33252-64-1

Basic information

• Product Name: 2-HYDROXY-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE
• Synonyms: 3-NITRO-5-(TRIFLUOROMETHYL)PYRIDIN-2-OL;3-NITRO-5-(TRIFLUOROMETHYL)-2-PYRIDONE;2-HYDROXY-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE;2-HYDROXY-3-NITRO-5-(TRIFLUOROMETHYL)PYRIDINE;3-Nitro-5-(trifluoromethyl)pyridin-2-one;2-Hydroxy-3-nitro-5-(trifluoromethyl)pyridine 98%;2-Hydroxy-3-nitro-5-(trifluoromethyl)pyridine98%;3-Nitro-5-(trifluoromethyl)pyridin-2-ol, 3-Nitro-5-(trifluoromethyl)pyridin-2(1H)-one
• CAS NO: 33252-64-1
• Molecular Formula: C₆H₃F₃N₂O₃
• Molecular Weight: 208.09
• EINECS: 1592732-453-0
• Product Categories: Pyridines;Pyridine
• Mol File: 33252-64-1.mol
• Article Data: 9

Chemical Properties

• Melting Point: 189 °C
• Boiling Point: 292.891 °C at 760 mmHg
• Flash Point: 130.936 °C
• Appearance: Off-white/Solid
• Density: 1.646 g/cm³
• Vapor Pressure: 0.0165mmHg at 25°C
• Refractive Index: 1.489
• Storage Temp.: Room temperature.
• PKA: 5.89±0.10(Predicted)
• CAS DataBase Reference: 2-HYDROXY-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-HYDROXY-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE(33252-64-1)
• EPA Substance Registry System: 2-HYDROXY-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE(33252-64-1)

Safety Data

• Hazard Codes: Xi
• Statements: 20/21/22-36/37/38
• Safety Statements: 22-26-36/37/39
• HazardClass: IRRITANT
• Hazardous Substances Data: 33252-64-1(Hazardous Substances Data)

Usage

General Description

2-Hydroxy-5-nitro-3-(trifluoromethyl)pyridine is a chemical compound with the molecular formula C6H3F3N2O3. It is a yellow crystalline solid that is commonly used in the production of pharmaceuticals and agrochemicals. 2-HYDROXY-5-NITRO-3-(TRIFLUOROMETHYL)PYRIDINE is a derivative of pyridine and contains a hydroxyl group, a nitro group, and a trifluoromethyl group, making it a versatile building block for various organic synthesis reactions. It is known for its anti-inflammatory, analgesic, and antipyretic properties, and has been studied for its potential therapeutic applications in the treatment of various diseases. However, due to its potential toxicity and hazardous properties, 2-hydroxy-5-nitro-3-(trifluoromethyl)pyridine requires careful handling and storage.

InChI:InChI=1/C6H3F3N2O3/c7-6(8,9)4-1-3(11(13)14)2-10-5(4)12/h1-2H,(H,10,12)

Synthetic route

5-(Trifluoromethyl)-3-nitro-2-aminopyridine (53359-69-6) → 3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1)

Conditions	Yield
With sulfuric acid; sodium nitrite In water at 0 - 20℃; Inert atmosphere;	73%

2-hydroxy-5-(trifluoromethyl)pyridine (33252-63-0) → 3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1)

Conditions	Yield
Stage #1: 2-hydroxy-5-(trifluoromethyl)pyridine With sulfuric acid; nitric acid at 0 - 65℃; for 25h; Stage #2: With sodium hydroxide In water at 20℃;	58%
With sulfuric acid; nitric acid at 80 - 85℃;	28%
With sulfuric acid; potassium nitrate at 0 - 65℃; for 4h;
With sulfuric acid; nitric acid In water at 80℃; for 1h;
With sulfuric acid; nitric acid In water at 60℃; for 18h;

