5446-92-4

Basic information

• Product Name: 2-Methoxy-5-nitropyridine
• Synonyms: METHOXY(2-)-5-NITROPYRIDINE;5-NITRO-2-METHOXY PYRIDINE;2-METHOXY-5-NITROPYRIDINE;Pyridine,2-methoxy-5-nitro-;2-Methoxy-5-nitropyridine ,99%;6-Methoxy-3-nitropyridine;2-Methoxy-5-nitropyridine,97%;2-Methoxy-5-nitropyridine 97%
• CAS NO: 5446-92-4
• Molecular Formula: C₆H₆N₂O₃
• Molecular Weight: 154.12
• EINECS: 226-661-7
• Product Categories: blocks;Pyridines;Pyridine;Pyridines, Pyrimidines, Purines and Pteredines;Pyridines derivates;Boronic Acid;C6;Heterocyclic Building Blocks
• Mol File: 5446-92-4.mol
• Article Data: 15

Chemical Properties

• Melting Point: 104-108 °C(lit.)
• Boiling Point: 277.46°C (rough estimate)
• Flash Point: 130 °C
• Appearance: Clear colorless to yellow/Liquid
• Density: 0.45
• Vapor Pressure: 0.0216mmHg at 25°C
• Refractive Index: 1.5100 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: -0?+-.0.10(Predicted)
• Water Solubility: insoluble
• BRN: 126991
• CAS DataBase Reference: 2-Methoxy-5-nitropyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methoxy-5-nitropyridine(5446-92-4)
• EPA Substance Registry System: 2-Methoxy-5-nitropyridine(5446-92-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39-36
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 5446-92-4(Hazardous Substances Data)

Usage

Chemical Description

2-methoxy-5-nitropyridine is a nitroaromatic compound with the formula C6H6N2O3.

Chemical Properties

VERY SLIGHTLY YELLOW ADHERING POWDER

Uses

2-Methoxy-5-nitropyridine is used in the synthesis of pyrrolopyridones as a potential protein tyrosine kinase inhibitors.

InChI:InChI=1/C6H6N2O3/c1-11-6-3-2-5(4-7-6)8(9)10/h2-4H,1H3

Synthetic route

methanol (67-56-1) + 2-chloro-5-nitropyridine (4548-45-2) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
With sodium at 70℃; for 24h; Heating;	99%
With potassium tert-butylate at 20℃; for 1h;	93%
With potassium tert-butylate at 20℃; for 1h;	93%

2-chloro-5-nitropyridine (4548-45-2) + sodium methylate (124-41-4) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
In methanol for 1h; Concentration; Reflux;	95.36%
In methanol; dimethyl sulfoxide at 20℃; Rate constant; formation of Meisenheimer complex;
In methanol for 6h; Heating;

methanol (67-56-1) + 2-iodo-5-nitropyridine (28080-54-8) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
Stage #1: methanol With N-benzyl-trimethylammonium hydroxide for 0.166667h; Neat (no solvent); Stage #2: 2-iodo-5-nitropyridine at 20℃; for 0.0833333h; Neat (no solvent);	95%

methanol (67-56-1) + 2-chloro-5-nitropyridine (4548-45-2) + sodium methylate (124-41-4) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
Reflux;	92.1%

2-methoxypyridine N-oxide hydrochloride (96530-76-6) → 2-methoxy-5-nitropyridine (5446-92-4) + 2-methoxy-4-nitropyridine N-oxide (14395-39-2) + 2-methoxy-5-nitropyridine N-oxide (96530-77-7)

Conditions	Yield
With sulfuric acid; nitric acid In sulfuric acid at 90 - 100℃; for 3h;	A 20% B 62% C 11%

2-methoxy-pyridine-5-boronic acid (163105-89-3) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
With N–nitrosuccinimide; tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate In acetonitrile at 20℃; for 19h; Inert atmosphere; Irradiation;	35%

