N-fluorobenzenesulfonamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 6-Amino-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (17) (250 mg, 0.822 mmol), N-fluorobenzenesulphonamide (259 mg, 0.822 mmol), and DMF (4 mL) were warmed to 90° C. behind an explosion shield. After 48 h, the reaction was concentrated in vacuo and the residue was purified by flash chromatography (ethyl acetate:hexane 1:1) to afford 6-Amino-5-fluoro-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (28): Mass Spectrum (CI) 323 (MH+). the reaction was concentrated in vacuo the residue was purified by flash chromatography (ethyl acetate:hexane 1:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5,6-dichloro-9-tosyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (300 mg, 0.7 mmol) in anhydrous THF (10 mL), cooled to −78° C., LiHMDS (1.47 mL, 1.4 mmol, 1M solution in THF) was added slowly. The reaction mixture was slowly warmed to 0° C. and stirred for an additional 30 min. while maintaining the temperature at 0° C. The reaction mixture was then cooled to −78° C. and N-fluoro benzene sulfonamide (0.22 g, 0.9 mmol), dissolved in THF (3 mL), was added dropwise. The reaction mixture was slowly warmed to 0° C. and stirred for 15 min during which time the reaction was complete. The reaction was quenched with saturated NH4Cl and extracted with EtOAc (3×25 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (1:9) as eluant] to give the title compound (100 mg, 32%). 1H NMR (500 MHz, CDCl3, δ in ppm) 8.27 (d, J=9.5 Hz, 1H), 8.07 (d, J=8.5 Hz, 2H), 7.59 (d, J=9.5 Hz, 1H), 7.35 (d, J=8.5 Hz, 2H), 5.30-5.13 (m, 1H), 3.71-3.66 (m, 1H), 3.35-3.28 (m, 1H), 2.58-2.55 (m, 1H), 2.43 (s, 3H), 2.40-2.38 (m, 1H) while maintaining the temperature at 0° C The reaction mixture was then cooled to −78° C. was added dropwise The reaction mixture was slowly warmed to 0° C. stirred for 15 min during which time the reaction The reaction was quenched with saturated NH4Cl extracted with EtOAc (3×25 mL) The combined organic extracts were dried over Na2SO4 concentrated under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (1:9) as eluant]

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5,6-dichloro-9-tosyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (300 mg, 0.7 mmol) in anhydrous THF (10 mL), cooled to −78° C., LiHMDS (1.47 mL, 1.4 mmol, 1M solution in THF) was added slowly. The reaction mixture was slowly warmed to 0° C. and stirred for an additional 30 min. while maintaining the temperature at 0° C. The reaction mixture was then cooled to −78° C. and N-fluoro benzene sulfonamide (0.22 g, 0.9 mmol), dissolved in THF (3 mL), was added dropwise. The reaction mixture was slowly warmed to 0° C. and stirred for 15 min during which time the reaction was complete. The reaction was quenched with saturated NH4Cl and extracted with EtOAc (3×25 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (1:9) as eluant] to give the title compound (100 mg, 32%). 1H NMR (500 MHz, CDCl3, δ in ppm) 8.27 (d, J=9.5 Hz, 1H), 8.07 (d, J=8.5 Hz, 2H), 7.59 (d, J=9.5 Hz, 1H), 7.35 (d, J=8.5 Hz, 2H), 5.30-5.13 (m, 1H), 3.71-3.66 (m, 1H), 3.35-3.28 (m, 1H), 2.58-2.55 (m, 1H), 2.43 (s, 3H), 2.40-2.38 (m, 1H) while maintaining the temperature at 0° C The reaction mixture was then cooled to −78° C. was added dropwise The reaction mixture was slowly warmed to 0° C. stirred for 15 min during which time the reaction The reaction was quenched with saturated NH4Cl extracted with EtOAc (3×25 mL) The combined organic extracts were dried over Na2SO4 concentrated under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (1:9) as eluant]

