7-bromo-5-chloro-1H-indole-3-carbonitrile

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:

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

Procedure: Sodium hydride (0.081 g, 2.020 mmol) (60% in oil) was added slowly to a 0° C. solution of 7-bromo-5-chloro-1H-indole-3-carbonitrile (0.43 g, 1.683 mmol) in THF (10 mL). Bubbling occurred, and the reaction was stirred at 0° C. for 30 min, then 2-(Trimethylsilyl)ethoxymethyl chloride (0.418 mL, 2.356 mmol) was added. After stirring 30 min at ambient temperature, the reaction was quenched with aqueous sodium bicarbonate (10 mL) and extracted with ethyl acetate (2×20 mL). The organic layer was dried with MgSO4 and evaporated, and the residue was purified by chromatography on SiO2 with 5% ethyl acetate/hexanes to give 7-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile (620 mg, 1.607 mmol, 95% yield) as a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 7.71 (s, 1H), 7.69 (d, J=2.0 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 5.82 (s, 2H), 3.52 (app T, J=8.1 Hz, 2H), 0.90 (app t, J=8.2 Hz, 2H), −0.05 (s, 9H). LC/MS (HPLC method 4): tR=4.07 min, 385.4(MH)+. Bubbling After stirring 30 min at ambient temperature the reaction was quenched with aqueous sodium bicarbonate (10 mL) extracted with ethyl acetate (2×20 mL) The organic layer was dried with MgSO4 evaporated the residue was purified by chromatography on SiO2 with 5% ethyl acetate/hexanes

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

Procedure: Sodium hydride (0.081 g, 2.020 mmol) (60% in oil) was added slowly to a 0° C. solution of 7-bromo-5-chloro-1H-indole-3-carbonitrile (0.43 g, 1.683 mmol) in THF (10 mL). Bubbling occurred, and the reaction was stirred at 0° C. for 30 min, then 2-(Trimethylsilyl)ethoxymethyl chloride (0.418 mL, 2.356 mmol) was added. After stirring 30 min at ambient temperature, the reaction was quenched with aqueous sodium bicarbonate (10 mL) and extracted with ethyl acetate (2×20 mL). The organic layer was dried with MgSO4 and evaporated, and the residue was purified by chromatography on SiO2 with 5% ethyl acetate/hexanes to give 7-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile (620 mg, 1.607 mmol, 95% yield) as a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 7.71 (s, 1H), 7.69 (d, J=2.0 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 5.82 (s, 2H), 3.52 (app T, J=8.1 Hz, 2H), 0.90 (app t, J=8.2 Hz, 2H), −0.05 (s, 9H). LC/MS (HPLC method 4): tR=4.07 min, 385.4(MH)+. Bubbling After stirring 30 min at ambient temperature the reaction was quenched with aqueous sodium bicarbonate (10 mL) extracted with ethyl acetate (2×20 mL) The organic layer was dried with MgSO4 evaporated the residue was purified by chromatography on SiO2 with 5% ethyl acetate/hexanes

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

Procedure: A mixture of 7-bromo-5-chloro-1H-indole-3-carbaldehyde (0.80 g, 3.09 mmol), Ammonium phosphate, dibasic (1.269 mL, 15.47 mmol), and 1-nitropropane (0.276 mL, 3.09 mmol) in Acetic Acid (20 mL) was heated at reflux. The solvent was evaporated, the residue was taken up in aqueous sodium bicarbonate (300 mL) and extracted with ethyl acetate (3×20 mL). The organic layers were dried with MgSO4 and evaporated. The residue was purified by chromatography on SiO2 with 20%-25% ethyl acetate/hexanes to give 7-bromo-5-chloro-1H-indole-3-carbonitrile (0.43 g, 1.683 mmol, 54.4% yield) as a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 8.27 (bs, 1H), 7.79 (s, 1H), 7.72 (d, J=1.8 Hz, 1H), 7.49 (d, J=1.8 Hz, 1H). LC/MS (HPLC method 4): tR=3.12 min, 255.01(MH)+. was heated at reflux The solvent was evaporated extracted with ethyl acetate (3×20 mL) The organic layers were dried with MgSO4 evaporated The residue was purified by chromatography on SiO2 with 20%-25% ethyl acetate/hexanes

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

Procedure: Sodium hydride (0.081 g, 2.020 mmol) (60% in oil) was added slowly to a 0° C. solution of 7-bromo-5-chloro-1H-indole-3-carbonitrile (0.43 g, 1.683 mmol) in THF (10 mL). Bubbling occurred, and the reaction was stirred at 0° C. for 30 min, then 2-(Trimethylsilyl)ethoxymethyl chloride (0.418 mL, 2.356 mmol) was added. After stirring 30 min at ambient temperature, the reaction was quenched with aqueous sodium bicarbonate (10 mL) and extracted with ethyl acetate (2×20 mL). The organic layer was dried with MgSO4 and evaporated, and the residue was purified by chromatography on SiO2 with 5% ethyl acetate/hexanes to give 7-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile (620 mg, 1.607 mmol, 95% yield) as a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 7.71 (s, 1H), 7.69 (d, J=2.0 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 5.82 (s, 2H), 3.52 (app T, J=8.1 Hz, 2H), 0.90 (app t, J=8.2 Hz, 2H), −0.05 (s, 9H). LC/MS (HPLC method 4): tR=4.07 min, 385.4(MH)+. Bubbling After stirring 30 min at ambient temperature the reaction was quenched with aqueous sodium bicarbonate (10 mL) extracted with ethyl acetate (2×20 mL) The organic layer was dried with MgSO4 evaporated the residue was purified by chromatography on SiO2 with 5% ethyl acetate/hexanes

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

Procedure: A mixture of 7-bromo-5-chloro-1H-indole-3-carbaldehyde (0.80 g, 3.09 mmol), Ammonium phosphate, dibasic (1.269 mL, 15.47 mmol), and 1-nitropropane (0.276 mL, 3.09 mmol) in Acetic Acid (20 mL) was heated at reflux. The solvent was evaporated, the residue was taken up in aqueous sodium bicarbonate (300 mL) and extracted with ethyl acetate (3×20 mL). The organic layers were dried with MgSO4 and evaporated. The residue was purified by chromatography on SiO2 with 20%-25% ethyl acetate/hexanes to give 7-bromo-5-chloro-1H-indole-3-carbonitrile (0.43 g, 1.683 mmol, 54.4% yield) as a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 8.27 (bs, 1H), 7.79 (s, 1H), 7.72 (d, J=1.8 Hz, 1H), 7.49 (d, J=1.8 Hz, 1H). LC/MS (HPLC method 4): tR=3.12 min, 255.01(MH)+. was heated at reflux The solvent was evaporated extracted with ethyl acetate (3×20 mL) The organic layers were dried with MgSO4 evaporated The residue was purified by chromatography on SiO2 with 20%-25% ethyl acetate/hexanes