2-methoxypyridine N-oxide (20773-98-2) → 2-methoxy-5-nitropyridine (5446-92-4) + 2-methoxy-4-nitropyridine (18614-54-5) + 2-methoxy-4-nitropyridine N-oxide (14395-39-2) + 2-methoxy-5-nitropyridine N-oxide (96530-77-7)

Conditions	Yield
With sulfuric acid; nitric acid at 75℃; for 1.5h;	A n/a B n/a C 30% D 2.9 g
With sulfuric acid; nitric acid at 75℃; for 1.5h; Title compound not separated from byproducts;	A n/a B n/a C 6.4 g D 2.9 g
With sulfuric acid; nitric acid at 75℃; for 1.5h;	A n/a B n/a C 6.4 g D 2.9 g

2-methoxypyridine (1628-89-3) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
With sulfuric acid; nitric acid at 70℃; Rate constant; other concentration of H2SO4;
With sulfuric acid; nitric acid

2-Fluoro-5-nitropyridine (456-24-6) → 2-methoxy-5-nitropyridine (5446-92-4)

2-chloro-5-nitropyridine (4548-45-2) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
With methanol; water; sodium sulfite

2-iodo-5-nitropyridine (28080-54-8) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
With methanol; sodium methylate

6-ethoxy-2-(5-nitro-[2]pyridylmercapto)-[3]pyridylamine (100518-03-4) → 2-methoxy-5-nitropyridine (5446-92-4) + 6-ethoxy-2-methylsulfanyl-[3]pyridylamine (98489-61-3)

Conditions	Yield
With potassium hydroxide anschliessendes Behandeln mit CH3I;

2-bromo-5-nitropyridine (4487-59-6) + sodium methylate (124-41-4) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
In methanol; dimethyl sulfoxide at 20℃; Rate constant; formation of Meisenheimer complex;

2-iodo-5-nitropyridine (28080-54-8) + sodium methylate (124-41-4) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
In methanol; dimethyl sulfoxide at 20℃; Rate constant; formation of Meisenheimer complex;

2-(3-methylphenoxy)-5-nitropyridine (28232-33-9) + sodium methylate (124-41-4) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
In methanol; dimethyl sulfoxide at 20℃; Rate constant; formation of Meisenheimer complex;

3-nitro-6-phenoxypyridine (28222-02-8) + sodium methylate (124-41-4) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
In methanol; dimethyl sulfoxide at 20℃; Rate constant; formation of Meisenheimer complex;

2-(m-chlorophenoxy)-5-nitropyridine (28222-04-0) + sodium methylate (124-41-4) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
In methanol; dimethyl sulfoxide at 20℃; Rate constant; formation of Meisenheimer complex;

sodium methylate (124-41-4) + 2-(m-nitrophenoxy)-5-nitropyridine (6960-10-7) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
In methanol; dimethyl sulfoxide at 20℃; Rate constant; formation of Meisenheimer complex;

ethanol (64-17-5) + methyl iodide (74-88-4) + silver salt of 5-nitro-2-oxy-pyridine → 2-methoxy-5-nitropyridine (5446-92-4)

methanol (67-56-1) + 3-Nitro-6-(methylsulfonyl)pyridine (79134-11-5) + ammonia (7664-41-7) → 5-nitro-pyridin-2-ylamine (4214-76-0) + 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
at 37℃;

methyl iodide (74-88-4) + silver-salt of 5-nitro-pyridin-2-ol → 2-methoxy-5-nitropyridine (5446-92-4) + 1-methyl-5-nitro-2(1H)-pyridone (32896-90-5)

Conditions	Yield
With methanol

methanol (67-56-1) + potassium 5-nitropyridine-2-sulfonate → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
With sodium hydride at 23℃; for 16h;	102 mg

methanol (67-56-1) + 5-nitropyridine-2-sulfonic acid (465529-94-6) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
at 65℃; for 20h;	115 mg

5-Hydroxyaminopyridine-2-sulfonic acid (280584-87-4) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. KMnO4 / 10 h / 20 °C 2: 115 mg / 20 h / 65 °C View Scheme

