tert-butyl N-(azetidin-3-yl)carbamate;hydrochloride

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

実験手順: A solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (prepared according to J. Antibiot. 1986, 39, 1243-1256, 0.755 g), Proton-Sponge® (0.85 g) and sulfamide (0.42 g) in dioxane (23 ml) was heated at reflux for 48 h. The residue was partitioned between H2O and EtOAc, and the aqueous layer then extracted with further EtOAc (×4). The combined organic extracts were washed quickly with 2M aqueous hydrochloric acid (×3) then with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate, filtered and evaporated to afford the subtitle compound as a pale brown powder. Yield: 0.44 g at reflux for 48 h The residue was partitioned between H2O and EtOAc the aqueous layer then extracted with further EtOAc (×4) The combined organic extracts were washed quickly with 2M aqueous hydrochloric acid (×3) with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate filtered evaporated

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cesium carbonate (4.68 g, 14.4 mmol), 2-chloroquinoline (0.782 g, 4.8 mmol) and tert-butyl azetidin-3-yl-carbamate hydrochloride (1.0 g, 4.8 mmol) were dissolved in dry dimethylformamide (15 mL) and the resulting mixture was heated at 120° C. overnight. The mixture was diluted with water (40 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (30 mL) and brine (30 mL), then dried over sodium sulfate. The organic was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 40% ethyl acetate in petroleum ether) to give tert-butyl (1-(quinolin-2-yl)azetidin-3-yl)-carbamate (1.14 g, 3.84 mmol, 80% yield) as white solid. extracted with ethyl acetate (2×50 mL) The combined organic extracts were washed with water (30 mL) and brine (30 mL) dried over sodium sulfate The organic was evaporated in vacuo the residue was purified by flash column chromatography on silica gel (20% to 40% ethyl acetate in petroleum ether)

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cesium carbonate (4.68 g, 14.4 mmol), 2-chloroquinoline (0.782 g, 4.8 mmol) and tert-butyl azetidin-3-yl-carbamate hydrochloride (1.0 g, 4.8 mmol) were dissolved in dry dimethylformamide (15 mL) and the resulting mixture was heated at 120° C. overnight. The mixture was diluted with water (40 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (30 mL) and brine (30 mL), then dried over sodium sulfate. The organic was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 40% ethyl acetate in petroleum ether) to give tert-butyl (1-(quinolin-2-yl)azetidin-3-yl)-carbamate (1.14 g, 3.84 mmol, 80% yield) as white solid. extracted with ethyl acetate (2×50 mL) The combined organic extracts were washed with water (30 mL) and brine (30 mL) dried over sodium sulfate The organic was evaporated in vacuo the residue was purified by flash column chromatography on silica gel (20% to 40% ethyl acetate in petroleum ether)

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

実験手順: Diisopropylethylamine (787 μl, 4.63 mmol) and tert-butyl azetidin-3-ylcarbamate hydrochloride (483 mg, 2.31 mmol) were added to a dichloromethane (20 ml) solution of 2-chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (553 mg, 1.93 mmol), followed by stirring at room temperature for 30 minutes. With cooling with ice, aqueous 10% citric acid solution (10 ml) was added to the reaction liquid, followed by extraction with chloroform (50 ml), then the organic layer was washed with saturated brine (50 ml). After drying over anhydrous sodium sulfate and concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=2:1) to obtain the entitled compound (815 mg, 100%) as a colorless oily substance. was added to the reaction liquid followed by extraction with chloroform (50 ml) the organic layer was washed with saturated brine (50 ml) After drying over anhydrous sodium sulfate and concentration under reduced pressure the resulting residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=2:1)

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

実験手順: Diisopropylethylamine (787 μl, 4.63 mmol) and tert-butyl azetidin-3-ylcarbamate hydrochloride (483 mg, 2.31 mmol) were added to a dichloromethane (20 ml) solution of 2-chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (553 mg, 1.93 mmol), followed by stirring at room temperature for 30 minutes. With cooling with ice, aqueous 10% citric acid solution (10 ml) was added to the reaction liquid, followed by extraction with chloroform (50 ml), then the organic layer was washed with saturated brine (50 ml). After drying over anhydrous sodium sulfate and concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=2:1) to obtain the entitled compound (815 mg, 100%) as a colorless oily substance. was added to the reaction liquid followed by extraction with chloroform (50 ml) the organic layer was washed with saturated brine (50 ml) After drying over anhydrous sodium sulfate and concentration under reduced pressure the resulting residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=2:1)

