7-bromo-1H-indole-2,3-dione

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

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

Procedure: A suspension of 7-bromoisatin (6.0 g) in acetone (27 ml) was treated with sodium hydroxide (4.6 g) in water (23 ml). The mixture was heated to reflux for 8 h, cooled and solvent reduced in volume at reduced pressure to approx. 25 ml. The residual aqueous phase was acidified with conc. HCl, extracted with ethyl acetate, the organic phase dried (MgSO4) and solvent removed at reduced pressure to give the title compound (7.2 g) as a yellow solid. 1H NMR δ: 2.85 (3H, s), 7.40 (1H, m), 7.90 (1H, s), 8.05 (1H, dd, J=1.2, 7.6 Hz), 8.79 (1H, dd, J=1.0, 8.5 Hz). The mixture was heated to reflux for 8 h cooled extracted with ethyl acetate the organic phase dried (MgSO4) and solvent removed at reduced pressure

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

Procedure: A suspension of 7-bromoisatin (6.0 g) in acetone (27 ml) was treated with sodium hydroxide (4.6 g) in water (23 ml). The mixture was heated to reflux for 8 h, cooled and solvent reduced in volume at reduced pressure to approx. 25 ml. The residual aqueous phase was acidified with conc. HCl, extracted with ethyl acetate, the organic phase dried (MgSO4) and solvent removed at reduced pressure to give the title compound (7.2 g) as a yellow solid. 1H NMR δ: 2.85 (3H, s), 7.40 (1H, m), 7.90 (1H, s), 8.05 (1H, dd, J=1.2, 7.6 Hz), 8.79 (1H, dd, J=1.0, 8.5 Hz). The mixture was heated to reflux for 8 h cooled extracted with ethyl acetate the organic phase dried (MgSO4) and solvent removed at reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sesamol (7.32 g, 53.1 mmol) in anhydrous tetrahydrofuran (150 mL) were added a solution of isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 30.1 mL, 60.2 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 30 min, followed by the addition of 7-bromo isatin (8.0 g, 35.4 mmol). The suspended mixture was stirred at ambient temperature for 16 h. The reaction mixture was diluted with a saturated aqueous solution of ammonium chloride (300 mL) and ethyl acetate (250 mL), and the phases were separated. The aqueous phase was extracted with ethyl acetate (200 mL), and the combined organic solution was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude solid was triturated with diethyl ether, filtered and dried under the reduced pressure to afford 7-bromo-3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-one (9.8 g, 77%) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ10.64 (s, 1H), 9.18 (s, 1H), 7.33 (dd, J=7.8, 1.4 Hz, 1H), 7.21 (s, 1H), 6.84-6.75 (m, 2H), 6.54 (s, 1H), 6.21 (s, 1H), 5.92 (dd, J=6.1, 0.8 Hz, 2H); MS (ES+) m/z 363.8 (M+1), 365.8 (M+1). The suspended mixture was stirred at ambient temperature for 16 h the phases were separated The aqueous phase was extracted with ethyl acetate (200 mL) the combined organic solution was washed with brine (100 mL) dried over anhydrous sodium sulfate filtered concentrated in vacuo The crude solid was triturated with diethyl ether filtered dried under the reduced pressure

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sesamol (7.32 g, 53.1 mmol) in anhydrous tetrahydrofuran (150 mL) were added a solution of isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 30.1 mL, 60.2 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 30 min, followed by the addition of 7-bromo isatin (8.0 g, 35.4 mmol). The suspended mixture was stirred at ambient temperature for 16 h. The reaction mixture was diluted with a saturated aqueous solution of ammonium chloride (300 mL) and ethyl acetate (250 mL), and the phases were separated. The aqueous phase was extracted with ethyl acetate (200 mL), and the combined organic solution was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude solid was triturated with diethyl ether, filtered and dried under the reduced pressure to afford 7-bromo-3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-one (9.8 g, 77%) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ10.64 (s, 1H), 9.18 (s, 1H), 7.33 (dd, J=7.8, 1.4 Hz, 1H), 7.21 (s, 1H), 6.84-6.75 (m, 2H), 6.54 (s, 1H), 6.21 (s, 1H), 5.92 (dd, J=6.1, 0.8 Hz, 2H); MS (ES+) m/z 363.8 (M+1), 365.8 (M+1). The suspended mixture was stirred at ambient temperature for 16 h the phases were separated The aqueous phase was extracted with ethyl acetate (200 mL) the combined organic solution was washed with brine (100 mL) dried over anhydrous sodium sulfate filtered concentrated in vacuo The crude solid was triturated with diethyl ether filtered dried under the reduced pressure

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

Procedure: This compound was synthesized by the procedure described above for Compound 2, reacting 7-Bromo-1H-indole-2,3-dione (1.00 g, 4.42 mmol) with intermediate 2 (1.25 g, 5.53 mmol). The crude acid was purified as described above for Compound 3, then recrystallized from acetonitrile to give product as large, bright yellow crystals (Compound 9, 0.398 g, 23% yield): 1H NMR (400 MHz, DMSO-D6) δ 4.35 (s, 2H) 7.35 (m, 4H) 7.46 (dd, J=8.6, 7.6 Hz, 1H) 7.92 (dd, J=7.5, 1.1 Hz, 1H) 8.50 (dd, J=8.6, 1.3 Hz, 1H); HRMS (ESI/FTMS) calcd for C17H12BrClNO3 (MH+) 391.9684, found 391.9689. Anal. Calcd for C17H11BrClNO3: C, 52.00; H, 2.82; N, 3.57. Found: C, 51.72; H, 2.77; N, 3.53. This compound was synthesized by the procedure The crude acid was purified recrystallized from acetonitrile