5-nitro-pyridin-2-ylamine (4214-76-0) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous hydrofluoric acid / Behandeln der Reaktionsloesung mit Natriumnitrit View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride; sodium nitrite / water / 0.67 h / 0 - 6 °C 2: trichlorophosphate / N,N-dimethyl-formamide / 2 h / 20 °C / Reflux 3: methanol / 1 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / Reflux 2: trichlorophosphate / N,N-dimethyl-formamide / Reflux 3: Reflux View Scheme

2-aminopyridine (504-29-0) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: nitric acid; sulfuric acid / 1,2-dichloro-ethane / 10 h / 58 °C 2: hydrogenchloride; sodium nitrite / water / 0.67 h / 0 - 6 °C 3: trichlorophosphate / N,N-dimethyl-formamide / 2 h / 20 °C / Reflux 4: methanol / 1 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: nitric acid; sulfuric acid / 80 °C 2: sodium hydroxide / Reflux 3: trichlorophosphate / N,N-dimethyl-formamide / Reflux 4: Reflux View Scheme

5-nitro-2-hydroxypyridine (5418-51-9) → 2-methoxy-5-nitropyridine (5446-92-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: trichlorophosphate / N,N-dimethyl-formamide / 2 h / 20 °C / Reflux 2: methanol / 1 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: trichlorophosphate / N,N-dimethyl-formamide / Reflux 2: Reflux View Scheme

2-methoxy-5-nitropyridine (5446-92-4) → 6-methoxy-pyridin-3-ylamine (6628-77-9)

Conditions	Yield
With potassium fluoride; polymethylhydrosiloxane; palladium diacetate In tetrahydrofuran at 20℃; for 0.5h;	100%
With cyclohexa-1,4-diene; 5%-palladium/activated carbon In methanol at 120℃; for 0.0833333h; Microwave irradiation;	99%
With iron; calcium chloride In ethanol for 2h; Heating;	97%

2-methoxy-5-nitropyridine (5446-92-4) + (4-chlorophenoxy)acetonitrile (3598-13-8) → 2-(6-methoxy-3-nitropyridin-2-yl)acetonitrile (111795-99-4)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at -20℃; for 35h; Inert atmosphere;	95%
With potassium tert-butylate In tetrahydrofuran at -10℃; for 3.5h;	94%
With potassium tert-butylate In tetrahydrofuran at -10℃; for 3h;	86%

2-methoxy-5-nitropyridine (5446-92-4) → N,N'-Bis-(6-methoxy-pyridin-3-yl)-diazene N-oxide

Conditions	Yield
With sodium tetrahydroborate; sodium methylate In methanol at 25℃;	92%

2-methoxy-5-nitropyridine (5446-92-4) → 2-chloro-5-nitropyridine (4548-45-2)

Conditions	Yield
With N,N-dimethyl-formamide; trichlorophosphate at 85℃; for 8h;	91%

2-methoxy-5-nitropyridine (5446-92-4) + N-Methyl-sarkosin-trimethylamid-Kation → 2-(6-methoxy-3-nitro-pyridin-2-yl)-N,N-dimethyl-acetamide

Conditions	Yield
With sodium hydroxide In dimethyl sulfoxide at 20 - 25℃; for 5h;	91%

2-methoxy-5-nitropyridine (5446-92-4) + trimethyl-(2-oxo-2-pyrrolidin-1-yl-ethyl)-ammonium; perchlorate → 2-(6-methoxy-3-nitro-pyridin-2-yl)-1-pyrrolidin-1-yl-ethanone

Conditions	Yield
With sodium hydroxide In dimethyl sulfoxide at 20 - 25℃; for 5h;	90%

2-methoxy-5-nitropyridine (5446-92-4) + ethyl chlorofluoroacetate (401-56-9, 96290-79-8) → ethyl 2,2-difluoro-2-(6-methoxy-3-nitropyridin-2-yl)acetate

Conditions	Yield
Stage #1: 2-methoxy-5-nitropyridine; ethyl chlorofluoroacetate With potassium tert-butylate In N,N-dimethyl-formamide at -42℃; for 0.75h; Inert atmosphere; Stage #2: With Selectfluor In N,N-dimethyl-formamide at -42℃; for 1h; Inert atmosphere;	90%

