1-(1-benzofuran-3-yl)-2-bromoethanone

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

Procedure: A mixture of 3-(2-bromoacetyl)benzo[b]furan (36.9 g), 2-imidazolidinethione (15.75 g), ethanol (600 ml) and acetic acid (400 ml) was heated under reflux for 21 hours then allowed to cool to ambient temperature. The resulting solid was collected by filtration, washed with ether (500 ml), and dissolved in hot methanol (500 ml). Charcoal (2 g) was added and the hot mixture was stirred for a few minutes, then filtered and allowed to cool to ambient temperature. The resulting solid was collected by filtration, ground to a fine powder, and dried in vacuo at 80° C. to give 3-(benzo[b]furan-3-yl)-5,6-dihydroimidazo[2,1-b]thiazole monohydrobromide 0.7 hydrate as an off-white solid (28.1 g), m.p. 251°-254.50C. was heated under reflux for 21 hours The resulting solid was collected by filtration washed with ether (500 ml) dissolved in hot methanol (500 ml) Charcoal (2 g) was added filtered to cool to ambient temperature The resulting solid was collected by filtration, ground to a fine powder dried in vacuo at 80° C.

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

Procedure: A mixture of 3-(2-bromoacetyl)benzo[b]furan (0.25 g), 2-imidazolidinethione (0.11 g), ethanol (30 ml) and acetic acid (20 ml) was heated under reflux for 20 hours, then allowed to cool to ambient temperature. The resulting solid was collected by filtration, washed with ether, and dried in vacuo at ambient temperature to give 3-(benzo[b]furan-3-yl)-5,6-dihydroimidazo[2,1-b]thiazole monohydrobromide monohydrate as a white solid (0.145 g), m.p. 242°-244° C. was heated under reflux for 20 hours The resulting solid was collected by filtration washed with ether dried in vacuo at ambient temperature

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

Procedure: A solution of phenyltrimethylammonium tribromide (2.47 g) in tetrahydrofuran (20 ml) was added dropwise at ambient temperature under nitrogen over 5 minutes to a stirred solution of 3-acetylbenzo[b]furan (1 g) in tetrahydrofuran (20 ml), then the mixture was stirred at ambient temperature for a further 1.5 hours, filtered, and the solvent removed in vacuo. The residue was triturated with ether, and the resulting solid was collected by filtration and dried in vacuo at ambient temperature to give 3-(2-bromoacetyl)benzo[b]furan as an off-white solid (0.25 g). filtered the solvent removed in vacuo The residue was triturated with ether the resulting solid was collected by filtration dried in vacuo at ambient temperature

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

Procedure: To a stirred solution of 2-(1-trityl-1H-imidazol-4-yl)phenol (0.5 mmol) in anhydrous DMF (3 mL) at 0° C. was added NaH (36.0 mg, 0.75 mmol). The resulting suspension was allowed to stir for 10 min. To the resulting solution was added 1-(benzofuran-3-yl)-2-bromoethanone (0.50 mmol). After stirring overnight, the reaction mixture was carefully diluted, with water and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water, brine and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product was purified by column chromatography. Yield 60%. 1H NMR: 5.16 (s, 2H), 6.88 (d, 1H, J=8.10 Hz), 7.06-7.47 (m, 20H), 7.54 (d, 2H, J=7.92 Hz), 8.22 (dd, 2H, J=7.60 Hz, 1.35 Hz), 8.33 (s, 1H). After stirring overnight extracted with ethyl acetate (2×10 mL) The combined organic layers were washed with water, brine dried (Na2SO4) The solvent was removed under reduced pressure the crude product was purified by column chromatography

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

Procedure: A solution of 1-benzofuran-3-yl-2-bromo-ethanone (Intermediate I1) (commercially available from Maybridge) (2.1 g, 8.8 mmol) in toluene at reflux was treated with tributyltin hydride (2.9 mL, 10.6 mmol) and 2,2′-azobisisobutyronitrile (AIBN, catalyst) for 2 h. The mixture was cooled to rt and concentrated onto silica gel under reduced pressure. The product was eluted from a column of silica gel with 5% EtOAc: hexane to give 1-benzofuran-3-yl-ethanone (Intermediate I2) as an oil, 1.45 g (99%). concentrated onto silica gel under reduced pressure The product was eluted from a column of silica gel with 5% EtOAc

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

Procedure: A mixture of 3-(2-bromoacetyl)benzo[b]furan (36.9 g), 2-imidazolidinethione (15.75 g), ethanol (600 ml) and acetic acid (400 ml) was heated under reflux for 21 hours then allowed to cool to ambient temperature. The resulting solid was collected by filtration, washed with ether (500 ml), and dissolved in hot methanol (500 ml). Charcoal (2 g) was added and the hot mixture was stirred for a few minutes, then filtered and allowed to cool to ambient temperature. The resulting solid was collected by filtration, ground to a fine powder, and dried in vacuo at 80° C. to give 3-(benzo[b]furan-3-yl)-5,6-dihydroimidazo[2,1-b]thiazole monohydrobromide 0.7 hydrate as an off-white solid (28.1 g), m.p. 251°-254.50C. was heated under reflux for 21 hours The resulting solid was collected by filtration washed with ether (500 ml) dissolved in hot methanol (500 ml) Charcoal (2 g) was added filtered to cool to ambient temperature The resulting solid was collected by filtration, ground to a fine powder dried in vacuo at 80° C.

