4-amino-7-bromoisoindole-1,3-dione

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner to Step 2 of Example 1, 3-amino-6-bromophthalimide (80.0 mg, 0.332 mmol) was dissolved in acetonitrile (4.0 mL), and, the solution was treated with 2-benzofuraneboronic acid (161 mg, 0.996 mmol), palladium acetate (9.0 mg, 0.040 mmol), tri(o-tolyl)phosphine (24.3 mg, 0.080 mmol) and triethylamine (0.463 mL, 3.32 mmol), followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=15/1) to obtain Compound 171 (30.1 mg, yield 33%). followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=15/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Amino-6-bromophthalimide (3.10 g, 12.9 mmol) was dissolved in THF (240 mL), and the solution was added with diisobutylaluminiumhydride (0.94 mol/L, 68.6 mL, 64.5 mmol) by drops at −78° C. for 25 minutes, then the reaction mixture was warmed to room temperature, followed by stirring for 1.5 hours. Then, the reaction mixture was ice-cooled, added with water and filtered using Celite. The filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by slurry using chloroform to obtain 7-amino-4-bromo-3-hydroxyisoindolinone (2.26 g, yield 72%). cooled filtered The filtrate was extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure The residue was purified by slurry

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Iodine (6.29 g, 24.8 mmol) was dissolved in ethanol (225 mL), and the solution was added with silver sulfate (3.87 g, 12.4 mmol) and 3-amino-6-bromophthalimide (3.00 g, 12.4 mmol), followed by stirring at room temperature for 23 hours. The reaction mixture was added with 10% aqueous sodium thiosulfate solution and extracted with ethyl acetate. The organic layer was washed with 0.5 mol/L hydrochloric acid and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by slurry using hexane and methanol to obtain 3-amino-4-iodo-6-bromophthalimide (4.3 g. yield 96%). extracted with ethyl acetate The organic layer was washed with 0.5 mol/L hydrochloric acid and saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by slurry

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Amino-6-bromophthalimide (100 mg, 0.415 mmol) was dissolved in acetonitrile (7 mL), and the solution was added with 1-(tert-butoxycarbonyl)indole-2-boronic acid (217 mg, 0.830 mmol), palladium acetate (7.5 mg, 0.033 mmol), tri(o-tolyl)phosphine (20 mg, 0.066 mmol) and triethylamine (0.578 mL, 4.15 mmol), followed by stirring under reflux for 7.5 hours under argon atmosphere. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by preparative thin-layer chromatography (chloroform/methanol=20/1, chloroform/acetonitrile=15/1) to obtain 3-amino-6-[1-(tert-butoxycarbonyl)indol-2-yl]phthalimide (106 mg, yield 67%). under reflux for 7.5 hours under argon atmosphere extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by preparative thin-layer chromatography (chloroform/methanol=20/1, chloroform/acetonitrile=15/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Aminophthalimide (2.00 g, 12.3 mmol) was dissolved in methanol (200 mL), and the solution was added with N-bromosuccinimide (2.19 g, 12.3 mmol), followed by stirring at room temperature for 50 minutes. The obtained solid was collected by filtration and washed with methanol to obtain 3-amino-6-bromophthalimide (2.21 g, yield 74%). The obtained solid was collected by filtration washed with methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner to Step 2 of Example 1, 3-amino-6-bromophthalimide (80.0 mg, 0.332 mmol) was dissolved in acetonitrile (4.0 mL), and, the solution was treated with 2-benzofuraneboronic acid (161 mg, 0.996 mmol), palladium acetate (9.0 mg, 0.040 mmol), tri(o-tolyl)phosphine (24.3 mg, 0.080 mmol) and triethylamine (0.463 mL, 3.32 mmol), followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=15/1) to obtain Compound 171 (30.1 mg, yield 33%). followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=15/1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Amino-6-bromophthalimide (3.10 g, 12.9 mmol) was dissolved in THF (240 mL), and the solution was added with diisobutylaluminiumhydride (0.94 mol/L, 68.6 mL, 64.5 mmol) by drops at −78° C. for 25 minutes, then the reaction mixture was warmed to room temperature, followed by stirring for 1.5 hours. Then, the reaction mixture was ice-cooled, added with water and filtered using Celite. The filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by slurry using chloroform to obtain 7-amino-4-bromo-3-hydroxyisoindolinone (2.26 g, yield 72%). cooled filtered The filtrate was extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure The residue was purified by slurry

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Iodine (6.29 g, 24.8 mmol) was dissolved in ethanol (225 mL), and the solution was added with silver sulfate (3.87 g, 12.4 mmol) and 3-amino-6-bromophthalimide (3.00 g, 12.4 mmol), followed by stirring at room temperature for 23 hours. The reaction mixture was added with 10% aqueous sodium thiosulfate solution and extracted with ethyl acetate. The organic layer was washed with 0.5 mol/L hydrochloric acid and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by slurry using hexane and methanol to obtain 3-amino-4-iodo-6-bromophthalimide (4.3 g. yield 96%). extracted with ethyl acetate The organic layer was washed with 0.5 mol/L hydrochloric acid and saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by slurry