(5-methyl-pyridin-2-yl)amine (1603-41-4) + 2-methoxy-5-nitropyridine (5446-92-4) + carbon monoxide (201230-82-2) → N-(5-methyl-2-pyridyl)-N'-(6-methoxy-3-pyridyl)urea

Conditions	Yield
With selenium(IV) oxide; triethylamine In toluene at 130℃; under 22501.8 Torr;	89%

2-Amino-6-methylpyridine (1824-81-3) + 2-methoxy-5-nitropyridine (5446-92-4) + carbon monoxide (201230-82-2) → N-(6-methyl-2-pyridyl)-N'-(6-methoxy-3-pyridyl)urea

Conditions	Yield
With selenium(IV) oxide; triethylamine In toluene at 130℃; under 22501.8 Torr;	88%

2-methoxy-5-nitropyridine (5446-92-4) → 6-methoxy-3-nitropyridin-2-amine (73896-36-3)

Conditions	Yield
With O-Methylhydroxylamin; potassium tert-butylate; zinc(II) chloride In dimethyl sulfoxide Ambient temperature;	87%
With potassium permanganate; ammonia at -33℃; for 5h;	75%
With N,N-tetramethylene-thiocarbamoyl-sulphenamide	42%

2-methoxy-5-nitropyridine (5446-92-4) + 3,5-dimethylbenzamide (5692-35-3) → N-(6-methoxy-pyridin-3-yl)-3,5-dimethyl-benzamide

Conditions	Yield
With carbon monoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; selenium In toluene at 160℃; under 22502.3 Torr; for 4h;	87%

O-Methylhydroxylamin (67-62-9) + 2-methoxy-5-nitropyridine (5446-92-4) + zinc(II) chloride (7646-85-7) → 6-methoxy-3-nitropyridin-2-amine (73896-36-3)

Conditions	Yield
With ammonium chloride; potassium tert-butylate In dimethyl sulfoxide	87%

2-Amino-4-methylpyridine (695-34-1) + 2-methoxy-5-nitropyridine (5446-92-4) + carbon monoxide (201230-82-2) → N-(4-methyl-2-pyridyl)-N'-(6-methoxy-3-pyridyl)urea

Conditions	Yield
With selenium(IV) oxide; triethylamine In toluene at 130℃; under 22501.8 Torr;	85%

2-methoxy-5-nitropyridine (5446-92-4) + 2-chloro-propanoic acid, ethyl ester (535-13-7) → ethyl 2-fluoro-2-(2-methoxy-5-nitropyridin-4-yl)propanoate

Conditions	Yield
Stage #1: 2-methoxy-5-nitropyridine; 2-chloro-propanoic acid, ethyl ester With potassium tert-butylate In N,N-dimethyl-formamide at -42℃; for 0.75h; Inert atmosphere; Stage #2: With Selectfluor In N,N-dimethyl-formamide at -42℃; for 1h; Inert atmosphere;	85%

2-methoxy-5-nitropyridine (5446-92-4) + ethyl 1,1-dichloroacetate (535-15-9) → Chloro-(6-methoxy-3-nitro-pyridin-2-yl)-acetic acid ethyl ester (121555-74-6)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide for 0.0833333h; -5 to 0 deg C;	84%

2-methoxy-5-nitropyridine (5446-92-4) + para-methylbenzamide (619-55-6) → N-(6-methoxy-pyridin-3-yl)-4-methyl-benzamide

Conditions	Yield
With carbon monoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; selenium In toluene at 160℃; under 22502.3 Torr; for 4h;	84%

2-methoxy-5-nitropyridine (5446-92-4) + 1-thiopropane (107-03-9) + carbon monoxide (201230-82-2) → N-(6-methoxypyridine-3-yl)thiocarbamic acid S-propyl ester

Conditions	Yield
With selenium; triethylamine at 60℃; for 10h;	84%
With selenium; triethylamine In acetone at 20℃; under 760.051 Torr; for 15h;	77%