2-amino-5-trifluoromethylpyridine (74784-70-6) → 3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: nitric acid; sulfuric acid / 0 - 20 °C / Inert atmosphere 2: sulfuric acid; sodium nitrite / water / 0 - 20 °C / Inert atmosphere View Scheme

benzyltrimethylammonium chloride (56-93-9) + 3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-chloro-3-nitro-5-(trifluoromethyl)pyridine (72587-15-6)

Conditions	Yield
With trichlorophosphate In acetonitrile for 3h; Heating;	92%

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-chloro-3-nitro-5-(trifluoromethyl)pyridine (72587-15-6)

Conditions	Yield
With quinoline; trichlorophosphate at 50 - 120℃; for 1.5h; Inert atmosphere;	88%
With quinoline; trichlorophosphate for 18h; Heating / reflux;	87%
With trichlorophosphate In DMF (N,N-dimethyl-formamide) at 110℃; for 0.5h;	86%

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) + methyl iodide (74-88-4) → 1-methyl-3-nitro-5-(trifluoromethyl)pyridin-2(1H)-one (1573056-08-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 3h;	70%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 16h;
With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 1.5h;

phosphorus pentachloride (10026-13-8, 874483-75-7) + 3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-chloro-3-nitro-5-(trifluoromethyl)pyridine (72587-15-6)

Conditions	Yield
With trichlorophosphate	52%
With trichlorophosphate	52%

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 6-Trifluoromethyl-1,3-dihydro-pyrrolo[3,2-b]pyridin-2-one

Conditions	Yield
Multi-step reaction with 4 steps 1: 66 percent / PCl5, POCl3 / 80 °C 2: 1.) NaH / 1.) DME, RT, 1 h, 2.) DME, RT, 18 h 3: 73 percent / Fe, glacial AcOH / 2 h / Heating 4: 43 percent / H2 / 10percent Pd/C / acetic acid / 3 h / 2280 Torr View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 3-benzyloxycarbonyl-6-trifluoromethyl-4-azaoxindole (136888-31-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 66 percent / PCl5, POCl3 / 80 °C 2: 1.) NaH / 1.) DME, RT, 1 h, 2.) DME, RT, 18 h 3: 73 percent / Fe, glacial AcOH / 2 h / Heating View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-bis(benzyloxycarbonyl)methyl-3-nitro-5-trifluoromethylpyridine (136888-30-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 66 percent / PCl5, POCl3 / 80 °C 2: 1.) NaH / 1.) DME, RT, 1 h, 2.) DME, RT, 18 h View Scheme

p-methyloxycarbonylbenzyl chloride (34040-64-7) + 3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → methyl 4-(3-nitro-5-trifluoromethylpyridine-2-yloxymethyl)benzoate (209687-69-4)

Conditions	Yield
In argon; toluene

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-hydroxy-3-amino-5-trifluoromethylpyridine (90778-25-9)

Conditions	Yield
With hydrogen; 5% Pd(II)/C(eggshell) In methanol at 20℃; under 760.051 Torr; for 2h;
With hydrogen; 5% Pd(II)/C(eggshell) In methanol at 20℃; under 760.051 Torr; for 2h;
With hydrogen; 5%-palladium/activated carbon In methanol at 20℃; under 760.051 Torr; for 2h;

