5-fluoro-2-iodoaniline

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

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

Procedure: 5-Fluoro-2-iodoaniline (30 g, 126 mmol) and 3-fluorophenylacetylene (20 g, 166 mmol) were dissolved in diethylamine (500 ml) and the mixture purged with nitrogen for 10 min. Tetrakis(triphenylphosphine)palladium (2 g) and copper(I) iodide (0.4 g) were added and the mixture stirred at room temperature for 15 h. The solvent was removed in vacuo and the residue partitioned between diethyl ether (500 ml) and water (500 ml), the organic layer was separated and washed with water (2×500 ml), saturated sodium chloride (200 ml), dried over MgSO4, filtered through a short plug of Florisil and evaporated in vacuo. The solid was dissolved in anhydrous DMF (500 ml), copper(I) iodide (12 g, 63 mmol) and calcium carbonate (12.6 g, 126 mmol) added and the mixture heated at 120° C. under an atmosphere of nitrogen for 48 h. The mixture was filtered through hyflo and the filtrate evaporated in vacuo. The residue was partitioned between ethyl acetate (500 ml) and water (500 ml), the organic layer was separated and washed with water (2×500 ml) and saturated sodium chloride (100 ml), dried over MgSO4 and evaporated in vacuo. The residue was triturated with a mixture of diethyl ether and hexane, the solid filtered and dried in vacuo to afford 25 g (109 mmol; 87%) of 2-(3-fluorophenyl)-6-fluoroindole as a brown solid. δH (360 MHz; CDCl3) 6.78 (1H, d, J 1.8, indole H3), 6.88 (1H, m, aromatic), 6.99 (1H, m, aromatic), 7.05 (1H, dd, J 9.5 and 2.2, aromatic), 7.29 (1H, dd, J 8.6 and 1.0, aromatic), 7.36 (2H, m, aromatics), 7.51 (1H, dd, J 8.6 and 5.3, indole H4), 8.37 (1H, br s, NH). the mixture purged with nitrogen for 10 min Tetrakis(triphenylphosphine)palladium (2 g) and copper(I) iodide (0.4 g) were added The solvent was removed in vacuo the residue partitioned between diethyl ether (500 ml) and water (500 ml) the organic layer was separated washed with water (2×500 ml), saturated sodium chloride (200 ml) dried over MgSO4 filtered through a short plug of Florisil evaporated in vacuo The solid was dissolved in anhydrous DMF (500 ml) the mixture heated at 120° C. under an atmosphere of nitrogen for 48 h The mixture was filtered through hyflo the filtrate evaporated in vacuo The residue was partitioned between ethyl acetate (500 ml) and water (500 ml) the organic layer was separated washed with water (2×500 ml) and saturated sodium chloride (100 ml) dried over MgSO4 evaporated in vacuo The residue was triturated with a mixture of diethyl ether and hexane the solid filtered dried in vacuo

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

Procedure: 5-Fluoro-2-iodoaniline (30 g, 126 mmol) and 3-fluorophenylacetylene (20 g, 166 mmol) were dissolved in diethylamine (500 ml) and the mixture purged with nitrogen for 10 min. Tetrakis(triphenylphosphine)palladium (2 g) and copper(I) iodide (0.4 g) were added and the mixture stirred at room temperature for 15 h. The solvent was removed in vacuo and the residue partitioned between diethyl ether (500 ml) and water (500 ml), the organic layer was separated and washed with water (2×500 ml), saturated sodium chloride (200 ml), dried over MgSO4, filtered through a short plug of Florisil and evaporated in vacuo. The solid was dissolved in anhydrous DMF (500 ml), copper(I) iodide (12 g, 63 mmol) and calcium carbonate (12.6 g, 126 mmol) added and the mixture heated at 120° C. under an atmosphere of nitrogen for 48 h. The mixture was filtered through hyflo and the filtrate evaporated in vacuo. The residue was partitioned between ethyl acetate (500 ml) and water (500 ml), the organic layer was separated and washed with water (2×500 ml) and saturated sodium chloride (100 ml), dried over MgSO4 and evaporated in vacuo. The residue was triturated with a mixture of diethyl ether and hexane, the solid filtered and dried in vacuo to afford 25 g (109 mmol; 87%) of 2-(3-fluorophenyl)-6-fluoroindole as a brown solid. δH (360 MHz; CDCl3) 6.78 (1H, d, J 1.8, indole H3), 6.88 (1H, m, aromatic), 6.99 (1H, m, aromatic), 7.05 (1H, dd, J 9.5 and 2.2, aromatic), 7.29 (1H, dd, J 8.6 and 1.0, aromatic), 7.36 (2H, m, aromatics), 7.51 (1H, dd, J 8.6 and 5.3, indole H4), 8.37 (1H, br s, NH). the mixture purged with nitrogen for 10 min Tetrakis(triphenylphosphine)palladium (2 g) and copper(I) iodide (0.4 g) were added The solvent was removed in vacuo the residue partitioned between diethyl ether (500 ml) and water (500 ml) the organic layer was separated washed with water (2×500 ml), saturated sodium chloride (200 ml) dried over MgSO4 filtered through a short plug of Florisil evaporated in vacuo The solid was dissolved in anhydrous DMF (500 ml) the mixture heated at 120° C. under an atmosphere of nitrogen for 48 h The mixture was filtered through hyflo the filtrate evaporated in vacuo The residue was partitioned between ethyl acetate (500 ml) and water (500 ml) the organic layer was separated washed with water (2×500 ml) and saturated sodium chloride (100 ml) dried over MgSO4 evaporated in vacuo The residue was triturated with a mixture of diethyl ether and hexane the solid filtered dried in vacuo

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

Procedure: 3-Ethynylpyridine and 3-fluoro-6-iodoaniline are processed according to the method described in Example 86 to give 6-fluoro-2-pyridin-3-yl-1H-indole. MS (ESI) m/z 213.0 (M+H)+.

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

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

Procedure: 3-Ethynylpyridine and 3-fluoro-6-iodoaniline are processed according to the method described in Example 86 to give 6-fluoro-2-pyridin-3-yl-1H-indole. MS (ESI) m/z 213.0 (M+H)+.

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

Procedure: 160 mL of THF were placed in the flask and degassed with argon. Then 10 g (45 mmol) 5-fluoro-2-iodo-aniline, 1.5 g (2.1 mmol) PdCl2(PPh3)2 and 0.40 g (2.1 mmol) copper iodide were added and the flask was rinsed with argon. Then 18 mL (0.13 mol) triethylamine were added and 3.0 g (55 mmol) 1-butyne (in gaseous form) were passed through the solution. The reaction mixture was stirred for 3 h at RT, then diluted with diethyl ether, filtered through kieselguhr and evaporated down. degassed with argon the flask was rinsed with argon filtered through kieselguhr evaporated down

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

Procedure: 3-Ethynylpyridine and 3-fluoro-6-iodoaniline are processed according to the method described in Example 86 to give 6-fluoro-2-pyridin-3-yl-1H-indole. MS (ESI) m/z 213.0 (M+H)+.

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

Procedure: 5-Fluoro-2-iodoaniline (30 g, 126 mmol) and 3-fluorophenylacetylene (20 g, 166 mmol) were dissolved in diethylamine (500 ml) and the mixture purged with nitrogen for 10 min. Tetrakis(triphenylphosphine)palladium (2 g) and copper(I) iodide (0.4 g) were added and the mixture stirred at room temperature for 15 h. The solvent was removed in vacuo and the residue partitioned between diethyl ether (500 ml) and water (500 ml), the organic layer was separated and washed with water (2×500 ml), saturated sodium chloride (200 ml), dried over MgSO4, filtered through a short plug of Florisil and evaporated in vacuo. The solid was dissolved in anhydrous DMF (500 ml), copper(I) iodide (12 g, 63 mmol) and calcium carbonate (12.6 g, 126 mmol) added and the mixture heated at 120° C. under an atmosphere of nitrogen for 48 h. The mixture was filtered through hyflo and the filtrate evaporated in vacuo. The residue was partitioned between ethyl acetate (500 ml) and water (500 ml), the organic layer was separated and washed with water (2×500 ml) and saturated sodium chloride (100 ml), dried over MgSO4 and evaporated in vacuo. The residue was triturated with a mixture of diethyl ether and hexane, the solid filtered and dried in vacuo to afford 25 g (109 mmol; 87%) of 2-(3-fluorophenyl)-6-fluoroindole as a brown solid. δH (360 MHz; CDCl3) 6.78 (1H, d, J 1.8, indole H3), 6.88 (1H, m, aromatic), 6.99 (1H, m, aromatic), 7.05 (1H, dd, J 9.5 and 2.2, aromatic), 7.29 (1H, dd, J 8.6 and 1.0, aromatic), 7.36 (2H, m, aromatics), 7.51 (1H, dd, J 8.6 and 5.3, indole H4), 8.37 (1H, br s, NH). the mixture purged with nitrogen for 10 min Tetrakis(triphenylphosphine)palladium (2 g) and copper(I) iodide (0.4 g) were added The solvent was removed in vacuo the residue partitioned between diethyl ether (500 ml) and water (500 ml) the organic layer was separated washed with water (2×500 ml), saturated sodium chloride (200 ml) dried over MgSO4 filtered through a short plug of Florisil evaporated in vacuo The solid was dissolved in anhydrous DMF (500 ml) the mixture heated at 120° C. under an atmosphere of nitrogen for 48 h The mixture was filtered through hyflo the filtrate evaporated in vacuo The residue was partitioned between ethyl acetate (500 ml) and water (500 ml) the organic layer was separated washed with water (2×500 ml) and saturated sodium chloride (100 ml) dried over MgSO4 evaporated in vacuo The residue was triturated with a mixture of diethyl ether and hexane the solid filtered dried in vacuo

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

Procedure: 3-Ethynylpyridine and 3-fluoro-6-iodoaniline are processed according to the method described in Example 86 to give 6-fluoro-2-pyridin-3-yl-1H-indole. MS (ESI) m/z 213.0 (M+H)+.