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

Procedure: A mixture of 3-(2-bromoacetyl)benzo[b]furan (36.9 g), 2-imidazolidinethione (15.75 g), ethanol (600 ml) and acetic acid (400 ml) was heated under reflux for 21 hours then allowed to cool to ambient temperature. The resulting solid was collected by filtration, washed with ether (500 ml), and dissolved in hot methanol (500 ml). Charcoal (2 g) was added and the hot mixture was stirred for a few minutes, then filtered and allowed to cool to ambient temperature. The resulting solid was collected by filtration, ground to a fine powder, and dried in vacuo at 80° C. to give 3-(benzo[b]furan-3-yl)-5,6-dihydroimidazo[2,1-b]thiazole monohydrobromide 0.7 hydrate as an off-white solid (28.1 g), m.p. 251°-254.50C. was heated under reflux for 21 hours The resulting solid was collected by filtration washed with ether (500 ml) dissolved in hot methanol (500 ml) Charcoal (2 g) was added filtered to cool to ambient temperature The resulting solid was collected by filtration, ground to a fine powder dried in vacuo at 80° C.

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

Procedure: A mixture of 3-(2-bromoacetyl)benzo[b]furan (0.25 g), 2-imidazolidinethione (0.11 g), ethanol (30 ml) and acetic acid (20 ml) was heated under reflux for 20 hours, then allowed to cool to ambient temperature. The resulting solid was collected by filtration, washed with ether, and dried in vacuo at ambient temperature to give 3-(benzo[b]furan-3-yl)-5,6-dihydroimidazo[2,1-b]thiazole monohydrobromide monohydrate as a white solid (0.145 g), m.p. 242°-244° C. was heated under reflux for 20 hours The resulting solid was collected by filtration washed with ether dried in vacuo at ambient temperature

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

Procedure: A solution of phenyltrimethylammonium tribromide (2.47 g) in tetrahydrofuran (20 ml) was added dropwise at ambient temperature under nitrogen over 5 minutes to a stirred solution of 3-acetylbenzo[b]furan (1 g) in tetrahydrofuran (20 ml), then the mixture was stirred at ambient temperature for a further 1.5 hours, filtered, and the solvent removed in vacuo. The residue was triturated with ether, and the resulting solid was collected by filtration and dried in vacuo at ambient temperature to give 3-(2-bromoacetyl)benzo[b]furan as an off-white solid (0.25 g). filtered the solvent removed in vacuo The residue was triturated with ether the resulting solid was collected by filtration dried in vacuo at ambient temperature

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

Procedure: A solution of phenyltrimethylammonium tribromide (2.47 g) in tetrahydrofuran (20 ml) was added dropwise at ambient temperature under nitrogen over 5 minutes to a stirred solution of 3-acetylbenzo[b]furan (1 g) in tetrahydrofuran (20 ml), then the mixture was stirred at ambient temperature for a further 1.5 hours, filtered, and the solvent removed in vacuo. The residue was triturated with ether, and the resulting solid was collected by filtration and dried in vacuo at ambient temperature to give 3-(2-bromoacetyl)benzo[b]furan as an off-white solid (0.25 g). filtered the solvent removed in vacuo The residue was triturated with ether the resulting solid was collected by filtration dried in vacuo at ambient temperature

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

Procedure: In a glass tube, 250 mg of 1-(benzofuran-3-yl)-2-bromoethanone, 181 mg of 5-bromopyridin-2-ylamine and 105 mg of sodium hydrogencarbonate are dissolved in 15 ml of n-propanol. The tube is closed and heated at 80° C. for 20 h. After cooling, 20 ml of water are added and the reaction mixture is stirred for 1 hour at ambient temperature. A precipitate forms, and is recovered by filtration, washed with water and then with diisopropyl ether, and dried in a desiccator under reduced pressure. 250 mg of compound are obtained. The tube is closed After cooling A precipitate forms, and is recovered by filtration washed with water with diisopropyl ether, and dried in a desiccator under reduced pressure

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

Procedure: To a stirred solution of 2-(1-trityl-1H-imidazol-4-yl)phenol (0.5 mmol) in anhydrous DMF (3 mL) at 0° C. was added NaH (36.0 mg, 0.75 mmol). The resulting suspension was allowed to stir for 10 min. To the resulting solution was added 1-(benzofuran-3-yl)-2-bromoethanone (0.50 mmol). After stirring overnight, the reaction mixture was carefully diluted, with water and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water, brine and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product was purified by column chromatography. Yield 60%. 1H NMR: 5.16 (s, 2H), 6.88 (d, 1H, J=8.10 Hz), 7.06-7.47 (m, 20H), 7.54 (d, 2H, J=7.92 Hz), 8.22 (dd, 2H, J=7.60 Hz, 1.35 Hz), 8.33 (s, 1H). After stirring overnight extracted with ethyl acetate (2×10 mL) The combined organic layers were washed with water, brine dried (Na2SO4) The solvent was removed under reduced pressure the crude product was purified by column chromatography