16133-25-8

Basic information

• Product Name: PYRIDINE-3-SULFONYL CHLORIDE HYDROCHLORIDE
• Synonyms: 3-CHLOROSULFONYL-PYRIDINIUM, CHLORIDE;3-PYRIDINESULFONYL CHLORIDE, HCL;3-PYRIDINESULFONYL CHLORIDE HYDROCHLORIDE;PYRIDINE-3-SULFONYL CHLORIDE HYDROCHLORIDE;PYRIDINE-3-SULPHONYL CHLORIDE HYDROCHLORIDE;3-Pyridine sulphonyl chloride;pyridine-3-sulfonyl chloride(SALTDATA: 0.8HCl 0.3H2O);m-Pyridinesulfonyl chloride
• CAS NO: 16133-25-8
• Molecular Formula: C5H4ClNO2S
• Molecular Weight: 177.61
• EINECS: -0
• Mol File: 16133-25-8.mol
• Article Data: 45

Chemical Properties

• Melting Point: 144 °C
• Boiling Point: 284℃
• Flash Point: 126℃
• Appearance: /
• Density: 1.488
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -1.77±0.11(Predicted)
• CAS DataBase Reference: PYRIDINE-3-SULFONYL CHLORIDE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: PYRIDINE-3-SULFONYL CHLORIDE HYDROCHLORIDE(16133-25-8)
• EPA Substance Registry System: PYRIDINE-3-SULFONYL CHLORIDE HYDROCHLORIDE(16133-25-8)

Safety Data

• Hazard Codes: Xi,C
• Statements: 34-43
• Safety Statements: 26-36/37/39-45
• RIDADR: 3261
• WGK Germany: 3
• HazardClass: IRRITANT
• PackingGroup: Ⅲ
• Hazardous Substances Data: 16133-25-8(Hazardous Substances Data)

Usage

Uses

3-pyridinesulfonyl Chloride is a reagent used in the synthesis of pyrimidine derivatives with anti-proliferative activity against negative breast cancer cells.

Synthetic route

3-pyridinesulfonic acid (636-73-7) → Pyridine-3-sulfonyl chloride (16133-25-8)

Conditions	Yield
With phosphorus pentachloride In trichlorophosphate at 120℃; for 12h;	98%
With phosphorus pentachloride; trichlorophosphate for 3h; Heating / reflux;	94%
With phosphorus pentachloride In toluene Heating;	92%

pyridine-3-sulfonyl chloride hydrochloride (42899-76-3) → Pyridine-3-sulfonyl chloride (16133-25-8)

Conditions	Yield
In chlorobenzene at 85℃; under 172.517 Torr;	92.9%
With sodium hydrogencarbonate In dichloromethane; water

pyridin-3-ylamine (462-08-8) → Pyridine-3-sulfonyl chloride (16133-25-8)

Conditions	Yield
Stage #1: pyridin-3-ylamine With hydrogenchloride; sodium nitrite In water at -5 - 0℃; Large scale; Green chemistry; Stage #2: With thionyl chloride; sulphurous acid; copper(l) chloride In water at 0 - 4℃; for 1.5h; Concentration; Reagent/catalyst; Large scale; Green chemistry;	91%
Stage #1: pyridin-3-ylamine With hydrogenchloride; sodium tetrafluoroborate; sodium nitrite In water at 0 - 5℃; Stage #2: With thionyl chloride; copper(l) chloride In water at 0 - 5℃;	90.7%
Stage #1: pyridin-3-ylamine With hydrogenchloride; sodium nitrite In water at -20℃; for 2h; Stage #2: With copper(II) choride dihydrate; sulfur dioxide In dichloromethane; water at -5 - 0℃; for 1h;	52.1%
Stage #1: pyridin-3-ylamine With hydrogenchloride In water at 30℃; Sandmeyer reaction; Stage #2: With sodium nitrite In water at -5 - 0℃; for 0.916667h; Sandmeyer reaction; Stage #3: With thionyl chloride; water; copper(l) chloride at -5 - 0℃; for 2.83333h; Sandmeyer reaction;	38.4%

pyridine-3-thiol (16133-26-9) → Pyridine-3-sulfonyl chloride (16133-25-8)

