7-iodo-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: This compound was prepared according to the procedure described by Lisowski et al. J. Org. Chem., 2000, 65, 4193. To a 1 L 3-necked round-bottomed flask fitted with a reflux condenser were added intermediate 6 (2.0 g, 7.3 mmol) and tetrakis[triphenylphosphine]palladium (0.424 g, 0.367 mmol), followed by 115 mL ethylene glycol dimethyl ether. The atmosphere in the reaction vessel was made inert by opening to vacuum, then to a positive pressure of nitrogen (3×). Next, 3-thiopheneboronic acid (Aldrich, 1.03 g, 8.06 mmol) and a solution of sodium bicarbonate (1.23 g, 14.7 mmol) in 115 mL water were added, and the evacuation/nitrogen procedure repeated one more time. The reaction mixture was then refluxed until t.l.c. (10% ethyl acetate in dichloromethane) showed complete disappearance of 7-iodoisatin, 6, (1-3 hours). After cooling to room temperature, the organic solvent was removed under reduced pressure. The residue was diluted with 1M aqueous hydrochloric acid and extracted into ethyl acetate (3×). The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by flash chromatography over silica gel, eluting with 3% ethyl acetate in dichloromethane, to give 7-(thien-3-yl)isatin, Intermediate 8, as a bright red crystalline material (0.91 g, 54% yield): 1H NMR (400 MHz, DMSO-D6) δ 7.15 (t, 1H) 7.36 (dd, J=4.9, 1.4 Hz, 1H) 7.50 (dt, J=7.3, 1.0 Hz, 1H) 7.68 (d, J=1.5 Hz, 1H) 7.71 (m, 2H) 7.75 (dd, J=2.9, 1.4 Hz, 1H) 10.86 (s, 1H). This compound was prepared To a 1 L 3-necked round-bottomed flask fitted with a reflux condenser The reaction mixture was then refluxed until t.l.c the organic solvent was removed under reduced pressure The residue was diluted with 1M aqueous hydrochloric acid extracted into ethyl acetate (3×) The organic layer was washed with brine dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure The crude product was purified by flash chromatography over silica gel eluting with 3% ethyl acetate in dichloromethane

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

Procedure: This compound was prepared according to the procedure described by Lisowski et al. J. Org. Chem., 2000, 65, 4193. To a 1 L 3-necked round-bottomed flask fitted with a reflux condenser were added intermediate 6 (2.0 g, 7.33 mmol) and tetrakis[triphenylphosphine]palladium (0.424 g, 0.367 mmol), followed by 225 mL 1,2-dimethoxyethane. The atmosphere in the reaction vessel was made inert by opening to vacuum, then to a positive pressure of nitrogen (3×). Phenylboronic acid (Aldrich, 0.983 g, 8.06 mmol) and a solution of sodium bicarbonate (1.23 g, 14.7 mmol) in 225 mL water were added, and the evacuation/nitrogen procedure repeated one more time. The reaction mixture was then refluxed until t.l.c. (10% ethyl acetate in dichloromethane) showed complete disappearance of 7-iodoisatin (1-2 hours). After cooling to room temperature, the 1,2-dimethoxyethane was removed under reduced pressure. The residue was diluted with 1M aqueous hydrochloric acid and extracted into ethyl acetate (3×). The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure to give crude 7-phenylisatin 7. This compound was prepared To a 1 L 3-necked round-bottomed flask fitted with a reflux condenser The reaction mixture was then refluxed until t.l.c the 1,2-dimethoxyethane was removed under reduced pressure The residue was diluted with 1M aqueous hydrochloric acid extracted into ethyl acetate (3×) The organic layer was washed with brine dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure

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

Procedure: This compound was prepared according to the procedure described by Lisowski et al. J. Org. Chem., 2000, 65, 4193. To a 1 L 3-necked round-bottomed flask fitted with a reflux condenser were added intermediate 6 (2.0 g, 7.33 mmol) and tetrakis[triphenylphosphine]palladium (0.424 g, 0.367 mmol), followed by 225 mL 1,2-dimethoxyethane. The atmosphere in the reaction vessel was made inert by opening to vacuum, then to a positive pressure of nitrogen (3×). Phenylboronic acid (Aldrich, 0.983 g, 8.06 mmol) and a solution of sodium bicarbonate (1.23 g, 14.7 mmol) in 225 mL water were added, and the evacuation/nitrogen procedure repeated one more time. The reaction mixture was then refluxed until t.l.c. (10% ethyl acetate in dichloromethane) showed complete disappearance of 7-iodoisatin (1-2 hours). After cooling to room temperature, the 1,2-dimethoxyethane was removed under reduced pressure. The residue was diluted with 1M aqueous hydrochloric acid and extracted into ethyl acetate (3×). The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure to give crude 7-phenylisatin 7. This compound was prepared To a 1 L 3-necked round-bottomed flask fitted with a reflux condenser The reaction mixture was then refluxed until t.l.c the 1,2-dimethoxyethane was removed under reduced pressure The residue was diluted with 1M aqueous hydrochloric acid extracted into ethyl acetate (3×) The organic layer was washed with brine dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure

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

Procedure: To a ice cold solution of 7-iodoindoline-2,3-dione (2.9 g, 0.0106 mol) in an aq. solution of 2 N NaOH (15 mL) was added drop wise an aq. solution of 35% H2O2 (3 mL) and then allowed to stir at room temperature over night. After the reaction is completed, the reaction mixture was diluted with water (50 mL), adjusted the pH to 2 with conc. HCl.

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(hydroxyimino)-N-(2-iodophenyl)acetamide (3.2 g, 0.011 mmol) was added to conc. H2SO4 (15 mL) in small portions at 60° C. The reaction mixture was further heated at 85° C. for 5 h. After the reaction completion, the reaction mixture was cooled to room temperature and poured into crushed ice. A brown color solid product precipitated. It was then filtered and washed with chilled water several times, then dried in a vacuum oven to get 2.9 g of the required product as a red coloured solid (87%). After the reaction completion, the reaction mixture was cooled to room temperature poured into crushed ice A brown color solid product precipitated It was then filtered washed with chilled water several times dried in a vacuum oven

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

Procedure: 7-iodoisatin (0.136 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