3,5-dichlorobenzohydrazide

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

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

Procedure: To a suspension of compound 5 (328 mg, 1.0 mmol) in DCM (10 ml) was added compound 6 (150 mg, 1.0 mmol), EDC (288 mg, 1.5 mmol) and HOBt (202 mg, 1.5 mmol). The mixture was stirred at ambient temperature for 2 hours. The mixture was concentrated and purified by chromatography to give compound 7 as a white solid (230 mg). Yield: 50%. The mixture was concentrated purified by chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of compound 5 (700 mg, 2.14 mmol), compound 6 (222 mg, 1.86 mmol) and K2CO3 (772 mg, 5.59 mmol, 2 eq.) in 10 ml of DMF was heated to 100° C. for 3 hours. The reaction mixture was brought to ambient temperature, filtered and the filtrate was evaporated to obtain a crude residue which was purified by column chromatography using EtOAc/hexane (50:50) as an eluent to obtain compound 7 as a colorless liquid (340 mg). Yield: 50%. was brought to ambient temperature filtered the filtrate was evaporated to obtain a crude residue which was purified by column chromatography

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

Procedure: To a mixture of 3,5-dichlorobenzohydrazide 5 (0.5 g, 2.4 mmol) and K2CO3 (0.61 g, 4.4 mmol) in acetonitrile (30 mL) was added 2-chloroacetyl chloride (0.41 g, 3.66 mmol) dropwise at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 hours. The solid was collected, washed with H2O and ether, and dried to afford 3,5-dichloro-N′-(2-chloroacetyl)benzohydrazide 6 (0.63 g, 92%) which was used for the next step without further purification. A mixture of 3,5-dichloro-N′-(2-chloroacetyl)benzohydrazide 6 (0.63 g, 2.24 mmol) and phosphorous oxychloride (0.51 g, 3.36 mmol) in acetonitrile (20 mL) was stirred under reflux for 16 hours and concentrated. The residue was subjected to flush column chromatography eluting with 10-25% acetone/hexanes to give compound 7 (0.52 g). Yield: 88%. The solid was collected washed with H2O and ether dried

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general method as outlined in Example 1, into a suspension of 5-iodo-1H-indole-2,3-dione in acetic acid was added 3,5-dichlorobenzohydrazide. After stirring at 100° C., the reaction mixture was cooled to rt and a yellow solid precipitated out. Filtration on a fritté, washing with AcOH, water and drying under vacuo at 60° C. overnight gave 159 mg of the title compound (69%) as a orange solid in 90% purity by HPLC (Rt: 5.86, 6.66, gradient of 10 min, MaxPlot detection between 230 and 400 nm). the reaction mixture was cooled to rt a yellow solid precipitated out Filtration on a fritté washing with AcOH, water drying under vacuo at 60° C. overnight

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

Procedure: To a suspension of compound 5 (328 mg, 1.0 mmol) in DCM (10 ml) was added compound 6 (150 mg, 1.0 mmol), EDC (288 mg, 1.5 mmol) and HOBt (202 mg, 1.5 mmol). The mixture was stirred at ambient temperature for 2 hours. The mixture was concentrated and purified by chromatography to give compound 7 as a white solid (230 mg). Yield: 50%. The mixture was concentrated purified by chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of compound 5 (700 mg, 2.14 mmol), compound 6 (222 mg, 1.86 mmol) and K2CO3 (772 mg, 5.59 mmol, 2 eq.) in 10 ml of DMF was heated to 100° C. for 3 hours. The reaction mixture was brought to ambient temperature, filtered and the filtrate was evaporated to obtain a crude residue which was purified by column chromatography using EtOAc/hexane (50:50) as an eluent to obtain compound 7 as a colorless liquid (340 mg). Yield: 50%. was brought to ambient temperature filtered the filtrate was evaporated to obtain a crude residue which was purified by column chromatography

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

Procedure: To a mixture of 3,5-dichlorobenzohydrazide 5 (0.5 g, 2.4 mmol) and K2CO3 (0.61 g, 4.4 mmol) in acetonitrile (30 mL) was added 2-chloroacetyl chloride (0.41 g, 3.66 mmol) dropwise at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 hours. The solid was collected, washed with H2O and ether, and dried to afford 3,5-dichloro-N′-(2-chloroacetyl)benzohydrazide 6 (0.63 g, 92%) which was used for the next step without further purification. A mixture of 3,5-dichloro-N′-(2-chloroacetyl)benzohydrazide 6 (0.63 g, 2.24 mmol) and phosphorous oxychloride (0.51 g, 3.36 mmol) in acetonitrile (20 mL) was stirred under reflux for 16 hours and concentrated. The residue was subjected to flush column chromatography eluting with 10-25% acetone/hexanes to give compound 7 (0.52 g). Yield: 88%. The solid was collected washed with H2O and ether dried

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

Procedure: To a mixture of 3,5-dichlorobenzohydrazide 5 (0.5 g, 2.4 mmol) and K2CO3 (0.61 g, 4.4 mmol) in acetonitrile (30 mL) was added 2-chloroacetyl chloride (0.41 g, 3.66 mmol) dropwise at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 hours. The solid was collected, washed with H2O and ether, and dried to afford 3,5-dichloro-N′-(2-chloroacetyl)benzohydrazide 6 (0.63 g, 92%) which was used for the next step without further purification. A mixture of 3,5-dichloro-N′-(2-chloroacetyl)benzohydrazide 6 (0.63 g, 2.24 mmol) and phosphorous oxychloride (0.51 g, 3.36 mmol) in acetonitrile (20 mL) was stirred under reflux for 16 hours and concentrated. The residue was subjected to flush column chromatography eluting with 10-25% acetone/hexanes to give compound 7 (0.52 g). Yield: 88%. The solid was collected washed with H2O and ether dried

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general method as outlined in Example 1, into a suspension of 5-iodo-1H-indole-2,3-dione in acetic acid was added 3,5-dichlorobenzohydrazide. After stirring at 100° C., the reaction mixture was cooled to rt and a yellow solid precipitated out. Filtration on a fritté, washing with AcOH, water and drying under vacuo at 60° C. overnight gave 159 mg of the title compound (69%) as a orange solid in 90% purity by HPLC (Rt: 5.86, 6.66, gradient of 10 min, MaxPlot detection between 230 and 400 nm). the reaction mixture was cooled to rt a yellow solid precipitated out Filtration on a fritté washing with AcOH, water drying under vacuo at 60° C. overnight

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

Procedure: To a suspension of compound 5 (328 mg, 1.0 mmol) in DCM (10 ml) was added compound 6 (150 mg, 1.0 mmol), EDC (288 mg, 1.5 mmol) and HOBt (202 mg, 1.5 mmol). The mixture was stirred at ambient temperature for 2 hours. The mixture was concentrated and purified by chromatography to give compound 7 as a white solid (230 mg). Yield: 50%. The mixture was concentrated purified by chromatography