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → N-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]isonicotinamide (1192021-84-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / 5% Pd(II)/C(eggshell) / methanol / 2 h / 20 °C / 760.05 Torr 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; pyridine / 2 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / pyridine / 2 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; pyridine / 2 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / ethyl acetate / 2 h / 20 °C / 760.05 Torr 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; pyridine / 2 h / 80 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; pyridine / 2 h / 80 °C View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 3-chloro-N-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]isonicotinamide (1192021-85-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / 5% Pd(II)/C(eggshell) / methanol / 2 h / 20 °C / 760.05 Torr 2: triethylamine / N,N-dimethyl-formamide / 1.5 h / 50 °C / Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C 2: triethylamine / N,N-dimethyl-formamide / 1.5 h / 20 - 50 °C / Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2: triethylamine / N,N-dimethyl-formamide / 1.5 h / 20 - 50 °C / Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / ethyl acetate / 2 h / 20 °C / 760.05 Torr 2: triethylamine / N,N-dimethyl-formamide / 1.5 h / 20 - 50 °C / Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2: triethylamine / N,N-dimethyl-formamide / 50 °C / Cooling with ice View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → N-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]-3-(methoxymethyl)isonicotinamide (1192021-96-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / 5% Pd(II)/C(eggshell) / methanol / 2 h / 20 °C / 760.05 Torr 2: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 3 h / 20 - 50 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C 2: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 3 h / 20 - 50 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / ethyl acetate / 2 h / 20 °C / 760.05 Torr 2: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 3 h / 20 - 50 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 3 h / 20 - 50 °C View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 3-amino-5-trifluoromethyl-2-mercaptopyridine (89571-66-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trichlorophosphate; quinoline / 5.5 h / Reflux 1.2: Cooling with ice 2.1: thiourea / ethanol / 5.5 h / 50 °C 2.2: 1.5 h / 20 °C 2.3: Cooling with ice 3.1: acetic acid; iron / ethyl acetate; water / 0.17 h / 70 °C View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-(3-fluoropyridin-4-yl)-6-(trifluoromethyl)thiazolo[5,4-b]pyridine (1286196-41-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: trichlorophosphate; quinoline / 5.5 h / Reflux 1.2: Cooling with ice 2.1: thiourea / ethanol / 5.5 h / 50 °C 2.2: 1.5 h / 20 °C 2.3: Cooling with ice 3.1: acetic acid; iron / ethyl acetate; water / 0.17 h / 70 °C 4.1: dimethyl sulfoxide / 2 h / 170 °C View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-(3-ethoxypyridin-4-yl)-6-(trifluoromethyl)thiazolo[5,4-b]pyridine (1286196-43-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: trichlorophosphate; quinoline / 5.5 h / Reflux 1.2: Cooling with ice 2.1: thiourea / ethanol / 5.5 h / 50 °C 2.2: 1.5 h / 20 °C 2.3: Cooling with ice 3.1: acetic acid; iron / ethyl acetate; water / 0.17 h / 70 °C 4.1: dimethyl sulfoxide / 2 h / 170 °C 5.1: potassium carbonate / 8 h / Reflux View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-[3-(2,2-difluoroethoxy)pyridin-4-yl]-6-(trifluoromethyl)thiazolo[5,4-b]pyridine (1286196-45-9)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: trichlorophosphate; quinoline / 5.5 h / Reflux 1.2: Cooling with ice 2.1: thiourea / ethanol / 5.5 h / 50 °C 2.2: 1.5 h / 20 °C 2.3: Cooling with ice 3.1: acetic acid; iron / ethyl acetate; water / 0.17 h / 70 °C 4.1: dimethyl sulfoxide / 2 h / 170 °C 5.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 20 °C 5.2: 1 h / 20 °C / Cooling with ice View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-[3-(methylthio)pyridin-4-yl]-6-(trifluoromethyl)thiazolo[5,4-b]pyridine (1286196-46-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: trichlorophosphate; quinoline / 5.5 h / Reflux 1.2: Cooling with ice 2.1: thiourea / ethanol / 5.5 h / 50 °C 2.2: 1.5 h / 20 °C 2.3: Cooling with ice 3.1: acetic acid; iron / ethyl acetate; water / 0.17 h / 70 °C 4.1: dimethyl sulfoxide / 2 h / 170 °C 5.1: N,N-dimethyl-formamide / 2 h / Cooling with ice View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-[3-(ethylthio)pyridin-4-yl]-6-(trifluoromethyl)thiazolo[5,4-b]pyridine (1286196-47-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: trichlorophosphate; quinoline / 5.5 h / Reflux 1.2: Cooling with ice 2.1: thiourea / ethanol / 5.5 h / 50 °C 2.2: 1.5 h / 20 °C 2.3: Cooling with ice 3.1: acetic acid; iron / ethyl acetate; water / 0.17 h / 70 °C 4.1: dimethyl sulfoxide / 2 h / 170 °C 5.1: N,N-dimethyl-formamide / 1 h / Cooling with ice View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-[3-(ethanesulfinyl)pyridin-4-yl]-6-(trifluoromethyl)thiazolo[5,4-b]pyridine (1286196-49-3) + 2-[3-(ethanesulfonyl)pyridin-4-yl]-6-(trifluoromethyl)thiazolo[5,4-b]pyridine (1286196-48-2)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: trichlorophosphate; quinoline / 5.5 h / Reflux 1.2: Cooling with ice 2.1: thiourea / ethanol / 5.5 h / 50 °C 2.2: 1.5 h / 20 °C 2.3: Cooling with ice 3.1: acetic acid; iron / ethyl acetate; water / 0.17 h / 70 °C 4.1: dimethyl sulfoxide / 2 h / 170 °C 5.1: N,N-dimethyl-formamide / 1 h / Cooling with ice 6.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 1 h / 0 °C View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 5-trifluoromethyl-2-mercapto-3-nitropyridine (89571-67-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: trichlorophosphate; quinoline / 5.5 h / Reflux 1.2: Cooling with ice 2.1: thiourea / ethanol / 5.5 h / 50 °C 2.2: 1.5 h / 20 °C 2.3: Cooling with ice View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-[2-(2,2,2-trifluoroethoxy)-phenyl]-6-trifluoromethyl-oxazolo[5,4-b]pyridine (1282532-89-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2.1: tetrahydrofuran / 22.5 h / 20 °C / Cooling with ice 2.2: 4.5 h 3.1: trichlorophosphate / 4 h / 120 °C 3.2: pH 7 / Cooling with ice View Scheme
Multi-step reaction with 3 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C 2.1: tetrahydrofuran / 22.5 h / 20 °C / Cooling with ice 2.2: 4.5 h / 20 °C 3.1: trichlorophosphate / 4 h / 120 °C 3.2: pH 7 / Cooling with ice View Scheme
Multi-step reaction with 3 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2.1: tetrahydrofuran / 22.5 h / 20 °C / Cooling with ice 2.2: 4.5 h 3.1: trichlorophosphate / 4 h / 120 °C 3.2: pH ~ 7 / Cooling with ice View Scheme
Multi-step reaction with 3 steps 1.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate / 2 h / 20 °C / 760.05 Torr 2.1: tetrahydrofuran / 22.5 h / 20 °C / Cooling with ice 2.2: 4.5 h 3.1: trichlorophosphate / 4 h / 120 °C 3.2: pH ~ 7 / Cooling with ice View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → N-(2-hydroxy-5-trifluoromethylpyridin-3-yl)-3-(2,2,2-trifluoroethoxy)-isonicotinamide (1282541-13-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C 2.1: tetrahydrofuran / 22.5 h / 20 °C / Cooling with ice 2.2: 4.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2.1: tetrahydrofuran / 22.5 h / 20 °C / Cooling with ice 2.2: 4.5 h View Scheme
Multi-step reaction with 2 steps 1.1: hydrogen / 5%-palladium/activated carbon / ethyl acetate / 2 h / 20 °C / 760.05 Torr 2.1: tetrahydrofuran / 22.5 h / 20 °C / Cooling with ice 2.2: 4.5 h View Scheme
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2: tetrahydrofuran / 20 °C / Cooling with ice View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → N-[2-hydroxy-6-(trifluoromethyl)pyridin-3-yl]-isonicotinamide (1192021-97-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / ethyl acetate / 2 h / 20 °C / 760.05 Torr 2: triethylamine / N,N-dimethyl-formamide / 3.5 h / 20 - 50 °C View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 2-[2-(2,2,2-trifluoroethoxy)phenyl]-6-trifluoromethyloxazolo[5,4-b]pyridine

