6-amino-2,3-difluorophenol

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: The urea was prepared from 2-hydroxy 3,4-difluoro aniline (0.290 g, 2 mmol) and 2-bromo phenyl isocyanate (0.4 g) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane (0.254 g, 37%). EI-MS m/z 343 (M+H)+ It was purified by dilution with methylene chloride and precipitation with hexane (0.254 g, 37%)

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

実験手順: 2,3 difluoro 6-nitro phenol (2 g, 11 mmol) was treated with 10% Pd/C (1 g) at 23° C. The reaction mixture was flushed with hydrogen gas and the reaction was allowed to stir 12 h before it was filtered through celite. The filtrate was concentrated in vacuo to afforded the title compound (1.6 g, 97%). EI-MS m/z 146 (M+H)+ The reaction mixture was flushed with hydrogen gas was filtered through celite The filtrate was concentrated in vacuo

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

実験手順: 6-Amino-2,3-diflourophenol (81KK30a) (0.113 g, 0.78 mmol), 2-chloroacetyl chloride (0.10 g, 0.89 mmol) and K2CO3 (0.226 g, 1.6 mmol) were mixed according to GP1 to give the title compound as a crude (81MF2082A) (0.12 g)

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

実験手順: 6-Amino-2,3-diflourophenol (81KK30a) (0.113 g, 0.78 mmol), 2-chloroacetyl chloride (0.10 g, 0.89 mmol) and K2CO3 (0.226 g, 1.6 mmol) were mixed according to GP1 to give the title compound as a crude (81MF2082A) (0.12 g)

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2-amino-5-bromo-pyridine-3-carboxylic acid (1 g) and 6-amino-2,3-difluoro-phenol (0.669 g) placed in a round bottom flask was added polyphosphoric acid (10 g). The mixture was heated at 200° C. for 5 hours. A homogenous black mixture was obtained. The mixture was diluted in water and neutralizing to pH 8 with NaOH 2N. The heterogeneous mixture was diluted with dichloromethane. The insoluble was filtered. The organic phase was separated. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with brine, dried on sodium sulfate, evaporated and dried to afford 5-bromo-3-(6,7-difluoro-1,3-benzoxazol-2-yl)pyridin-2-amine (0.338 g). NMR Spectrum: (DMSOd6) 7.54 (ddd, 1H), 7.70 (ddd, 1H), 7.79 (bs, 2H), 8.34 (d, 1H), 8.38 (d, 1H); Mass spectrum: M+H+ 326-328 placed in a round bottom flask A homogenous black mixture was obtained The insoluble was filtered The organic phase was separated The aqueous phase was extracted twice with dichloromethane The combined organic phases were washed with brine dried on sodium sulfate evaporated dried

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2-amino-5-bromo-pyridine-3-carboxylic acid (1 g) and 6-amino-2,3-difluoro-phenol (0.669 g) placed in a round bottom flask was added polyphosphoric acid (10 g). The mixture was heated at 200° C. for 5 hours. A homogenous black mixture was obtained. The mixture was diluted in water and neutralizing to pH 8 with NaOH 2N. The heterogeneous mixture was diluted with dichloromethane. The insoluble was filtered. The organic phase was separated. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with brine, dried on sodium sulfate, evaporated and dried to afford 5-bromo-3-(6,7-difluoro-1,3-benzoxazol-2-yl)pyridin-2-amine (0.338 g). NMR Spectrum: (DMSOd6) 7.54 (ddd, 1H), 7.70 (ddd, 1H), 7.79 (bs, 2H), 8.34 (d, 1H), 8.38 (d, 1H); Mass spectrum: M+H+ 326-328 placed in a round bottom flask A homogenous black mixture was obtained The insoluble was filtered The organic phase was separated The aqueous phase was extracted twice with dichloromethane The combined organic phases were washed with brine dried on sodium sulfate evaporated dried

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

実験手順: Prepared by the method of Example 15a), from 2-amino-5,6-difluorophenol (334 mg, 2.3 mmol) and 2-fluoro-5-nitrobenzoyl chloride (468 mg, 2.3 mmol) the subtitle compound was obtained. The product was used directly in the next step without purification.

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

実験手順: The urea was prepared from 2-hydroxy 3,4-difluoro aniline(0.290 g, 2 mmol) and 2-bromophenylisocyanate(0.4 g) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane(0.254 g, 37%). EI-MS m/z 343(M+H)+. It was purified by dilution with methylene chloride and precipitation with hexane(0.254 g, 37%)

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

実験手順: 2,3 difluoro 6-nitrophenol (2 g, 11 mmol) was treated with 10% Pd/C(1 g) at 23° C. The reaction mixture was flushed with hydrogen gas and the reaction was allowed to stir 12 h before it was filtered through celite. The filtrate was concentrated in vacuo to afforded the title compound (1.6 g, 97%). EI-MS m/z 146(M+H)+. The reaction mixture was flushed with hydrogen gas was filtered through celite The filtrate was concentrated in vacuo

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

実験手順: 2,3 difluoro 6-nitrophenol (2 g, 11 mmol) was treated with 10% Pd/C(1 g) at 23° C. The reaction mixture was flushed with hydrogen gas and the reaction was allowed to stir 12 h before it was filtered through celite. The filtrate was concentrated in vacuo to afforded the title compound (1.6 g, 97%). EI-MS m/z 146(M+H)+. The reaction mixture was flushed with hydrogen gas was filtered through celite The filtrate was concentrated in vacuo

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

実験手順: 13.44 ml (66.34 mmol) of diethyl ethoxymethylenmalonate of are added to a solution of 9.6 g (66.34 mmol) of 3,4-difluoro-2-hydroxy-aniline [3] in 50 ml of n-heptane. The reaction mixture is reflux heated for 1 hour and then cooled at room temperature until a precipitate is obtained which is filtered at vacuum and washed with 20 ml of n-heptane. 17.5 g (81%) of diethyl (3,4-difluoro-2-hydroxyaniline)-methylenmalonate [4] are obtained and it does not need to be subject to a subsequent purification treatment. The reaction mixture is reflux heated for 1 hour is obtained which is filtered at vacuum washed with 20 ml of n-heptane