ethenylsulfanylbenzene

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-ylamine (1.00 g, 2.46 mmol), tris(2-tolyl)phosphine (16 mg, 0.05 mmol) and a stir bar were added to a pressure vessel. Palladium(II) acetate (6 mg, 0.025 mmol), phenyl vinyl sulfide (0.330 mL, 2.53 mmol) and triethylamine (0.685 mL, 4.92 mmol) were subsequently added, followed by toluene (5 mL). The vessel was sealed with a TEFLON cap and the reaction was heated at 110° C. for 40 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, eluting with a linear gradient of 1-7% methanol in dichloromethane), followed by recrystallization from acetonitrile to provide 0.35 g of 2-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylthio)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine hydrobromide as yellow-orange crystals, mp 220-221° C. cap The reaction mixture was cooled to ambient temperature concentrated under reduced pressure The residue was purified by flash column chromatography (silica gel eluting with a linear gradient of 1-7% methanol in dichloromethane), followed by recrystallization from acetonitrile

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-ylamine (1.00 g, 2.46 mmol), tris(2-tolyl)phosphine (16 mg, 0.05 mmol) and a stir bar were added to a pressure vessel. Palladium(II) acetate (6 mg, 0.025 mmol), phenyl vinyl sulfide (0.330 mL, 2.53 mmol) and triethylamine (0.685 mL, 4.92 mmol) were subsequently added, followed by toluene (5 mL). The vessel was sealed with a TEFLON cap and the reaction was heated at 110° C. for 40 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, eluting with a linear gradient of 1-7% methanol in dichloromethane), followed by recrystallization from acetonitrile to provide 0.35 g of 2-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylthio)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine hydrobromide as yellow-orange crystals, mp 220-221° C. cap The reaction mixture was cooled to ambient temperature concentrated under reduced pressure The residue was purified by flash column chromatography (silica gel eluting with a linear gradient of 1-7% methanol in dichloromethane), followed by recrystallization from acetonitrile

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

Procedure: To a solution of maleic anhydride (0.39 g, 4 mmol) and phenyl vinyl sulfide (0.52, 4 mmol) in 17 mL of 1,2-dichloroethane under nitrogen, was added 2 mL (0.5 equiv) of ethylaluminum dichloride. The resultant solution was stirred at ambient temperature for 0.5 h and then diluted with 75 mL of methylene chloride. The methylene chloride solution was washed three times with saturated aqueous ammonium chloride solution and once with brine, dried over anhydrous sodium sulfate and concentrated to give 0.85 g of the title compound; EI-MS, m/e (rel intensity): 234 (M+, 23), 136 (100), 109 (12), 91 (21). The methylene chloride solution was washed three times with saturated aqueous ammonium chloride solution once with brine, dried over anhydrous sodium sulfate concentrated

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

Procedure: To a solution of maleic anhydride (0.39 g, 4 mmol) and phenyl vinyl sulfide (0.52, 4 mmol) in 17 mL of 1,2-dichloroethane under nitrogen, was added 2 mL (0.5 equiv) of ethylaluminum dichloride. The resultant solution was stirred at ambient temperature for 0.5 h and then diluted with 75 mL of methylene chloride. The methylene chloride solution was washed three times with saturated aqueous ammonium chloride solution and once with brine, dried over anhydrous sodium sulfate and concentrated to give 0.85 g of the title compound; EI-MS, m/e (rel intensity): 234 (M+, 23), 136 (100), 109 (12), 91 (21). The methylene chloride solution was washed three times with saturated aqueous ammonium chloride solution once with brine, dried over anhydrous sodium sulfate concentrated

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

Procedure: To a solution of dimethyl maleate (0.50 mL, 4 mmol) and phenyl vinyl sulfide (0.52 mL, 4 mmol) in 17 mL of 1,2-dichloroethane under nitrogen atmosphere, was added 1 equivalent (4 mL of a 1 M solution in hexane) of ethylaluminum dichloride. The resultant solution was heated at 85° C. for 18 h and then diluted with 75 mL of methylene chloride. The methylene chloride solution was washed three times with saturated aqueous ammonium chloride and once with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 0.98 g of the title compound; EI-MS, m/e (rel intensity): 280 (M+, 14), 136 (100). The methylene chloride solution was washed three times with saturated aqueous ammonium chloride once with brine, dried over anhydrous sodium sulfate filtered concentrated

