2-氯-3-氟-6-甲氧基苯甲醛

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:

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: The title compound was prepared from 6-chloro-3-fluoro-2-methoxybenzaldehyde following the procedures for the synthesis of 5-bromo-3-[1-(2-chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine from 2-chloro-3-fluoro-6-methoxybenzaldehyde, vide supra. 6-Chloro-3-fluoro-2-methoxybenzaldehyde was prepared from the known 6-chloro-2,3-difluorobenzaldehyde by reaction with sodium methoxide in methanol. 1H NMR (300 MHz, CDCl3): δ=1.78 (d, J=7.2 Hz, 3H), 3.44 (brs, 3H), 4.94 (q, J=7.2 Hz, 1H), 6.93 (dd, J=9.0, 9.0 Hz, 1H), 7.09 (dd, J=8.7, 4.5 Hz, 1H), 7.30 (s, 1H), 7.71 (d, J=1.5 Hz, 1H), 8.28 (d, J=1.5 Hz, 1H), 9.68 (brs, 1H).

反应条件: temp:-74.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Chloro-3-fluoro-6-methoxybenzaldehyde (46.0 g, 245 mmol) was added in a three neck flask equipped with a nitrogen inlet, a thermometer and an addition funnel. DCM (800 mL) was added and cooled to −70 to −78° C. using an acetone/dry ice bath. Boron tribromide (25.4 mL, 269 mmol) was diluted in 200 mL of dichloromethane and added to the reaction mixture slowly over a period of 1 h. The reaction mixture was allowed to warm to room temperature and stirred for 16 h. Then the reaction mixture was cooled to 0° C. in an ice bath and quenched by adding methanol (150 mL) over a period of 30 minutes and stirred at room temperature for 20 min. The solvents were removed, and the residue was diluted with dichloromethane and washed with aq. sodium bicarbonate solution followed by water. The organic layer was dried over sodium sulfate, filtered and concentrated to give crude product. It was purified by column chromatography on silica gel eluting with 2→3% methanol in dichloromethane, giving 34 g (80% yield) of the title compound. 1HNMR (300 MHz, CDCl3): δ=11.68 (s, 1H), 10.39 (s, 1H), 7.26-7.35 (m, 1H), 6.86-6.90 (m, 1H). equipped with a nitrogen inlet added to the reaction mixture slowly over a period of 1 h to warm to room temperature Then the reaction mixture was cooled to 0° C. in an ice bath quenched by adding methanol (150 mL) over a period of 30 minutes stirred at room temperature for 20 min The solvents were removed the residue was diluted with dichloromethane washed with aq. sodium bicarbonate solution The organic layer was dried over sodium sulfate filtered concentrated to give crude product It was purified by column chromatography on silica gel eluting with 2→3% methanol in dichloromethane

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

实验步骤: To a solution of 3-chloro-4-fluoroanisole (28.5 g, 178 mmol) in t-butyl methyl ether (200 mL, dried over anhydrous MgSO4) at −78° C. was added 2.5 M n-butyl lithium in hexanes (107 mL, 267.5 mmol). After 3 h, methyl formate (18.76 mL) was added drop-wise while keeping the temperature below −60° C. The reaction mixture was quenched with sat. aq. ammonium chloride (250 mL) after 45 minutes and the organic layer was separated. The aq. layer was extracted with ethyl acetate (2×100 mL) and the combined organic layer was washed with water (200 mL) followed by brine, dried (Na2SO4) and concentrated to give a residue which on trituration with hexanes gave solids. The solids were filtered, taken again in hexanes and heated over steam bath. It was cooled, the light yellow desired product filtered and air dried to give the title compound. 1H NMR (400 MHz, CDCl3): δ=10.48 (d, J=0.8 Hz, 1H), 7.31 (dd, J=9.4, 7.8 Hz, 1H), 6.88 (dd, J=7.8, 3.8 Hz, 1H), 3.92 (s, 3H). the temperature below −60° C The reaction mixture was quenched with sat. aq. ammonium chloride (250 mL) after 45 minutes the organic layer was separated The aq. layer was extracted with ethyl acetate (2×100 mL) the combined organic layer was washed with water (200 mL) dried (Na2SO4) concentrated to give a residue which on trituration with hexanes gave solids The solids were filtered heated over steam bath It was cooled the light yellow desired product filtered air dried

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

实验步骤: A solution of 2-chloro-3-fluoro-6-methoxybenzaldehyde (10.55 g, 55.82 mmol), 5-bromo-7-azaindole (10.0 g, 50.76 mmol) and KOH (4.0 g, 71 mmol) in methanol (200 mL) was stirred at ambient temperature for 12 h. The reaction mixture was quenched with water and the crystallizing solid was filtered and dried to give the title compound as a white solid. 1H NMR (DMSO-d6, 300 MHz): □ δ=3.71 (s, 3H), 5.69 (d, 1H, J=6.3 Hz), 6.55 (d, 1H, J=4.5 Hz), 7.07 (dd, 1H, J=4.5, 4.2 Hz), 7.19 (s, 1H), 7.32 (t, J=8.0 Hz), 8.30 (s, 1H), 9.60 (s, 1H), 11.38 (s, br, 1H). The reaction mixture was quenched with water the crystallizing solid was filtered dried