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen / 5%-palladium/activated carbon / methanol / 2 h / 20 °C / 760.05 Torr 2: tetrahydrofuran / 20 °C / Cooling with ice 3: trichlorophosphate / 4 h / 120 °C View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 3-nitro-5-trifluoromethyl-pyridine-2-carbonitrile (866775-16-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: phosphorus(V) oxybromide / acetonitrile / 20 °C / Reflux 2: tetrabutylammomium bromide / toluene / 10 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: phosphorus(V) oxybromide / acetonitrile / 20 °C / Reflux 2: tetrabutylammomium bromide / toluene / 9 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: phosphorus(V) oxybromide / 20 °C / Reflux 2: tetrabutylammomium bromide / toluene / 9 h / Reflux View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 3-amino-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (866775-17-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: phosphorus(V) oxybromide / acetonitrile / 20 °C / Reflux 2.1: tetrabutylammomium bromide / toluene / 10 h / Reflux 3.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 18 h / Inert atmosphere 4.1: hydrogenchloride; water / 24 h / Reflux 5.1: sulfuric acid / 48 h / Reflux 5.2: 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: phosphorus(V) oxybromide / acetonitrile / 20 °C / Reflux 2.1: tetrabutylammomium bromide / toluene / 9 h / Reflux 3.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 18 h 3.2: 24 h / Reflux 3.3: 84 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: phosphorus(V) oxybromide / 20 °C / Reflux 2.1: tetrabutylammomium bromide / toluene / 9 h / Reflux 3.1: palladium 10% on activated carbon; hydrogen / ethyl acetate / 18 h 3.2: 24 h / Reflux 3.3: 84 h / Reflux View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 3-amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (866775-18-0)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: phosphorus(V) oxybromide / acetonitrile / 20 °C / Reflux 2.1: tetrabutylammomium bromide / toluene / 10 h / Reflux 3.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 18 h / Inert atmosphere 4.1: hydrogenchloride; water / 24 h / Reflux 5.1: sulfuric acid / 48 h / Reflux 5.2: 20 °C 6.1: bromine; sulfuric acid; acetic acid / water / 20 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: phosphorus(V) oxybromide / acetonitrile / 20 °C / Reflux 2.1: tetrabutylammomium bromide / toluene / 9 h / Reflux 3.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 18 h 3.2: 24 h / Reflux 3.3: 84 h / Reflux 4.1: bromine; acetic acid; sulfuric acid / water / 19.5 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: phosphorus(V) oxybromide / 20 °C / Reflux 2.1: tetrabutylammomium bromide / toluene / 9 h / Reflux 3.1: palladium 10% on activated carbon; hydrogen / ethyl acetate / 18 h 3.2: 24 h / Reflux 3.3: 84 h / Reflux 4.1: bromine; acetic acid; sulfuric acid / water / 19.5 h / 20 °C View Scheme