2-methoxy-5-nitropyridine (5446-92-4) + chloromethyl phenyl sulfone (7205-98-3) → 6-Methoxy-3-nitro-2-[(phenylsulfonyl)methyl]-pyridine (115663-39-3)

Conditions	Yield
With potassium tert-butylate; dimethyl sulfoxide at 20℃; for 0.416667h;	83%
In tetrahydrofuran; acetic acid	80%
Stage #1: 2-methoxy-5-nitropyridine; chloromethyl phenyl sulfone With potassium tert-butylate In tetrahydrofuran at -40℃; for 0.75h; Stage #2: With acetic acid In tetrahydrofuran at -40℃;	80%
Stage #1: chloromethyl phenyl sulfone With potassium tert-butylate In N,N-dimethyl-formamide at -40℃; for 0.00833333h; Inert atmosphere; Stage #2: 2-methoxy-5-nitropyridine In N,N-dimethyl-formamide at -40℃; for 0.0833333h; Inert atmosphere;	67%
With potassium tert-butylate In tetrahydrofuran at -65 - -20℃; for 1h;

2-methoxy-5-nitropyridine (5446-92-4) + cyanomethylenetrimethylammonium iodide (82272-28-4) → 2-(6-methoxy-3-nitropyridin-2-yl)acetonitrile (111795-99-4)

Conditions	Yield
With sodium hydride In dimethyl sulfoxide at 20 - 25℃; for 5h;	83%

2-aminopyridine (504-29-0) + 2-methoxy-5-nitropyridine (5446-92-4) + carbon monoxide (201230-82-2) → N-(2-pyridyl)-N'-(6-methoxy-3-pyridyl)urea

Conditions	Yield
With selenium(IV) oxide; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 130℃; under 22501.8 Torr; for 4h;	83%

1-ethynyl-4-fluorobenzene (766-98-3) + 2-methoxy-5-nitropyridine (5446-92-4) → 2-(4-fluorophenylethynyl)-6-methoxy-3-nitropyridine

Conditions	Yield
Stage #1: 1-ethynyl-4-fluorobenzene With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.566667h; Inert atmosphere; Stage #2: 2-methoxy-5-nitropyridine In tetrahydrofuran; hexane at -70℃; for 1h; Inert atmosphere; Stage #3: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In tetrahydrofuran; hexane at -70 - 20℃; for 1.33333h; Inert atmosphere;	83%

3-methylpyridin-2-ylamine (1603-40-3) + 2-methoxy-5-nitropyridine (5446-92-4) + carbon monoxide (201230-82-2) → N-(3-methyl-2-pyridyl)-N'-(6-methoxy-3-pyridyl)urea

Conditions	Yield
With selenium(IV) oxide; triethylamine In toluene at 130℃; under 22501.8 Torr;	82%

2-methoxy-5-nitropyridine (5446-92-4) + m-toluamide (618-47-3) → N-(6-methoxy-pyridin-3-yl)-3-methyl-benzamide

Conditions	Yield
With carbon monoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; selenium In toluene at 160℃; under 22502.3 Torr; for 4h;	81%

2-methoxy-5-nitropyridine (5446-92-4) + o-Methylbenzamid (527-85-5) → N-(6-methoxy-pyridin-3-yl)-2-methyl-benzamide

Conditions	Yield
With carbon monoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; selenium In toluene at 160℃; under 22502.3 Torr; for 4h;	80%

(2-hydroxyethyl)(methyl)amine (109-83-1) + 2-methoxy-5-nitropyridine (5446-92-4) → 2-(N-hydroxyethyl-N-methylamino)-5-nitropyridine

Conditions	Yield
In water	78%

2-methoxy-5-nitropyridine (5446-92-4) + phenylacetylene (536-74-3) → 6-methoxy-3-nitro-2-(phenylethynyl)pyridine

Conditions	Yield
Stage #1: phenylacetylene With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.566667h; Inert atmosphere; Stage #2: 2-methoxy-5-nitropyridine In tetrahydrofuran; hexane at -70℃; for 1h; Inert atmosphere; Stage #3: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In tetrahydrofuran; hexane at -70 - 20℃; for 1.33333h; Inert atmosphere;	77%

