2-bromoisoindole-1,3-dione

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

実験手順: 2,2′-Azobis(4-methoxy-2,4-dimethylvaleronitrile) (50 mg) was added by three portions to the mixture of 1-(4-fluoro-3-methylphenyl)-5-(trifluoromethyl)-1H-tetrazole and N-bromophtalimide (1.44 g) in dichloromethane (16 ml) at 30° C. and the whole was stirred at reflux for 3 hours. After being cooled to room temperature, the mixture was washed with aqueous sodium hydrogen carbonate and aqueous sodium thiosulfate successively. The organic layer was separated, dried over magnesium sulfate, and evaporated under reduced pressure to give a crude 1-[3-(bromomethyl)-4-fluorophenyl]-5-(trifluoromethyl)-1H-tetrazole (3:7). at reflux for 3 hours the mixture was washed with aqueous sodium hydrogen carbonate and aqueous sodium thiosulfate successively The organic layer was separated dried over magnesium sulfate 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-Bromo-1H-isoindole-1,3(2H)-dione (22.0 mg; 0.12 mmol) was added to a solution of 4-[2-(benzyloxy)-4-fluorophenyl]-5-fluoro-N-{3-[(methylsulfanyl)methyl]phenyl}pyrimidin-2-amine (37.0 mg; 0.08 mmol), cyanamide (4.5 mg; 0.11 mmol) and potassium 2-methylpropan-2-olate (11.1 mg; 0.10 mmol) in MeOH (0.44 mL) at RT. The batch was stirred for 4 hours before it was diluted with DCM and aqueous sodium thiosulfate solution. The batch was extracted with DCM (2×). The combined organic phases were filtered using a Whatman filter and concentrated to give crude (rac)-[[3-({4-[2-(benzyloxy)-4-fluorophenyl]-5-fluoropyrimidin-2-yl}amino)benzyl](methyl)-λ4-sulfanylidene]-cyanamide that was used without further purification. The batch was extracted with DCM (2×) The combined organic phases were filtered filter concentrated

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

実験手順: 2-Bromo-1H-isoindole-1,3(2H)-dione (22.0 mg; 0.12 mmol) was added to a solution of 4-[2-(benzyloxy)-4-fluorophenyl]-5-fluoro-N-{3-[(methylsulfanyl)methyl]phenyl}pyrimidin-2-amine (37.0 mg; 0.08 mmol), cyanamide (4.5 mg; 0.11 mmol) and potassium 2-methylpropan-2-olate (11.1 mg; 0.10 mmol) in MeOH (0.44 mL) at RT. The batch was stirred for 4 hours before it was diluted with DCM and aqueous sodium thiosulfate solution. The batch was extracted with DCM (2×). The combined organic phases were filtered using a Whatman filter and concentrated to give crude (rac)-[[3-({4-[2-(benzyloxy)-4-fluorophenyl]-5-fluoropyrimidin-2-yl}amino)benzyl](methyl)-λ4-sulfanylidene]-cyanamide that was used without further purification. The batch was extracted with DCM (2×) The combined organic phases were filtered filter concentrated

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

実験手順: 2-Bromo-1H-isoindole-1,3(2H)-dione (22.0 mg; 0.12 mmol) was added to a solution of 4-[2-(benzyloxy)-4-fluorophenyl]-5-fluoro-N-{3-[(methylsulfanyl)methyl]phenyl}pyrimidin-2-amine (37.0 mg; 0.08 mmol), cyanamide (4.5 mg; 0.11 mmol) and potassium 2-methylpropan-2-olate (11.1 mg; 0.10 mmol) in MeOH (0.44 mL) at RT. The batch was stirred for 4 hours before it was diluted with DCM and aqueous sodium thiosulfate solution. The batch was extracted with DCM (2×). The combined organic phases were filtered using a Whatman filter and concentrated to give crude (rac)-[[3-({4-[2-(benzyloxy)-4-fluorophenyl]-5-fluoropyrimidin-2-yl}amino)benzyl](methyl)-λ4-sulfanylidene]-cyanamide that was used without further purification. The batch was extracted with DCM (2×) The combined organic phases were filtered filter concentrated

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

実験手順: Following the procedure of Example 1, 5-nitro-2-(3-phthalimidomethyl-4H-1,2,4-triazol-4-yl)-2'-chlorobenzophenone is reacted with N-bromophthalimide to form 5-nitro-2-(3-bromo-5-phthalimidomethyl-4H-1,2,4-triazol-4yl)-2'-chlorobenzophenone.

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

実験手順: 2,2′-Azobis(4-methoxy-2,4-dimethylvaleronitrile) (50 mg) was added by three portions to the mixture of 1-(4-fluoro-3-methylphenyl)-5-(trifluoromethyl)-1H-tetrazole and N-bromophtalimide (1.44 g) in dichloromethane (16 ml) at 30° C. and the whole was stirred at reflux for 3 hours. After being cooled to room temperature, the mixture was washed with aqueous sodium hydrogen carbonate and aqueous sodium thiosulfate successively. The organic layer was separated, dried over magnesium sulfate, and evaporated under reduced pressure to give a crude 1-[3-(bromomethyl)-4-fluorophenyl]-5-(trifluoromethyl)-1H-tetrazole (3:7). at reflux for 3 hours the mixture was washed with aqueous sodium hydrogen carbonate and aqueous sodium thiosulfate successively The organic layer was separated dried over magnesium sulfate evaporated under reduced pressure