3-nitro-5-trifluoromethylpyridin-2-ol (33252-64-1) → 3-amino-6-methoxy-5-trifluoromethylpyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methylpropyl)amide (1334546-75-6)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: phosphorus(V) oxybromide / acetonitrile / 20 °C / Reflux 2.1: tetrabutylammomium bromide / toluene / 10 h / Reflux 3.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 18 h / Inert atmosphere 4.1: hydrogenchloride; water / 24 h / Reflux 5.1: sulfuric acid / 48 h / Reflux 5.2: 20 °C 6.1: bromine; sulfuric acid; acetic acid / water / 20 h / 20 °C 7.1: toluene-4-sulfonic acid / toluene / 2 h / Reflux 8.1: sodium hydroxide; water / 1 h / 20 °C 8.2: pH 1 9.1: hydroxylamine hydrochloride; triethylamine; ethanol / 5 h / Reflux 10.1: N-ethyl-N,N-diisopropylamine; HATU / 1-methyl-pyrrolidin-2-one / 2 h View Scheme
Multi-step reaction with 8 steps 1.1: phosphorus(V) oxybromide / acetonitrile / 20 °C 2.1: tetrabutylammomium bromide; copper(l) cyanide / toluene / 10 h / Reflux 3.1: palladium 10% on activated carbon; hydrogen / ethyl acetate / 18 h 3.2: 24 h / Reflux 3.3: 48 h / Reflux 4.1: sulfuric acid / water / 0.5 h 4.2: 18 h / 20 °C 5.1: toluene-4-sulfonic acid / toluene / 20 °C / Reflux; Dean-Stark 6.1: sodium hydroxide; methanol / 1 h / 20 °C 7.1: triethylamine; hydroxylamine hydrochloride / water; ethanol / 5 h / Reflux 8.1: HATU; N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 1 h View Scheme

