288385-88-6

Basic information

• Product Name: 4-Fluoro-5-hydroxy-2-methylindole
• Synonyms: 4-FLUORO-5-HYDROXY-2-METHYLINDOLE;4-FLUORO-2-METHYL-1H-INDOL-5-OL;2-Methyl-4-fluoro-5-hydroxyindole;4-Fluoro-5-hydroxy-2-methyl-1H-indole;4-fluoro-5-hydroxy-2-Methylindole, 4-fluoro-2-Methyl-1H-indol-5-ol, 4-fluoro-5-hydroxy-2-Methyl-1H-indole;1H-Indol-5-ol, 4-fluoro-2-Methyl-;4-FLUORO-5-HYDROXY-2-ME
• CAS NO: 288385-88-6
• Molecular Formula: C₉H₈FNO
• Molecular Weight: 165.16
• EINECS: 1592732-453-0
• Product Categories: Boronic Acid;Heterocyclic Compounds
• Mol File: 288385-88-6.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 327.324 °C at 760 mmHg
• Flash Point: 151.761 °C
• Appearance: /
• Density: 1.367
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.672
• Storage Temp.: 2-8°C(protect from light)
• PKA: 7.39±0.50(Predicted)
• CAS DataBase Reference: 4-Fluoro-5-hydroxy-2-methylindole(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Fluoro-5-hydroxy-2-methylindole(288385-88-6)
• EPA Substance Registry System: 4-Fluoro-5-hydroxy-2-methylindole(288385-88-6)

Safety Data

• Hazardous Substances Data: 288385-88-6(Hazardous Substances Data)

Usage

General Description

4-Fluoro-5-hydroxy-2-methylindole is a chemical compound with the formula C9H8FNO and molar mass of 175.2 g/mol. It is a derivative of 2-methylindole and contains a fluorine atom and a hydroxy group on the 5th position of the indole ring. 4-Fluoro-5-hydroxy-2-methylindole is used in organic synthesis, particularly in the pharmaceutical industry for the development of new drugs. Its specific properties and potential applications are still under investigation, but it is known to exhibit biological activity and may have potential use in the development of new pharmaceuticals.

InChI:InChI=1/C9H8FNO/c1-5-4-6-7(11-5)2-3-8(12)9(6)10/h2-4,11-12H,1H3

Synthetic route

1-(2-fluoro-3-benzyloxy-6-nitrophenyl)-2-methoxypropene → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In methanol at 55 - 60℃; under 1500.15 - 2250.23 Torr; for 4h; Autoclave;	91.3%

1-(2-fluoro-3-benzyloxy-6-nitrophenyl)-2-ethoxypropene → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In methanol at 45 - 50℃; under 2250.23 - 3000.3 Torr; for 6h; Autoclave;	91%

1-(2-fluoro-3-(4-methoxybenzyloxy)-6-nitrophenyl)-2-methoxypropene → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
With hydrogen In acetonitrile at 50 - 55℃; under 2250.23 - 3000.3 Torr; for 5h; Autoclave;	89.7%

1-(2-fluoro-3-hydroxy-6-nitrophenyl)propan-2-one (649736-31-2) → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
With sodium dithionite In water at 0 - 30℃; for 1h;	81%
With sodium dithionite In methanol; water at 20 - 25℃; for 5h; Reissert Indole Synthesis; Large scale;	69%
With sodium dithionite; potassium carbonate In water at 25℃; for 2h; Product distribution / selectivity; Industry scale;	68%

2-methyl-4-fluoro-5-methoxy-1H-indole (288385-93-3) → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
With boron tribromide In dichloromethane	70%
With boron tribromide In dichloromethane	70%
With boron tribromide In dichloromethane	70%

1-(3-benzyloxy-2-fluoro-6-nitro-phenyl)-propan-2-one (288385-98-8) → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
With ammonium formate; palladium 10% on activated carbon In methanol at 20℃;	61%
With acetic acid; palladium on charcoal In ethanol; ethyl acetate	30%
With acetic acid; palladium on charcoal In ethanol; ethyl acetate	30%

