methyl 4-isocyanatobutanoate

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

Procedure: A solution of 5-amino-3-(4-nitrophenyl)isothiazole-4-carbonitrile (25.0 g, 0.101 mol) in tetrahydrofuran (300 mL) dimethylsulfoxide (40 mL) at ambient temperature was treated with potassium carbonate (35.0 g, 0.25 mol). The resulting mixture was stirred at ambient temperature for 15 min. The reaction mixture was treated with 4-isocyanato-butyric acid methyl ester (21.8 g, 0.15 mol) at ambient temperature. The mixture was stirred at ambient temperature overnight. The reaction mixture was filtered through celite and filtrate concentrated in vacuo. The residue was dissolved EtOAc (600 mL) and washed with water and brine then dried (sodium sulfate), filtered, solvent concentrated in vacuo. The crude residue was purified by column chromatography (20% ethyl acetate in dichloromethane) to give the title compound as a light brown solid (31.5 g, 78%). The mixture was stirred at ambient temperature overnight The reaction mixture was filtered through celite and filtrate concentrated in vacuo The residue was dissolved EtOAc (600 mL) washed with water and brine then dried (sodium sulfate) filtered solvent concentrated in vacuo The crude residue was purified by column chromatography (20% ethyl acetate in dichloromethane)

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

Procedure: 6.6 g (0.02 mol) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid are dissolved in a solution of 0.4 g of sodium hydroxide in 40 ml of water, and a solution of 3.2 g (0.022 mol) of methyl 4-isocyanato-butyrate in 12 ml of dioxane is added, while cooling with ice. Thereafter, stirring is continued for 2 hours at room temperature, the pH is adjusted to 5 with 2N hydrochloric acid and the precipitate is filtered off under suction and recrystallised from methanol. 6 g (63% of theory) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-{4-[(3-methoxycarbonylpropyl)-carbamoyl]-piperazin-1-yl}-quinoline-3-carboxylic acid of melting point 198°-200° C. are obtained. while cooling with ice the precipitate is filtered off under suction recrystallised from methanol

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

Procedure: 6.6 g (0.02 mol) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid are dissolved in a solution of 0.4 g of sodium hydroxide in 40 ml of water, and a solution of 3.2 g (0.022 mol) of methyl 4-isocyanato-butyrate in 12 ml of dioxane is added, while cooling with ice. Thereafter, stirring is continued for 2 hours at room temperature, the pH is adjusted to 5 with 2N hydrochloric acid and the precipitate is filtered off under suction and recrystallised from methanol. 6 g (63% of theory) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-{4-[(3-methoxycarbonylpropyl)-carbamoyl]-piperazin-1-yl}-quinoline-3-carboxylic acid of melting point 198°-200° C. are obtained. while cooling with ice the precipitate is filtered off under suction recrystallised from methanol

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

Procedure: A solution of 5-amino-3-(4-nitrophenyl)isothiazole-4-carbonitrile (25.0 g, 0.101 mol) in tetrahydrofuran (300 mL) dimethylsulfoxide (40 mL) at ambient temperature was treated with potassium carbonate (35.0 g, 0.25 mol). The resulting mixture was stirred at ambient temperature for 15 min. The reaction mixture was treated with 4-isocyanato-butyric acid methyl ester (21.8 g, 0.15 mol) at ambient temperature. The mixture was stirred at ambient temperature overnight. The reaction mixture was filtered through celite and filtrate concentrated in vacuo. The residue was dissolved EtOAc (600 mL) and washed with water and brine then dried (sodium sulfate), filtered, solvent concentrated in vacuo. The crude residue was purified by column chromatography (20% ethyl acetate in dichloromethane) to give the title compound as a light brown solid (31.5 g, 78%). The mixture was stirred at ambient temperature overnight The reaction mixture was filtered through celite and filtrate concentrated in vacuo The residue was dissolved EtOAc (600 mL) washed with water and brine then dried (sodium sulfate) filtered solvent concentrated in vacuo The crude residue was purified by column chromatography (20% ethyl acetate in dichloromethane)

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

Procedure: 6.6 g (0.02 mol) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid are dissolved in a solution of 0.4 g of sodium hydroxide in 40 ml of water, and a solution of 3.2 g (0.022 mol) of methyl 4-isocyanato-butyrate in 12 ml of dioxane is added, while cooling with ice. Thereafter, stirring is continued for 2 hours at room temperature, the pH is adjusted to 5 with 2N hydrochloric acid and the precipitate is filtered off under suction and recrystallised from methanol. 6 g (63% of theory) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-{4-[(3-methoxycarbonylpropyl)-carbamoyl]-piperazin-1-yl}-quinoline-3-carboxylic acid of melting point 198°-200° C. are obtained. while cooling with ice the precipitate is filtered off under suction recrystallised from methanol