6-bromo-8-fluoro-3,4-dihydro-1H-quinolin-2-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 6-bromo-8-fluoro-3,4-dihydroquinolin-2(1H)-one (1-3, 2.00 g, 8.19 mmol) in toluene (50 mL) was added Lawesson's reagent (1.66 g, 4.10 mmol). After refluxing the reaction mixture for 2 h, the toluene was distilled off to yield the crude product, which was then purified by flash chromatography on silica gel to obtain the title compound as a yellow solid; 1H NMR (DMSO-D6, 500 MHz) δ=12.14 (s, 1H), 7.46 (dd, J=2.0 Hz, JHF=10.0 Hz, 1H), 7.34 (s, 1H), 2.94 (d, J=8.0 Hz, 2H), 2.84 (d, J=8.0 Hz, 2H). After refluxing the reaction mixture for 2 h the toluene was distilled off to yield the crude product, which was then purified by flash chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 6-bromo-8-fluoro-3,4-dihydroquinolin-2(1H)-one (1-3, 2.00 g, 8.19 mmol) in toluene (50 mL) was added Lawesson's reagent (1.66 g, 4.10 mmol). After refluxing the reaction mixture for 2 h, the toluene was distilled off to yield the crude product, which was then purified by flash chromatography on silica gel to obtain the title compound as a yellow solid; 1H NMR (DMSO-D6, 500 MHz) δ=12.14 (s, 1H), 7.46 (dd, J=2.0 Hz, JHF=10.0 Hz, 1H), 7.34 (s, 1H), 2.94 (d, J=8.0 Hz, 2H), 2.84 (d, J=8.0 Hz, 2H). After refluxing the reaction mixture for 2 h the toluene was distilled off to yield the crude product, which was then purified by flash chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 8-fluoro-3,4-dihydroquinolin-2(1H)-one (1-2; 8.30 g, 50.10 mmol) in N,N-dimethylformamide (250 mL) was added N-bromosuccinimide (9.80 g, 55.10 mmol) in N,N-dimethylformamide (120 mL) at 0° C. The reaction mixture was stirred at room temperature for 18 h, cooled, and diluted with ice cold water (500 mL). The resulting precipitated was filtered and dried to obtain the title compound as a white solid; 1H NMR (DMSO-D6, 500 MHz) δ=10.20 (s, 1H), 7.37 (dd, J=2.0 Hz, JHF=10.0 Hz, 1H), 7.26 (s, 1H), 2.93 (t, J=7.0 Hz, 2H), 2.47 (t, J=7.5 Hz, 2H). cooled The resulting precipitated was filtered dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 6-bromo-8-fluoro-3,4-dihydro-1H-quinolin-2-one (0.21 g, 0.86 mmol) in DMF (2 mL) was treated with potassium tert-butoxide (0.19 g, 1.72 mmol) at 0° C. The resulting mixture was stirred at 0° C. for 30 min before methyl iodide (0.18 g, 1.29 mmol) was added. After stirring for 2 h, the reaction mixture was treated with water, extracted with EtOAc, washed with water and brine in sequence, and dried over anhy. Na2SO4. After removal of the solvents under reduced pressure, the crude product (0.18 g, 80% yield) was obtained as a white solid. MS: 258.0 (M+H)+. was added extracted with EtOAc washed with water and brine in sequence dried over anhy After removal of the solvents under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: NBS (0.62 g, 3.5 mmol) dissolved in DMF (5 mL) was added to a solution of 8-fluoro-3,4-dihydro-1H-quinolin-2-one (0.52 g, 3.2 mmol) in DMF (5 mL) dropwise at 0° C. The resulting reaction mixture was stirred at room temperature for 12 hr before it was treated with water. The precipitated solid was collected through filtration, washed with ether, and dried over vacuum to afford title compound (0.65 g, 85% yield) as a white solid. MS: 244.1 (M+H)+. The resulting reaction mixture The precipitated solid was collected through filtration washed with ether dried over vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: NBS (0.62 g, 3.5 mmol) dissolved in DMF (5 mL) was added to a solution of 8-fluoro-3,4-dihydro-1H-quinolin-2-one (0.52 g, 3.2 mmol) in DMF (5 mL) dropwise at 0° C. The resulting reaction mixture was stirred at room temperature for 12 hr before it was treated with water. The precipitated solid was collected through filtration, washed with ether, and dried over vacuum to afford title compound (0.65 g, 