2,3,4-trifluoronitrobenzene (771-69-7) → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium tert-butylate / tetrahydrofuran / 7.75 h / 10 °C / Large scale 1.2: 5.5 h / 10 - 22 °C / Large scale 2.1: sulfuric acid / acetic acid / 6.42 h / 70 °C / Large scale 3.1: potassium carbonate / 18.83 h / 9 - 25 °C / Reflux; Large scale 4.1: aluminum (III) chloride; trimethylamine hydrochloride / dichloromethane / 6.75 h / 22 - 42 °C / 2250.23 Torr / Large scale 5.1: sodium dithionite / methanol; water / 5 h / 20 - 25 °C / Large scale View Scheme
Multi-step reaction with 5 steps 1: sodium hydride / tetrahydrofuran / 12 h / 5 - 20 °C 2: hydrogenchloride; acetic acid / 12 h / Reflux 3: N,N-dimethyl-formamide / 10 h / 100 °C 4: hydrogen; palladium on activated charcoal / N,N-dimethyl-formamide; ethanol / 10 h / 40 °C 5: sodium hydrogencarbonate; water / methanol / 10 h / 20 °C View Scheme

2-(2,3-difluoro-6-nitrophenyl)-3-oxobutanoic acid ethyl ester (1022112-32-8) → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / acetic acid / 6.42 h / 70 °C / Large scale 2: potassium carbonate / 18.83 h / 9 - 25 °C / Reflux; Large scale 3: aluminum (III) chloride; trimethylamine hydrochloride / dichloromethane / 6.75 h / 22 - 42 °C / 2250.23 Torr / Large scale 4: sodium dithionite / methanol; water / 5 h / 20 - 25 °C / Large scale View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride; acetic acid / 12 h / Reflux 2: N,N-dimethyl-formamide / 10 h / 100 °C 3: hydrogen; palladium on activated charcoal / N,N-dimethyl-formamide; ethanol / 10 h / 40 °C 4: sodium hydrogencarbonate; water / methanol / 10 h / 20 °C View Scheme

1-(2,3-difluoro-6-nitrophenyl)propan-2-one (121247-16-3) → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / 18.83 h / 9 - 25 °C / Reflux; Large scale 2: aluminum (III) chloride; trimethylamine hydrochloride / dichloromethane / 6.75 h / 22 - 42 °C / 2250.23 Torr / Large scale 3: sodium dithionite / methanol; water / 5 h / 20 - 25 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 10 h / 100 °C 2: hydrogen; palladium on activated charcoal / N,N-dimethyl-formamide; ethanol / 10 h / 40 °C 3: sodium hydrogencarbonate; water / methanol / 10 h / 20 °C View Scheme

1-(2-fluoro-3-methoxy-6-nitrophenyl)propan-2-one (288385-99-9) → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride; trimethylamine hydrochloride / dichloromethane / 6.75 h / 22 - 42 °C / 2250.23 Torr / Large scale 2: sodium dithionite / methanol; water / 5 h / 20 - 25 °C / Large scale View Scheme

C11H10FNO5 → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen; palladium on activated charcoal / N,N-dimethyl-formamide; ethanol / 10 h / 40 °C 2: sodium hydrogencarbonate; water / methanol / 10 h / 20 °C View Scheme

C11H10FNO2 → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
With water; sodium hydrogencarbonate In methanol at 20℃; for 10h;

2-fluoro-3-(4-methoxybenzyloxy)-6-nitrotoluene → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(l) chloride / tetrahydrofuran / 5 h / 65 - 70 °C 2: hydrogen / acetonitrile / 5 h / 50 - 55 °C / 2250.23 - 3000.3 Torr / Autoclave View Scheme

2-fluoro-3-bromo-6-nitrotoluene → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 4 h / 100 - 105 °C 2: copper(l) chloride / tetrahydrofuran / 5 h / 65 - 70 °C 3: hydrogen / acetonitrile / 5 h / 50 - 55 °C / 2250.23 - 3000.3 Torr / Autoclave View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 105 - 110 °C 2: zinc(II) chloride / tetrahydrofuran / 5 h / 65 - 70 °C 3: 5%-palladium/activated carbon; hydrogen / methanol / 4 h / 55 - 60 °C / 1500.15 - 2250.23 Torr / Autoclave View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 105 - 110 °C 2: zinc(II) chloride / tetrahydrofuran / 5 h / 75 - 80 °C 3: 5%-palladium/activated carbon; hydrogen / methanol / 6 h / 45 - 50 °C / 2250.23 - 3000.3 Torr / Autoclave View Scheme