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

Procedure: This compound was synthesized by the procedure described above for Compound 2, reacting 7-Bromo-1H-indole-2,3-dione (1.00 g, 4.42 mmol) with intermediate 2 (1.25 g, 5.53 mmol). The crude acid was purified as described above for Compound 3, then recrystallized from acetonitrile to give product as large, bright yellow crystals (Compound 9, 0.398 g, 23% yield): 1H NMR (400 MHz, DMSO-D6) δ 4.35 (s, 2H) 7.35 (m, 4H) 7.46 (dd, J=8.6, 7.6 Hz, 1H) 7.92 (dd, J=7.5, 1.1 Hz, 1H) 8.50 (dd, J=8.6, 1.3 Hz, 1H); HRMS (ESI/FTMS) calcd for C17H12BrClNO3 (MH+) 391.9684, found 391.9689. Anal. Calcd for C17H11BrClNO3: C, 52.00; H, 2.82; N, 3.57. Found: C, 51.72; H, 2.77; N, 3.53. This compound was synthesized by the procedure The crude acid was purified recrystallized from acetonitrile

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-bromo-1H-indole-2,3-dione (4.5 g), Cs2CO3 (10 g) and 1-bromomethyl-4-trifluoromethylbenzene (5 g) in 50 ml of DMF was stirred at 55° C. for 6 h. The reaction mixture was cooled to r.t., diluted with 100 ml of 1:1 hexane/EtOAc and filtered through a pad of silica gel. The filtrate was concentrated under vacuum and the crude product was dissolved in 100 ml of ethanol and 10 ml of 50% aqueous solution of hydrazine. The resulting mixture was heated to reflux for 10 h and diluted with 50 ml of water. After cooling to r.t., solid was collected by filtration and air-dried to give the title compound as a white solid (5.2 g). The reaction mixture was cooled to r.t. filtered through a pad of silica gel The filtrate was concentrated under vacuum the crude product was dissolved in 100 ml of ethanol The resulting mixture was heated to reflux for 10 h diluted with 50 ml of water After cooling to r.t. solid was collected by filtration air-dried

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-bromoisatin (0.113 g) and nitromethane (0.15 ml) were added to water and the reaction mixture was vigorously stirred at a temperature of 30° C. for 24 hours. The obtained product was extracted with ethyl acetate and purified by silica gel column chromatography using ethyl acetate/hexane as eluents to afford pure product. The obtained product was extracted with ethyl acetate purified by silica gel column chromatography to afford pure product

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sesamol (7.32 g, 53.1 mmol) in anhydrous tetrahydrofuran (150 mL) were added a solution of isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 30.1 mL, 60.2 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 30 min, followed by the addition of 7-bromo isatin (8.0 g, 35.4 mmol). The suspended mixture was stirred at ambient temperature for 16 h. The reaction mixture was diluted with a saturated aqueous solution of ammonium chloride (300 mL) and ethyl acetate (250 mL), and the phases were separated. The aqueous phase was extracted with ethyl acetate (200 mL), and the combined organic solution was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude solid was triturated with diethyl ether, filtered and dried under the reduced pressure to afford 7-bromo-3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-one (9.8 g, 77%) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ10.64 (s, 1H), 9.18 (s, 1H), 7.33 (dd, J=7.8, 1.4 Hz, 1H), 7.21 (s, 1H), 6.84-6.75 (m, 2H), 6.54 (s, 1H), 6.21 (s, 1H), 5.92 (dd, J=6.1, 0.8 Hz, 2H); MS (ES+) m/z 363.8 (M+1), 365.8 (M+1). The suspended mixture was stirred at ambient temperature for 16 h the phases were separated The aqueous phase was extracted with ethyl acetate (200 mL) the combined organic solution was washed with brine (100 mL) dried over anhydrous sodium sulfate filtered concentrated in vacuo The crude solid was triturated with diethyl ether filtered dried under the reduced pressure

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

Procedure: A suspension of 7-bromoisatin (6.0 g) in acetone (27 ml) was treated with sodium hydroxide (4.6 g) in water (23 ml). The mixture was heated to reflux for 8 h, cooled and solvent reduced in volume at reduced pressure to approx. 25 ml. The residual aqueous phase was acidified with conc. HCl, extracted with ethyl acetate, the organic phase dried (MgSO4) and solvent removed at reduced pressure to give the title compound (7.2 g) as a yellow solid. 1H NMR δ: 2.85 (3H, s), 7.40 (1H, m), 7.90 (1H, s), 8.05 (1H, dd, J=1.2, 7.6 Hz), 8.79 (1H, dd, J=1.0, 8.5 Hz). The mixture was heated to reflux for 8 h cooled extracted with ethyl acetate the organic phase dried (MgSO4) and solvent removed at reduced pressure