2-amino-6-bromophenol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: Using the above procedure, but starting with 8-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine (prepared by reducing 8-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one, which in turn was prepared from 2-amino-6-bromophenol and 2-bromo-2-methylproprionyl bromide via the procedure described by Van Hes et al., WO 01/14330) and 2-fluorobenzenesulfonyl chloride, 8-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine was obtained as a white solid. MP.: 108.0-110.1°. prepared

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

実験手順: Using the above procedure, but starting with 8-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine (prepared by reducing 8-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one, which in turn was prepared from 2-amino-6-bromophenol and 2-bromo-2-methylproprionyl bromide via the procedure described by Van Hes et al., WO 01/14330) and 2-fluorobenzenesulfonyl chloride, 8-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine was obtained as a white solid. MP.: 108.0-110.1°. prepared

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

実験手順: 2-Amino-6-bromophenol (1.0 g, 5.32 mmol) was dissolved in DMF (20 mL), and potassium carbonate (1.6 g, 11.7 mmol) and chloroacetyl chloride (0.466 mL, 5.85 mmol) were added thereto, and stirred at room temperature overnight. After diluted with ethyl acetate, the resultant was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled away, and the residue washed with an ethyl acetate-hexane mixture solvent to thus obtain the title compound. the resultant was washed with water and saturated brine dried over anhydrous magnesium sulfate The solvent was distilled away the residue washed with an ethyl acetate-hexane mixture solvent

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

実験手順: 2-Amino-6-bromophenol (1.0 g, 5.32 mmol) was dissolved in DMF (20 mL), and potassium carbonate (1.6 g, 11.7 mmol) and chloroacetyl chloride (0.466 mL, 5.85 mmol) were added thereto, and stirred at room temperature overnight. After diluted with ethyl acetate, the resultant was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled away, and the residue washed with an ethyl acetate-hexane mixture solvent to thus obtain the title compound. the resultant was washed with water and saturated brine dried over anhydrous magnesium sulfate The solvent was distilled away the residue washed with an ethyl acetate-hexane mixture solvent

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

実験手順: 600 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride and 550 mg of 2-amino-6-bromophenol are added to a solution of 500 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate prepared in stage 2 of example 1, in 4 ml of pyridine. The reaction mixture is stirred at ambient temperature for 20 hours, and then concentrated under reduced pressure. Water and ethyl acetate are added and the resulting mixture is thus stirred for 30 minutes. The precipitate formed is filtered off, and rinsed with water, ethyl ether and petroleum ether. The solid obtained is dried under vacuum. 543 mg of N-(3-bromo-2-hydroxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a beige solid, the characteristics of which are the following: concentrated under reduced pressure Water and ethyl acetate are added the resulting mixture is thus stirred for 30 minutes The precipitate formed is filtered off rinsed with water, ethyl ether and petroleum ether The solid obtained is dried under vacuum

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

実験手順: 2-Bromo-6-nitrophenol (1.506 g, 0.0057 mol, containing 2,4-di-bromo-6-nitrophenol, 18% w/w) and sodium hydrosulfite (3.05 g, 85%, 0.015 mol) were heated at reflux in ethanol/water (50 ml of a 5:1 v/v mixture). After 2 hours, the reaction mixture was diluted with water (150 ml) and extracted with dichloromethane (3×50 ml), and ethyl acetate (100 ml). The organic extracts were combined, dried over calcium sulfate, evaporated in vacuo, and purified by flash chromatography (SiO2, petrol/ether 1:1 v/v) to furnish a mixture of the title compound and 6-amino-2,4-di-bromophenol (0.600 g, of a 76:24 w/w mixture as judged by 1 H-NMR). Yield 6-amino-2-bromophenol, 43%. extracted with dichloromethane (3×50 ml), and ethyl acetate (100 ml) dried over calcium sulfate evaporated in vacuo purified by flash chromatography (SiO2, petrol/ether 1:1 v/v) to furnish

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

実験手順: Pyridine (1.8 ml, 22.3 mmol) was added to a solution of 2-Amino-6-bromo-phenol (4.198 g, 22.3 mmol) in dry CH2Cl2 (200 ml). The mixture was cooled in ice and then a solution of 2-bromo-2-methyl-propionylbromide (2.8 ml, 22.6 mmol) was added slowly. The mixture was stirred at the room temperature for an hour and was poured into CH2Cl2 and water. The organic layer was washed with water, dried and concentrated in vacuo to yield crude 2-bromo-N-(3-bromo-2-hydroxy-phenyl)-2-methyl-propionamide, which was used directly in step 2. The mixture was cooled in ice The organic layer was washed with water dried concentrated in vacuo

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

実験手順: 2-Bromopropionyl chloride (1.47 ml, 14.6 mmol) was added dropwise to a vigorously stirred and ice-cooling mixture of 2-amino-6-bromophenol (2.74 g, 14.6 mmol) and sodium bicarbonate (3.06 g, 36.4 mmol) in ethyl acetate (50 ml)/water (15 ml). The mixture was stirred at 0° C. for 3 h and diluted with water. The aqueous layer was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under vacuum. The residue used for the following step without further purification to afford 4.71 g (99%) of the title compound. ice-cooling The mixture was stirred at 0° C. for 3 h The aqueous layer was extracted with ethyl acetate The extract was washed with brine dried over magnesium sulfate concentrated under vacuum The residue used for the following step without further purification

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

実験手順: 2-Bromopropionyl chloride (1.47 ml, 14.6 mmol) was added dropwise to a vigorously stirred and ice-cooling mixture of 2-amino-6-bromophenol (2.74 g, 14.6 mmol) and sodium bicarbonate (3.06 g, 36.4 mmol) in ethyl acetate (50 ml)/water (15 ml). The mixture was stirred at 0° C. for 3 h and diluted with water. The aqueous layer was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under vacuum. The residue used for the following step without further purification to afford 4.71 g (99%) of the title compound. ice-cooling The mixture was stirred at 0° C. for 3 h The aqueous layer was extracted with ethyl acetate The extract was washed with brine dried over magnesium sulfate concentrated under vacuum The residue used for the following step without further purification