2-fluoro-3-benzyloxy-6-nitrotoluene (1229454-43-6) → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc(II) chloride / tetrahydrofuran / 5 h / 65 - 70 °C 2: 5%-palladium/activated carbon; hydrogen / methanol / 4 h / 55 - 60 °C / 1500.15 - 2250.23 Torr / Autoclave View Scheme

2-fluoro-3-iodo-6-nitrotoluene → 4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 90 - 95 °C 2: zinc(II) chloride / tetrahydrofuran / 5 h / 65 - 70 °C 3: 5%-palladium/activated carbon; hydrogen / methanol / 4 h / 55 - 60 °C / 1500.15 - 2250.23 Torr / Autoclave View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / 90 - 95 °C 2: zinc(II) chloride / tetrahydrofuran / 5 h / 75 - 80 °C 3: 5%-palladium/activated carbon; hydrogen / methanol / 6 h / 45 - 50 °C / 2250.23 - 3000.3 Torr / Autoclave View Scheme

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 7-benzyloxy-4-chloro-6-methoxyquinazoline (162364-72-9) → 7-(benzyloxy)-4-[(4-fluoro-2-methyl-1H-indol-5-yl)-oxy]-6-methoxyquinazoline (574745-75-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 85℃; Inert atmosphere;	100%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 24h;	75%
With caesium carbonate In N,N-dimethyl-formamide at 20 - 100℃; for 16h; Inert atmosphere;	53%
Stage #1: 4-fluoro-2-methyl-1H-indol-5-ol With sodium hydroxide In water; acetonitrile at 0℃; for 0.25h; Industry scale; Stage #2: 7-benzyloxy-4-chloro-6-methoxyquinazoline In 1-methyl-pyrrolidin-2-one; water; acetonitrile at 80℃; for 4.75h; Industry scale;
With potassium carbonate In N,N-dimethyl acetamide at 90℃; for 2h; Solvent; Temperature; Reagent/catalyst; Inert atmosphere;

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 4,6-dichloro-5-cyanopyrimidine (5305-45-3) → 4-chloro-6-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)pyrimidine-5-carbonitrile

Conditions	Yield
Stage #1: 4-fluoro-2-methyl-1H-indol-5-ol With potassium carbonate In N,N-dimethyl-formamide; acetonitrile at 20℃; for 1h; Inert atmosphere; Stage #2: 4,6-dichloro-5-cyanopyrimidine In N,N-dimethyl-formamide; acetonitrile at 20℃; for 1h; Inert atmosphere;	99%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) → 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yl pivalate (952490-01-6)

Conditions	Yield
Stage #1: 4-fluoro-2-methyl-1H-indol-5-ol With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 20 - 29℃; for 1.16667h; Large scale; Stage #2: 4-chloro-5-methylpyrrolo[1,2-f ][1,2,4]triazin-6-yl pivalate In acetonitrile at 26 - 28℃; for 3h; Large scale;	96.2%
With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 20 - 50℃; for 1.67 - 19h; Product distribution / selectivity;

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 6-(benzyloxy)-4-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazine (649736-27-6)

Conditions	Yield
Stage #1: 4-fluoro-2-methyl-1H-indol-5-ol With sodium hydride In DMF (N,N-dimethyl-formamide) at -20 - 0℃; for 0.5h; Stage #2: 6-(benzyloxy)-4-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazine In DMF (N,N-dimethyl-formamide) at 20℃; for 0.5h;	95%
Stage #1: 4-fluoro-2-methyl-1H-indol-5-ol With sodium hydride In N,N-dimethyl-formamide at -78 - 20℃; Stage #2: 6-(benzyloxy)-4-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazine In N,N-dimethyl-formamide at 20℃; for 1h;

4-fluoro-2-methyl-1H-indol-5-ol + 4-amino-6-chloro-pyrimidine-5-carbaldehyde (14160-93-1) → 4-amino-6-(4-fluoro-2-methyl-1H-indol-5-yloxy)-pyrimidine-5-carbaldehyde (951152-69-5)

