1-chlorobutane-2,3-dione

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of thiourea (8.87 g, 115 mmol) in ethanol (20.9 mL) was added 1-chloro-2,3-butanedione (13.90 g, 115 mmol) dropwise, a slight exothermic reaction resulted. The mixture was stirred at ambient temperature for 1 hour. The reaction mixture was filtered and the precipitate washed with ethyl ether (2×). The tan solid was air dried then dried under high vacuum overnight to give 1-(2-amino-thiazol-4-yl)-ethanone hydrochloride as a tan solid (21.5 g, 97%). a slight exothermic reaction resulted The reaction mixture was filtered the precipitate washed with ethyl ether (2×) dried then dried under high vacuum overnight

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-chloro-2,3-butanedione (0.717 g, 5.95 mmol) in ethanol (3 ml) was added dropwise to a solution of 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbothioic acid amide (prepared as in Example 16; 1.20 g, 3.97 mmol) in ethanol (12 ml) at room temperature, and then the resulting mixture was stirred at room temperature for 3 days. The reaction mixture was concentrated in vacuo and the obtained residue was mixed with dichloromethane (50 ml) and washed sequentially with water and brine, dried over magnesium sulfate and concentrated in vacuo. The obtained residue was purified by column chromatography eluting with 33% (v/v) ethyl acetate in n-heptane to afford 1-{2-[1-(cyclohexyl)methyl-7-methoxy-1H-indol-3-yl]thiazol-4-yl}ethanone as a brown solid (1.11 g). The reaction mixture was concentrated in vacuo the obtained residue was mixed with dichloromethane (50 ml) washed sequentially with water and brine dried over magnesium sulfate concentrated in vacuo The obtained residue was purified by column chromatography eluting with 33% (v/v) ethyl acetate in n-heptane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of thiourea (8.87 g, 115 mmol) in ethanol (20.9 mL) was added 1-chloro-2,3-butanedione (13.90 g, 115 mmol) dropwise, a slight exothermic reaction resulted. The mixture was stirred at ambient temperature for 1 hour. The reaction mixture was filtered and the precipitate washed with ethyl ether (2×). The tan solid was air dried then dried under high vacuum overnight to give 1-(2-amino-thiazol-4-yl)-ethanone hydrochloride as a tan solid (21.5 g, 97%). a slight exothermic reaction resulted The reaction mixture was filtered the precipitate washed with ethyl ether (2×) dried then dried under high vacuum overnight

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of thiourea (8.87 g, 115 mmol) in ethanol (20.9 mL) was added 1-chloro-2,3-butanedione (13.90 g, 115 mmol) dropwise, a slight exothermic reaction resulted. The mixture was stirred at ambient temperature for 1 hour. The reaction mixture was filtered and the precipitate washed with ethyl ether (2×). The tan solid was air dried then dried under high vacuum overnight to give 1-(2-amino-thiazol-4-yl)-ethanone hydrochloride as a tan solid (21.5 g, 97%). a slight exothermic reaction resulted The reaction mixture was filtered the precipitate washed with ethyl ether (2×) dried then dried under high vacuum overnight

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of thiourea (6.79 g, 89.2 mmol) in absolute ethanol (100 mL) was added 1-chloro-butane-2,3-dione (prepared as described by Bonnema, J. et al., Rec. Trav. Chim. Pays-Bas 1960, 79, 1137) (10.75 g, 89.2 mmol) and the mixture stirred at room temperature for 72 hours. The dark brown suspension was concentrated in vacuo, the residue taken up in water (350 mL), acidified with 1M aqueous hydrochloric acid (20 mL) and extracted with ethyl acetate (2×100 mL). The aqueous layer was then neutralized with solid sodium bicarbonate to form a light brown solid which was isolated by filtration. The precipitate was washed with 1:1 hexanes/ether (100 mL), 1:1 hexanes/ethyl acetae (100 mL) and then dried in vacuo over potassium hydroxide to give 1-(2-amino-thiazol-4-yl)-ethanone as a light brown solid (9.91 g, 78%). The dark brown suspension was concentrated in vacuo extracted with ethyl acetate (2×100 mL) to form a light brown solid which was isolated by filtration The precipitate was washed with 1:1 hexanes/ether (100 mL), 1:1 hexanes/ethyl acetae (100 mL) dried in vacuo over potassium hydroxide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of thiourea (6.79 g, 89.2 mmol) in absolute ethanol (100 mL) was added 1-chloro-butane-2,3-dione (prepared as described by Bonnema, J. et al., Rec. Trav. Chim. Pays-Bas 1960, 79, 1137) (10.75 g, 89.2 mmol) and the mixture stirred at room temperature for 72 hours. The dark brown suspension was concentrated in vacuo, the residue taken up in water (350 mL), acidified with 1M aqueous hydrochloric acid (20 mL) and extracted with ethyl acetate (2×100 mL). The aqueous layer was then neutralized with solid sodium bicarbonate to form a light brown solid which was isolated by filtration. The precipitate was washed with 1:1 hexanes/ether (100 mL), 1:1 hexanes/ethyl acetae (100 mL) and then dried in vacuo over potassium hydroxide to give 1-(2-amino-thiazol-4-yl)-ethanone as a light brown solid (9.91 g, 78%). The dark brown suspension was concentrated in vacuo extracted with ethyl acetate (2×100 mL) to form a light brown solid which was isolated by filtration The precipitate was washed with 1:1 hexanes/ether (100 mL), 1:1 hexanes/ethyl acetae (100 mL) dried in vacuo over potassium hydroxide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: It will be appreciated that reaction of 1-chloro-2,3-butanedione with thioformamide will lead to 4-acetylthiazoles, similarly, reaction of 2-bromo-3,4hexanedione with thioacetamide will yield 2,5-dimethyl-4-propionylthiazole.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-chloro-2,3-butanedione (0.717 g, 5.95 mmol) in ethanol (3 ml) was added dropwise to a solution of 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbothioic acid amide (prepared as in Example 16; 1.20 g, 3.97 mmol) in ethanol (12 ml) at room temperature, and then the resulting mixture was stirred at room temperature for 3 days. The reaction mixture was concentrated in vacuo and the obtained residue was mixed with dichloromethane (50 ml) and washed sequentially with water and brine, dried over magnesium sulfate and concentrated in vacuo. The obtained residue was purified by column chromatography eluting with 33% (v/v) ethyl acetate in n-heptane to afford 1-{2-[1-(cyclohexyl)methyl-7-methoxy-1H-indol-3-yl]thiazol-4-yl}ethanone as a brown solid (1.11 g). The reaction mixture was concentrated in vacuo the obtained residue was mixed with dichloromethane (50 ml) washed sequentially with water and brine dried over magnesium sulfate concentrated in vacuo The obtained residue was purified by column chromatography eluting with 33% (v/v) ethyl acetate in n-heptane