艾沙康唑杂质66

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Bromo-1-(2,5-difluorophenyl)ethanone (1.5 g) was added to an ethanol (8.2 ml) solution of methyl 2-aminoisonicotinate (1.0 g), and the obtained mixture was then stirred in a nitrogen atmosphere at 60° C. for 18 hours. Thereafter, 2-bromo-1-(2,5-difluorophenyl)ethanone (0.77 g) was added to the reaction solution, and the obtained mixture was then stirred for 6 hours at the same temperature as described above. Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue. The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) and was then dried, so as to obtain the title compound (2.5 g) in the form of a pink solid. the obtained mixture was then stirred for 6 hours at the same temperature Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) was then dried

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Bromo-1-(2,5-difluorophenyl)ethanone (1.5 g) was added to an ethanol (8.2 ml) solution of methyl 2-aminoisonicotinate (1.0 g), and the obtained mixture was then stirred in a nitrogen atmosphere at 60° C. for 18 hours. Thereafter, 2-bromo-1-(2,5-difluorophenyl)ethanone (0.77 g) was added to the reaction solution, and the obtained mixture was then stirred for 6 hours at the same temperature as described above. Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue. The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) and was then dried, so as to obtain the title compound (2.5 g) in the form of a pink solid. the obtained mixture was then stirred for 6 hours at the same temperature Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) was then dried

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Bromo-1-(2,5-difluorophenyl)ethanone (1.5 g) was added to an ethanol (8.2 ml) solution of methyl 2-aminoisonicotinate (1.0 g), and the obtained mixture was then stirred in a nitrogen atmosphere at 60° C. for 18 hours. Thereafter, 2-bromo-1-(2,5-difluorophenyl)ethanone (0.77 g) was added to the reaction solution, and the obtained mixture was then stirred for 6 hours at the same temperature as described above. Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue. The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) and was then dried, so as to obtain the title compound (2.5 g) in the form of a pink solid. the obtained mixture was then stirred for 6 hours at the same temperature Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) was then dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of potassium carbonate (0.399 g, 2.89 mmol), 2,5-difluorophenacyl bromide (0.408 g, 1.73 mmol) and 5,6-dimethyl-2-mercaptonicotine nitrile (0.19 g, 1.16 mmol) in dry DMF (4 ml) is stirred at room temperature for 16 h. The resulting mixture is diluted with ethyl acetate and washed with water. Drying over sodium sulfate, filtering, evaporating the solvent and purification of the residue by silicagel column chromatography yields the title compound with a m.p. of 188° C. washed with water Drying over sodium sulfate filtering evaporating the solvent and purification of the residue by silicagel column chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of potassium carbonate (0.399 g, 2.89 mmol), 2,5-difluorophenacyl bromide (0.408 g, 1.73 mmol) and 5,6-dimethyl-2-mercaptonicotine nitrile (0.19 g, 1.16 mmol) in dry DMF (4 ml) is stirred at room temperature for 16 h. The resulting mixture is diluted with ethyl acetate and washed with water. Drying over sodium sulfate, filtering, evaporating the solvent and purification of the residue by silicagel column chromatography yields the title compound with a m.p. of 188° C. washed with water Drying over sodium sulfate filtering evaporating the solvent and purification of the residue by silicagel column chromatography

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Bromo-1-(2,5-difluorophenyl)ethanone (1.5 g) was added to an ethanol (8.2 ml) solution of methyl 2-aminoisonicotinate (1.0 g), and the obtained mixture was then stirred in a nitrogen atmosphere at 60° C. for 18 hours. Thereafter, 2-bromo-1-(2,5-difluorophenyl)ethanone (0.77 g) was added to the reaction solution, and the obtained mixture was then stirred for 6 hours at the same temperature as described above. Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue. The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) and was then dried, so as to obtain the title compound (2.5 g) in the form of a pink solid. the obtained mixture was then stirred for 6 hours at the same temperature Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) was then dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 10.1 g. (0.065 mole) of 3,4-difluoroacetophenone in 100 ml. of glacial acetic acid was added 3.4 ml. (0.065 mole) of bromine dropwise. When the addition was complete the solution was stirred for 0.5 hr. and then stripped to dryness under reduced pressure. The residue was dissolved in chloroform and washed with aqueous sodium bicarbonate. Evaporation of the organic phase provided 14.8 g. (97%) of colorless liquid product. Similarly prepared were 2,4-dichlorophenacyl bromide, o-ethylphenacyl bromide, p-isopropylphenacyl bromide, m-isobutylphenacyl bromide, 3,4-dimethylphenacyl bromide, m-ethoxyphenacyl bromide, p-isopropoxyphenacyl bromide, 3,4-diethoxyphenacyl bromide, and 2,5-difluorophenacyl bromide. When the addition washed with aqueous sodium bicarbonate Evaporation of the organic phase provided 14.8 g Similarly prepared

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Bromo-1-(2,5-difluorophenyl)ethanone (1.5 g) was added to an ethanol (8.2 ml) solution of methyl 2-aminoisonicotinate (1.0 g), and the obtained mixture was then stirred in a nitrogen atmosphere at 60° C. for 18 hours. Thereafter, 2-bromo-1-(2,5-difluorophenyl)ethanone (0.77 g) was added to the reaction solution, and the obtained mixture was then stirred for 6 hours at the same temperature as described above. Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue. The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) and was then dried, so as to obtain the title compound (2.5 g) in the form of a pink solid. the obtained mixture was then stirred for 6 hours at the same temperature Thereafter, the reaction solution was concentrated under reduced pressure, and ethyl acetate (10 ml) was then added to the obtained residue The precipitated solid was collected by filtration, and it was washed with ethyl acetate (15 ml) and heptane (6 ml) was then dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 10.1 g. (0.065 mole) of 3,4-difluoroacetophenone in 100 ml. of glacial acetic acid was added 3.4 ml. (0.065 mole) of bromine dropwise. When the addition was complete the solution was stirred for 0.5 hr. and then stripped to dryness under reduced pressure. The residue was dissolved in chloroform and washed with aqueous sodium bicarbonate. Evaporation of the organic phase provided 14.8 g. (97%) of colorless liquid product. Similarly prepared were 2,4-dichlorophenacyl bromide, o-ethylphenacyl bromide, p-isopropylphenacyl bromide, m-isobutylphenacyl bromide, 3,4-dimethylphenacyl bromide, m-ethoxyphenacyl bromide, p-isopropoxyphenacyl bromide, 3,4-diethoxyphenacyl bromide, and 2,5-difluorophenacyl bromide. When the addition washed with aqueous sodium bicarbonate Evaporation of the organic phase provided 14.8 g Similarly prepared

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was synthesized in analogy to Example 68, using 3-oxo-butyric acid methyl ester as compound of formula R, 2-bromo-1-(2,5-difluorophenyl)-ethanone as compound of formula S, c-cyclohexyl-methylamine as R3—(CH2)m—NH2 and cis-2-aminomethyl-1-cyclohexanol as R1R2NH, MS (ISP) 445.4 (M+H)+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was synthesized in analogy to Example 68, using 3-oxo-butyric acid methyl ester as compound of formula R, 2-bromo-1-(2,5-difluorophenyl)-ethanone as compound of formula S, c-cyclohexyl-methylamine as R3—(CH2)m—NH2 and trans-2-aminomethyl-1-cyclohexanol as R1R2NH, MS (ISP) 445.5 (M+H)+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was synthesized in analogy to Example 68, using 3-oxo-butyric acid methyl ester as compound of formula R, 2-bromo-1-(2,5-difluorophenyl)-ethanone as compound of formula S, c-cyclohexyl-methylamine as R3—(CH2)m—NH2 and cis-2-aminomethyl-1-cyclohexanol as R1R2NH, MS (ISP) 445.4 (M+H)+.