(E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloropyrimidine (71 mg, 0.476 mmol) in dioxane (4 mL) and sodium carbonate (2M in water, 0.25 mL, 0.5 mmol) were added (3E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol (100 mg, 0.476 mmol) and tetrakis triphenylphosphine palladium(0) (55 mg, 0.048 mmol). The solution was degassed by bubbling nitrogen gas and heated to 90° C. for 2 hr. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes) to afford (3E)-4-(2-chloropyrimidin-4-yl)-2-methylbut-3-en-2-ol as a colorless oil. MS ESI: [M+H]+ m/z 199.1. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J=5.1, 1H) 7.24 (d, J=15.6, 1H) 7.12 (d, J=5.1, 1H) 6.60 (d, J=15.6, 1H); 1.22 (s, 6H). The solution was degassed by bubbling nitrogen gas The solution was diluted with EtOAc washed with brine dried with MgSO4 filtered concentrated to dryness The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloropyrimidine (71 mg, 0.476 mmol) in dioxane (4 mL) and sodium carbonate (2M in water, 0.25 mL, 0.5 mmol) were added (3E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol (100 mg, 0.476 mmol) and tetrakis triphenylphosphine palladium(0) (55 mg, 0.048 mmol). The solution was degassed by bubbling nitrogen gas and heated to 90° C. for 2 hr. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes) to afford (3E)-4-(2-chloropyrimidin-4-yl)-2-methylbut-3-en-2-ol as a colorless oil. MS ESI: [M+H]+ m/z 199.1. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J=5.1, 1H) 7.24 (d, J=15.6, 1H) 7.12 (d, J=5.1, 1H) 6.60 (d, J=15.6, 1H); 1.22 (s, 6H). The solution was degassed by bubbling nitrogen gas The solution was diluted with EtOAc washed with brine dried with MgSO4 filtered concentrated to dryness The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloropyrimidine (71 mg, 0.476 mmol) in dioxane (4 mL) and sodium carbonate (2M in water, 0.25 mL, 0.5 mmol) were added (3E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol (100 mg, 0.476 mmol) and tetrakis triphenylphosphine palladium(0) (55 mg, 0.048 mmol). The solution was degassed by bubbling nitrogen gas and heated to 90° C. for 2 hr. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes) to afford (3E)-4-(2-chloropyrimidin-4-yl)-2-methylbut-3-en-2-ol as a colorless oil. MS ESI: [M+H]+ m/z 199.1. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J=5.1, 1H) 7.24 (d, J=15.6, 1H) 7.12 (d, J=5.1, 1H) 6.60 (d, J=15.6, 1H); 1.22 (s, 6H). The solution was degassed by bubbling nitrogen gas The solution was diluted with EtOAc washed with brine dried with MgSO4 filtered concentrated to dryness The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloropyrimidine (71 mg, 0.476 mmol) in dioxane (4 mL) and sodium carbonate (2M in water, 0.25 mL, 0.5 mmol) were added (3E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol (100 mg, 0.476 mmol) and tetrakis triphenylphosphine palladium(0) (55 mg, 0.048 mmol). The solution was degassed by bubbling nitrogen gas and heated to 90° C. for 2 hr. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes) to afford (3E)-4-(2-chloropyrimidin-4-yl)-2-methylbut-3-en-2-ol as a colorless oil. MS ESI: [M+H]+ m/z 199.1. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J=5.1, 1H) 7.24 (d, J=15.6, 1H) 7.12 (d, J=5.1, 1H) 6.60 (d, J=15.6, 1H); 1.22 (s, 6H). The solution was degassed by bubbling nitrogen gas The solution was diluted with EtOAc washed with brine dried with MgSO4 filtered concentrated to dryness The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloropyrimidine (71 mg, 0.476 mmol) in dioxane (4 mL) and sodium carbonate (2M in water, 0.25 mL, 0.5 mmol) were added (3E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol (100 mg, 0.476 mmol) and tetrakis triphenylphosphine palladium(0) (55 mg, 0.048 mmol). The solution was degassed by bubbling nitrogen gas and heated to 90° C. for 2 hr. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes) to afford (3E)-4-(2-chloropyrimidin-4-yl)-2-methylbut-3-en-2-ol as a colorless oil. MS ESI: [M+H]+ m/z 199.1. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J=5.1, 1H) 7.24 (d, J=15.6, 1H) 7.12 (d, J=5.1, 1H) 6.60 (d, J=15.6, 1H); 1.22 (s, 6H). The solution was degassed by bubbling nitrogen gas The solution was diluted with EtOAc washed with brine dried with MgSO4 filtered concentrated to dryness The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 6-[(2,6-dichloro-4-iodophenyl)amino]pyrido[4,3-c]-1,6-naphthyridin-10(9H)-one (Example 156, Step 1) (30 mg, 0.06 mmol) in DMF (1.5 mL) were added sodium carbonate (2 M, 0.5 mL), tetrakis(triphenylphosphine)palladium (0) (14.3 mg, 0.12 mmol), and (3E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol (13.2 mg, 0.06 mmol). The solution was degassed by bubbling nitrogen gas and heated to 80° C. overnight. After cooling to room temperature, the mixture was extracted with 3:1 CHCl3/iPrOH. The organic layers were combined, dried with MgSO4, filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH) afforded the title compound. The solution was degassed by bubbling nitrogen gas After cooling to room temperature the mixture was extracted with 3:1 CHCl3/iPrOH dried with MgSO4 filtered concentrated under reduced pressure Purification by column chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloropyrimidine (71 mg, 0.476 mmol) in dioxane (4 mL) and sodium carbonate (2M in water, 0.25 mL, 0.5 mmol) were added (3E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol (100 mg, 0.476 mmol) and tetrakis triphenylphosphine palladium(0) (55 mg, 0.048 mmol). The solution was degassed by bubbling nitrogen gas and heated to 90° C. for 2 hr. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes) to afford (3E)-4-(2-chloropyrimidin-4-yl)-2-methylbut-3-en-2-ol as a colorless oil. MS ESI: [M+H]+ m/z 199.1. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J=5.1, 1H) 7.24 (d, J=15.6, 1H) 7.12 (d, J=5.1, 1H) 6.60 (d, J=15.6, 1H); 1.22 (s, 6H). The solution was degassed by bubbling nitrogen gas The solution was diluted with EtOAc washed with brine dried with MgSO4 filtered concentrated to dryness The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4-dichloropyrimidine (71 mg, 0.476 mmol) in dioxane (4 mL) and sodium carbonate (2M in water, 0.25 mL, 0.5 mmol) were added (3E)-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-ol (100 mg, 0.476 mmol) and tetrakis triphenylphosphine palladium(0) (55 mg, 0.048 mmol). The solution was degassed by bubbling nitrogen gas and heated to 90° C. for 2 hr. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes) to afford (3E)-4-(2-chloropyrimidin-4-yl)-2-methylbut-3-en-2-ol as a colorless oil. MS ESI: [M+H]+ m/z 199.1. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J=5.1, 1H) 7.24 (d, J=15.6, 1H) 7.12 (d, J=5.1, 1H) 6.60 (d, J=15.6, 1H); 1.22 (s, 6H). The solution was degassed by bubbling nitrogen gas The solution was diluted with EtOAc washed with brine dried with MgSO4 filtered concentrated to dryness The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexanes)