3,5-二氯-4-乙氧基苯胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: Trifluoroacetic acid (5 mL) is added to solid (3,5-dichloro-4-ethoxy-phenyl)-carbamic acid tert-butyl ester (0.97 g) and the mixture is stirred for approximately 45 minutes at room temperature. Water is then added, and the mixture is cooled in an ice bath and basified with solid potassium carbonate. The solution is extracted three times with ethyl acetate and the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate. Concentration under reduced pressure and recrystallization from hexanes provides the desired product as a pale yellow crystalline solid. the mixture is cooled in an ice bath The solution is extracted three times with ethyl acetate the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate Concentration under reduced pressure and recrystallization from hexanes

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

实验步骤: Trifluoroacetic acid (5 mL) is added to solid (3,5-dichloro-4-ethoxy-phenyl)-carbamic acid tert-butyl ester (0.97 g) and the mixture is stirred for approximately 45 minutes at room temperature. Water is then added, and the mixture is cooled in an ice bath and basified with solid potassium carbonate. The solution is extracted three times with ethyl acetate and the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate. Concentration under reduced pressure and recrystallization from hexanes provides the desired product as a pale yellow crystalline solid. the mixture is cooled in an ice bath The solution is extracted three times with ethyl acetate the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate Concentration under reduced pressure and recrystallization from hexanes

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

实验步骤: Trifluoroacetic acid(5 mL) is added to solid (3,5-dichloro-4-ethoxy-phenyl)-carbamic acid tert-butyl ester (0.97 g) and the mixture is stirred for approximately 45 minutes at room temperature. Water is then added, and the mixture is cooled in an ice bath and basified with solid potassium carbonate. The solution is extracted three times with ethyl acetate and the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate. Concentration under reduced pressure and recrystallization from hexanes provides the desired product as a pale yellow crystalline solid. the mixture is cooled in an ice bath The solution is extracted three times with ethyl acetate the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate Concentration under reduced pressure and recrystallization from hexanes

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

实验步骤: Trifluoroacetic acid (5 mL) is added to solid (3,5-dichloro-4-ethoxy-phenyl)-carbamic acid tert-butyl ester (0.97 g) and the mixture is stirred for approximately 45 minutes at room temperature. Water is then added, and the mixture is cooled in an ice bath and basified with solid potassium carbonate. The solution is extracted three times with ethyl acetate and the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate. Concentration under reduced pressure and recrystallization from hexanes provides the desired product as a pale yellow crystalline solid. the mixture is cooled in an ice bath The solution is extracted three times with ethyl acetate the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate Concentration under reduced pressure and recrystallization from hexanes

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

实验步骤: Trifluoroacetic acid (5 mL) is added to solid (3,5-dichloro-4-ethoxy-phenyl)-carbamic acid tert-butyl ester (0.97 g) and the mixture is stirred for approximately 45 minutes at room temperature. Water is then added, and the mixture is cooled in an ice bath and basified with solid potassium carbonate. The solution is extracted three times with ethyl acetate and the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate. Concentration under reduced pressure and recrystallization from hexanes provides the desired product as a pale yellow crystalline solid. the mixture is cooled in an ice bath The solution is extracted three times with ethyl acetate the combined organic phases are washed with saturated aqueous sodium chloride then dried over anhydrous sodium sulfate Concentration under reduced pressure and recrystallization from hexanes

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

实验步骤: 5-(Methoxycarbonyl)-2-pyridine carboxylic acid (50 mg, 276 μmol) was dissolved in DMF (2 mL) and treated with CDI (60 mg, 370 μmol). The reaction mixture was stirred at RT for 2 h. 3,5-Dichloro-4-ethoxyaniline (2) (57 mg, 276 μmol) and DIPEA (96 μL, 552 μmol) were added sequentially and the reaction mixture was stirred at RT overnight, then at 70° C. for 19 h. The reaction mixture was partitioned between EtOAc and aqueous HCl (1 M). The organic layer was washed successively with water and brine, and then dried over MgSO4, filtered and concentrated in vacuo. The residue was crystallised from methanol to afford methyl 6-(3,5-dichloro-4-ethoxyphenylcarbamoyl)nicotinate (3) (46 mg, 45%) as a white solid: m/z 369 [M+H]+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 11.12 (1H, s), 9.18 (1H, dd), 8.55 (1H, dd), 8.29 (1H, dd), 8.13 (2H, s), 4.06 (2H, q), 3.94 (3H, s), 1.37 (3H, t). the reaction mixture was stirred at RT overnight at 70° C. for 19 h The reaction mixture was partitioned between EtOAc and aqueous HCl (1 M) The organic layer was washed successively with water and brine dried over MgSO4 filtered concentrated in vacuo The residue was crystallised from methanol

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Amino-2,6-dichlorophenol (1) (1.00 g, 5.62 mmol) was dissolved in dry DMF (9 mL) and cooled to 0° C. Sodium hydride (142 mg, 5.90 mmol) was added to the mixture portionwise. The dark purple solution was stirred for 1 h at RT, then iodoethane (468 μL, 5.79 mmol) was added. The reaction mixture was stirred for 3 h and partitioned between EtOAc and aqueous NaOH (1 M). The organic layer was washed successively with water and brine, and then dried over MgSO4, filtered and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography (5% EtOAc/isohexane) to afford 3,5-dichloro-4-ethoxyaniline (2) (460 mg, 40%): m/z 206 [M+H]+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 6.60 (2H, s), 4.01 (2H, q), 3.60 (2H, s), 1.42 (3H, t). The reaction mixture was stirred for 3 h partitioned between EtOAc and aqueous NaOH (1 M) The organic layer was washed successively with water and brine dried over MgSO4 filtered the solvent evaporated in vacuo The residue was purified by silica gel chromatography (5% EtOAc/isohexane)

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: 5-(Methoxycarbonyl)-2-pyridine carboxylic acid (50 mg, 276 μmol) was dissolved in DMF (2 mL) and treated with CDI (60 mg, 370 μmol). The reaction mixture was stirred at RT for 2 h. 3,5-Dichloro-4-ethoxyaniline (2) (57 mg, 276 μmol) and DIPEA (96 μL, 552 μmol) were added sequentially and the reaction mixture was stirred at RT overnight, then at 70° C. for 19 h. The reaction mixture was partitioned between EtOAc and aqueous HCl (1 M). The organic layer was washed successively with water and brine, and then dried over MgSO4, filtered and concentrated in vacuo. The residue was crystallised from methanol to afford methyl 6-(3,5-dichloro-4-ethoxyphenylcarbamoyl)nicotinate (3) (46 mg, 45%) as a white solid: m/z 369 [M+H]+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 11.12 (1H, s), 9.18 (1H, dd), 8.55 (1H, dd), 8.29 (1H, dd), 8.13 (2H, s), 4.06 (2H, q), 3.94 (3H, s), 1.37 (3H, t). the reaction mixture was stirred at RT overnight at 70° C. for 19 h The reaction mixture was partitioned between EtOAc and aqueous HCl (1 M) The organic layer was washed successively with water and brine dried over MgSO4 filtered concentrated in vacuo The residue was crystallised from methanol

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Amino-2,6-dichlorophenol (1) (1.00 g, 5.62 mmol) was dissolved in dry DMF (9 mL) and cooled to 0° C. Sodium hydride (142 mg, 5.90 mmol) was added to the mixture portionwise. The dark purple solution was stirred for 1 h at RT, then iodoethane (468 μL, 5.79 mmol) was added. The reaction mixture was stirred for 3 h and partitioned between EtOAc and aqueous NaOH (1 M). The organic layer was washed successively with water and brine, and then dried over MgSO4, filtered and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography (5% EtOAc/isohexane) to afford 3,5-dichloro-4-ethoxyaniline (2) (460 mg, 40%): m/z 206 [M+H]+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 6.60 (2H, s), 4.01 (2H, q), 3.60 (2H, s), 1.42 (3H, t). The reaction mixture was stirred for 3 h partitioned between EtOAc and aqueous NaOH (1 M) The organic layer was washed successively with water and brine dried over MgSO4 filtered the solvent evaporated in vacuo The residue was purified by silica gel chromatography (5% EtOAc/isohexane)