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

Procedure: To a solution of 1.06 g (7.34 mmol) of dimethyl fumarate in 20 mL of dry 1,2-dichloroethane under nitrogen atmosphere, was added with stirring, 7.34 mmol of a 1.0 M solution of ethylaluminum dichloride in hexane. The resultant yellow solution was heated to reflux and a solution of 1.0 g (7.34 mmol) of phenyl vinyl sulfide in 4 mL of dry 1,2-dichloroethane was added dropwise, via syringe, over a period of 20 minutes. The reaction mixture was allowed to stir at reflux for 3 h. After cooling to ambient temperature, the reaction was quenched carefully with 100 mL of 1.0 N hydrochloric acid solution and the reaction mixture was extracted with 3×50 mL of ethyl acetate. The organic extract was washed with 2×50 mL of water and 50 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated to a viscous orange oil. The oil (1.56 g) was chromatographed on silica gel (25 g) eluted with 300 mL of 3% ethyl acetate in 1,2-dichloroethane. The resultant yellow oil was purified by bulb-to-bulb distillation to give the title compound as a yellow oil; b.p 120° C. (0.05 mm Hg); EI-MS, m/e (relative intensity): 280 (M+, 18), 136 (100), 91 (13); 1H NMR (CDCl3) δ 2.20 (q, 1H), 2.61 (m, 1H), 3.22 (q, 1H), 3.34 (t, 1H), 3.66 (s, 3H), 3.67 (s, 3H), 3.87 (m, 1H), 7.30 (m, 5H). The resultant yellow solution was heated to reflux to stir at reflux for 3 h the reaction was quenched carefully with 100 mL of 1.0 N hydrochloric acid solution the reaction mixture was extracted with 3×50 mL of ethyl acetate The organic extract was washed with 2×50 mL of water and 50 mL of brine dried over anhydrous magnesium sulfate filtered concentrated to a viscous orange oil The oil (1.56 g) was chromatographed on silica gel (25 g) eluted with 300 mL of 3% ethyl acetate in 1,2-dichloroethane The resultant yellow oil was purified by bulb-to-bulb distillation

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-ylamine (1.00 g, 2.46 mmol), tris(2-tolyl)phosphine (16 mg, 0.05 mmol) and a stir bar were added to a pressure vessel. Palladium(II) acetate (6 mg, 0.025 mmol), phenyl vinyl sulfide (0.330 mL, 2.53 mmol) and triethylamine (0.685 mL, 4.92 mmol) were subsequently added, followed by toluene (5 mL). The vessel was sealed with a TEFLON cap and the reaction was heated at 110° C. for 40 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, eluting with a linear gradient of 1-7% methanol in dichloromethane), followed by recrystallization from acetonitrile to provide 0.35 g of 2-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylthio)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine hydrobromide as yellow-orange crystals, mp 220-221° C. cap The reaction mixture was cooled to ambient temperature concentrated under reduced pressure The residue was purified by flash column chromatography (silica gel eluting with a linear gradient of 1-7% methanol in dichloromethane), followed by recrystallization from acetonitrile

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

Procedure: To a solution of maleic anhydride (0.39 g, 4 mmol) and phenyl vinyl sulfide (0.52, 4 mmol) in 17 mL of 1,2-dichloroethane under nitrogen, was added 2 mL (0.5 equiv) of ethylaluminum dichloride. The resultant solution was stirred at ambient temperature for 0.5 h and then diluted with 75 mL of methylene chloride. The methylene chloride solution was washed three times with saturated aqueous ammonium chloride solution and once with brine, dried over anhydrous sodium sulfate and concentrated to give 0.85 g of the title compound; EI-MS, m/e (rel intensity): 234 (M+, 23), 136 (100), 109 (12), 91 (21). The methylene chloride solution was washed three times with saturated aqueous ammonium chloride solution once with brine, dried over anhydrous sodium sulfate concentrated

