[5-chloro-2-(trifluoromethoxy)phenyl]boronic acid

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

実験手順: Under argon (in a flask dried by heating), 125 mg (0.28 mmol) of tert-butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate), 80 mg (0.33 mmol, 1.2 eq.) of 5-chloro-2-trifluoromethoxyphenylboronic acid, 115 mg (0.83 mmol, 3.0 eq.) of potassium carbonate and 23 mg (0.03 mmol, 0.1 eq.) of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were suspended in 5.0 ml of dioxane and stirred overnight in an oil bath already preheated to 110° C. The reaction mixture was filtered through Celite and the residue was washed with dioxane. The combined filtrates were concentrated under reduced pressure. The residue was triturated with water, filtered off, washed with water and dried under reduced pressure. Yield: 155 mg (purity 83%, 82% of theory) already preheated to 110° C The reaction mixture was filtered through Celite the residue was washed with dioxane The combined filtrates were concentrated under reduced pressure The residue was triturated with water filtered off washed with water dried under reduced pressure

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

実験手順: 127 mg (purity 70%, 0.2 mmol) of tert-butyl 4-{[2-(4-bromo-5-cyano-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate) and 58 mg (0.24 mmol) of 5-chloro-2-trifluoromethoxyphenylboronic acid in the presence of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were reacted according to General Method 2A. Yield: 107 mg (purity 94%, 89% of theory)

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

実験手順: 110 mg (purity 80%, 0.19 mmol) of tert-butyl 4-{[2-(4-bromo-2-oxopyridin-1(2H)-yl)-3-cyclopropylpropanoyl]amino}benzoate (racemate), 46 mg (0.19 mmol) of 5-chloro-2-trifluoromethoxyphenylboronic acid and 22 mg (0.02 mmol) of tetrakis(triphenylphosphine)palladium(0) were taken up in 2.5 ml of dioxane and 2.5 ml of saturated aqueous sodium carbonate solution and irradiated in a microwave at 130° C. for 12 min. The crude product was purified by flash chromatography (silica gel 60, cyclohexane/ethyl acetate mixtures). Yield: 77 mg (purity 92%, 64% of theory) The crude product was purified by flash chromatography (silica gel 60, cyclohexane/ethyl acetate mixtures)

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

実験手順: To a solution of the 4-chloro(trifluoromethoxy)benzene (2.0 g, 10.18 mmol) in dry tetrahydrofuran (THF, 30 ml) at −78° C., was added ethylenediaminetetraacetic acid (EDTA, 1.24 g, 10.7 mmol) followed by a 1.3 M solution of sec-butyllithium in cyclohexane (7.63 ml, 10.7 mmol) and the reaction stirred for 2 hours under nitrogen. To this reaction mixture at −78° C., was then added dropwise the preformed dimethoxyfluoroborane mixture. The reaction was stirred at −78° C. for 30 minutes, warmed to room temperature for 30 minutes, and then quenched with water (10 ml). The reaction mixture was extracted with diethyl ether (4×50 ml). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. To purify, the residue was dissolved in diethyl ether (10 ml) and washed with an aqueous solution of 10% NaOH (50 ml). The aqueous layer was acidified and extracted with ethyl acetate (3×40 ml). The combined ethyl acetate extracts were dried over MgSO4 and concentrated in vacuo to afford a mixture of the title compound and its corresponding regioisomer as a white solid (0.862 g). The reaction was stirred at −78° C. for 30 minutes quenched with water (10 ml) The reaction mixture was extracted with diethyl ether (4×50 ml) The combined organic extracts were dried over MgSO4 concentrated in vacuo To purify the residue was dissolved in diethyl ether (10 ml) washed with an aqueous solution of 10% NaOH (50 ml) extracted with ethyl acetate (3×40 ml) The combined ethyl acetate extracts were dried over MgSO4 concentrated in vacuo to afford

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

実験手順: Under argon (in a flask dried by heating), 125 mg (0.28 mmol) of tert-butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate), 80 mg (0.33 mmol, 1.2 eq.) of 5-chloro-2-trifluoromethoxyphenylboronic acid, 115 mg (0.83 mmol, 3.0 eq.) of potassium carbonate and 23 mg (0.03 mmol, 0.1 eq.) of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were suspended in 5.0 ml of dioxane and stirred overnight in an oil bath already preheated to 110° C. The reaction mixture was filtered through Celite and the residue was washed with dioxane. The combined filtrates were concentrated under reduced pressure. The residue was triturated with water, filtered off, washed with water and dried under reduced pressure. Yield: 155 mg (purity 83%, 82% of theory) already preheated to 110° C The reaction mixture was filtered through Celite the residue was washed with dioxane The combined filtrates were concentrated under reduced pressure The residue was triturated with water filtered off washed with water dried under reduced pressure

