(2-amino-5-chlorophenyl)-(4-fluorophenyl)methanone

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

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

Procedure: The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 125 mg of (2-Amino-5-chloro-phenyl)-(4-fluoro-phenyl)-methanone and 116 mg of 4-tert-butyl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 1.21 (s, 9H), 7.09 (t, 2H, J=8.8 Hz), 7.29 (m, 3H), 7.43-7.50 (m, 3H), 7.59 (m, 2H), 7.77 (d, 1H, J=8.8 Hz), 9.72 (s, 1H). MS: m/z 446.0 (M++1).

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

Procedure: In a manner similar to that described above for compound 1t, p-toluidine and 2,6-difluorobenzoyl chloride were converted to 1aj (16% yield) MS m/z=248 (M+H).

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

Procedure: The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 125 mg of (2-Amino-5-chloro-phenyl)-(4-fluoro-phenyl)-methanone and 116 mg of 4-tert-butyl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 1.21 (s, 9H), 7.09 (t, 2H, J=8.8 Hz), 7.29 (m, 3H), 7.43-7.50 (m, 3H), 7.59 (m, 2H), 7.77 (d, 1H, J=8.8 Hz), 9.72 (s, 1H). MS: m/z 446.0 (M++1).

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

Procedure: To a solution of (2-amino-5-chlorophenyl)-(4-fluorophenyl)methanone (10.0 g) in 100 mL of toluene was added 8.3g (1.6 equivalents) of ethyl acetoacetate and 0.30 g of p-toluenesulfonic acid. The resulting mixture was heated to reflux with azeotropic removal of water. After one and one-half hours, the mixture was cooled to room temperature and concentrated under vacuum. The crude product was purified by flash chromatography over silica gel to give 10.18 g of 6-chloro-4-(4-fluorophenyl)-2-methyl-3-quinolinecarboxylic acid, ethyl ester as an off-white solid. The resulting mixture was heated concentrated under vacuum The crude product was purified by flash chromatography over silica gel

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

Procedure: To a 0° C. solution of 1.0M 4-fluorophenylmagnesium bromide in THF (196.6 mL, 196.6 mmol) was added a THF solution (100 mL) of 2-amino-5-chlorobenzonitrile (10.0 gm, 65.5 mmol) over 0.5 h. The ice bath was removed and the reaction stirred at ambient temperature for 17 h. The brown solution was cooled in an ice bath, treated with a drop wise addition of aqueous 1N HCl (300 mL) and extracted with ether (2×250 mL). The combined organic extracts were washed with aqueous 1N HCl (100 mL), water (2×150 ml), saturated aqueous sodium bicarbonate (150 ml), brine (100 mL), dried over MgSO4, filtered, concentrated in vacuo to 30 mL and diluted with 60 mL hexane. The resulting precipitate was filtered to give (2-amino-5-chlorophenyl)(4-fluorophenyl)methanone as a yellow solid. The ice bath was removed The brown solution was cooled in an ice bath treated with a drop wise addition of aqueous 1N HCl (300 mL) extracted with ether (2×250 mL) The combined organic extracts were washed with aqueous 1N HCl (100 mL), water (2×150 ml), saturated aqueous sodium bicarbonate (150 ml), brine (100 mL) dried over MgSO4 filtered concentrated in vacuo to 30 mL diluted with 60 mL hexane The resulting precipitate was filtered

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

Procedure: The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously desribed using 125 mg of (2-Amino-5-chloro-phenyl)-(4-fluoro-phenyl)-methanone and 116 mg of 4-tert-butyl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 1.21 (s, 9H), 7.09 (t, 2H, J=NMR 8.8 Hz), 7.29 (m, 3H), 7.43-7.50 (m, 3H), 7.59 (m, 2H), 7.77 (d, 1H, J=8.8 Hz), 9.72 (s, 1H). MS: m/z 446.0 (M++1).

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

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

Procedure: To a solution of (2-amino-5-chlorophenyl)-(4-fluorophenyl)methanone (10.0 g) in 100 mL of toluene was added 8.3g (1.6 equivalents) of ethyl acetoacetate and 0.30 g of p-toluenesulfonic acid. The resulting mixture was heated to reflux with azeotropic removal of water. After one and one-half hours, the mixture was cooled to room temperature and concentrated under vacuum. The crude product was purified by flash chromatography over silica gel to give 10.18 g of 6-chloro-4-(4-fluorophenyl)-2-methyl-3-quinolinecarboxylic acid, ethyl ester as an off-white solid. The resulting mixture was heated concentrated under vacuum The crude product was purified by flash chromatography over silica gel

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

Procedure: To a 0° C. solution of 1.0M 4-fluorophenylmagnesium bromide in THF (196.6 mL, 196.6 mmol) was added a THF solution (100 mL) of 2-amino-5-chlorobenzonitrile (10.0 gm, 65.5 mmol) over 0.5 h. The ice bath was removed and the reaction stirred at ambient temperature for 17 h. The brown solution was cooled in an ice bath, treated with a drop wise addition of aqueous 1N HCl (300 mL) and extracted with ether (2×250 mL). The combined organic extracts were washed with aqueous 1N HCl (100 mL), water (2×150 ml), saturated aqueous sodium bicarbonate (150 ml), brine (100 mL), dried over MgSO4, filtered, concentrated in vacuo to 30 mL and diluted with 60 mL hexane. The resulting precipitate was filtered to give (2-amino-5-chlorophenyl)(4-fluorophenyl)methanone as a yellow solid. The ice bath was removed The brown solution was cooled in an ice bath treated with a drop wise addition of aqueous 1N HCl (300 mL) extracted with ether (2×250 mL) The combined organic extracts were washed with aqueous 1N HCl (100 mL), water (2×150 ml), saturated aqueous sodium bicarbonate (150 ml), brine (100 mL) dried over MgSO4 filtered concentrated in vacuo to 30 mL diluted with 60 mL hexane The resulting precipitate was filtered

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

Procedure: The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously desribed using 125 mg of (2-Amino-5-chloro-phenyl)-(4-fluoro-phenyl)-methanone and 116 mg of 4-tert-butyl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 1.21 (s, 9H), 7.09 (t, 2H, J=NMR 8.8 Hz), 7.29 (m, 3H), 7.43-7.50 (m, 3H), 7.59 (m, 2H), 7.77 (d, 1H, J=8.8 Hz), 9.72 (s, 1H). MS: m/z 446.0 (M++1).

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

Procedure: In a manner similar to that described above for compound 1t, p-toluidine and 2,6-difluorobenzoyl chloride were converted to 1aj (16% yield) MS m/z=248 (M+H).