4-羟基-2-甲基苯硼酸

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-(2,4-Difluoro-phenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine from Example 11 (0.5 g, 0.99 mmol) was dissolved in 10 mL of dry dioxane, and the reaction mixture was degassed by treatment with vacuum and flushed with argon. Tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.1 mmol) was added, and the reaction mixture was stirred for 10 minutes. A solution of 4-hydroxy-2-methylphenyl boronic acid (0.311 g, 2.0 mmol) in 3 mL EtOH was added, and the reaction mixture was degassed, purged with argon, and stirred for 10 minutes. AA solution of potassium carbonate (0.411 g, 3.0 mmol) in 1 mL water was then added, and the reaction mixture was again degassed and flushed with argon. The reaction mixture was heated to 90° C. with stirring for 16 hours under argon. The reaction mixture was cooled, filtered, and the filtrate was partitioned between water and ethyl acetate. The organic phase was separated, and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting residue was subject to flash chromatography (hexanes/EtOAc 1:0 to 2:1) to yield 0.308 g (0.64 mmol, 64%) of 4-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol. the reaction mixture was degassed by treatment with vacuum flushed with argon the reaction mixture was degassed purged with argon stirred for 10 minutes the reaction mixture was again degassed flushed with argon with stirring for 16 hours under argon The reaction mixture was cooled filtered the filtrate was partitioned between water and ethyl acetate The organic phase was separated the aqueous phase was extracted three times with EtOAc The combined organic layers were dried over MgSO4 filtered evaporated under reduced pressure

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-(2,4-Difluoro-phenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine from Example 11 (0.5 g, 0.99 mmol) was dissolved in 10 mL of dry dioxane, and the reaction mixture was degassed by treatment with vacuum and flushed with argon. Tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.1 mmol) was added, and the reaction mixture was stirred for 10 minutes. A solution of 4-hydroxy-2-methylphenyl boronic acid (0.311 g, 2.0 mmol) in 3 mL EtOH was added, and the reaction mixture was degassed, purged with argon, and stirred for 10 minutes. AA solution of potassium carbonate (0.411 g, 3.0 mmol) in 1 mL water was then added, and the reaction mixture was again degassed and flushed with argon. The reaction mixture was heated to 90° C. with stirring for 16 hours under argon. The reaction mixture was cooled, filtered, and the filtrate was partitioned between water and ethyl acetate. The organic phase was separated, and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting residue was subject to flash chromatography (hexanes/EtOAc 1:0 to 2:1) to yield 0.308 g (0.64 mmol, 64%) of 4-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol. the reaction mixture was degassed by treatment with vacuum flushed with argon the reaction mixture was degassed purged with argon stirred for 10 minutes the reaction mixture was again degassed flushed with argon with stirring for 16 hours under argon The reaction mixture was cooled filtered the filtrate was partitioned between water and ethyl acetate The organic phase was separated the aqueous phase was extracted three times with EtOAc The combined organic layers were dried over MgSO4 filtered evaporated under reduced pressure

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-hydroxy-2-methylphenylboronic acid (110 mg, 0.66 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.33 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98] to yield BA60 (42 mg, 22% yield). ESI-MS (M+H)+ m/z calcd 284, found 284. After cooling the reaction was extracted with saturated NaCl and CH2Cl2 concentrated in vacuo purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98]

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-hydroxy-2-methylphenylboronic acid (110 mg, 0.66 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.33 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98] to yield BA60 (42 mg, 22% yield). ESI-MS (M+H)+ m/z calcd 284, found 284. After cooling the reaction was extracted with saturated NaCl and CH2Cl2 concentrated in vacuo purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98]