Upstream product

• 33252-63-0 2-hydroxy-5-(trifluoromethyl)pyridine 
• 53359-69-6 5-(Trifluoromethyl)-3-nitro-2-aminopyridine 
• 74784-70-6 2-amino-5-trifluoromethylpyridine 
• 33252-63-0 5-(trifluoromethyl)-2(1H)-pyridone 
• 7664-93-9 sulfuric acid 
• 5326-23-8 6-Chloro-3-pyridinecarboxylic acid 
• 52334-81-3 2-chloro-5-trifluoromethylpyridine 

Downstream Products

• 136888-31-8 3-benzyloxycarbonyl-6-trifluoromethyl-4-azaoxindole 
• 136888-30-7 2-bis(benzyloxycarbonyl)methyl-3-nitro-5-trifluoromethylpyridine 
• 209687-69-4 methyl 4-(3-nitro-5-trifluoromethylpyridine-2-yloxymethyl)benzoate 
• 52334-82-4 3-benzoylamino-5-trifluoromethyl-2-pyridone 
• 90778-25-9 3-amino-5-(trifluoromethyl)pyridin-2-ol 
• 89571-67-5 5-trifluoromethyl-2-mercapto-3-nitropyridine 
• 866775-16-8 3-nitro-5-trifluoromethyl-pyridine-2-carbonitrile 
• 866775-17-9 3-amino-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester 
• 866775-18-0 3-amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester 
• 1334546-83-6 3-amino-6-(2,4-dichlorophenyl)-5-trifluoromethylpyridine-2-carboxylic acid 
• 1214336-90-9 3-amino-6-(2,6-difluorophenyl)-5-trifluoromethyl-2-pyridinecarboxylicacid 
• 1214370-77-0 3-amino-5-trifluoromethylpyridine-2-carboxylic acid 
• 1334547-21-5 3-amino-6-(4-fluorophenyl)-5-trifluoromethylpyridine-2-carboxylic acid 
• 1334547-23-7 3-amino-6-(2,4-dichlorophenyl)-5-trifluoromethylpyridine-2-carboxylic acid methyl ester 

Relevant articles and documents

6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS

The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.

New tetracyclic 1,4-oxazepines constructed via practically simple tandem condensation strategy from readily available synthons

A streamlined synthetic methodology towards novel tetracyclic 1,4-oxazepines from readily available precursors is described. The compounds, designed as more soluble version of the earlier described, poorly soluble dibenzo[b,f][1,4]oxazepines, were obtained in high yields and as a single regioisomer as a result of three tandem chemical events - nucleophilic aromatic substitution, Smiles rearrangement and denitrocyclization.

HETEROCYCLIC COMPOUND AND ITS USE FOR CONTROL OF AN ARTHROPOD PEST

A heterocyclic compound represented by formula (1): wherein A1, A2, R1, R2, R3, R4, n and so on are defined in that description, has an excellent control effect on arthropod pests and is useful for control of arthropod pests.