1-Iodo-4-isopropylbenzene

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

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

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

Procedure: The crude 4-isopropylphenylacetylene was dissolved in triethylamine (100 mL). 4-iodoisopropylbenzene (12.3 g, 50 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.70 g, 1 mmol), and copper(I) iodide (1.5 g) were added. The reaction was stirred at room temperature for 2 days, heated to reflux for 1 hour, cooled, diluted with hexanes, and filtered. The filtrate was evaporated under reduced pressure. The residue was filtered through a pad of silica gel with hexanes, and the solvent was evaporated to give 11.40 g (87%) of 1,2-bis(4-(2-propyl)phenyl)acetylene. heated to reflux for 1 hour cooled filtered The filtrate was evaporated under reduced pressure The residue was filtered through a pad of silica gel with hexanes the solvent was evaporated

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

Procedure: To a solution of 4-iodoisopropylbenzene (12.3 g, 50 mmol, Lancaster Chemical Co.) in triethylamine (150 mL) was added trimethylsilylacetylene (5.89 g, 60 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.70 g, 1 mmol, Aldrich), and copper(I) iodide (1.5 g). The reaction was stirred at room temperature for 18 hours, diluted with hexanes and filtered. The filtrate was evaporated under reduced pressure to give crude 1-(4-(2-propyl)phenyl)-2-trimethylsilyl acetylene. filtered The filtrate was evaporated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 0.025 g (0.10 mmol) 4-iodoisopropylbenzene are added 20 g (0.10 mmol) N-ethyl-2-(4-ethynyl-phenyl)-propionamide (XVII.1) in 1 mL THF, followed by the addition of 0.5 mL 2-butylamine and 0.75 mL water. Subsequently 3 mg (0.05 mmol) bis-(triphenylphosphine)-palladium dichloride are added and the mixture is stirred at 80° C. for 5 h. After that time, the solvent is removed. The residue is taken up in DMF and the desired product was purified using RP-HPLC (water/MeOH+0.1% TFA). After that time, the solvent is removed the desired product was purified

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

Procedure: (C9H11I), FW=246.09 g/mol. Cumene (45.0 g, 377 mmol), iodine (38.25 g, 151 mmol) and iodic acid (15.38 g, 87.4 mmol) were dissolved in a solution of acetic acid (188 mL), water (30 mL), dichloromethane (19 mL), and sulfuric acid (7.5 mL). The solution was heated to 85° C. for three hours. Once the reaction was complete, the reaction was worked up with water and dichloromethane. The dichloromethane was washed with sodium hydrosulfite, dried over magnesium sulfate and concentrated, yielding a red liquid in 94% yield. Rf 0.63 (hexanes) 1H NMR (300 MHz, CDCl3, ppm) d 7.58 (d, 2H, J=8.3 Hz), 6.96 (s, 2H, J=8.3 Hz), 2.83 (septet, 1H, J=6.9 Hz), 1.20 (d, 6H, J=6.9 Hz); 13C NMR (75.5 MHz, CDCl3, ppm) d 148.2, 137.2, 128.5, 90.7, 33.6, 23.8; LR MS (EI) m/z 246. The dichloromethane was washed with sodium hydrosulfite dried over magnesium sulfate concentrated yielding a red liquid in 94% yield

