(3,5-difluorophenyl)thiourea

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

実験手順: In certain cases the requisite 2-amino-1,3-benzothiazole was prepared from the corresponding thiourea as described above for the preparation of N-(3,5-difluorophenyl) thiourea and 5,7-difluoro-1,3-benzothiazol-2-amine.

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of N-(3,5-difluorophenyl) thiourea (3.40 g, 18.07 mmol) in DCE (95 mL) was added a solution of bromine in DCE (5 mL) below 30° C. The mixture was heated at reflux for 2.5 h, then cooled to 10° C., and the precipitate formed was collected by filtration and washed with DCE. The solid was stirred with water (200 mL), basified by treatment with conc. ammonium hydroxide, filtered, and dried in a vacuum oven to afford 5,7-difluoro-1,3-benzothiazol-2-amine (3.05 g, 90%). ret. time 2.18; m/z 187.1 (MH+) 1H NMR (400 MHz, DMSO-d6) δ 6.92 (m, 1H), 7.00 (m, 2H), 7.92 (s, 2H). The mixture was heated at reflux for 2.5 h the precipitate formed was collected by filtration washed with DCE filtered dried in a vacuum oven

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Benzoyl chloride (5.44 g, 38.73 mmol) was added to a stirred solution of ammonium thiocyanate (3.83 g, 50.35 mmol) in acetone (80 mL) at 30° C. The mixture was stirred at reflux for 30 minutes, then cooled to 50° C., and a solution of 3,5-difluoroaniline (5.00 g, 38.73 mmol) in acetone (10 mL) was added in one portion. The mixture was stirred at reflux for 30 minutes. A solution of NaOH (5.42 g, 135.54 mmol) in water (65 mL) was added, and the mixture was stirred at reflux for 20 minutes and then cooled to 20° C. Concentrated HCl was added to adjust the acidity to pH=5, and then the mixture was adjusted to slightly alkaline by the addition of conc. ammonium hydroxide. After 30 minutes, the mixture was cooled to 10° C. and extracted with EtOAc, and the combined organic layer was washed with brine, filtered, and concentrated to afford N-(3,5-difluorophenyl)thiourea (3.52 g, 48%). ret. time 1.73; m/z 189.0 (MH+); 1H NMR (400 MHz, MeOH-d4) δ 6.72 (m, 1H), 7.16 (m, 2H). at reflux for 30 minutes The mixture was stirred at reflux for 30 minutes the mixture was stirred at reflux for 20 minutes cooled to 20° C the mixture was cooled to 10° C. extracted with EtOAc the combined organic layer was washed with brine filtered concentrated

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

実験手順: In certain cases the requisite 2-amino-1,3-benzothiazole was prepared from the corresponding thiourea as described above for the preparation of N-(3,5-difluorophenyl)thiourea and 5,7-difluoro-1,3-benzothiazol-2-amine.

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of N-(3,5-difluorophenyl) thiourea (3.40 g, 18.07 mmol) in DCE (95 mL) was added a solution of bromine in DCE (5 mL) below 30° C. The mixture was heated at reflux for 2.5 h, then cooled to 10° C., and the precipitate formed was collected by filtration and washed with DCE. The solid was stirred with water (200 mL), basified by treatment with conc. ammonium hydroxide, filtered, and dried in a vacuum oven to afford 5,7-difluoro-1,3-benzothiazol-2-amine (3.05 g, 90%). ret. time 2.18; m/z 187.1 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 6.92 (m, 1H), 7.00 (m, 2H), 7.92 (s, 2H). The mixture was heated at reflux for 2.5 h the precipitate formed was collected by filtration washed with DCE filtered dried in a vacuum oven

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Benzoyl chloride (5.44 g, 38.73 mmol) was added to a stirred solution of ammonium thiocyanate (3.83 g, 50.35 mmol) in acetone (80 mL) at 30° C. The mixture was stirred at reflux for 30 minutes, then cooled to 50° C., and a solution of 3,5-difluoroaniline (5.00 g, 38.73 mmol) in acetone (10 mL) was added in one portion. The mixture was stirred at reflux for 30 minutes. A solution of NaOH (5.42 g, 135.54 mmol) in water (65 mL) was added, and the mixture was stirred at reflux for 20 minutes and then cooled to 20° C. Concentrated HCl was added to adjust the acidity to pH=5, and then the mixture was adjusted to slightly alkaline by the addition of conc. ammonium hydroxide. After 30 minutes, the mixture was cooled to 10° C. and extracted with EtOAc, and the combined organic layer was washed with brine, filtered, and concentrated to afford N-(3,5-difluorophenyl) thiourea (3.52 g, 48%). ret. time 1.73; m/z 189.0 (MH+); 1H NMR (400 MHz, MeOH-d4) δ 6.72 (m, 1H), 7.16 (m, 2H). at reflux for 30 minutes The mixture was stirred at reflux for 30 minutes the mixture was stirred at reflux for 20 minutes cooled to 20° C the mixture was cooled to 10° C. extracted with EtOAc the combined organic layer was washed with brine filtered concentrated

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

実験手順: In certain cases the requisite 2-amino-1,3-benzothiazole was prepared from the corresponding thiourea as described above for the preparation of N-(3,5-difluorophenyl) thiourea and 5,7-difluoro-1,3-benzothiazol-2-amine.

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of N-(3,5-difluorophenyl) thiourea (3.40 g, 18.07 mmol) in DCE (95 mL) was added a solution of bromine in DCE (5 mL) below 30° C. The mixture was heated at reflux for 2.5 h, then cooled to 10° C., and the precipitate formed was collected by filtration and washed with DCE. The solid was stirred with water (200 mL), basified by treatment with conc. ammonium hydroxide, filtered, and dried in a vacuum oven to afford 5,7-difluoro-1,3-benzothiazol-2-amine (3.05 g, 90%). ret. time 2.18; m/z 187.1 (NH+); 1H NMR (400 MHz, DMSO-d6) δ 6.92 (m, 1H), 7.00 (m, 2H), 7.92 (s, 2H). The mixture was heated at reflux for 2.5 h the precipitate formed was collected by filtration washed with DCE filtered dried in a vacuum oven

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Benzoyl chloride (5.44 g, 38.73 mmol) was added to a stirred solution of ammonium thiocyanate (3.83 g, 50.35 mmol) in acetone (80 mL) at 30° C. The mixture was stirred at reflux for 30 minutes, then cooled to 50° C., and a solution of 3,5-difluoroaniline (5.00 g, 38.73 mmol) in acetone (10 mL) was added in one portion. The mixture was stirred at reflux for 30 minutes. A solution of NaOH (5.42 g, 135.54 mmol) in water (65 mL) was added, and the mixture was stirred at reflux for 20 minutes and then cooled to 20° C. Concentrated HCl was added to adjust the acidity to pH=5, and then the mixture was adjusted to slightly alkaline by the addition of conc. ammonium hydroxide. After 30 minutes, the mixture was cooled to 10° C. and extracted with EtOAc, and the combined organic layer was washed with brine, filtered, and concentrated to afford N-(3,5-difluorophenyl) thiourea (3.52 g, 48%). ret. time 1.73; m/z 189.0 (MH+); 1H NMR (400 MHz, MeOH-d4) δ 6.72 (m, 1H), 7.16 (m, 2H). at reflux for 30 minutes The mixture was stirred at reflux for 30 minutes the mixture was stirred at reflux for 20 minutes cooled to 20° C the mixture was cooled to 10° C. extracted with EtOAc the combined organic layer was washed with brine filtered concentrated

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

実験手順: In certain cases the requisite 2-amino-1,3-benzothiazole was prepared from the corresponding thiourea as described above for the preparation of N-(3,5-difluorophenyl)thiourea and 5,7-difluoro-1,3-benzothiazol-2-amine.

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of N-(3,5-difluorophenyl) thiourea (3.40 g, 18.07 mmol) in DCE (95 mL) was added a solution of bromine in DCE (5 mL) below 30° C. The mixture was heated at reflux for 2.5 h, then cooled to 10° C., and the precipitate formed was collected by filtration and washed with DCE. The solid was stirred with water (200 mL), basified by treatment with conc. ammonium hydroxide, filtered, and dried in a vacuum oven to afford 5,7-difluoro-1,3-benzothiazol-2-amine (3.05 g, 90%). ret. time 2.18; m/z 187.1 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 6.92 (m, 1H), 7.00 (m, 2H), 7.92 (s, 2H). The mixture was heated at reflux for 2.5 h the precipitate formed was collected by filtration washed with DCE filtered dried in a vacuum oven

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Benzoyl chloride (5.44 g, 38.73 mmol) was added to a stirred solution of ammonium thiocyanate (3.83 g, 50.35 mmol) in acetone (80 mL) at 30° C. The mixture was stirred at reflux for 30 minutes, then cooled to 50° C., and a solution of 3,5-difluoroaniline (5.00 g, 38.73 mmol) in acetone (10 mL) was added in one portion. The mixture was stirred at reflux for 30 minutes. A solution of NaOH (5.42 g, 135.54 mmol) in water (65 mL) was added, and the mixture was stirred at reflux for 20 minutes and then cooled to 20° C. Concentrated HCl was added to adjust the acidity to pH=5, and then the mixture was adjusted to slightly alkaline by the addition of conc. ammonium hydroxide. After 30 minutes, the mixture was cooled to 10° C. and extracted with EtOAc, and the combined organic layer was washed with brine, filtered, and concentrated to afford N-(3,5-difluorophenyl) thiourea (3.52 g, 48%). ret. time 1.73; m/z 189.0 (MH+); 1H NMR (400 MHz, MeOH-d4) δ 6.72 (m, 1H), 7.16 (m, 2H). at reflux for 30 minutes The mixture was stirred at reflux for 30 minutes the mixture was stirred at reflux for 20 minutes cooled to 20° C the mixture was cooled to 10° C. extracted with EtOAc the combined organic layer was washed with brine filtered concentrated