1408282-26-7

Basic information

• Product Name: 8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one
• Synonyms: 8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one;8-fluoro-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one;8-Fluoro-1,3,4,5-tetrahydro-6H-pyrrolo[4,3,2-ef][2]benzazepin-6-one;8-fluoro-3,4-dihydro-2H-azepino[5,4,3-cd]indol-1(6H)-one;8-fluoro-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-1-one;6-fluoro-3,10-diazatricyclo[6.4.1.0,13]trideca-1,4(13),5,7-tetraen-9-one;8-fluoro-4;Rucaparib Intermediate 3
• CAS NO: 1408282-26-7
• Molecular Formula: C₁₁H₉FN₂O
• Molecular Weight: 204.2003632
• EINECS: -0
• Mol File: 1408282-26-7.mol

Chemical Properties

• Boiling Point: 526.5±50.0 °C(Predicted)
• Appearance: /
• Density: 1.404±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 14.27±0.20(Predicted)
• CAS DataBase Reference: 8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one(CAS DataBase Reference)
• NIST Chemistry Reference: 8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one(1408282-26-7)
• EPA Substance Registry System: 8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one(1408282-26-7)

Safety Data

• Hazardous Substances Data: 1408282-26-7(Hazardous Substances Data)

Usage

Uses

Used in Medicinal Chemistry:
8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one serves as a scaffold for the synthesis of novel bioactive compounds. Its distinctive structural features make it a promising candidate for the development of new drugs and pharmaceuticals.
Used in Drug Discovery:
In the field of drug discovery, 8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one is utilized for its potential to yield derivatives with various biological activities. Studies have indicated that these derivatives possess anticancer, antiviral, and antibacterial properties, highlighting the compound's value for further research and development in creating effective therapeutic agents.

Synthetic route

C12H9FN2O2 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen; acetic acid In methanol at 40℃; under 4500.45 Torr; Pressure; Reagent/catalyst; Temperature;	95.7%

3-(2-(phthalimido)ethyl)-6-fluoro-1H-indole-4-carboxylic acid methyl ester (1408282-25-6) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With methylamine In water at 0 - 20℃; for 24h;	94%
With methylamine In water at 20℃; for 17h; Large scale;	89%

6-fluoro-3-(2-nitroethyl)-1H-indole-4-carboxylic acid methyl ester → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With palladium on activated charcoal; hydrogen In methanol at 40℃; under 15001.5 Torr; for 8h; Solvent; Temperature; Industrial scale;	81.4%

N-(2,2-dimethoxyethyl)-6-fluoro-1H-indole-4-carboxamide → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With tributylsilane; trifluoroacetic acid In dichloromethane at 0 - 20℃; for 8h; Reagent/catalyst;	78%

C16H17FN2O2 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With water; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 24h;	75%

4-chlorobutyraldehyde (6139-84-0) + 3-fluoro-5-hydrazinobenzoic acid methyl ester → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
In ethanol; water for 7h; Reflux;	73.2%

N-(2,2-diethoxyethyl)-6-fluoro-1H-indole-4-carboxamide → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With tributylsilane; boron trifluoride diethyl etherate In dichloromethane at 0 - 20℃; for 12h; Reagent/catalyst;	69%

4-chlorobutyraldehyde (6139-84-0) + methyl 3-[2-(diphenylmethylene)hydrazino]-5-fluorobenzoate → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With toluene-4-sulfonic acid In ethanol; water for 10h; Reflux;	65.8%

C12H8ClFN2O4 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With 10% Pt/activated carbon; hydrogen In methanol at 20℃; for 6h; Time;	1.2 g

3-fluoro-5-nitrobenzoic acid (14027-75-9) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: N-chloro-succinimide / N,N-dimethyl-formamide / 4 h / 35 °C 2: tetrahydrofuran / 1 h / -30 °C 3: thionyl chloride / 4 h / 0 - 30 °C 4: trichlorophosphate / 2.67 h / 60 °C / Cooling with ice 5: ammonium acetate / 3.5 h / 60 °C 6: 10% Pt/activated carbon; hydrogen / methanol / 6 h / 20 °C View Scheme