Conditions	Yield
With chlorine In water; acetic acid at 15 - 17℃; for 0.5h;	81%

3-Bromopyridine (626-55-1) → Pyridine-3-sulfonyl chloride (16133-25-8)

Conditions	Yield
Stage #1: 3-Bromopyridine With isopropylmagnesium chloride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: With sulfur dioxide In tetrahydrofuran at -40℃; for 0.5h; Stage #3: With sulfuryl dichloride In tetrahydrofuran at -40 - 20℃;
Stage #1: 3-Bromopyridine With isopropylmagnesium chloride In tetrahydrofuran at 10℃; Inert atmosphere; Stage #2: With sulfuryl dichloride In tetrahydrofuran; toluene at -10 - 10℃;
Stage #1: 3-Bromopyridine With isopropylmagnesium chloride In tetrahydrofuran at 20℃; for 0.583333h; Inert atmosphere; Stage #2: With 1,4-diazabicyclo [2.2.2] octane-1,4-diium-1,4-disulfinate In tetrahydrofuran at -40℃; for 1h; Inert atmosphere; Stage #3: With sulfuryl dichloride In tetrahydrofuran at -40 - 20℃; Inert atmosphere;

pyridine (110-86-1) → Pyridine-3-sulfonyl chloride (16133-25-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: fuming H2SO4; HgSO4 / 230 °C 2: PCl5 / 120 °C View Scheme
Multi-step reaction with 2 steps 1: fuming H2SO4; HgSO4 / 300 °C 2: PCl5 / 120 °C View Scheme

morpholine (110-91-8) + 3-pyridinesulfonic acid (636-73-7) → Pyridine-3-sulfonyl chloride (16133-25-8)

Conditions	Yield
With phosphorus pentachloride; triethylamine In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; toluene

3-pyridinesulfonic acid (636-73-7) + phosphorus pentachloride (10026-13-8, 874483-75-7) → Pyridine-3-sulfonyl chloride (16133-25-8)

Conditions	Yield
With hydrogenchloride; trichlorophosphate In chloroform

3-pyridinesulfonic acid (636-73-7) → Pyridine-3-sulfonyl chloride (16133-25-8) + 5-[2-(Piperidin-4-yl)ethyl]thieno-[2,3-b]thiophene-2-N-[3-2(S)-(2-ethoxyethanesulfonylamino)propionic acid]carboxamide

Conditions	Yield
With phosphorus pentachloride In toluene	A 30.7 g (92%) B n/a

3,4-dihydro-2H-pyran (110-87-2) + N-(4-hydroxybutyl)pyridine-3-sulfonamide + 4-Aminobutanol (13325-10-5) → Pyridine-3-sulfonyl chloride (16133-25-8) + N-(4-(2-tetrahydropyranyloxy)butyl)pyridine-3-sulfonamide (173843-37-3)

Conditions	Yield
With p-toluenesulfonic acid monohydrate; triethylamine In dichloromethane; chloroform; ethyl acetate

Pyridine-3-sulfonyl chloride (16133-25-8) + 5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde (881674-60-8) → 1-(pyridin-3-ylsulfonyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde (881677-15-2)

Conditions	Yield
Stage #1: 5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: Pyridine-3-sulfonyl chloride With 15-crown-5 In tetrahydrofuran at 0 - 20℃;	100%

Pyridine-3-sulfonyl chloride (16133-25-8) + (3-(tert-butyl)phenyl)methanamine (608515-16-8) → N-(3-tert-butylbenzyl)pyridin-3-ylsulfonamide (1313217-72-9)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h;	100%

Pyridine-3-sulfonyl chloride (16133-25-8) + N,N-Dimethyltrimethylsilylamine (2083-91-2) → N,N-Dimethyl-3-pyridinsulfonsaeureamid

Conditions	Yield
In acetonitrile for 1h; Reflux; Inert atmosphere;	99%

8-amino quinoline (578-66-5) + Pyridine-3-sulfonyl chloride (16133-25-8) → N-(quinolin-8-yl)pyridine-3-sulfonamide (1136429-51-0)