85% yield) as a white solid. MS: 244.1 (M+H)+. The resulting reaction mixture The precipitated solid was collected through filtration washed with ether dried over vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 6-bromo-8-fluoro-3,4-dihydro-1H-quinolin-2-one (0.21 g, 0.86 mmol) in DMF (2 mL) was treated with potassium tert-butoxide (0.19 g, 1.72 mmol) at 0° C. The resulting mixture was stirred at 0° C. for 30 minutes before methyl iodide (0.18 g, 1.29 mmol) was added. After stirring for 2 hours, the reaction mixture was treated with water, extracted with EtOAc, washed with water and brine in sequence, and dried over anhydrous Na2SO4. After removal of solvent under reduced pressure, the crude product (0.18 g, 80%) was obtained as a white solid. MS: 258.0 (M+H+)+. was added extracted with EtOAc washed with water and brine in sequence dried over anhydrous Na2SO4 After removal of solvent under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At 0° C., NBS (0.62 g, 3.5 mmol) was added dropwise to a solution of 8-fluoro-3,4-dihydro-1H-quinolin-2-one (0.52 g, 3.2 mmol) in DMF (5 mL). The resulting reaction mixture was stirred at room temperature for 12 hours before it was treated with water. The precipitated solid was collected through filtration, washed with ether, and dried in a vacuum to afford title compound (0.65 g, 85%) as a white solid. MS: 244.1 (M+H+)+. The resulting reaction mixture The precipitated solid was collected through filtration washed with ether dried in a vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 6-bromo-8-fluoro-3,4-dihydroquinolin-2(1H)-one (157-3, 2.00 g, 8.19 mmol) in toluene (50 mL) was added Lawesson's reagent (1.66 g, 4.10 mmol). After reflux for 2 h, toluene was distilled off to yield the crude product, which was then purified by flash chromatography on silica gel to obtain title compound (yellow solid). 1H NMR (DMSO-D6, 500 MHz) 6=12.14 (s, 1H), 7.46 (dd, J=2.0 Hz, JHF=10.0 Hz, 1H), 7.34 (s, 1H), 2.94 (d, J=8.0 Hz, 2H), 2.84 (d, J=8.0 Hz, 2H). After reflux for 2 h toluene was distilled off to yield the crude product, which was then purified by flash chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 8-fluoro-3,4-dihydroquinolin-2(1H)-one (157-2; 8.30 g, 50.10 mmol) in N,N-dimethylformamide (250 mL) was added N-bromosuccinimide (9.80 g, 55.10 mmol) in N,N-dimethylformamide (120 mL) at 0° C. Reaction mixture was allowed to stir at room temperature for 18 h, then cooled and diluted with ice cold water (500 mL). The resulting precipitated was filtered and dried to obtain title compound (white solid). 1H NMR (DMSO-D6, 500 MHz) 6=10.20 (s, 1H), 7.37 (dd, J=2.0 Hz, JHF=10.0 Hz, 1H), 7.26 (s, 1H), 2.93 (t, J=7.0 Hz, 2H), 2.47 (t, J=7.5 Hz, 2H). Reaction mixture cooled The resulting precipitated was filtered dried

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6-bromo-8-fluoro-3,4-dihydroquinolin-2(1H)-one (109-3; 8 g, 0.032 mol) in toluene (30 mL) was added Lawesson's reagent (13.26 g, 0.032 mol). Reaction mass was refluxed at 100° C. for 12 h. The reaction mixture was concentrated and directly purified by silica gel column chromatography to obtain title compound. MS (M+1): 262.0. Reaction mass The reaction mixture was concentrated directly purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 8-fluoro-3,4-dihydroquinolin-2(1H)-one (109-2; 7 g, 0.0424 mol) in N,N-dimethylformamide (30 mL) was added N-bromosuccinimide (9.06 g, 0.050 mol) portion wise at 0° C. Reaction mixture was allowed to stir at room temperature for 12 h. The reaction mixture was concentrated and diluted with ice cold water (150 mL) with constant stirring and the solid residue was filtered and dried to obtain the title compound. MS (M+1): 245.1 Reaction mixture The reaction mixture was concentrated diluted with ice cold water (150 mL) with constant stirring the solid residue was filtered dried