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 20℃; for 2h;	94%
With caesium carbonate In dimethyl sulfoxide

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 6-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(methylsulfonyl)pyrimidin-4-amine (1609119-39-2) → 6-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)pyrimidin-4-amine (1609119-41-6)

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol at 50℃;	85%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + C9(13)C3H14ClN(15)N2O2 (1316667-91-0) → C18(13)C3H21FN2(15)N2O3 (1316667-95-4)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 48℃; for 1.5h; Inert atmosphere;	82%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (199327-69-0) → cediranib

Conditions	Yield
With potassium carbonate In acetonitrile at 70 - 75℃; for 5.5h; Inert atmosphere;	80%
With potassium carbonate In N,N-dimethyl-formamide Heating;	55.2 g
With potassium carbonate In N,N-dimethyl-formamide Heating;	30.09 g

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 4-chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (398487-42-8) → 6-cyano-4-(4-fluoro-2-methylindol-5-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (398487-43-9)

Conditions	Yield
With caesium carbonate In methanol; dichloromethane; N,N-dimethyl-formamide	79%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 4,6-dichloro-2-(methylsulfonyl)pyrimidine (4489-34-3) → 5-((4,6-dichloropyrimidin-2-yl)oxy)-4-fluoro-2-methyl-1H-indole (1609119-40-5)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at -70 - 20℃;	79%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 6,7-dimethoxy-4-chloroquinazoline (13790-39-1) → 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6,7-dimethoxyquinazoline (1622317-21-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 24h;	78%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + tert-butyl (3-((4-chloro-3-cyano-6-methoxyquinolin-7-yloxy)methyl)cyclobutyl)carbamate → tert-butyl (3-((3-cyano-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-yloxy)methyl)cyclobutyl)carbamate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 100℃;	76%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + Ethyl 6-(7-(benzyloxy)-4-chloroquinazolin-6-yloxy)hexanoate (1133461-71-8) → Ethyl 6-(7-(benzyloxy)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)quinazolin-6-yloxy)-hexanoate (1133461-74-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 24h;	71%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + trifluoromethylsulfonic anhydride (358-23-6) → trifluoro-methanesulfonic acid 4-fluoro-2-methyl-1H-indol-5-yl ester (1401727-01-2)

Conditions	Yield
With 2,6-dimethylpyridine In dichloromethane at 20℃;	70%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 6-chloro-N-(5-propenyl-1H-pyrazol-3-yl)-2-(methylsulfonyl)pyrimidin-4-amine (1609119-44-9) → (E)-6-chloro-2-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-N-(5-(prop-1-en-1-yl)-1H-pyrazol-3-yl)pyrimidin-4-amine (1609119-45-0)

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol at 55℃; for 16h;	64%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 1-(3-azidobut-1-yn-1-yl)-4-fluorobenzene → C19H16F2N4O

Conditions	Yield
With silver trifluoromethanesulfonate In acetonitrile at 60℃; for 24h;	64%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + methyl 4-chloro-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (832113-96-9) → 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester

Conditions	Yield
In N,N-dimethyl-formamide at 95℃; for 0.75h;	45%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 4-chloro-5-((3,3-difluoro-1-methylpiperidin-4-yl)oxy)-7-methoxyquinazoline → 5-((3,3-difluoro-1-methylpiperidin-4-yl)oxy)-4-((4-fluoro-2-methyl-1H-indole- 5-yl)oxy)-7-methoxyquinazoline

Conditions	Yield
With caesium carbonate In acetonitrile at 70℃; for 1h; Inert atmosphere;	45%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 1-chloro-4-(pyridin-4-yl-methyl)-phthalazine (101094-85-3) → 1-(4-fluoro-2-methylindol-5-yloxy)-4-(pyridin-4-ylmethyl)phthalazine (397842-88-5)

Conditions	Yield
With caesium carbonate In dichloromethane; ethyl acetate; N,N-dimethyl-formamide	41%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 7-(benzyloxy)-4-chloro-6-methoxycinnoline (398127-72-5) → 7-benzyloxy-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxycinnoline (398127-73-6)

