2-(2-oxopropyl)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: 1.33 g (6.55 mmol) of N-(2-oxopropyl)phthalimide was dissolved in 30 ml of ethanol and to the solution was added 1.64 g (19.7 mmol) of O-methylhydroxylamine hydrochloride. To this suspension was added 20 ml of 2N aqueous sodium hydroxide solution, followed by being stirred at room temperature for 12 hours. The reaction mixture was poured into 100 ml of water and extracted with chloroform (30 ml×3), and the combined organic layer was dried over magnesium sulfate. Chloroform was distilled off and the residual solids were washed with hexane to give 1.03 g (yield 68%) of the titled compound as colorless crystals. extracted with chloroform (30 ml×3) the combined organic layer was dried over magnesium sulfate Chloroform was distilled off the residual solids were washed with hexane

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

実験手順: 1.33 g (6.55 mmol) of N-(2-oxopropyl)phthalimide was dissolved in 30 ml of ethanol and to the solution was added 1.64 g (19.7 mmol) of O-methylhydroxylamine hydrochloride. To this suspension was added 20 ml of 2N aqueous sodium hydroxide solution, followed by being stirred at room temperature for 12 hours. The reaction mixture was poured into 100 ml of water and extracted with chloroform (30 ml×3), and the combined organic layer was dried over magnesium sulfate. Chloroform was distilled off and the residual solids were washed with hexane to give 1.03 g (yield 68%) of the titled compound as colorless crystals. extracted with chloroform (30 ml×3) the combined organic layer was dried over magnesium sulfate Chloroform was distilled off the residual solids were washed with hexane

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

実験手順: Cyanoacetamide (62 g, 1.5 eq) and powdered lithium hydroxide (18 g, 1.5 eq) were mixed in 500 ml DMF and it was stirred at room temperature for 30 min. To the mixture was added a solution of phthalimidoacetone (100 g, 0.49 mol, purchased from TCI America, Portland, Oreg., USA, or prepared according to Lei, et al, J. Am. Chem. Soc. 2004, 126, 1626) in DMF (200 ml) over 1 h at room temperature. Additional DMF (25 ml) was used as a rinse. After stirring at room temperature for 5 min, HPLC/MS showed formation of the adol compound (MS: MH+=222.1, MNa+=244.0). Methanol (50 ml) was added followed by 25% sodium methoxide solution (160 g, 1.5 eq) and methanol rinse (50 ml). This mixture was heated at 60-65° C. for 2 h to form 2-amino-4-methyl-1H-pyrrole-3-carboxamide. To this reaction mixture was added ethyl formate (100 ml, 2.5 eq) at 40-60° C. After stirring for 15 min, more methanol (50 ml) was added followed by simultaneous addition of ethyl formate (100 ml, 2.5 eq) and 25% sodium methoxide solution (266 g, 2.5 eq) over 30 min. Additional methanol (50 ml) was added as rinse. The resulting mixture was heated at 60° C. for 5 h. More 25% sodium methoxide solution (113 ml, 1 eq) was added, and heating continued for 1 h more to convert all of the pyrrole N-formyl intermediate (MS: MH+=151.1). Water (400 ml) was added and mixture was heated at 60° C. for 30 min. Solution assay indicated the final product was formed in 69% yield. The hydrolyzed reaction mixture was concentrated under vacuum and diluted with water (1000 ml). The pH was adjusted to about 7.6 with 6 N HCl at 60-65° C. The resulting slurry was heated at 60-65° C. for 15 min and cooled slowly to 10° C. The solids were filtered, washed with water, and dried at 50-60° C. under vacuum. The final product was obtained as a light purple solid (39.5 g, 54% yield, purity: 99.8% by HPLC area). After stirring at room temperature for 5 min rinse (50 ml) This mixture was heated at 60-65° C. for 2 h

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

実験手順: Cyanoacetamide (62 g, 1.5 eq) and powdered lithium hydroxide (18 g, 1.5 eq) were mixed in 500 ml DMF and it was stirred at room temperature for 30 min. To the mixture was added a solution of phthalimidoacetone (100 g, 0.49 mol, purchased from TCI America, Portland, Oreg., USA, or prepared according to Lei, et al, J. Am. Chem. Soc. 2004, 126, 1626) in DMF (200 ml) over 1 h at room temperature. Additional DMF (25 ml) was used as a rinse. After stirring at room temperature for 5 min, HPLC/MS showed formation of the adol compound (MS: MH+=222.1, MNa+=244.0). Methanol (50 ml) was added followed by 25% sodium methoxide solution (160 g, 1.5 eq) and methanol rinse (50 ml). This mixture was heated at 60-65° C. for 2 h to form 2-amino-4-methyl-1H-pyrrole-3-carboxamide. To this reaction mixture was added ethyl formate (100 ml, 2.5 eq) at 40-60° C. After stirring for 15 min, more methanol (50 ml) was added followed by simultaneous addition of ethyl formate (100 ml, 2.5 eq) and 25% sodium methoxide solution (266 g, 2.5 eq) over 30 min. Additional methanol (50 ml) was added as rinse. The resulting mixture was heated at 60° C. for 5 h. More 25% sodium methoxide solution (113 ml, 1 eq) was added, and heating continued for 1 h more to convert all of the pyrrole N-formyl intermediate (MS: MH+=151.1). Water (400 ml) was added and mixture was heated at 60° C. for 30 min. Solution assay indicated the final product was formed in 69% yield. The hydrolyzed reaction mixture was concentrated under vacuum and diluted with water (1000 ml). The pH was adjusted to about 7.6 with 6 N HCl at 60-65° C. The resulting slurry was heated at 60-65° C. for 15 min and cooled slowly to 10° C. The solids were filtered, washed with water, and dried at 50-60° C. under vacuum. The final product was obtained as a light purple solid (39.5 g, 54% yield, purity: 99.8% by HPLC area). After stirring at room temperature for 5 min rinse (50 ml) This mixture was heated at 60-65° C. for 2 h