4-chloro-3-fluoro-5-nitrobenzoic acid → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: tetrahydrofuran / 1 h / -30 °C 2: thionyl chloride / 4 h / 0 - 30 °C 3: trichlorophosphate / 2.67 h / 60 °C / Cooling with ice 4: ammonium acetate / 3.5 h / 60 °C 5: 10% Pt/activated carbon; hydrogen / methanol / 6 h / 20 °C View Scheme

C9H5ClFNO2 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / 4 h / 0 - 30 °C 2: trichlorophosphate / 2.67 h / 60 °C / Cooling with ice 3: ammonium acetate / 3.5 h / 60 °C 4: 10% Pt/activated carbon; hydrogen / methanol / 6 h / 20 °C View Scheme

C10H7ClFNO2 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: trichlorophosphate / 2.67 h / 60 °C / Cooling with ice 2: ammonium acetate / 3.5 h / 60 °C 3: 10% Pt/activated carbon; hydrogen / methanol / 6 h / 20 °C View Scheme

C16H17ClFNO2 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: aluminum (III) chloride; chloroacetyl chloride / 2 h / 20 °C 2: hydroxylamine hydrochloride; sodium acetate / tetrahydrofuran; methanol; water / 2 h / 50 °C 3: thionyl chloride / 1,4-dioxane / 6 h / 70 °C 4: 1,8-diazabicyclo[5.4.0]undec-7-ene; water / tetrahydrofuran / 24 h / 20 °C View Scheme

C16H16FNO2 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydroxylamine hydrochloride; sodium acetate / tetrahydrofuran; methanol; water / 2 h / 50 °C 2: thionyl chloride / 1,4-dioxane / 6 h / 70 °C 3: 1,8-diazabicyclo[5.4.0]undec-7-ene; water / tetrahydrofuran / 24 h / 20 °C View Scheme

6-fluoro-1H-indole (399-51-9) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: acetic anhydride; acetic acid / 48 h / 50 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 2.2: 1 h 3.1: thionyl chloride / 1,2-dichloro-ethane / 1 h / 20 °C 4.1: aluminum (III) chloride; chloroacetyl chloride / 2 h / 20 °C 5.1: hydroxylamine hydrochloride; sodium acetate / tetrahydrofuran; methanol; water / 2 h / 50 °C 6.1: thionyl chloride / 1,4-dioxane / 6 h / 70 °C 7.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; water / tetrahydrofuran / 24 h / 20 °C View Scheme

C16H17FN2O2 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / 1,4-dioxane / 6 h / 70 °C 2: 1,8-diazabicyclo[5.4.0]undec-7-ene; water / tetrahydrofuran / 24 h / 20 °C View Scheme

6-Fluoroindole-3-propionic acid (141071-78-5) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C 1.2: 1 h 2.1: thionyl chloride / 1,2-dichloro-ethane / 1 h / 20 °C 3.1: aluminum (III) chloride; chloroacetyl chloride / 2 h / 20 °C 4.1: hydroxylamine hydrochloride; sodium acetate / tetrahydrofuran; methanol; water / 2 h / 50 °C 5.1: thionyl chloride / 1,4-dioxane / 6 h / 70 °C 6.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; water / tetrahydrofuran / 24 h / 20 °C View Scheme

C16H18FNO3 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: thionyl chloride / 1,2-dichloro-ethane / 1 h / 20 °C 2: aluminum (III) chloride; chloroacetyl chloride / 2 h / 20 °C 3: hydroxylamine hydrochloride; sodium acetate / tetrahydrofuran; methanol; water / 2 h / 50 °C 4: thionyl chloride / 1,4-dioxane / 6 h / 70 °C 5: 1,8-diazabicyclo[5.4.0]undec-7-ene; water / tetrahydrofuran / 24 h / 20 °C View Scheme

methyl 5-fluoro-2-hydroxybenzoate (391-92-4) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions

Yield

Multi-step reaction with 6 steps 1: potassium nitrate; acetic anhydride; acetic acid / 2 h / 10 °C 2: bis-triphenylphosphine-palladium(II) chloride; trifluoromethylsulfonic anhydride; triethylamine / N,N-dimethyl-formamide / 2 h / 50 °C 3: palladium 10% on activated carbon; hydrogen / methanol / 6 h / 50 °C 4: copper(l) iodide / N,N-dimethyl-formamide / 12 h / 90 °C 5: acetic acid / 12 h / 50 °C 6: hydrogen / methanol / 12 h / 50 °C / 7600.51 Torr View Scheme

5-fluoro-2-hydroxy-3-nitrobenzoic acid methyl ester (880160-63-4) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: bis-triphenylphosphine-palladium(II) chloride; trifluoromethylsulfonic anhydride; triethylamine / N,N-dimethyl-formamide / 2 h / 50 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 6 h / 50 °C 3: copper(l) iodide / N,N-dimethyl-formamide / 12 h / 90 °C 4: acetic acid / 12 h / 50 °C 5: hydrogen / methanol / 12 h / 50 °C / 7600.51 Torr View Scheme

C13H14FNO4Si → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: palladium 10% on activated carbon; hydrogen / methanol / 6 h / 50 °C 2: copper(l) iodide / N,N-dimethyl-formamide / 12 h / 90 °C 3: acetic acid / 12 h / 50 °C 4: hydrogen / methanol / 12 h / 50 °C / 7600.51 Torr View Scheme

C13H16FNO2Si → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: copper(l) iodide / N,N-dimethyl-formamide / 12 h / 90 °C 2: acetic acid / 12 h / 50 °C 3: hydrogen / methanol / 12 h / 50 °C / 7600.51 Torr View Scheme

C12H9FN2O4 → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
With hydrogen In methanol at 50℃; under 7600.51 Torr; for 12h; Temperature; Pressure;	10.1 g

methyl 3-amino-5-fluorobenzoate (884497-46-5) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium nitrite; hydrogenchloride / water / 1.75 h / -10 °C 1.2: 2 h 2.1: water; ethanol / 7 h / Reflux View Scheme

methyl 3,5-difluorobenzoate → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / dimethyl sulfoxide / 24 h / 60 °C 2: water; ethanol / 7 h / Reflux View Scheme

6-fluoro-1H-indole-4-carbonitrile (1082040-44-5) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water / 8 h / 120 °C 2.1: oxalyl dichloride / dichloromethane / 2 h / 0 °C 2.2: 2 h / Heating 3.1: trifluoroacetic acid; tributylsilane / dichloromethane / 8 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / water / 8 h / 120 °C 2: HATU / N,N-dimethyl-formamide / 8 h / 20 °C 3: tributylsilane; boron trifluoride diethyl etherate / dichloromethane / 12 h / 0 - 20 °C View Scheme

4-bromo-6-fluoro-1H-indole (885520-70-7) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / dimethyl sulfoxide / 8 h / 120 °C / Inert atmosphere 2.1: sodium hydroxide / water / 8 h / 120 °C 3.1: oxalyl dichloride / dichloromethane / 2 h / 0 °C 3.2: 2 h / Heating 4.1: trifluoroacetic acid; tributylsilane / dichloromethane / 8 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: N,N-dimethyl-formamide / 6 h / 150 °C / Inert atmosphere 2.1: sodium hydroxide / water / 8 h / 120 °C 3.1: oxalyl dichloride / dichloromethane / 2 h / 0 °C 3.2: 2 h / Heating 4.1: trifluoroacetic acid; tributylsilane / dichloromethane / 8 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / dimethyl sulfoxide / 8 h / 120 °C / Inert atmosphere 2: sodium hydroxide / water / 8 h / 120 °C 3: HATU / N,N-dimethyl-formamide / 8 h / 20 °C 4: tributylsilane; boron trifluoride diethyl etherate / dichloromethane / 12 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: N,N-dimethyl-formamide / 6 h / 150 °C / Inert atmosphere 2: sodium hydroxide / water / 8 h / 120 °C 3: HATU / N,N-dimethyl-formamide / 8 h / 20 °C 4: tributylsilane; boron trifluoride diethyl etherate / dichloromethane / 12 h / 0 - 20 °C View Scheme