Conditions	Yield
With caesium carbonate In dichloromethane; ethyl acetate; N,N-dimethyl-formamide	39%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)cinnoline (398127-69-0) → 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)cinnoline (398127-70-3)

Conditions	Yield
With caesium carbonate In methanol; 2,4-dichlorophenoxyacetic acid dimethylamine; pentane	38%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 7-methoxy-6-cyano-4-chloro-quinoline (398487-31-5) → 6-cyano-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinoline (398487-52-0)

Conditions	Yield
With caesium carbonate In methanol; ethyl acetate; N,N-dimethyl-formamide	35%

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) + 7-(benzyloxy)-4-chloro-6-methoxyquinoline (286371-49-1) → 7-(benzyloxy)-4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinoline (1210828-43-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 100℃; for 16h; Inert atmosphere;	27%
With dmap In 1,4-dioxane for 72h; Reflux;

4-fluoro-2-methyl-1H-indol-5-ol (288385-88-6) → 4-(4-fluoro-2-methylindol-5-yloxy)thieno[3,2-d]pyrimidine (397842-86-3)

Conditions	Yield
	7%

Upstream product

• 1229454-43-6 2-fluoro-3-benzyloxy-6-nitrotoluene 
• 288385-99-9 1-(2-fluoro-3-methoxy-6-nitrophenyl)propan-2-one 
• 121247-16-3 1-(2,3-difluoro-6-nitrophenyl)propan-2-one 
• 1022112-32-8 2-(2,3-difluoro-6-nitrophenyl)-3-oxobutanoic acid ethyl ester 
• 771-69-7 2,3,4-trifluoronitrobenzene 
• 288385-93-3 2-methyl-4-fluoro-5-methoxy-1H-indole 
• 649736-31-2 1-(2-fluoro-3-hydroxy-6-nitrophenyl)propan-2-one 
• 288385-98-8 1-(3-benzyloxy-2-fluoro-6-nitro-phenyl)-propan-2-one 

Downstream Products

• 649736-29-8 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester 
• 1210828-43-5 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-benzyloxyquinoline 

Relevant articles and documents

Preparation method of 4-fluoro-5-hydroxy-2-methyl-1H-indole

The invention provides a preparation method of 4-fluoro-5-hydroxy-2-methyl-1H-indole. The preparation method comprises the steps that 2-fluoro-3-halo-6-nitrotoluene is used as a raw material and subjected to a substitution reaction with alcohol to prepare 2-fluoro-3-GO substituent-6-nitrotoluene, then 2-fluoro-3-GO substituent-6-nitrotoluene is subjected to a condensation reaction with trimethyl orthoacetate or triethyl orthoacetate to obtain 1-(2-fluoro-3-GO substituent-6-nitrophenyl)-2-alkoxy propylene, and then 1-(2-fluoro-3-GO substituent-6-nitrophenyl)-2-alkoxy propylene is further subjected to a reduction-cyclization reaction to obtain 4-fluoro-5-hydroxy-2-methyl-1H-indole. The preparation method is safe and green, simple in operation, low in cost, high in selectivity and high in yield and purity of a final product.

Commercial synthesis of a pyrrolotriazine-fluoroindole intermediate to brivanib alaninate: Process development directed toward impurity control

The development of a practical, commercial process for the preparation of 4-fluoro-2-methyl-indol-5-ol and its subsequent coupling with a pyrrolotriazine to form an advanced intermediate of the oncology therapy brivanib alaninate is described. A key aspect is the multikilogram-scale preparation of the fluoroindole intermediate from trifluoronitrobenzene and the subsequent coupling while achieving impurity minimalization. As brivanib alaninate is a high-dose drug, the synthesis of highquality API with low levels of impurities is critical.

CHEMICAL PROCESS

The present invention relates to chemical processes for the manufacture of certain quinazoline derivatives, or pharmaceutically acceptable salts thereof. The invention also relates to processes for the manufacture of certain intermediates useful in the manufacture of the quinazoline derivatives and to processes for the manufacture of the quinazoline derivatives utilising said intermediates. In particular, the present invention relates to chemical processes and intermediates useful in the manufacture of the compound 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline.