methyl 4-amino-2-fluorobenzoate

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:

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

実験手順: Sodium nitrite (0.54 g, 8.0 mmol) was added portion wise to a stirred solution of methyl 4-amino-2-fluorobenzoate (1.0 g, 6.0 mmol) in acetic acid (7 ml) and HCl (concentrated, 2.5 ml) while maintaining the temperature below 15° C. This solution was then added drop wise to a stirred solution of saturated sulfur dioxide, copper (II) chloride (0.25 g, 1.0 mmol) and water (0.5 ml) in acetic acid (5 ml) at 5° C. The reaction mixture was allowed to warm to room temperature and poured over ice water and stirred for a further 15 minutes. The resulting precipitate was collected by filtration, washed with water and dried overnight in a vacuum oven to give the title compound (1.5 g, 55% yield) as a pale brown solid which was used without further purification. while maintaining the temperature below 15° C The resulting precipitate was collected by filtration washed with water dried overnight in a vacuum oven

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: In the same manner as that of Example 24, 4,5-diisopropylthiophene-2-carboxylic acid (80 mg, 0.377 mmol) and methyl 2-fluoro-4-aminobenzoate (115 mg, 0.680 mmol) were condensed, the reaction mixture was treated in a conventional manner, and then the residue was purified by silica gel chromatography [n-hexane-ethyl acetate (40:1)] and recrystallized to obtain methyl 2-fluoro-4-[(4,5-diisopropylthiophene-2-carbonyl)amino]benzoate (45 mg, 33%) as colorless prisms. condensed the reaction mixture was treated in a conventional manner the residue was purified by silica gel chromatography [n-hexane-ethyl acetate (40:1)] recrystallized

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

実験手順: In the same manner as that of Example 24, 4,5-diisopropylthiophene-2-carboxylic acid (80 mg, 0.377 mmol) and methyl 2-fluoro-4-aminobenzoate (115 mg, 0.680 mmol) were condensed, the reaction mixture was treated in a conventional manner, and then the residue was purified by silica gel chromatography [n-hexane-ethyl acetate (40:1)] and recrystallized to obtain methyl 2-fluoro-4-[(4,5-diisopropylthiophene-2-carbonyl)amino]benzoate (45 mg, 33%) as colorless prisms. condensed the reaction mixture was treated in a conventional manner the residue was purified by silica gel chromatography [n-hexane-ethyl acetate (40:1)] recrystallized

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

実験手順: In the same manner as that of Example 2, 4,5-diisopropylfuran-2-carboxylic acid (80 mg, 0.408 mmol) and methyl 2-fluoro-4-aminobenzoate (125 mg, 0.739 mmol) were condensed, the reaction mixture was treated in a conventional manner, and then the residue was purified by silica gel chromatography [hexane-ethyl acetate (40:1)] and recrystallized to obtain methyl 2-fluoro-4-[(4,5-diisopropylfuran-2-carbonyl)amino]benzoate (95 mg, 67%) as colorless prisms. condensed the reaction mixture was treated in a conventional manner the residue was purified by silica gel chromatography [hexane-ethyl acetate (40:1)] recrystallized

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

実験手順: Prepared using General Procedures 6 and 9. To a stirring solution of 2-(4-methoxy-2-(trifluoromethyl)phenyl)acetic acid (500 mg, 2.13 mmol) and methyl 4-amino-2-fluorobenzoate (361 mg, 2.13 mmol) in DMF (5 mL) were added HATU (852 mg, 2.24 mmol) and TEA (744 μl, 5.34 mmol). After stirring at room temperature for 18 h the reaction mixture was diluted with EA (20 mL) and washed with NaHCO3 (2×20 mL) and 1 M HCl (2×20 mL). The organic phase was concentrated in vacuo to afford an orange solid which was dissolved in THF (5 mL) and MeOH (2 mL) and 1 M LiOH (4.3 μL, 4.27 mmol) was added. After stirring at room temperature for 2 h the reaction mixture was concentrated in vacuo, the residue dissolved in water (10 mL) and acidified to pH 1 using 1 M HCl. A white precipitate was formed and the mixture was filtered under vacuum. The captured solid was washed with MeOH (5 mL) to afford a pale brown solid. The solid was triturated with MeOH (5 mL) to afford 198 mg (25%) of 2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid INT-78 as a white solid. LCMS-ESI (m/z) calculated for C17H13F4NO4: 371; found 372 [M+H]+, tR=1.94 min (Method 10). Prepared washed with NaHCO3 (2×20 mL) and 1 M HCl (2×20 mL) The organic phase was concentrated in vacuo to afford an orange solid which After stirring at room temperature for 2 h the reaction mixture was concentrated in vacuo the residue dissolved in water (10 mL) A white precipitate was formed the mixture was filtered under vacuum The captured solid was washed with MeOH (5 mL) to afford a pale brown solid The solid was triturated with MeOH (5 mL)

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

実験手順: The titled compound was prepared following the procedure A using 4-[(4-butylphenyl)ethynyl]benzaldehyde and methyl 4-amino-2-fluorobenzoate as a beige powder (63%). M− (ESI): 414.1; M+ (ESI): 416.9. HPLC, Rt: 5.58 min (Purity: 96.9%).