52092-47-4

Basic information

• Product Name: 5-Chloro-2-nitropyridine
• Synonyms: 5-CHLORO-2-NITROPYRIDINE;3-Chloro-6-nitropyridine;5-CHLORO-2-NITROPYRIDINE/2-NITRO-5-CHLOROPYRIDINE;6-nitro-3-chloropyridine
• CAS NO: 52092-47-4
• Molecular Formula: C₅H₃ClN₂O₂
• Molecular Weight: 158.54
• EINECS: 1592732-453-0
• Product Categories: Pyridine;Pyridines;pyridine series;Building Blocks;C5;C5 to C6;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks;Heterocycle-Pyridine series;Pyrazines
• Mol File: 52092-47-4.mol
• Article Data: 8

Chemical Properties

• Melting Point: 119-123℃
• Boiling Point: 275.3 °C at 760 mmHg
• Flash Point: 120.3 °C
• Appearance: /
• Density: 1.489 g/cm³
• Vapor Pressure: 0.00865mmHg at 25°C
• Refractive Index: 1.587
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: -4.87±0.22(Predicted)
• CAS DataBase Reference: 5-Chloro-2-nitropyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chloro-2-nitropyridine(52092-47-4)
• EPA Substance Registry System: 5-Chloro-2-nitropyridine(52092-47-4)

Safety Data

• Hazard Codes: Xi,N,Xn
• Statements: 20/21/22-36/37/38-50-41-22
• Safety Statements: 26-36/37/39-36-61-37/39
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 2
• Hazardous Substances Data: 52092-47-4(Hazardous Substances Data)

Usage

Uses

5-Chloro-2-nitropyridine can be used as organic synthesis intermediate and pharmaceutical intermediate, mainly used in laboratory research and development process and chemical production process.

Synthesis

To concentrated H2SO4 (50 ml) was added 30 % H2O2 (25mL) at 0 °C and a solution of 5-chloropyridin-2-amine (5.0 g, 39 mmol) in concentrated H2SO4 (20 mL) was added at 0 °C. The mixture was stirred for 20 hours at room temperature. The mixture was poured into ice water under vigorously stirring and the resulting solid was filtered. The solid was recrystallized from ethanol to give 5-chloro-2-nitropyridine. 5-chloro-2-nitropyridine. MS m/z 159 (M+ 1)+.

InChI:InChI=1/C5H3ClN2O2/c6-4-1-2-5(7-3-4)8(9)10/h1-3H

Synthetic route

5-chloro-2-pyridylamine (1072-98-6) → 5-chloro-2-nitropyridine (52092-47-4)

Conditions	Yield
With sulfuric acid; dihydrogen peroxide at 20℃; for 48h;	71%
With caro's acid
Multi-step reaction with 2 steps 1: 94 percent / trifluoroacetic anhydride / CH2Cl2 / -60 °C 2: 62 percent / trifluoroacetic acid, H2O2 / CH2Cl2 / 1.5 h / 0 °C View Scheme

2-dimethylsulfilimino-5-chloropyridine (134251-85-7) → 5-chloro-2-nitropyridine (52092-47-4) + 5-Chloro-2-nitro-pyridine 1-oxide (134251-87-9)

Conditions	Yield
With dihydrogen peroxide; trifluoroacetic acid In dichloromethane at 0℃; for 1.5h;	A 62% B 38%

(3-chloro-6-nitro-[2]pyridyl)-hydrazine (99848-04-1) → 5-chloro-2-nitropyridine (52092-47-4)

Conditions	Yield
With water; silver(I) acetate

3-hydroxy-2-nitropyridine (15128-82-2) → 5-chloro-2-nitropyridine (52092-47-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic acid anhydride; nitric acid 2: phosphorus (V)-chloride / 130 °C 3: methanol; N2H4 4: silver acetate; water View Scheme
Multi-step reaction with 4 steps 1: acetic acid; acetic acid anhydride; nitric acid 2: phosphorus (V)-chloride / 130 °C 3: methanol; N2H4 4: silver acetate; water View Scheme

3-hydroxy-2,6-dinitropyridine (15128-91-3) → 5-chloro-2-nitropyridine (52092-47-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus (V)-chloride / 130 °C 2: methanol; N2H4 3: silver acetate; water View Scheme

3-chloro-2,6-dinitro-pyridine (101079-67-8) → 5-chloro-2-nitropyridine (52092-47-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol; N2H4 2: silver acetate; water View Scheme

5-chloro-2-pyridylamine (1072-98-6) + concentrated H2 SO4 + dihydrogen peroxide (7722-84-1) → 5-chloro-2-nitropyridine (52092-47-4)

Conditions	Yield
In ethyl acetate; toluene

methanol (67-56-1) + 5-chloro-2-nitropyridine (52092-47-4) + sodium methylate (124-41-4) → 3-methoxy-6-nitropyridine (126739-64-8)

Conditions	Yield
at 20℃;	100%

5-chloro-2-nitropyridine (52092-47-4) + p-cresol (106-44-5) → 2-nitro-5-(p-tolyloxy)pyridine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 12h;	94%

piperazine (110-85-0) + 5-chloro-2-nitropyridine (52092-47-4) → 1-(6-nitropyridin-3-yl)piperazine (775288-71-6)

Conditions	Yield
In butan-1-ol at 22 - 100℃;	89.5%
In isopropyl alcohol at 80 - 85℃; for 24h; Time;	102.2 g

5-chloro-2-nitropyridine (52092-47-4) + sodium phenyl-methanolate (20194-18-7) → 2-nitro-5-phenylmethoxypyridine

Conditions	Yield
In tetrahydrofuran at 20℃;	89.1%

5-chloro-2-nitropyridine (52092-47-4) + 4-Fluorophenol (371-41-5) → 5-(4-fluorophenoxy)-2-nitropyridine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 12h;	86%

5-chloro-2-nitropyridine (52092-47-4) + benzyl (3-fluoro-4-hydroxyphenyl)carbamate (1195781-15-7) → benzyl {3-fluoro-4-[(6-nitropyridin-3-yl)oxy]phenyl}carbamate (1195781-16-8)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 20℃; for 3h;	83%

piperazine (110-85-0) + 5-chloro-2-nitropyridine (52092-47-4) → 1-(6-nitropyridin-3-yl)piperazine hydrochloride (1221726-34-6)

Conditions	Yield
In butan-1-ol at 95℃; for 24h; Inert atmosphere;	82.3%

5-chloro-2-nitropyridine (52092-47-4) → 5-chloro-2-pyridylamine (1072-98-6)

Conditions	Yield
With sulfuric acid; hydrogen In ethanol at 25℃; Electrochemical reaction;	82%
With boron dimethyl-trifluoro sulphide In dichloromethane at 60℃; for 0.5h; Sealed tube;	72%
With hydrogenchloride; sodium hydrogensulfide
With hydrogenchloride; tin(ll) chloride
With ammonium hydroxide; iron(II) sulfate

5-chloro-2-nitropyridine (52092-47-4) + (S)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (147081-29-6) → (3S)-tert-butyl 3-methyl-4-(6-nitropyridin-3-yl)piperazine-1-carboxylate (1433849-53-6)

Conditions	Yield
With potassium phosphate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,4-dioxane at 95 - 105℃; Inert atmosphere;	80.5%
With potassium phosphate; palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 80 - 90℃; for 20h; Inert atmosphere; Industrial scale;

5-chloro-2-nitropyridine (52092-47-4) + N-(2-fluoro-5-hydroxyphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide (1005788-04-4) → N-{2-fluoro-5-[(6-nitropyridin-3-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (1092394-02-9)

Conditions	Yield
With potassium carbonate In water; dimethyl sulfoxide at 75 - 85℃; for 6h; Large scale;	78%

5-chloro-2-nitropyridine (52092-47-4) + benzyl (2-fluoro-4-hydroxyphenyl)carbamate (1195781-24-8) → benzyl {2-fluoro-4-[(6-nitropyridin-3-yl)oxy]phenyl}carbamate (1195781-25-9)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 20℃; for 6h;	77%

5-chloro-2-nitropyridine (52092-47-4) + 4-bromo-phenol (106-41-2) → 5-(4-bromophenoxy)-2-nitropyridine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 12h;	77%

1-(1-methylethyl)piperazine (4318-42-7) + 5-chloro-2-nitropyridine (52092-47-4) → 1-isopropyl-4-(6-nitropyridin-3-yl)piperazine (943758-04-1)

Conditions	Yield
In acetonitrile for 5h; Reflux;	76%

5-chloro-2-nitropyridine (52092-47-4) + 5-hydroxy-2-fluoroaniline (62257-16-3) → 2-fluoro-5-(6-nitropyridin-3-yloxy)benzenamine (1020173-38-9)

Conditions	Yield
With potassium phosphate In water; dimethyl sulfoxide at 75 - 80℃; for 9h;	76%

3-HYDROXYPYRIDINE (109-00-2) + 5-chloro-2-nitropyridine (52092-47-4) → 2-nitro-5-(pyridine-3-yloxy)pyridine

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 5h;	76%

5-chloro-2-nitropyridine (52092-47-4) + 3-monochlorophenol (108-43-0) → 5-(3-chlorophenoxy)-2-nitropyridine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 12h;	75%

1-methyl-piperazine (109-01-3) + 5-chloro-2-nitropyridine (52092-47-4) → 1-methyl-4-(6-nitro-pyridin-3-yl)-piperazine (657410-79-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 3h;	75%

5-chloro-2-nitropyridine (52092-47-4) + 2,4,6,8-tetramethyl-2,4,6,8-tetravinyl-cyclotetrasiloxane (2554-06-5) → 2-nitro-5-vinylpyridine (125889-39-6)

Conditions	Yield
With XPhos; tetrabutyl ammonium fluoride; palladium diacetate In tetrahydrofuran at 67℃; for 24h; Inert atmosphere; Schlenk technique;	74%

5-chloro-2-nitropyridine (52092-47-4) + 1,3-dimethyl-1H-pyrazol-5-ol (5203-77-0) → 5-((1,3-dimethyl-1H-pyrazol-5-yl)oxy)-2-nitropyridine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 12h; Inert atmosphere;	71%

5-chloro-2-nitropyridine (52092-47-4) + 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane (201733-56-4) → C10H15BN2O2

Conditions	Yield
Stage #1: 5-chloro-2-nitropyridine; 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 80 - 90℃; Suzuki Coupling; Inert atmosphere; Stage #2: With hydrogen In 1,4-dioxane at 20℃; under 2280.15 Torr;	68%

4-HYDROXYPIPERIDINE (5382-16-1) + 5-chloro-2-nitropyridine (52092-47-4) → 1-(6-nitropyridin-3-yl)piperidin-4-ol

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 90℃;	65%
With potassium carbonate In dimethyl sulfoxide at 90℃; Sealed tube;	65%

5-chloro-2-nitropyridine (52092-47-4) + phenylmethanethiol (100-53-8) → 5-(benzylthio)-2-nitropyridine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h;	65%

5-chloro-2-nitropyridine (52092-47-4) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → 4-(6-nitropyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (571189-16-7)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 100 - 110℃; Microwave irradiation;	63.81%
With cesium fluoride In dimethyl sulfoxide at 80℃; for 16h;	30.15%

5-chloro-2-nitropyridine (52092-47-4) + diethyl malonate (105-53-3) → diethyl 2-(6-nitro-3-pyridinyl)malonate

Conditions	Yield
Stage #1: diethyl malonate With sodium hydride In N,N-dimethyl-formamide at 10 - 20℃; for 0.5h; Inert atmosphere; Stage #2: 5-chloro-2-nitropyridine In N,N-dimethyl-formamide at 80℃; for 12h;	60.66%
Stage #1: diethyl malonate With sodium hydride In N,N-dimethyl-formamide at 10 - 20℃; for 0.5h; Inert atmosphere; Stage #2: 5-chloro-2-nitropyridine In N,N-dimethyl-formamide at 80℃; for 12h; Inert atmosphere;	60.66%

Upstream product

• 1072-98-6 5-chloro-2-pyridylamine 
• 7722-84-1 dihydrogen peroxide 
• 101079-67-8 3-chloro-2,6-dinitro-pyridine 
• 15128-91-3 3-hydroxy-2,6-dinitropyridine 
• 15128-82-2 3-hydroxy-2-nitropyridine 
• 134251-85-7 2-dimethylsulfilimino-5-chloropyridine 
• 99848-04-1 (3-chloro-6-nitro-[2]pyridyl)-hydrazine 

Downstream Products

• 77012-86-3 5-(4-chloro-phenylsulfanyl)-2-nitro-pyridine 
• 1221726-34-6 1-(6-nitropyridin-3-yl)piperazine hydrochloride 
• 1374129-87-9 N-benzal-5-(methylthio)pyridine-2-amine 
• 1374129-89-1 C₁₃H₁₁FN₂S 
• 1374129-90-4 C₁₅H₁₂FN₃S 
• 1374129-91-5 C₁₄H₁₄N₂S 
• 1374129-92-6 C₁₆H₁₅N₃S 
• 1374129-93-7 C₁₃H₁₀Cl₂N₂S 
• 1374129-94-8 C₁₅H₁₁Cl₂N₃S 
• 1374129-95-9 C₁₄H₁₄N₂OS 
• 1374129-96-0 C₁₆H₁₅N₃OS 
• 1374129-98-2 C₁₆H₁₄FN₃OS 
• 1374129-97-1 C₁₄H₁₃FN₂OS 
• 1374128-88-7 2-(4-chloro-5-(4-fluorophenyl)-1H-imidazol-1-yl)-5-(methylsulfonyl)pyridine 

Relevant articles and documents

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL

no abstract published

INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL

Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included.

Amide compounds and medications containing the same technical field

The present invention provides to a novel compound having an ACAT inhibiting activity. The present invention relates to compounds represented by formula (I) wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group,Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring,X represents —NH—, an oxygen atom or a sulfur atom,Y represents —NR4—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone,Z represents a single bond or —NR5—,R4 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group,R5 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, andn is integer of from 1 to 15, or salts or solvates thereof, and a pharmaceutical composition containing at one of these compounds.