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

実験手順: 1.33 g (6.55 mmol) of N-(2-oxopropyl)phthalimide was dissolved in 30 ml of ethanol and to the solution was added 1.64 g (19.7 mmol) of O-methylhydroxylamine hydrochloride. To this suspension was added 20 ml of 2N aqueous sodium hydroxide solution, followed by being stirred at room temperature for 12 hours. The reaction mixture was poured into 100 ml of water and extracted with chloroform (30 ml×3), and the combined organic layer was dried over magnesium sulfate. Chloroform was distilled off and the residual solids were washed with hexane to give 1.03 g (yield 68%) of the titled compound as colorless crystals. extracted with chloroform (30 ml×3) the combined organic layer was dried over magnesium sulfate Chloroform was distilled off the residual solids were washed with hexane

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(2-oxopropyl)isoindoline-1,3-dione (1 g, 4.9 mmol) in 20 mL of DMF-DMA was added some of 4 A molecular sieve. The reaction mixture was stirred at 100° C. under N2 for 15 hr. After cooling down to RT, the mixture was filtered and collected 600 mg (47.5%) of crude (E)-2-(4-(dimethylamino)-2-oxobut-3-enyl) isoindoline-1,3-dione as a solid. MS (ESI) m/e [M+1]+ 259.1. After cooling down to RT the mixture was filtered collected 600 mg (47.5%) of crude (E)-2-(4-(dimethylamino)-2-oxobut-3-enyl) isoindoline-1,3-dione as a solid

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(2-oxopropyl)isoindoline-1,3-dione (1 g, 4.9 mmol) in 20 mL of DMF-DMA was added some of 4 A molecular sieve. The reaction mixture was stirred at 100° C. under N2 for 15 hr. After cooling down to RT, the mixture was filtered and collected 600 mg (47.5%) of crude (E)-2-(4-(dimethylamino)-2-oxobut-3-enyl) isoindoline-1,3-dione as a solid. MS (ESI) m/e [M+1]+ 259.1. After cooling down to RT the mixture was filtered collected 600 mg (47.5%) of crude (E)-2-(4-(dimethylamino)-2-oxobut-3-enyl) isoindoline-1,3-dione as a solid

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: To a solution of phthalimidoacetone (4.04 g, 19.9 mmol) in methanol (100 mL) was added urea (1.19 g, 19.9 mmol) and bromine (3.18 g, 19.9 mmol) and the resulting solution was stirred at room temperature overnight. The reaction was concentrated in vacuo and the residue taken up in DCM (150 mL) and water (50 mL). The layers were separated and the organic layer was dried, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (EA/hexanes=0/100→50/50) to give 159 mg (3% yield) of the title compound. 1H NMR (300 MHz, CDCl3) δ: 7.90-7.86 (m, 2H), 7.79-7.73 (m, 2H), 4.78 (s, 2H), 4.01 (s, 2H). The reaction was concentrated in vacuo The layers were separated the organic layer was dried filtered concentrated in vacuo The residue was purified by silica gel chromatography (EA/hexanes=0/100→50/50)

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

実験手順: To a solution of phthalimidoacetone (4.04 g, 19.9 mmol) in methanol (100 mL) was added urea (1.19 g, 19.9 mmol) and bromine (3.18 g, 19.9 mmol) and the resulting solution was stirred at room temperature overnight. The reaction was concentrated in vacuo and the residue taken up in DCM (150 mL) and water (50 mL). The layers were separated and the organic layer was dried, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (EA/hexanes=0/100→50/50) to give 159 mg (3% yield) of the title compound. 1H NMR (300 MHz, CDCl3) δ: 7.90-7.86 (m, 2H), 7.79-7.73 (m, 2H), 4.78 (s, 2H), 4.01 (s, 2H). The reaction was concentrated in vacuo The layers were separated the organic layer was dried filtered concentrated in vacuo The residue was purified by silica gel chromatography (EA/hexanes=0/100→50/50)

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

実験手順: To a solution of phthalimidoacetone (4.04 g, 19.9 mmol) in methanol (100 mL) was added urea (1.19 g, 19.9 mmol) and bromine (3.18 g, 19.9 mmol) and the resulting solution was stirred at room temperature overnight. The reaction was concentrated in vacuo and the residue taken up in DCM (150 mL) and water (50 mL). The layers were separated and the organic layer was dried, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (EA/hexanes=0/100→50/50) to give 159 mg (3% yield) of the title compound. 1H NMR (300 MHz, CDCl3) δ: 7.90-7.86 (m, 2H), 7.79-7.73 (m, 2H), 4.78 (s, 2H), 4.01 (s, 2H). The reaction was concentrated in vacuo The layers were separated the organic layer was dried filtered concentrated in vacuo The residue was purified by silica gel chromatography (EA/hexanes=0/100→50/50)