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
• Article Data: 11

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

General Description

8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one is a chemical compound with the molecular formula C12H10FNO. It is a heterocyclic compound containing a six-membered azepine ring fused to a five-membered imidazolidinone ring with a fluorine atom attached to the eight position of the azepine ring. 8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one is used in the field of medicinal chemistry and drug discovery as a scaffold for the synthesis of novel bioactive compounds. Its unique structure and properties make it a potential candidate for the development of new drugs and pharmaceuticals. Studies have shown that derivatives of 8-fluoro-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one exhibit various biological activities, including anticancer, antiviral, and antibacterial properties, making it a valuable molecule for further research and development.

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

• 1408282-25-6 3-(2-(phthalimido)ethyl)-6-fluoro-1H-indole-4-carboxylic acid methyl ester 
• 14027-75-9 3-nitro-5-fluorobenzoic acid 
• 399-51-9 6-fluoro-1H-indole 
• 141071-78-5 6-Fluoroindole-3-propionic acid 
• 391-92-4 methyl 5-fluoro-2-hydroxybenzoate 
• 880160-63-4 5-fluoro-2-hydroxy-3-nitrobenzoic 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 

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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