Conditions	Yield
With pyridine at 25℃;	99%
With pyridine at 130℃; for 0.5h;	82%

Pyridine-3-sulfonyl chloride (16133-25-8) + 5-[(3,4-dichlorophenyl)methylamino]-1-(4-piperidyl)-6H-pyrazolo[4,3-d]pyrimidin-7-one → 5-((3,4-dichlorobenzyl)amino)-1-(1-(pyridin-3-ylsulfonyl)piperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one hydrochloride

Conditions	Yield
Stage #1: Pyridine-3-sulfonyl chloride; 5-[(3,4-dichlorophenyl)methylamino]-1-(4-piperidyl)-6H-pyrazolo[4,3-d]pyrimidin-7-one With triethylamine In dichloromethane at 0 - 20℃; for 1h; Stage #2: With hydrogenchloride	98.51%

1-ethenyl-2-pyrrolidinone (88-12-0) + Pyridine-3-sulfonyl chloride (16133-25-8) → (E)-1-(2-(pyridin-3-ylsulfonyl)vinyl)pyrrolidin-2-one (1429936-66-2)

Conditions	Yield
With sodium dihydrogenphosphate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate In acetonitrile at 20℃; for 8h; Inert atmosphere; Irradiation;	98%

Pyridine-3-sulfonyl chloride (16133-25-8) + Cyclopropylamine (765-30-0) → N-cyclopropylpyridine-3-sulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 22h; Schlenk technique; Inert atmosphere;	98%

Pyridine-3-sulfonyl chloride (16133-25-8) + tert-butyl {[5-(2-chloropyridin-3-yl)-4-fluoro-1H-pyrrol-3-yl]methyl}methylcarbamate (1055306-84-7) → tert-butyl {[5-(2-chloropyridin-3-yl)-4-fluoro-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (1055306-93-8)

Conditions	Yield
With 15-crown-5; sodium hydride In tetrahydrofuran at 0℃; for 0.25h;	97%

Pyridine-3-sulfonyl chloride (16133-25-8) + 2-Iodophenol (533-58-4) → 2-iodophenyl 3-pyridinesulfonate

Conditions	Yield
With pyridine; dmap at 20℃; for 72h;	97%

Pyridine-3-sulfonyl chloride (16133-25-8) + N,N-diethyl-1,3-benzenediamine (26513-20-2) → C15H19N3O2S (870274-40-1)

Conditions	Yield
Stage #1: Pyridine-3-sulfonyl chloride; N,N-diethyl-1,3-benzenediamine In 1,2-dichloro-ethane at 20 - 40℃; Stage #2: With sodium hydroxide In dichloromethane; water pH=7;	96%

Pyridine-3-sulfonyl chloride (16133-25-8) + 1-(piperidin-4-ylmethyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole → 1-((1-(pyridin-3-ylsulfonyl)piperidin-4-yl)methyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 6h;	96%

Pyridine-3-sulfonyl chloride (16133-25-8) + L-prolyl-L-O-(1-pyrrolidinylcarbonyl)tyrosine methyl ester (425388-80-3) → N-(3-pyridinesulfonyl)-L-prolyl-L-O-(1-pyrrolidinylcarbonyl)tyrosine methyl ester

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	96%

Pyridine-3-sulfonyl chloride (16133-25-8) + methyl 5-(2-fluorophenyl)-1H-pyrrole-3-carboxylate (1240949-59-0) → C17H13FN2O4S

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 6h;	95.8%

1-ethylpyrrolidine (7335-06-0) + Pyridine-3-sulfonyl chloride (16133-25-8) → 3-(pyrrolidin-1-ylsulfonyl)pyridine (26103-51-5)

Conditions	Yield
With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In tetrahydrofuran; decane at 80℃; for 4h; Sealed tube; chemoselective reaction;	95%

Pyridine-3-sulfonyl chloride (16133-25-8) + n-Octylamine (111-86-4) → N-octylpyridine-3-sulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	95%