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

実験手順: A solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (prepared according to J. Antibiot. 1986, 39, 1243-1256, 0.755 g), Proton-Sponge® (0.85 g) and sulfamide (0.42 g) in dioxane (23 ml) was heated at reflux for 48 h. The residue was partitioned between H2O and EtOAc, and the aqueous layer then extracted with further EtOAc (×4). The combined organic extracts were washed quickly with 2 M aqueous hydrochloric acid (×3) then with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate, filtered and evaporated to afford the subtitle compound as a pale brown powder. at reflux for 48 h The residue was partitioned between H2O and EtOAc the aqueous layer then extracted with further EtOAc (×4) The combined organic extracts were washed quickly with 2 M aqueous hydrochloric acid (×3) with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate filtered evaporated

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

実験手順: A solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (prepared according to J. Antibiot. 1986, 39, 1243-1256, 0.755 g), Proton-Sponge® (0.85 g) and sulfamide (0.42 g) in dioxane (23 ml) was heated at reflux for 48 h. The residue was partitioned between H2O and EtOAc, and the aqueous layer then extracted with further EtOAc (×4). The combined organic extracts were washed quickly with 2M aqueous hydrochloric acid (×3) then with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate, filtered and evaporated to afford the subtitle compound as a pale brown powder. at reflux for 48 h The residue was partitioned between H2O and EtOAc the aqueous layer then extracted with further EtOAc (×4) The combined organic extracts were washed quickly with 2M aqueous hydrochloric acid (×3) with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate filtered evaporated

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

実験手順: A solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (prepared according to J. Antibiot. 1986, 39, 1243-1256, 0.755 g), Proton-Sponge® (0.85 g) and sulfamide (0.42 g) in dioxane (23 ml) was heated at reflux for 48 h. The residue was partitioned between H2O and EtOAc, and the aqueous layer then extracted with further EtOAc (×4). The combined organic extracts were washed quickly with 2M aqueous hydrochloric acid (×3) then with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate, filtered and evaporated to afford the subtitle compound as a pale brown powder. at reflux for 48 h The residue was partitioned between H2O and EtOAc the aqueous layer then extracted with further EtOAc (×4) The combined organic extracts were washed quickly with 2M aqueous hydrochloric acid (×3) with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate filtered evaporated

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

実験手順: A solution of tert-butyl azetidin-3-ylcarbamate hydrochloride (prepared according to J. Antibiot. 1986, 39, 1243-1256, 0.755 g), Proton-Sponge® (0.85 g) and sulfamide (0.42 g) in dioxane (23 ml) was heated at reflux for 48 h. The residue was partitioned between H2O and EtOAc, and the aqueous layer then extracted with further EtOAc (×4). The combined organic extracts were washed quickly with 2M aqueous hydrochloric acid (×3) then with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate, filtered and evaporated to afford the subtitle compound as a pale brown powder. Yield: 0.44 g at reflux for 48 h The residue was partitioned between H2O and EtOAc the aqueous layer then extracted with further EtOAc (×4) The combined organic extracts were washed quickly with 2M aqueous hydrochloric acid (×3) with saturated aqueous sodium bicarbonate, H2O and saturated aqueous sodium chloride, dried with sodium sulfate filtered evaporated

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cesium carbonate (4.68 g, 14.4 mmol), 2-chloroquinoline (0.782 g, 4.8 mmol) and tert-butyl azetidin-3-yl-carbamate hydrochloride (1.0 g, 4.8 mmol) were dissolved in dry dimethylformamide (15 mL) and the resulting mixture was heated at 120° C. overnight. The mixture was diluted with water (40 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (30 mL) and brine (30 mL), then dried over sodium sulfate. The organic was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 40% ethyl acetate in petroleum ether) to give tert-butyl (1-(quinolin-2-yl)azetidin-3-yl)-carbamate (1.14 g, 3.84 mmol, 80% yield) as white solid. extracted with ethyl acetate (2×50 mL) The combined organic extracts were washed with water (30 mL) and brine (30 mL) dried over sodium sulfate The organic was evaporated in vacuo the residue was purified by flash column chromatography on silica gel (20% to 40% ethyl acetate in petroleum ether)

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

実験手順: Diisopropylethylamine (787 μl, 4.63 mmol) and tert-butyl azetidin-3-ylcarbamate hydrochloride (483 mg, 2.31 mmol) were added to a dichloromethane (20 ml) solution of 2-chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (553 mg, 1.93 mmol), followed by stirring at room temperature for 30 minutes. With cooling with ice, aqueous 10% citric acid solution (10 ml) was added to the reaction liquid, followed by extraction with chloroform (50 ml), then the organic layer was washed with saturated brine (50 ml). After drying over anhydrous sodium sulfate and concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=2:1) to obtain the entitled compound (815 mg, 100%) as a colorless oily substance. was added to the reaction liquid followed by extraction with chloroform (50 ml) the organic layer was washed with saturated brine (50 ml) After drying over anhydrous sodium sulfate and concentration under reduced pressure the resulting residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=2:1)