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

Procedure: To a solution of dimethyl maleate (0.50 mL, 4 mmol) and phenyl vinyl sulfide (0.52 mL, 4 mmol) in 17 mL of 1,2-dichloroethane under nitrogen atmosphere, was added 1 equivalent (4 mL of a 1 M solution in hexane) of ethylaluminum dichloride. The resultant solution was heated at 85° C. for 18 h and then diluted with 75 mL of methylene chloride. The methylene chloride solution was washed three times with saturated aqueous ammonium chloride and once with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 0.98 g of the title compound; EI-MS, m/e (rel intensity): 280 (M+, 14), 136 (100). The methylene chloride solution was washed three times with saturated aqueous ammonium chloride once with brine, dried over anhydrous sodium sulfate filtered concentrated

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

Procedure: To a solution of 1.06 g (7.34 mmol) of dimethyl fumarate in 20 mL of dry 1,2-dichloroethane under nitrogen atmosphere, was added with stirring, 7.34 mmol of a 1.0 M solution of ethylaluminum dichloride in hexane. The resultant yellow solution was heated to reflux and a solution of 1.0 g (7.34 mmol) of phenyl vinyl sulfide in 4 mL of dry 1,2-dichloroethane was added dropwise, via syringe, over a period of 20 minutes. The reaction mixture was allowed to stir at reflux for 3 h. After cooling to ambient temperature, the reaction was quenched carefully with 100 mL of 1.0 N hydrochloric acid solution and the reaction mixture was extracted with 3×50 mL of ethyl acetate. The organic extract was washed with 2×50 mL of water and 50 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated to a viscous orange oil. The oil (1.56 g) was chromatographed on silica gel (25 g) eluted with 300 mL of 3% ethyl acetate in 1,2-dichloroethane. The resultant yellow oil was purified by bulb-to-bulb distillation to give the title compound as a yellow oil; b.p 120° C. (0.05 mm Hg); EI-MS, m/e (relative intensity): 280 (M+, 18), 136 (100), 91 (13); 1H NMR (CDCl3) δ2.20 (q, 1H), 2.61 (m, 1H), 3.22 (q, 1H), 3.34 (t, 1H), 3.66 (s, 3H), 3.67 (s, 3H), 3.87 (m, 1H), 7.30 (m, 5H). The resultant yellow solution was heated to reflux to stir at reflux for 3 h the reaction was quenched carefully with 100 mL of 1.0 N hydrochloric acid solution the reaction mixture was extracted with 3×50 mL of ethyl acetate The organic extract was washed with 2×50 mL of water and 50 mL of brine dried over anhydrous magnesium sulfate filtered concentrated to a viscous orange oil The oil (1.56 g) was chromatographed on silica gel (25 g) eluted with 300 mL of 3% ethyl acetate in 1,2-dichloroethane The resultant yellow oil was purified by bulb-to-bulb distillation

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

Procedure: To a solution of maleic anhydride (0.39 g, 4 mmol) and phenyl vinyl sulfide (0.52, 4 mmol) in 17 mL of 1,2-dichloroethane under nitrogen, was added 2 mL (0.5 equiv) of ethylaluminum dichloride. The resultant solution was stirred at ambient temperature for 0.5 h and then diluted with 75 mL of methylene chloride. The methylene chloride solution was washed three times with saturated aqueous ammonium chloride solution and once with brine, dried over anhydrous sodium sulfate and concentrated to give 0.85 g of the title compound; EI-MS, m/e (rel intensity): 234 (M+, 23), 136 (100), 109 (12), 91 (21). The methylene chloride solution was washed three times with saturated aqueous ammonium chloride solution once with brine, dried over anhydrous sodium sulfate concentrated

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

Procedure: To a solution of dimethyl maleate (0.50 mL, 4 mmol) and phenyl vinyl sulfide (0.52 mL, 4 mmol) in 17 mL of 1,2-dichloroethane under nitrogen atmosphere, was added 1 equivalent (4 mL of a 1 M solution in hexane) of ethylaluminum dichloride. The resultant solution was heated at 85° C. for 18 h and then diluted with 75 mL of methylene chloride. The methylene chloride solution was washed three times with saturated aqueous ammonium chloride and once with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 0.98 g of the title compound; EI-MS, m/e (rel intensity): 280 (M+, 14), 136 (100). The methylene chloride solution was washed three times with saturated aqueous ammonium chloride once with brine, dried over anhydrous sodium sulfate filtered concentrated