6-fluoro-1H-indole-4-carboxylic acid → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: oxalyl dichloride / dichloromethane / 2 h / 0 °C 1.2: 2 h / Heating 2.1: trifluoroacetic acid; tributylsilane / dichloromethane / 8 h / 0 - 20 °C View Scheme

6-fluoro-1H-indole-4-carboxylic acid methyl ester (1082040-43-4) → 6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylsilane; trifluoroacetic acid / dichloromethane / 90 h / 8 - 20 °C 2: methylamine / water / 24 h / 0 - 20 °C View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → 2-bromo-8-fluoro-1,3,4,5-tetrahydro-6H-pyrrolo[4,3,2-ef][2]benzazepin-6-one (283173-80-8)

Conditions	Yield
With sodium carbonate; pyridinium hydrobromide perbromide In tetrahydrofuran; dichloromethane at 10 - 20℃; for 1h;	91%
With pyridinium hydrobromide perbromide In tetrahydrofuran at 10℃; for 1h; Temperature;	90.65%
With pyridinium hydrobromide perbromide In tetrahydrofuran; dichloromethane at 0 - 5℃; for 1h; Large scale;	83%

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → 4-(8-fluoro-6-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd] indol-2-yl)-benzaldehyde (283173-84-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 1 h / 0 - 5 °C / Large scale 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl acetamide / 2 h / 20 - 95 °C / Large scale 2.2: 9 h / 20 °C / Large scale View Scheme
Multi-step reaction with 2 steps 1: Pyr·HBr3 / tetrahydrofuran; dichloromethane / 2 h / 0 - 20 °C 2: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / 1,4-dioxane / 12 h / 90 °C View Scheme
Multi-step reaction with 2 steps 1: pyridinium hydrobromide perbromide / tetrahydrofuran / 1 h / 10 °C 2: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl acetamide; water / 2 h / 90 - 100 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: pyridinium hydrobromide perbromide; sodium carbonate / dichloromethane; tetrahydrofuran / 1 h / 10 - 20 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl acetamide / 1 h / 20 - 95 °C / Inert atmosphere 2.2: 2 h / 20 - 98 °C / Inert atmosphere View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → 8-fluoro-2-((4-methylaminomethyl)phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one hydrochloride (773059-19-1) + C18H15FN2O2

Conditions

Yield

Multi-step reaction with 4 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 1 h / 0 - 5 °C / Large scale 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl acetamide / 2 h / 20 - 95 °C / Large scale 2.2: 9 h / 20 °C / Large scale 3.1: methanol; tetrahydrofuran; ethanol / 2 h / Large scale 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C / Large scale 4.2: 1 h / Large scale 4.3: 18 h / Large scale View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → 8-fluoro-2-((4-methylaminomethyl)phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one hydrochloride (773059-19-1) + C37H31F2N5O2

Conditions

Yield

Multi-step reaction with 3 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 1 h / 0 - 5 °C / Large scale 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl acetamide / 2 h / 20 - 95 °C / Large scale 2.2: 9 h / 20 °C / Large scale 3.1: hydrogenchloride; sodium cyanoborohydride / methanol; water; tetrahydrofuran; ethanol / Large scale View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → Rucaparib (283173-50-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 1 h / 0 - 5 °C / Large scale 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl acetamide / 2 h / 20 - 95 °C / Large scale 2.2: 9 h / 20 °C / Large scale 3.1: hydrogenchloride; sodium cyanoborohydride / methanol; water; tetrahydrofuran; ethanol / Large scale 4.1: sodium hydroxide / methanol; water; tetrahydrofuran / 18 h / 20 °C / Large scale View Scheme
Multi-step reaction with 5 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 1 h / 0 - 5 °C / Large scale 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl acetamide / 2 h / 20 - 95 °C / Large scale 2.2: 9 h / 20 °C / Large scale 3.1: methanol; tetrahydrofuran; ethanol / 2 h / Large scale 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C / Large scale 4.2: 1 h / Large scale 4.3: 18 h / Large scale 5.1: sodium hydroxide / methanol; water; tetrahydrofuran / 18 h / 20 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1.1: Pyr·HBr3 / tetrahydrofuran; dichloromethane / 2 h / 0 - 20 °C 2.1: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / 1,4-dioxane / 12 h / 90 °C 3.1: methanol / 2 h / 20 °C 3.2: 0 - 20 °C View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → C19H16FN3O

Conditions	Yield
Multi-step reaction with 3 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 1 h / 0 - 5 °C / Large scale 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl acetamide / 2 h / 20 - 95 °C / Large scale 2.2: 9 h / 20 °C / Large scale 3.1: methanol; tetrahydrofuran; ethanol / 2 h / Large scale View Scheme
Multi-step reaction with 3 steps 1.1: pyridinium hydrobromide perbromide / dichloromethane / 0 - 5 °C 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / isopropyl alcohol / 1 h / 20 °C / Inert atmosphere 2.2: 3 h / 80 - 85 °C / Inert atmosphere 3.1: methanol; tetrahydrofuran / 2 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: pyridinium hydrobromide perbromide / tetrahydrofuran / 1 h / 10 °C 2: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl acetamide; water / 2 h / 90 - 100 °C / Inert atmosphere 3: toluene-4-sulfonic acid / ethanol / 2 h / 10 °C View Scheme
Multi-step reaction with 3 steps 1.1: pyridinium hydrobromide perbromide; sodium carbonate / dichloromethane; tetrahydrofuran / 1 h / 10 - 20 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl acetamide / 1 h / 20 - 95 °C / Inert atmosphere 2.2: 2 h / 20 - 98 °C / Inert atmosphere 3.1: tetrahydrofuran; methanol; ethanol / 12 h / 25 - 33 °C View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → 8-fluoro-2-((4-methylaminomethyl)phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one (S)-camphorsulfonate

Conditions	Yield
Multi-step reaction with 5 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 1 h / 0 - 5 °C / Large scale 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl acetamide / 2 h / 20 - 95 °C / Large scale 2.2: 9 h / 20 °C / Large scale 3.1: hydrogenchloride; sodium cyanoborohydride / methanol; water; tetrahydrofuran; ethanol / Large scale 4.1: sodium hydroxide / methanol; water; tetrahydrofuran / 18 h / 20 °C / Large scale 5.1: water; isopropyl alcohol / 1 h / 70 °C View Scheme
Multi-step reaction with 6 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 1 h / 0 - 5 °C / Large scale 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / N,N-dimethyl acetamide / 2 h / 20 - 95 °C / Large scale 2.2: 9 h / 20 °C / Large scale 3.1: methanol; tetrahydrofuran; ethanol / 2 h / Large scale 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C / Large scale 4.2: 1 h / Large scale 4.3: 18 h / Large scale 5.1: sodium hydroxide / methanol; water; tetrahydrofuran / 18 h / 20 °C / Large scale 6.1: water; isopropyl alcohol / 1 h / 70 °C View Scheme
Multi-step reaction with 5 steps 1.1: pyridinium hydrobromide perbromide; sodium carbonate / dichloromethane; tetrahydrofuran / 1 h / 10 - 20 °C 2.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl acetamide / 1 h / 20 - 95 °C / Inert atmosphere 2.2: 2 h / 20 - 98 °C / Inert atmosphere 3.1: tetrahydrofuran; methanol; ethanol / 12 h / 25 - 33 °C 4.1: palladium 10% on activated carbon; hydrogen / 12 h 5.1: water; methanol / 29 h / 0 - 40 °C / Reflux View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → C18H14FN3O2

Conditions	Yield
Multi-step reaction with 3 steps 1: Pyr·HBr3 / tetrahydrofuran; dichloromethane / 2 h / 0 - 20 °C 2: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / 1,4-dioxane / 12 h / 90 °C 3: hydroxylamine hydrochloride; sodium acetate / methanol; water / 1 h / 50 °C View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → C18H16FN3O

Conditions	Yield
Multi-step reaction with 4 steps 1: Pyr·HBr3 / tetrahydrofuran; dichloromethane / 2 h / 0 - 20 °C 2: tetrakis(triphenylphosphine) palladium(0); sodium carbonate / 1,4-dioxane / 12 h / 90 °C 3: hydroxylamine hydrochloride; sodium acetate / methanol; water / 1 h / 50 °C 4: zinc; hydrogenchloride / water; ethanol / 3 h / 0 - 20 °C View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one hydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1.1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 5 - 20 °C 2.1: potassium carbonate; bis(acetato)bis(triphenylphosphine)palladium(0) / ethanol; water / 17 h / 60 °C / Inert atmosphere 2.2: 17 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: pyridinium hydrobromide perbromide / dichloromethane / 0 - 5 °C 2.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / isopropyl alcohol / 1 h / 20 °C / Inert atmosphere 2.2: 3 h / 80 - 85 °C / Inert atmosphere 3.1: methanol; tetrahydrofuran / 2 h / 0 - 20 °C 4.1: sodium tetrahydroborate; methanol / tetrahydrofuran / 2 h / 0 - 20 °C 4.2: 2 h View Scheme

6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7-tetraen-9-one (1408282-26-7) → 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one acetate

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridinium hydrobromide perbromide / tetrahydrofuran; dichloromethane / 5 - 20 °C 2: bis(acetato)bis(triphenylphosphine)palladium(0); sodium carbonate / methanol; water / 4 h / 60 °C / Inert atmosphere 3: methanol; water / 48 h / 20 °C View Scheme

Upstream product

• 14027-75-9 3-nitro-5-fluorobenzoic acid 
• 391-92-4 methyl 5-fluoro-2-hydroxybenzoate 
• 880160-63-4 5-fluoro-2-hydroxy-3-nitrobenzoic acid methyl ester 
• 1408282-25-6 3-(2-(phthalimido)ethyl)-6-fluoro-1H-indole-4-carboxylic acid methyl ester 
• 74-89-5 methylamine 
• 697739-03-0 5-fluoro-2-methyl-3-nitrobenzoic acid methyl ester 
• 33184-16-6 5-fluoro-2-methylbenzoic acid 
• 1082040-43-4 6-fluoro-1H-indole-4-carboxylic acid methyl ester 
• 908600-71-5 6-fluoro-1H-indole-4-carboxylic acid 
• 885520-70-7 4-bromo-6-fluoro-1H-indole 
• 1082040-44-5 6-fluoro-1H-indole-4-carbonitrile 
• 216393-55-4 methyl 3,5-difluorobenzoate 
• 884497-46-5 methyl 3-amino-5-fluorobenzoate 

Downstream Products

• 283173-84-2 4-(8-fluoro-6-oxo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd] indol-2-yl)-benzaldehyde 
• 773059-19-1 8-fluoro-2-((4-methylaminomethyl)phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one hydrochloride 
• 283173-50-2 Rucaparib 

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