Upstream product

• 1628-89-3 2-methoxypyridine 
• 456-24-6 2-Fluoro-5-nitropyridine 
• 67-56-1 methanol 
• 4548-45-2 2-chloro-5-nitropyridine 
• 20773-98-2 2-methoxypyridine N-oxide 
• 124-41-4 sodium methylate 
• 4487-59-6 2-bromo-5-nitropyridine 
• 28080-54-8 2-iodo-5-nitropyridine 
• 28222-02-8 3-nitro-6-phenoxypyridine 
• 163105-89-3 2-methoxy-pyridine-5-boronic acid 
• 5418-51-9 5-nitro-2-hydroxypyridine 
• 504-29-0 2-aminopyridine 
• 280584-87-4 5-Hydroxyaminopyridine-2-sulfonic acid 
• 465529-94-6 5-nitropyridine-2-sulfonic acid 

Downstream Products

• 26820-61-1 5-nitro-2-piperidinopyridine 
• 111795-99-4 2-(6-methoxy-3-nitropyridin-2-yl)acetonitrile 
• 73896-36-3 6-methoxy-3-nitropyridin-2-amine 
• 115663-39-3 6-Methoxy-3-nitro-2-[(phenylsulfonyl)methyl]-pyridine 
• 450357-78-5 2-ethoxycarbonylmethyl-6-methoxy-3-nitropyridine 
• 66336-02-5 1-ethyl-5-nitro-2(1H)-pyridinone 
• 32896-90-5 1-methyl-5-nitro-2(1H)-pyridone 
• 59892-44-3 1-benzyl-5-nitropyridin-2(1H)-one 
• 1216790-22-5 C₁₃H₁₀F₂N₂O₂ 
• 6626-40-0 2-methoxy-7,10-dichloropyrido<3,2-b>quinoline 
• 81935-60-6 2-methoxy-7-chloro-10-(4'-hydroxyphenyl)aminobenzo[b]-1,5-naphthyridine 
• 74847-35-1 pyronaridine 

Relevant articles and documents

Methnaridine is an orally bioavailable, fast-killing and long-acting antimalarial agent that cures Plasmodium infections in mice

Background and Purpose: Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy. Experimental Approach: An integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed. Key Results: Methnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 μM; Dd2: IC50 = 0.0056 μM). In P. berghei-infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg?1·day?1) and cured the established infection (CD50 = 10.13 mg·kg?1·day?1). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four-dose oral regimen at a dosage of 25 mg·kg?1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross-resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long-lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg?1). In addition, following methnaridine treatment, infection-induced Th1 immune response was almost fully alleviated in mice. Conclusion and Implications: Methnaridine is an orally bioavailable, fast-acting and long-lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate.

Synthesis process of 2-methoxy-3-bromo-5-fluoropyridine

The invention discloses a synthesis process of 2-methoxy-3-bromo-5-fluoropyridine, which comprises the following steps: dissolving 2-methoxy-5-aminopyridine in an acid, adding nitrous acid or nitriteto prepare a diazotized intermediate state, reacting with a fluorinating reagent to obtain 2-methoxy-5-fluoropyridine, and carrying out a bromination reaction process on 2-methoxy-5-fluoropyridine anda bromination reagent to obtain 2-methoxy-3-bromo-5-fluoropyridine. The synthesis process provided by the invention has the advantages of cheap and easily available raw materials, mild reaction conditions, high yield, easiness in industrial production and the like.

TRI-HETEROCYCLIC DERIVATIVES, PREPARATION PROCESS AND USES THEREOF

The present invention relates to a tri-heterocyclic derivatives, preparation process and uses thereof, specifically relates to a tri-heterocyclic derivatives of the formula (I) or a pharmaceutically acceptable salt thereof, preparation process, and further relates to a pharmaceutically acceptable composition comprising compounds of formula (I), or a pharmaceutically acceptable salt thereof, and their pharmaceutical use as inhibitors of kinase.