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6,7-Dichloro-9-tosyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (intermediate 1c) (420 mg, 1.02 mmol) dissolved in anhydrous THF (10 mL) and cooled to −78° C. was mixed with LiHMDS (1.13 mL, 1.1 mmol, 1M solution in THF). The reaction mixture was slowly warmed to 0° C., stirred for an additional 30 min. at 0° C., then cooled to −78° C. and N-fluoro benzene sulfonamide (0.31 g, 1.3 mmol) was added. The resulting mixture was slowly warmed to room temperature and stirred for 15 min., quenched with saturated NH4Cl and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, the solvent was removed under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (7:93) as eluant] to obtain the title compound (160 mg, 37%). 1H NMR (500 MHz, CDCl3, δ in ppm) 8.53 (s, 1H), 8.082 (d, J=8.0 Hz, 2H), 7.69 (s, 1H), 7.35 (d, J=8.5 Hz, 2H), 5.26-5.13 (m, 1H), 3.14-3.11 (m, 1H), 3.01-2.95 (m, 1H), 2.62-2.55 (m, 1H), 2.42 (s, 3H), 2.38-2.41 (m, 1H). The reaction mixture was slowly warmed to 0° C. cooled to −78° C. The resulting mixture was slowly warmed to room temperature stirred for 15 min. quenched with saturated NH4Cl extracted with EtOAc (3×20 mL) The combined organic extracts were dried over Na2SO4 the solvent was removed under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (7:93) as eluant]

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6,7-Dichloro-9-tosyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (intermediate 1c) (420 mg, 1.02 mmol) dissolved in anhydrous THF (10 mL) and cooled to −78° C. was mixed with LiHMDS (1.13 mL, 1.1 mmol, 1M solution in THF). The reaction mixture was slowly warmed to 0° C., stirred for an additional 30 min. at 0° C., then cooled to −78° C. and N-fluoro benzene sulfonamide (0.31 g, 1.3 mmol) was added. The resulting mixture was slowly warmed to room temperature and stirred for 15 min., quenched with saturated NH4Cl and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, the solvent was removed under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (7:93) as eluant] to obtain the title compound (160 mg, 37%). 1H NMR (500 MHz, CDCl3, δ in ppm) 8.53 (s, 1H), 8.082 (d, J=8.0 Hz, 2H), 7.69 (s, 1H), 7.35 (d, J=8.5 Hz, 2H), 5.26-5.13 (m, 1H), 3.14-3.11 (m, 1H), 3.01-2.95 (m, 1H), 2.62-2.55 (m, 1H), 2.42 (s, 3H), 2.38-2.41 (m, 1H). The reaction mixture was slowly warmed to 0° C. cooled to −78° C. The resulting mixture was slowly warmed to room temperature stirred for 15 min. quenched with saturated NH4Cl extracted with EtOAc (3×20 mL) The combined organic extracts were dried over Na2SO4 the solvent was removed under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (7:93) as eluant]

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

Procedure: 6-Amino-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (17) (250 mg, 0.822 mmol), N-fluorobenzenesulphonamide (259 mg, 0.822 mmol), and DMF (4 mL) were warmed to 90° C. behind an explosion shield. After 48 h, the reaction was concentrated in vacuo and the residue was purified by flash chromatography (ethyl acetate: hexane 1:1) to afford 6-Amino-5-fluoro-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (28): Mass Spectrum (CI) 323 (MH+). the reaction was concentrated in vacuo the residue was purified by flash chromatography (ethyl acetate: hexane 1:1)

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

Procedure: 6-Amino-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (17) (250 mg, 0.822 mmol), N-fluorobenzenesulphonamide (259 mg, 0.822 mmol), and DMF (4 mL) were warmed to 90° C. behind an explosion shield. After 48 h, the reaction was concentrated in vacuo and the residue was purified by flash chromatography (ethyl acetate: hexane 1:1) to afford 6-Amino-5-fluoro-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (28): Mass Spectrum (CI) 323 (MH+). the reaction was concentrated in vacuo the residue was purified by flash chromatography (ethyl acetate: hexane 1:1)

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

Procedure: 6-Amino-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (17) (250 mg, 0.822 mmol), N-fluorobenzenesulphonamide (259 mg, 0.822 mmol), and DMF (4 mL) were warmed to 90° C. behind an explosion shield. After 48 h, the reaction was concentrated in vacuo and the residue was purified by flash chromatography (ethyl acetate:hexane 1:1) to afford 6-Amino-5-fluoro-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (28): Mass Spectrum (CI) 323 (MH+). the reaction was concentrated in vacuo the residue was purified by flash chromatography (ethyl acetate:hexane 1:1)