Pyridine-3-sulfonyl chloride (16133-25-8) + C9H6FN3O → C14H9FN4O3S

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 6h;	94.3%

methyl 4-[(2-amino-5-(trifluoromethyl)phenoxy)methyl]benzoate (907587-49-9) + Pyridine-3-sulfonyl chloride (16133-25-8) → methyl 4-{[2-[(pyridin-3-ylsulfonyl)amino]-5-(trifluoromethyl)phenoxy]methyl}benzoate (909896-93-1)

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 4h;	94%

C15H29N7 + Pyridine-3-sulfonyl chloride (16133-25-8) → N1-[4-([4,6-di(ethylamino)-1,3,5-triazin-2-yl]aminomethyl)cyclohexyl]methyl-3-pyridinesulfonamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane	94%

Pyridine-3-sulfonyl chloride (16133-25-8) + aniline (62-53-3) → pyridine-3-sulfonic acid phenylamide (103860-56-6)

Conditions	Yield
With sodium hydrogencarbonate In 1,4-dioxane; water at 90℃; for 3h;	94%
With sodium hydrogencarbonate In 1,4-dioxane at 90℃; for 3h;	94%
With triethylamine In dichloromethane at 0 - 20℃; for 24h; Inert atmosphere;	92%
Stage #1: Pyridine-3-sulfonyl chloride With pyridine In dichloromethane at 20℃; for 0.333333h; Stage #2: aniline In dichloromethane at 20℃; for 24h;	91.4%

Pyridine-3-sulfonyl chloride (16133-25-8) + 5-(2-fluorophenyl)-1H-pyrrole-3-carboxaldehyde (881674-56-2) → 5‐(2-fluorophenyl)‐1‐(pyridine-3-sulfonyl)-1H-pyrrole-3-carbaldehyde (881677-11-8)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 6h;	93.8%
With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 20 - 50℃; for 2h;	90.6%
With dmap; triethylamine In acetonitrile at 45℃; for 1.5h;	88.7%

Pyridine-3-sulfonyl chloride (16133-25-8) + tert-butyl N-{[5-(2-fluorophenyl)-1H-pyrrol-3-yl]methyl}-N-methylcarbamate → ((5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamic acid tert-butyl ester

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Solvent; Cooling with ice;	93.5%
Stage #1: tert-butyl N-{[5-(2-fluorophenyl)-1H-pyrrol-3-yl]methyl}-N-methylcarbamate With sodium hydride In diethyl ether at 30 - 35℃; Inert atmosphere; Cooling with ice; Stage #2: Pyridine-3-sulfonyl chloride In diethyl ether at 0 - 60℃; for 0.166667h; Solvent; Temperature;

Pyridine-3-sulfonyl chloride (16133-25-8) + 2,4-difluoro-3-ethynylaniline → N-(3-ethynyl-2,4-difluborophenyl)pyridine-3-ylsulfonamide

Conditions	Yield
With pyridine In dichloromethane at 20℃;	93%

Pyridine-3-sulfonyl chloride (16133-25-8) + 2-(2-fluorophenyl)-4-methyl-1H-pyrrole (1428932-17-5) → 5-(2-fluorophenyl)-3-methyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole

Conditions	Yield
With triethylamine In dichloromethane; toluene at 25℃; for 1h; Reagent/catalyst; Solvent; Temperature;	92.8%
With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 40℃; for 4h; Inert atmosphere;	87%

2-aminopyridine (504-29-0) + Pyridine-3-sulfonyl chloride (16133-25-8) → N-(2-pyridyl)-3-pyridylsulfonamide

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 4h;	92%
With pyridine

Pyridine-3-sulfonyl chloride (16133-25-8) + 5-(2-fluorophenyl)-1H-pyrrole-3-carbonitrile (1240948-77-9) → 5-(2-fluorophenyl)-1-(pyridin-3-yl-sulfonyl)-1H-pyrrole-3-carbonitrile

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 10 - 30℃; for 3h;	91.5%
With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 20 - 30℃; for 2h;	90.5%
With dmap; N-ethyl-N,N-diisopropylamine

Pyridine-3-sulfonyl chloride (16133-25-8) + 5-(2-bromophenyl)-1H-pyrrole-3-carbaldehyde (928324-88-3) → 5-(2-bromophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde (928324-94-1)

Conditions	Yield
Stage #1: 5-(2-bromophenyl)-1H-pyrrole-3-carbaldehyde With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: Pyridine-3-sulfonyl chloride With 15-crown-5 In tetrahydrofuran at 0 - 20℃;	91%

Pyridine-3-sulfonyl chloride (16133-25-8) + (4-(difluoromethoxy)phenyl)methanamine (177842-14-7) → N-(4-difluoromethoxybenzyl)pyridin-3-ylsulfonamide (1023230-97-8)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h;	91%

Upstream product

• 636-73-7 3-pyridinesulfonic acid 
• 110-86-1 pyridine 
• 110-91-8 morpholine 
• 10026-13-8 phosphorus pentachloride 
• 462-08-8 pyridin-3-ylamine 
• 42899-76-3 pyridine-3-sulfonyl chloride hydrochloride 
• 110-87-2 3,4-dihydro-2H-pyran 
• 13325-10-5 4-Aminobutanol 
• 626-55-1 3-Bromopyridine 
• 16133-26-9 pyridine-3-thiol 

Downstream Products

• 111664-38-1 pyridine-3-sulfonic acid-[3-(6-ethoxy-[2]quinolyl)-anilide] 
• 88842-76-6 pyridine-3-sulfonic acid-(3-benzo[f]quinolin-3-yl-anilide) 
• 88842-77-7 pyridine-3-sulfonic acid-(4-benzo[f]quinolin-3-yl-anilide) 
• 110936-40-8 pyridine-3-sulfonic acid-[4-(6-methoxy-[2]quinolyl)-anilide] 
• 111664-05-2 pyridine-3-sulfonic acid-[4-(6-ethoxy-[2]quinolyl)-anilide] 
• 110936-65-7 pyridine-3-sulfonic acid-[3-(6-methoxy-[2]quinolyl)-anilide] 
• 4810-42-8 N,N-diethylpyridine-3-sulfonamide 
• 2922-45-4 3-pyridinesulfonamide 
• 65227-53-4 pyridine-3-sulfonohydrazide 
• 262430-07-9 N₃-[4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]-3-pyridinesulfonamide 
• 62009-34-1 5-bromopyridine-3-sulfonic acid 
• 62009-33-0 5-bromopyridine-3-sulfonamide 
• 62009-37-4 5-bromo-pyridine-3-sulfonic acid diethylamide 
• 737799-50-7 (R)-5,5-dimethyl-3-(pyridin-3-ylsulfonyl)thiazolidine-4-carboxylic acid 

Relevant articles and documents

Regioselective Lithiation of 3-Pyridylsulfonic Acid Derivatives: A Convenient Route to Various New 4-Substituted 3-Pyridylsulfonamides

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Synthetic method of pyridine-3-sulfonyl chloride

The invention provides a synthetic method for synthesizing pyridine-3-sulfonyl chloride. The synthesis of pyridine-3-sulfonyl chloride comprises the following steps: taking 3-amino pyridine as an initial raw material, separating out an intermediate fluoboric acid diazonium salt, and then carrying out sulfonyl chlorination reaction. The method is low in cost, high in product content, convenient to operate, few in three wastes and suitable for industrial large-scale production.

Environment-friendly chemical synthetic method for 3-pyridine sulfonyl chloride

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We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent IKur current blocker with selectivity versus hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further characterization in vivo, compound 1 demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2′ position for a series of close analogues by employing hydrogen bond donors. As a result, 5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide (25) was identified as the lead compound in this series. Compound 25 showed robust effects in rabbit and canine pharmacodynamic models and an acceptable cross-species pharmacokinetic profile and was advanced as the clinical candidate. Further optimization of 25 to mitigate pH-dependent absorption resulted in identification of the corresponding phosphoramide prodrug (29) with an improved solubility and pharmacokinetic profile.