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-(2,4-Difluoro-phenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine from Example 11 (0.5 g, 0.99 mmol) was dissolved in 10 mL of dry dioxane, and the reaction mixture was degassed by treatment with vacuum and flushed with argon. Tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.1 mmol) was added, and the reaction mixture was stirred for 10 minutes. A solution of 4-hydroxy-2-methylphenyl boronic acid (0.311 g, 2.0 mmol) in 3 mL EtOH was added, and the reaction mixture was degassed, purged with argon, and stirred for 10 minutes. AA solution of potassium carbonate (0.411 g, 3.0 mmol) in 1 mL water was then added, and the reaction mixture was again degassed and flushed with argon. The reaction mixture was heated to 90° C. with stirring for 16 hours under argon. The reaction mixture was cooled, filtered, and the filtrate was partitioned between water and ethyl acetate. The organic phase was separated, and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting residue was subject to flash chromatography (hexanes/EtOAc 1:0 to 2:1) to yield 0.308 g (0.64 mmol, 64%) of 4-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol. the reaction mixture was degassed by treatment with vacuum flushed with argon the reaction mixture was degassed purged with argon stirred for 10 minutes the reaction mixture was again degassed flushed with argon with stirring for 16 hours under argon The reaction mixture was cooled filtered the filtrate was partitioned between water and ethyl acetate The organic phase was separated the aqueous phase was extracted three times with EtOAc The combined organic layers were dried over MgSO4 filtered evaporated under reduced pressure

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-hydroxy-2-methylphenylboronic acid (110 mg, 0.66 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.33 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98] to yield BA60 (42 mg, 22% yield). ESI-MS (M+H)+ m/z calcd 284, found 284. After cooling the reaction was extracted with saturated NaCl and CH2Cl2 concentrated in vacuo purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98]

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-(2,4-Difluoro-phenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine from Example 11 (0.5 g, 0.99 mmol) was dissolved in 10 mL of dry dioxane, and the reaction mixture was degassed by treatment with vacuum and flushed with argon. Tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.1 mmol) was added, and the reaction mixture was stirred for 10 minutes. A solution of 4-hydroxy-2-methylphenyl boronic acid (0.311 g, 2.0 mmol) in 3 mL EtOH was added, and the reaction mixture was degassed, purged with argon, and stirred for 10 minutes. AA solution of potassium carbonate (0.411 g, 3.0 mmol) in 1 mL water was then added, and the reaction mixture was again degassed and flushed with argon. The reaction mixture was heated to 90° C. with stirring for 16 hours under argon. The reaction mixture was cooled, filtered, and the filtrate was partitioned between water and ethyl acetate. The organic phase was separated, and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting residue was subject to flash chromatography (hexanes/EtOAc 1:0 to 2:1) to yield 0.308 g (0.64 mmol, 64%) of 4-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol. the reaction mixture was degassed by treatment with vacuum flushed with argon the reaction mixture was degassed purged with argon stirred for 10 minutes the reaction mixture was again degassed flushed with argon with stirring for 16 hours under argon The reaction mixture was cooled filtered the filtrate was partitioned between water and ethyl acetate The organic phase was separated the aqueous phase was extracted three times with EtOAc The combined organic layers were dried over MgSO4 filtered evaporated under reduced pressure

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-(2,4-Difluoro-phenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine from Example 11 (0.5 g, 0.99 mmol) was dissolved in 10 mL of dry dioxane, and the reaction mixture was degassed by treatment with vacuum and flushed with argon. Tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.1 mmol) was added, and the reaction mixture was stirred for 10 minutes. A solution of 4-hydroxy-2-methylphenyl boronic acid (0.311 g, 2.0 mmol) in 3 mL EtOH was added, and the reaction mixture was degassed, purged with argon, and stirred for 10 minutes. AA solution of potassium carbonate (0.411 g, 3.0 mmol) in 1 mL water was then added, and the reaction mixture was again degassed and flushed with argon. The reaction mixture was heated to 90° C. with stirring for 16 hours under argon. The reaction mixture was cooled, filtered, and the filtrate was partitioned between water and ethyl acetate. The organic phase was separated, and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting residue was subject to flash chromatography (hexanes/EtOAc 1:0 to 2:1) to yield 0.308 g (0.64 mmol, 64%) of 4-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol. the reaction mixture was degassed by treatment with vacuum flushed with argon the reaction mixture was degassed purged with argon stirred for 10 minutes the reaction mixture was again degassed flushed with argon with stirring for 16 hours under argon The reaction mixture was cooled filtered the filtrate was partitioned between water and ethyl acetate The organic phase was separated the aqueous phase was extracted three times with EtOAc The combined organic layers were dried over MgSO4 filtered evaporated under reduced pressure

