2-(1-hydroxy-2-methylpropan-2-yl)isoindole-1,3-dione

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 2-(1-hydroxy-2-methylpropan-2-yl)isoindoline-1,3-dione (1.10 g; 5 mmol) and 2-methyl-4-(1H-pyrazol-3-yl)benzonitrile (0.366 g; 2.0 mmol) were dissolved in 5 ml of THF under nitrogen atmosphere. Triphenylphosphine (1.05 g; 4.0 mmol) and DIAD (0.79 ml; 4.0 mmol) were added and the reaction stirred at RT over the weekend. Additional triphenylphosphine (0.525 g; 2.0 mmol) and DIAD (0.39 ml; 2.0 mmol) were added and the mixture was stirred at RT for 2 days and then refluxed for 2 hours. Solvent was evaporated, 50 ml of water was added and the mixture was washed with 3×50 ml of DCM, dried over Na2SO4, filtered and evaporated to dryness. The crude mixture was purified twice by CombiFlash (column: silica, eluent 0-100% EtOAc in heptane) to obtain 125 mg (16%) of the title product. 1H-NMR (400 MHz; CDCl3): δ 1.56 (s, 6H), 2.60 (s, 3H), 4.2-4.38 (m, 2H), 6.50 (d, 1H), 7.33-7.87 (m, 8H). the mixture was stirred at RT for 2 days refluxed for 2 hours Solvent was evaporated 50 ml of water was added the mixture was washed with 3×50 ml of DCM dried over Na2SO4 filtered evaporated to dryness The crude mixture was purified twice by CombiFlash (column: silica, eluent 0-100% EtOAc in heptane)

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

実験手順: 2-(1-hydroxy-2-methylpropan-2-yl)isoindoline-1,3-dione (1.10 g; 5 mmol) and 2-methyl-4-(1H-pyrazol-3-yl)benzonitrile (0.366 g; 2.0 mmol) were dissolved in 5 ml of THF under nitrogen atmosphere. Triphenylphosphine (1.05 g; 4.0 mmol) and DIAD (0.79 ml; 4.0 mmol) were added and the reaction stirred at RT over the weekend. Additional triphenylphosphine (0.525 g; 2.0 mmol) and DIAD (0.39 ml; 2.0 mmol) were added and the mixture was stirred at RT for 2 days and then refluxed for 2 hours. Solvent was evaporated, 50 ml of water was added and the mixture was washed with 3×50 ml of DCM, dried over Na2SO4, filtered and evaporated to dryness. The crude mixture was purified twice by CombiFlash (column: silica, eluent 0-100% EtOAc in heptane) to obtain 125 mg (16%) of the title product. 1H-NMR (400 MHz; CDCl3): δ 1.56 (s, 6H), 2.60 (s, 3H), 4.2-4.38 (m, 2H), 6.50 (d, 1H), 7.33-7.87 (m, 8H). the mixture was stirred at RT for 2 days refluxed for 2 hours Solvent was evaporated 50 ml of water was added the mixture was washed with 3×50 ml of DCM dried over Na2SO4 filtered evaporated to dryness The crude mixture was purified twice by CombiFlash (column: silica, eluent 0-100% EtOAc in heptane)

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

実験手順: 2-Amino-2-methyl-1-propanol (4.46 g, 50 mmol) and phthalic anhydride (7.41 g, 50 mmol) were heated at 170° C. for 30 minutes. Icewater was added to the cooled reaction mixture and then the mixture was extracted three times with DCM. Organic phase was dried over Na2SO4, filtered and evaporated to dryness. Crude product was purified by CombiFlash (column: silica, eluent: 0-10% MeOH in DCM) to obtain 3.611 g (33%) of the title compound. LC-MS: M+1=220. Icewater was added to the cooled reaction mixture the mixture was extracted three times with DCM Organic phase was dried over Na2SO4 filtered evaporated to dryness Crude product was purified by CombiFlash (column: silica, eluent: 0-10% MeOH in DCM)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 11.9 g of sulfur trioxide pyridine complex dissolved in 75 ml DMSO was added over a period of 20 minutes at room temperature to a solution of 5.48 g of 2-(2-hydroxy-1,1-dimethyl-ethyl)-isoindole-1,3-dione from Step 1 and 7.59 g of triethylamine in 780 ml DMSO. The reaction mixture was stirred at room temperature for 30 minutes, poured onto ice/water and extracted 3 times with tert-butyl methyl ether. The organic was washed with 1N HCl and 2 times H2O, dried over magnesium sulfate and the solvent was evaporated under reduced pressure to give 4.92 g crystals (mp 80-82° C.), which were used in the next step without further purification. poured onto ice/water extracted 3 times with tert-butyl methyl ether The organic was washed with 1N HCl and 2 times H2O dried over magnesium sulfate the solvent was evaporated under reduced pressure

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

実験手順: 2-(1-hydroxy-2-methylpropan-2-yl)isoindoline-1,3-dione (1.10 g; 5 mmol) and 2-methyl-4-(1H-pyrazol-3-yl)benzonitrile (0.366 g; 2.0 mmol) were dissolved in 5 ml of THF under nitrogen atmosphere. Triphenylphosphine (1.05 g; 4.0 mmol) and DIAD (0.79 ml; 4.0 mmol) were added and the reaction stirred at RT over the weekend. Additional triphenylphosphine (0.525 g; 2.0 mmol) and DIAD (0.39 ml; 2.0 mmol) were added and the mixture was stirred at RT for 2 days and then refluxed for 2 hours. Solvent was evaporated, 50 ml of water was added and the mixture was washed with 3×50 ml of DCM, dried over Na2SO4, filtered and evaporated to dryness. The crude mixture was purified twice by CombiFlash (column: silica, eluent 0-100% EtOAc in heptane) to obtain 125 mg (16%) of the title product. 1H-NMR (400 MHz; CDCl3): δ 1.56 (s, 6H), 2.60 (s, 3H), 4.2-4.38 (m, 2H), 6.50 (d, 1H), 7.33-7.87 (m, 8H). the mixture was stirred at RT for 2 days refluxed for 2 hours Solvent was evaporated 50 ml of water was added the mixture was washed with 3×50 ml of DCM dried over Na2SO4 filtered evaporated to dryness The crude mixture was purified twice by CombiFlash (column: silica, eluent 0-100% EtOAc in heptane)

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

実験手順: 2-Amino-2-methyl-1-propanol (4.46 g, 50 mmol) and phthalic anhydride (7.41 g, 50 mmol) were heated at 170° C. for 30 minutes. Icewater was added to the cooled reaction mixture and then the mixture was extracted three times with DCM. Organic phase was dried over Na2SO4, filtered and evaporated to dryness. Crude product was purified by CombiFlash (column: silica, eluent: 0-10% MeOH in DCM) to obtain 3.611 g (33%) of the title compound. LC-MS: M+1=220. Icewater was added to the cooled reaction mixture the mixture was extracted three times with DCM Organic phase was dried over Na2SO4 filtered evaporated to dryness Crude product was purified by CombiFlash (column: silica, eluent: 0-10% MeOH in DCM)