5-fluoro-6-iodo-1H-indole

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 6-iodo-5-fluoro-1H-indole (0.495 g, 1.890 mmol) in dry DMF (7.0 mL) was added sodium hydride (55% suspension in oil) (0.124 g, 2.840 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min, and then iodomethane (0.15 mL, 2.47 mmol) was added. The mixture was stirred for 1 hour at room temperature, and then quenched with ice and extracted with EtOAc (50 mL). The organic layer was washed with water, brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography (EtOAc-hexane, 1:9) to afford 5-fluoro-6-iodo-1-methyl-1H-indole as a colorless solid (0.50 g, 96%). The mixture was stirred for 1 hour at room temperature quenched with ice extracted with EtOAc (50 mL) The organic layer was washed with water, brine dried over MgSO4 filtered concentrated The residue was purified by column chromatography (EtOAc-hexane, 1:9)

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

Procedure: To a solution of 6-iodo-5-fluoro-1H-indole (0.495 g, 1.890 mmol) in dry DMF (7.0 mL) was added sodium hydride (55% suspension in oil) (0.124 g, 2.840 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min, and then iodomethane (0.15 mL, 2.47 mmol) was added. The mixture was stirred for 1 hour at room temperature, and then quenched with ice and extracted with EtOAc (50 mL). The organic layer was washed with water, brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography (EtOAc-hexane, 1:9) to afford 5-fluoro-6-iodo-1-methyl-1H-indole as a colorless solid (0.50 g, 96%). The mixture was stirred for 1 hour at room temperature quenched with ice extracted with EtOAc (50 mL) The organic layer was washed with water, brine dried over MgSO4 filtered concentrated The residue was purified by column chromatography (EtOAc-hexane, 1:9)

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

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

Procedure: To a microwave reaction vessel was added 5-fluoro-6-iodo-1H-indole (1 g), potassium ferrocyanide (1.41 g), Na2CO3 (0.80 g), PdCl2(dppf)-CH2Cl2 adduct (0.31 g) and N,N-dimethylacetamide (DMA). The reaction vessel was then sealed and heated in Biotage Initiator using initial high to 140° C. for 2 hours. After cooling the reaction, the solvent was evaporated and the residue was partitioned between water (50 mL) and ethyl acetate (50 mL). The insolubles were filtered, the organics were evaporated and the residue was chromatographed on silica gel to give the designed product 5-fluoro-1H-indole-6-carbonitrile (D151) (0.25 g). MS (ES): C9H5FN2 requires 160.0; found 161.1 (M+H+). To a microwave reaction vessel The reaction vessel was then sealed heated in Biotage Initiator high to 140° C. for 2 hours After cooling the reaction the solvent was evaporated the residue was partitioned between water (50 mL) and ethyl acetate (50 mL) The insolubles were filtered the organics were evaporated the residue was chromatographed on silica gel

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

Procedure: To a solution of 6-iodo-5-fluoro-1H-indole (0.495 g, 1.890 mmol) in dry DMF (7.0 mL) was added sodium hydride (55% suspension in oil) (0.124 g, 2.840 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min, and then iodomethane (0.15 mL, 2.47 mmol) was added. The mixture was stirred for 1 hour at room temperature, and then quenched with ice and extracted with EtOAc (50 mL). The organic layer was washed with water, brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography (EtOAc-hexane, 1:9) to afford 5-fluoro-6-iodo-1-methyl-1H-indole as a colorless solid (0.50 g, 96%). The mixture was stirred for 1 hour at room temperature quenched with ice extracted with EtOAc (50 mL) The organic layer was washed with water, brine dried over MgSO4 filtered concentrated The residue was purified by column chromatography (EtOAc-hexane, 1:9)