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Palladium(II)acetate (3.2 mg, 14.5 μmol) was added to ethyl 6-bromo-2-quinolinecarboxylate (81.1 mg, 289.5 μmol), (4-hydroxy-2-methylphenyl)boronic acid (66.0 mg, 434.2 μmol), triphenylphosphine (7.6 mg, 29.0 μmol), and potassium phosphate (215.1 mg, 1.01 mmol). Then, dioxane (2.8 mL) was added to the mixture, followed by water (289.5 μL), and the reaction mixture was heated open to the atmosphere at 60° C. in an oil bath for 18 hours, then allowed to cool to room temperature. Water was added, followed by ethyl acetate, and the mixture was filtered through Celite®. The filtrate was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate, then filtered and concentrated. The residue was purified by silica gel chromatography eluting with 2:3 ethyl acetate:hexanes to give 53.2 mg (60%) of ethyl 6-(4-hydroxy-2-methylphenyl)-2-quinolinecarboxylate as a solid. 1H NMR (400 MHz, d6-DMSO): δ 9.51 (s, 1H), 8.56 (d, J=9 Hz, 1H), 8.16 (d, J=9 Hz, 1H), 8.13 (d, J=9 Hz, 1H), 7.98 (s, 1H), 7.82 (d, J=9 Hz, 1H), 7.16 (d, J=8 Hz, 1H), 6.74 (s, 1H), 6.71 (dd, J=8, 2 Hz, 1H), 4.43 (q, J=7 Hz, 2H), 2.23 (s, 3H), 1.39 (t, J=7 Hz, 3H). ESI-LCMS m/z 308 (M+H)+. to cool to room temperature the mixture was filtered through Celite® The filtrate was extracted with ethyl acetate the organic layer was dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by silica gel chromatography eluting with 2:3 ethyl acetate

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

实验步骤: Sodium periodate (2.39 g, 11.15 mmol) was added to 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (870.4 mg, 3.72 mmol) and ammonium acetate (859.8 mg, 11.15 mmol) in acetone and water (2:1, 36 mL) at room temperature. The mixture was stirred for sixty-eight hours, then filtered, and concentrated. Sodium chloride was added to the filtrate, and it was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, then filtered and concentrated. The residue was purified by silica gel chromatography eluting with 1:4 ethyl acetate:hexanes to give 275.7 mg (49%) of (4-hydroxy-2-methylphenyl)boronic acid as a solid. 1H NMR (400 MHz, d6-DMSO): δ 9.28 (s, 1H), 7.70 (d, J=9 Hz, 1H), 6.56-6.52 (m, 2H), 2.55 (s, 3H). ESI-LCMS m/z 151 (M−H)−. filtered concentrated Sodium chloride was added to the filtrate, and it was extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by silica gel chromatography eluting with 1:4 ethyl acetate

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-hydroxy-2-methylphenylboronic acid (110 mg, 0.66 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.33 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98] to yield BA60 (42 mg, 22% yield). ESI-MS (M+H)+ m/z calcd 284, found 284. After cooling the reaction was extracted with saturated NaCl and CH2Cl2 concentrated in vacuo purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98]

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-(2,4-Difluoro-phenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine from Example 11 (0.5 g, 0.99 mmol) was dissolved in 10 mL of dry dioxane, and the reaction mixture was degassed by treatment with vacuum and flushed with argon. Tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.1 mmol) was added, and the reaction mixture was stirred for 10 minutes. A solution of 4-hydroxy-2-methylphenyl boronic acid (0.311 g, 2.0 mmol) in 3 mL EtOH was added, and the reaction mixture was degassed, purged with argon, and stirred for 10 minutes. AA solution of potassium carbonate (0.411 g, 3.0 mmol) in 1 mL water was then added, and the reaction mixture was again degassed and flushed with argon. The reaction mixture was heated to 90° C. with stirring for 16 hours under argon. The reaction mixture was cooled, filtered, and the filtrate was partitioned between water and ethyl acetate. The organic phase was separated, and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting residue was subject to flash chromatography (hexanes/EtOAc 1:0 to 2:1) to yield 0.308 g (0.64 mmol, 64%) of 4-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol. the reaction mixture was degassed by treatment with vacuum flushed with argon the reaction mixture was degassed purged with argon stirred for 10 minutes the reaction mixture was again degassed flushed with argon with stirring for 16 hours under argon The reaction mixture was cooled filtered the filtrate was partitioned between water and ethyl acetate The organic phase was separated the aqueous phase was extracted three times with EtOAc The combined organic layers were dried over MgSO4 filtered evaporated under reduced pressure