2-phenoxyacetamide

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: 3.0 g of 2-(phenoxy)acetamide was dissolved in 10 ml of dichloromethane and 6 ml of chlorosulfonic acid was slowly added at 0 ° C. The reaction mixture was stirred at room temperature for 10 hr. Dichloromethane was evaporated under reduced pressure. Residual material was poured on chopped ice. Solid was collected by filtration and dried in vacuo. 3.9 g of product was obtained. M.P. 166-171° C. (decomposition) Dichloromethane was evaporated under reduced pressure Residual material was poured on chopped ice Solid was collected by filtration dried in vacuo

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

実験手順: 3.0 g of 2-(phenoxy)acetamide was dissolved in 10 ml of dichloromethane and 6 ml of chlorosulfonic acid was slowly added at 0 ° C. The reaction mixture was stirred at room temperature for 10 hr. Dichloromethane was evaporated under reduced pressure. Residual material was poured on chopped ice. Solid was collected by filtration and dried in vacuo. 3.9 g of product was obtained. M.P. 166-171° C. (decomposition) Dichloromethane was evaporated under reduced pressure Residual material was poured on chopped ice Solid was collected by filtration dried in vacuo

反応条件: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of phenoxyacetyl chloride (6.18 g, 36.2 mmol) in 175 mL of THF was added 75 mL of NH4OH over 15 minutes. The reaction was stirred for 16 hours at 23° C. then concentrated under reduced pressure. The crude product was dissolved in 200 mL of EtOAc and washed with 100 mL of 2 N HCL, 100 mL NaHCO3, and 100 mL of brine. The organic phase was dried over Na2SO4 and concentrated. The product was purified by recrystallization from EtOAc/hexanes to provide 4.05 g (74% yield) of the desired product as a white powder. then concentrated under reduced pressure The crude product was dissolved in 200 mL of EtOAc washed with 100 mL of 2 N HCL, 100 mL NaHCO3, and 100 mL of brine The organic phase was dried over Na2SO4 concentrated The product was purified by recrystallization from EtOAc/hexanes

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Palladium (II) acetate (36 mg, 0.16 mmol) was added to a suspension of 3-chloro-1-(4-fluoro-phenyl)-1H-pyrazin-2-one (0.71 g, 3.2 mmol), phenoxyacetamide (0.57 g, 3.8 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.138 g, 0.24 mmol) and Cs2CO3 (1.5 g, 4.45 mmol) in 1,4-dioxane (10 mL). The mixture was stirred at 80° C. for 15 minutes. Then DCM was added, the solid was filtered off and washed with more DCM. The filtrate was separated and the solvent evaporated in vacuo and the crude product was purified by flash column chromatography (silica; AcOEt in DCM 1/99 to 1/4). The desired fractions were collected and the solvents evaporated in vacuo to yield N-[4-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-phenoxy-acetamide (0.38 g, 84% yield). the solid was filtered off washed with more DCM The filtrate was separated the solvent evaporated in vacuo the crude product was purified by flash column chromatography (silica; AcOEt in DCM 1/99 to 1/4) The desired fractions were collected the solvents evaporated in vacuo

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

実験手順: DMF (20 ml) was added to 1-(4-hydroxyphenyl)ethanone (1.81 g, 13.3 mmol), 2-bromo-N-(4-bromophenyl)acetamide (3.00 g, 10.2 mmol), and potassium carbonate (4.25 g, 30.7 mmol), and the mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by alumina column chromatography (developing solvent; ethyl acetate), and powderized with ethyl acetate-diisopropyl ether (1:5) to give a phenoxyacetamide derivative (3.44 g). The title compound was obtained by similar operations as in Reference Example 20, Reference Example 21, Example 10 and Example 6 and using this compound. washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the obtained residue was purified by alumina column chromatography (developing solvent; ethyl acetate)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4-hydroxy-3-methoxybenzaldehyde (2.02 g, 13.3 mmol), 2-bromo-N-(4-bromophenyl)acetamide (3.00 g, 10.2 mmol) and potassium carbonate (2.12 g, 15.4 mmol) was added propionitrile (10 ml), and the mixture was stirred at 80° C. for one day. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by alumina column chromatography (developing solvent; ethyl acetate), and powderized with ethyl acetate-diisopropyl ether (1:5) to give a phenoxyacetamide derivative (2.93 g). The title compound was obtained by similar operations as in Reference Example 43 and Example 6 and using this compound. washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the obtained residue was purified by alumina column chromatography (developing solvent; ethyl acetate)

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

実験手順: To a solution of phenoxyacetamide (50 g, 0.333 mol) in dichloromethane (500 mL) was added dropwise chlorosulfonic acid (174.7 g, 1.5 mol) at 0° C. at such a rate to maintain internal temperature between 0 to +5° C. (about 45 min). Some solid formed during this addition. The cooling bath was removed and the reaction mixture was stirred at room temperature overnight. The lower layer in the reaction mixture was added into a vigorously stirring mixture of water (500 mL) and crushed-ice (1500 g). The solid was collected, washed with water (750 mL), and pressed well with a rubber dam. The solid was suspended in acetone (100 mL), stirred for 30 min and collected. After drying, the title compound was isolated as a white solid, weighed 67.3 g (81%). to maintain internal temperature between 0 to +5° C. (about 45 min) Some solid formed during this addition The cooling bath was removed The lower layer in the reaction mixture was added into a vigorously stirring mixture of water (500 mL) crushed-ice (1500 g) The solid was collected washed with water (750 mL) stirred for 30 min collected After drying

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

実験手順: 3.0 g of 2-(phenoxy)acetamide was dissolved in 10 ml of dichloromethane and 6 ml of chlorosulfonic acid was slowly added at 0 ° C. The reaction mixture was stirred at room temperature for 10 hr. Dichloromethane was evaporated under reduced pressure. Residual material was poured on chopped ice. Solid was collected by filtration and dried in vacuo. 3.9 g of product was obtained. M.P. 166-171° C. (decomposition) Dichloromethane was evaporated under reduced pressure Residual material was poured on chopped ice Solid was collected by filtration dried in vacuo