyridine-4-carbaldehyde 
• 1613-71-4 [2,2'-bipyridine]-4-carbonitrile 
• 862593-13-3 2-(3-hydroxyphenylamino)isonicotinonitrile 
• 1073523-29-1 2-{methyl-[1-(3-trifluoromethyl-benzyl)-piperidin-4-yl]-amino}-isonicotinonitrile 
• 23794-15-2 1-(2-chloropyridin-4-yl)ethan-1-one 
• 1257437-26-5 2-[4-(trifluoromethyl)phenyl]pyridine-4-carbonitrile 
• 144900-57-2 1-(2-chloropyridin-4-yl)methanamine 
• 82019-89-4 2-chloropyridine-4-carboximidamide hydrochloride 
• 1335110-61-6 2,5-diphenylpyridine-4-carbonitrile 
• 111887-72-0 1-(2-fluoropyridin-4-yl)ethan-1-one 
• 1260030-03-2 methyl 3-bromo-5-(2-morpholinoisonicotinoyl)phenylcarbamate 
• 915412-67-8 N-[3-(1H-indol-4-yl)-5-(2-methoxypyridine-4-carbonyl)phenyl]methanesulfonamide 
• 915412-68-9 N-[3-bromo-5-(2-methoxypyridine-4-carbonyl)phenyl]methanesulfonamide 

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