(2-amino-5-fluorophenyl)-phenylmethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In the manner given in Preparation 1, 5-fluoro-2-aminobenzophenone is refluxed with hydrazine hydrate in diethylene glycol to give 5-fluoro-2-aminobenzophenone hydrazone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In the manner given in Preparation 1, 5-fluoro-2-aminobenzophenone is refluxed with hydrazine hydrate in diethylene glycol to give 5-fluoro-2-aminobenzophenone hydrazone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 115 mg of (2-amino-5-fluoro-phenyl)-phenyl-methanone and 101 mg of 4-methoxy-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 3.64 (s, 3H), 6.62 (d, 2H, J=9.2 Hz), 7.02 (m, 1H), 7.25 (m, 1H), 7.31 (m, 2H), 7.37 (m, 2H), 7.48 (m, 2H), 7.56 (m, 1H), 7.79 (q, 1H, J=9.2 Hz, 4.8 Hz), 9.34 (s, 1H). MS: m/z 386.0 (M++1).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure was in the same manner as described in example 15, except that the starting material was benzoic acid instead of p-chlorobenzoic acid and 4-fluoroaniline instead of 4-chloroaniline. The title compound was obtained as yellow needle crystal, and yield 37.9%, m.p. 112-113° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure was in the same manner as described in example 15, except that the starting material was benzoic acid instead of p-chlorobenzoic acid and 4-fluoroaniline instead of 4-chloroaniline. The title compound was obtained as yellow needle crystal, and yield 37.9%, m.p. 112-113° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In the manner given in Preparation 1, 5-fluoro-2-aminobenzophenone is refluxed with hydrazine hydrate in diethylene glycol to give 5-fluoro-2-aminobenzophenone hydrazone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 115 mg of (2-amino-5-fluoro-phenyl)-phenyl-methanone and 101 mg of 4-methoxy-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 3.64 (s, 3H), 6.62 (d, 2H, J=9.2 Hz), 7.02 (m, 1H), 7.25 (m, 1H), 7.31 (m, 2H), 7.37 (m, 2H), 7.48 (m, 2H), 7.56 (m, 1H), 7.79 (q, 1H, J=9.2 Hz, 4.8 Hz), 9.34 (s, 1H). MS: m/z 386.0 (M++1).

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (2-amino-5-fluorophenyl)(phenyl)methanone (6.60 g, 30.67 mmol) in CH2Cl2 (60 mL) was added carbonyldiimidazole (6.96 g, 42.93 mmol). The reaction was heated to 45° C. After 16 h at 45° C., the reaction was cooled to ambient temperature and the precipitate isolated by vacuum filtration and washed with fresh CH2Cl2 to give N-(2-benzoyl-4-fluorophenyl)-1H-imidazole-1-carboxamide as a white solid. 1H NMR (CDCl3, 400 MHz) 8.91 (s, NH); 7.47 (m, 3H, ArH); 7.25 (m, 1H, ArH); 7.18 (m, 4H, ArH); 6.99 (m, 1H, ArH); 6.95 (s, 1H, ArH); 6.53 (m, 1H, ArH); MS (Electrospray): m/z 332.1 (M+Na). the reaction was cooled to ambient temperature the precipitate isolated by vacuum filtration washed with fresh CH2Cl2

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a −78° C. solution of 2-amino-5-fluoro-N-methoxy-N-methylbenzamide in THF (100 mL) was added 1M phenylmagnesium bromide in THF (124.12 mL, 124.12 mmol). The reaction was stirred from −78° C. to ambient temperature over 3.5 h and then cooled again to −78° C. Additional 1M phenylmagnesium bromide in THF (62.06 mL, 62.06 mmol) was added and the reaction stirred at −78° C. for another hour. The reaction was then diluted with CH2Cl2 (500 mL) and quenched with saturated ammonium chloride solution (300 mL). The layers were separated and the organic one washed with brine (300 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by normal phase chromatography (3-8% MeOH/CH2Cl2) yielded (2-amino-5-fluorophenyl)(phenyl)methanone as a yellow solid. 1H NMR (CDCl3, 400 MHz) 7.63 (m, 2H, ArH); 7.55 (m, 1H, ArH); 7.47 (m, 2H, ArH); 7.15 (m, 1H, ArH); 7.08 (m, 1H, ArH); 6.70 (m, 1H, ArH); 5.91 (s, NH2); MS (Electrospray): m/z 216.1 (M+H). the reaction stirred at −78° C. for another hour quenched with saturated ammonium chloride solution (300 mL) The layers were separated the organic one washed with brine (300 mL) dried over Na2SO4 filtered concentrated in vacuo Purification by normal phase chromatography (3-8% MeOH/CH2Cl2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 115 mg of (2-amino-5-fluoro-phenyl)-phenyl-methanone and 101 mg of 4-methoxy-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 3.64 (s, 3H), 6.62 (d, 2H, J=9.2 Hz), 7.02 (m, 1H), 7.25 (m, 1H), 7.31 (m, 2H), 7.37 (m, 2H), 7.48 (m, 2H), 7.56 (m, 1H), 7.79 (q, 1H, J=9.2 Hz, 4.8 Hz), 9.34 (s, 1H). MS: m/z 386.0 (M++1).

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (2-amino-5-fluorophenyl)(phenyl)methanone (6.60 g, 30.67 mmol) in CH2Cl2 (60 mL) was added carbonyldiimidazole (6.96 g, 42.93 mmol). The reaction was heated to 45° C. After 16 h at 45° C., the reaction was cooled to ambient temperature and the precipitate isolated by vacuum filtration and washed with fresh CH2Cl2 to give N-(2-benzoyl-4-fluorophenyl)-1H-imidazole-1-carboxamide as a white solid. 1H NMR (CDCl3, 400 MHz) 8.91 (s, NH); 7.47 (m, 3H, ArH); 7.25 (m, 1H, ArH); 7.18 (m, 4H, ArH); 6.99 (m, 1H, ArH); 6.95 (s, 1H, ArH); 6.53 (m, 1H, ArH); MS (Electrospray): m/z 332.1 (M+Na). the reaction was cooled to ambient temperature the precipitate isolated by vacuum filtration washed with fresh CH2Cl2