2-(2,6-difluoro-3,5-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

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

実験手順: A mixture of 6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridine (333 mg, 1.40 mmol), 2-(2,6-difluoro-3,5-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (400.0 mg, 1.333 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (21.0 mg, 0.0266 mmol), and potassium phosphate (566 mg, 2.66 mmol) in tetrahydrofuran (3 mL) and water (5.5 mL) in a reaction vial was degassed and sealed. The mixture was stirred at r.t. for 30 min. The mixture was extracted with ethyl acetate. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (gradient: 0-50%) to afford the desired product (0.38 g, 76%). LCMS (M+H)+=376.1. vial was degassed sealed The mixture was extracted with ethyl acetate The organic layer was dried over MgSO4 filtered concentrated under reduced pressure The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (gradient: 0-50%)

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (477 mg, 2.00 mmol), 2-(2,6-difluoro-3,5-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (600. mg, 2.00 mmol), bis(tri-t-butylphosphine)palladium (150.0 mg, 0.300 mmol) and diisopropylethylamine (0.700 mL, 4.02 mmol) in 1,4-dioxane (20 mL) was degassed and recharged with nitrogen for three times. The mixture was stirred at 125° C. overnight. The solvent was removed under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (gradient: 0-50%) to afford the desired product (0.30 g, 40%). LCMS (M+H)+=377.2. was degassed The solvent was removed under reduced pressure The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (gradient: 0-50%)

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

実験手順: To a solution of 2,4-difluoro-3-iodo-1,5-dimethoxybenzene (1.50 g, 5.00 mmol) in tetrahedrofuran (THF, 20 mL) was slowly added 2.0 M isopropyl magnesium chloride in THF (2.87 mL, 5.75 mmol) at −10° C. under an atmosphere of nitrogen. After 10 min., 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.27 mL, 6.25 mmol)(Aldrich, Cat. No. 417149) was added. The reaction mixture was then stirred at ambient temperature for 2 h. The mixture was quenched with sat. NH4Cl, and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue (solid) was treated with ethyl ether, filtered, and dried under reduced pressure to afford the desired product (1.20 g, 80%). 1H-NMR (400 MHz, CDCl3): 6.70 (t, J=8.2 Hz, 1H), 3.85 (s, 6H), 1.38 (s, 12H). LCMS (M+H)+=301.1. at −10° C. 417149) was added The mixture was quenched with sat. NH4Cl extracted with ethyl acetate The combined organic layers were washed with water and brine dried over Na2SO4 filtered concentrated under reduced pressure The residue (solid) was treated with ethyl ether filtered dried under reduced pressure