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of [5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-acetonitrile (800 mg, 3.1 mmol), 1-iodo-4-isopropyl-benzene (1.13 g, 4.6 mmol), copper iodide (874 mg, 4.6 mmol), Cs2CO3 (1.50 g, 4.6 mmol) and ethylenediamine (30 μL, 4.6 mmol), and dioxane (100 mL) is heated to 60° C. under nitrogen for 18 h. The mixture is diluted with EtOAc and filtered over a small pad of silica gel. The obtained solution is concentrated under reduced pressure, and the residue is purified by chromatography on silica gel (hexane-EtOAc, 5:1) to afford [5-(2,6-diethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-acetonitrile as colorless oil. filtered over a small pad of silica gel The obtained solution is concentrated under reduced pressure the residue is purified by chromatography on silica gel (hexane-EtOAc, 5:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of [5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-acetonitrile (800 mg, 3.1 mmol), 1-iodo-4-isopropyl-benzene (1.13 g, 4.6 mmol), copper iodide (874 mg, 4.6 mmol), Cs2CO3 (1.50 g, 4.6 mmol) and ethylenediamine (30 μL, 4.6 mmol), and dioxane (100 mL) is heated to 60° C. under nitrogen for 18 h. The mixture is diluted with EtOAc and filtered over a small pad of silica gel. The obtained solution is concentrated under reduced pressure, and the residue is purified by chromatography on silica gel (hexane-EtOAc, 5:1) to afford [5-(2,6-diethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-acetonitrile as colorless oil. filtered over a small pad of silica gel The obtained solution is concentrated under reduced pressure the residue is purified by chromatography on silica gel (hexane-EtOAc, 5:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridine (700 mg, 2.8 mmol), 1-iodo-4-isopropyl-benzene (2.0 g, 8.1 mmol), CuI (1.0 g, 5.3 mmol), cesium carbonate (1.8 g, 5.5 mmol) and ethylenediamine (336 mg, 5.6 mmol) in dioxane (10 mL) is heated at 60° C. overnight. The reaction mixture is cooled, diluted with EtOAc, and filtered through Celite. The filtrate is concentrated under reduced pressure. The residue is purified by chromatography on silica gel (Hexane/EtOAc, 4:1) to afford 500 mg of 2.7 g of 5-(2,6-diethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridine as a solid. 1H NMR: (CDCl3) 8.97 (s, 1H), 7.41-7.52 (m, 6H), 7.28 (t, 1H), 7.15 (d, 2H), 6.68 (d, 1H), 3.03 (m, 1H), 2.36 (m, 4H), 1.34 (d, 6H), 1.01 (t, 6H). The reaction mixture is cooled filtered through Celite The filtrate is concentrated under reduced pressure The residue is purified by chromatography on silica gel (Hexane/EtOAc, 4:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of [5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-acetonitrile (800 mg, 3.1 mmol), 1-iodo-4-isopropyl-benzene (1.13 g, 4.6 mmol), copper iodide (874 mg, 4.6 mmol), Cs2CO3 (1.50 g, 4.6 mmol) and ethylenediamine (30 μL, 4.6 mmol), and dioxane (100 mL) is heated to 60° C. under nitrogen for 18 h. The mixture is diluted with EtOAc and filtered over a small pad of silica gel. The obtained solution is concentrated under reduced pressure, and the residue is purified by chromatography on silica gel (hexane-EtOAc, 5:1) to afford [5-(2,6-diethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-acetonitrile as colorless oil. filtered over a small pad of silica gel The obtained solution is concentrated under reduced pressure the residue is purified by chromatography on silica gel (hexane-EtOAc, 5:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridine (700 mg, 2.8 mmol), 1-iodo-4-isopropyl-benzene (2.0 g, 8.1 mmol), CuI (1.0 g, 5.3 mmol), cesium carbonate (1.8 g, 5.5 mmol) and ethylenediamine (336 mg, 5.6 mmol) in dioxane (10 mL) is heated at 60° C. overnight. The reaction mixture is cooled, diluted with EtOAc, and filtered through Celite. The filtrate is concentrated under reduced pressure. The residue is purified by chromatography on silica gel (Hexane/EtOAc, 4:1) to afford 500 mg of 2.7 g of 5-(2,6-diethyl-phenyl)-1-(4-isopropyl-phenyl)-1H-pyrrolo[2,3-c]pyridine as a solid. 1H NMR: (CDCl3) 8.97 (s, 1H), 7.41-7.52 (m, 6H), 7.28 (t, 1H), 7.15 (d, 2H), 6.68 (d, 1H), 3.03 (m, 1H), 2.36 (m, 4H), 1.34 (d, 6H), 1.01 (t, 6H). The reaction mixture is cooled filtered through Celite The filtrate is concentrated under reduced pressure The residue is purified by chromatography on silica gel (Hexane/EtOAc, 4:1)

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

Procedure: The crude 4-isopropylphenylacetylene was dissolved in triethylamine (100 mL). 4-iodoisopropylbenzene (12.3 g, 50 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.70 g, 1 mmol), and copper(I) iodide (1.5 g) were added. The reaction was stirred at room temperature for 2 days, heated to reflux for 1 hour, cooled, diluted with hexanes, and filtered. The filtrate was evaporated under reduced pressure. The residue was filtered through a pad of silica gel with hexanes, and the solvent was evaporated to give 11.40 g (87%) of 1,2-bis(4-(2-propyl)phenyl)acetylene. heated to reflux for 1 hour cooled filtered The filtrate was evaporated under reduced pressure The residue was filtered through a pad of silica gel with hexanes the solvent was evaporated