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

実験手順: 127 mg (purity 70%, 0.2 mmol) of tert-butyl 4-{[2-(4-bromo-5-cyano-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate) and 58 mg (0.24 mmol) of 5-chloro-2-trifluoromethoxyphenylboronic acid in the presence of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were reacted according to General Method 2A. Yield: 107 mg (purity 94%, 89% of theory)

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

実験手順: 110 mg (purity 80%, 0.19 mmol) of tert-butyl 4-{[2-(4-bromo-2-oxopyridin-1(2H)-yl)-3-cyclopropylpropanoyl]amino}benzoate (racemate), 46 mg (0.19 mmol) of 5-chloro-2-trifluoromethoxyphenylboronic acid and 22 mg (0.02 mmol) of tetrakis(triphenylphosphine)palladium(0) were taken up in 2.5 ml of dioxane and 2.5 ml of saturated aqueous sodium carbonate solution and irradiated in a microwave at 130° C. for 12 min. The crude product was purified by flash chromatography (silica gel 60, cyclohexane/ethyl acetate mixtures). Yield: 77 mg (purity 92%, 64% of theory) The crude product was purified by flash chromatography (silica gel 60, cyclohexane/ethyl acetate mixtures)

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

実験手順: Under argon (in a flask dried by heating), 125 mg (0.28 mmol) of tert-butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate), 80 mg (0.33 mmol, 1.2 eq.) of 5-chloro-2-trifluoromethoxyphenylboronic acid, 115 mg (0.83 mmol, 3.0 eq.) of potassium carbonate and 23 mg (0.03 mmol, 0.1 eq.) of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were suspended in 5.0 ml of dioxane and stirred overnight in an oil bath already preheated to 110° C. The reaction mixture was filtered through Celite and the residue was washed with dioxane. The combined filtrates were concentrated under reduced pressure. The residue was triturated with water, filtered off, washed with water and dried under reduced pressure. Yield: 155 mg (purity 83%, 82% of theory) already preheated to 110° C The reaction mixture was filtered through Celite the residue was washed with dioxane The combined filtrates were concentrated under reduced pressure The residue was triturated with water filtered off washed with water dried under reduced pressure

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

実験手順: 127 mg (purity 70%, 0.2 mmol) of tert-butyl 4-{[2-(4-bromo-5-cyano-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate) and 58 mg (0.24 mmol) of 5-chloro-2-trifluoromethoxyphenylboronic acid in the presence of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were reacted according to General Method 2A. Yield: 107 mg (purity 94%, 89% of theory)

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

実験手順: 110 mg (purity 80%, 0.19 mmol) of tert-butyl 4-{[2-(4-bromo-2-oxopyridin-1(2H)-yl)-3-cyclopropylpropanoyl]amino}benzoate (racemate), 46 mg (0.19 mmol) of 5-chloro-2-trifluoromethoxyphenylboronic acid and 22 mg (0.02 mmol) of tetrakis(triphenylphosphine)palladium(0) were taken up in 2.5 ml of dioxane and 2.5 ml of saturated aqueous sodium carbonate solution and irradiated in a microwave at 130° C. for 12 min. The crude product was purified by flash chromatography (silica gel 60, cyclohexane/ethyl acetate mixtures). Yield: 77 mg (purity 92%, 64% of theory) The crude product was purified by flash chromatography (silica gel 60, cyclohexane/ethyl acetate mixtures)

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

実験手順: To a solution of the 4-chloro(trifluoromethoxy)benzene (2.0 g, 10.18 mmol) in dry tetrahydrofuran (THF, 30 ml) at −78° C., was added ethylenediaminetetraacetic acid (EDTA, 1.24 g, 10.7 mmol) followed by a 1.3 M solution of sec-butyllithium in cyclohexane (7.63 ml, 10.7 mmol) and the reaction stirred for 2 hours under nitrogen. To this reaction mixture at −78° C., was then added dropwise the preformed dimethoxyfluoroborane mixture. The reaction was stirred at −78° C. for 30 minutes, warmed to room temperature for 30 minutes, and then quenched with water (10 ml). The reaction mixture was extracted with diethyl ether (4×50 ml). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. To purify, the residue was dissolved in diethyl ether (10 ml) and washed with an aqueous solution of 10% NaOH (50 ml). The aqueous layer was acidified and extracted with ethyl acetate (3×40 ml). The combined ethyl acetate extracts were dried over MgSO4 and concentrated in vacuo to afford a mixture of the title compound and its corresponding regioisomer as a white solid (0.862 g). The reaction was stirred at −78° C. for 30 minutes quenched with water (10 ml) The reaction mixture was extracted with diethyl ether (4×50 ml) The combined organic extracts were dried over MgSO4 concentrated in vacuo To purify the residue was dissolved in diethyl ether (10 ml) washed with an aqueous solution of 10% NaOH (50 ml) extracted with ethyl acetate (3×40 ml) The combined ethyl acetate extracts were dried over MgSO4 concentrated in vacuo to afford