3-butoxyazetidine;hydrochloride

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

実験手順: 3-Butoxyazetidine hydrochloride (33 mg, 0.20 mmol), EDCI (72 mg, 0.4 mmol), HOBt (54 mg, 0.4 mmol) and diisopropylethylamine (116 μL, 0.66 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (45 mg, 0.13 mmol) in dimethylformamide (5 mL) at room temperature. The reaction mixture was stirred overnight and then diluted by addition of ethyl acetate (40 mL) and water (40 mL). The aqueous phase was extracted with ethyl acetate (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (7:3 to 5:5) as eluent. After precipitation in DCM/Et2O and triturations in acetone, the title product was obtained as a white solid (10 mg, 17%). The aqueous phase was extracted with ethyl acetate (2×40 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel After precipitation in DCM/Et2O

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

実験手順: 3-Butoxyazetidine hydrochloride (100 mg, 0.6 mmol), EDCI (113 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (100 mg, 0.4 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight and then partioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was separated and extracted successively with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (99:1 to 97:3) as eluent. The title product was obtained as a grey solid (30 mg, 23%). The aqueous layer was separated extracted successively with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (180 μL, 1.6 mmol) was added to a solution of 1-benzhydryl-3-butoxyazetidine (370 mg, 1.2 mmol) in 1,2-dichloroethane (6 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (7 mL) was added. The reaction mixture was again heated up to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (179 mg, 86%) which was used in the next step without further purification. After cooling down to room temperature The reaction mixture was again heated up to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (180 μL, 1.6 mmol) was added to a solution of 1-benzhydryl-3-butoxyazetidine (370 mg, 1.2 mmol) in 1,2-dichloroethane (6 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (7 mL) was added. The reaction mixture was again heated up to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (179 mg, 86%) which was used in the next step without further purification. After cooling down to room temperature The reaction mixture was again heated up to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL)

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

実験手順: 3-Butoxyazetidine hydrochloride (33 mg, 0.20 mmol), EDCI (72 mg, 0.4 mmol), HOBt (54 mg, 0.4 mmol) and diisopropylethylamine (116 μL, 0.66 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (45 mg, 0.13 mmol) in dimethylformamide (5 mL) at room temperature. The reaction mixture was stirred overnight and then diluted by addition of ethyl acetate (40 mL) and water (40 mL). The aqueous phase was extracted with ethyl acetate (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (7:3 to 5:5) as eluent. After precipitation in DCM/Et2O and triturations in acetone, the title product was obtained as a white solid (10 mg, 17%). The aqueous phase was extracted with ethyl acetate (2×40 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel After precipitation in DCM/Et2O

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

実験手順: 3-Butoxyazetidine hydrochloride (100 mg, 0.6 mmol), EDCI (113 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (100 mg, 0.4 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight and then partioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was separated and extracted successively with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (99:1 to 97:3) as eluent. The title product was obtained as a grey solid (30 mg, 23%). The aqueous layer was separated extracted successively with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (180 μL, 1.6 mmol) was added to a solution of 1-benzhydryl-3-butoxyazetidine (370 mg, 1.2 mmol) in 1,2-dichloroethane (6 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (7 mL) was added. The reaction mixture was again heated up to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (179 mg, 86%) which was used in the next step without further purification. After cooling down to room temperature The reaction mixture was again heated up to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL)

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

実験手順: 3-Butoxyazetidine hydrochloride (33 mg, 0.20 mmol), EDCI (72 mg, 0.4 mmol), HOBt (54 mg, 0.4 mmol) and diisopropylethylamine (116 μL, 0.66 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (45 mg, 0.13 mmol) in dimethylformamide (5 mL) at room temperature. The reaction mixture was stirred overnight and then diluted by addition of ethyl acetate (40 mL) and water (40 mL). The aqueous phase was extracted with ethyl acetate (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (7:3 to 5:5) as eluent. After precipitation in DCM/Et2O and triturations in acetone, the title product was obtained as a white solid (10 mg, 17%). The aqueous phase was extracted with ethyl acetate (2×40 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel After precipitation in DCM/Et2O

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

実験手順: 3-Butoxyazetidine hydrochloride (100 mg, 0.6 mmol), EDCI (113 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (100 mg, 0.4 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight and then partioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was separated and extracted successively with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (99:1 to 97:3) as eluent. The title product was obtained as a grey solid (30 mg, 23%). The aqueous layer was separated extracted successively with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (180 μL, 1.6 mmol) was added to a solution of 1-benzhydryl-3-butoxyazetidine (370 mg, 1.2 mmol) in 1,2-dichloroethane (6 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (7 mL) was added. The reaction mixture was again heated up to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (179 mg, 86%) which was used in the next step without further purification. After cooling down to room temperature The reaction mixture was again heated up to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL)

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

実験手順: 3-Butoxyazetidine hydrochloride (33 mg, 0.20 mmol), EDCI (72 mg, 0.4 mmol), HOBt (54 mg, 0.4 mmol) and diisopropylethylamine (116 μL, 0.66 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (45 mg, 0.13 mmol) in dimethylformamide (5 mL) at room temperature. The reaction mixture was stirred overnight and then diluted by addition of ethyl acetate (40 mL) and water (40 mL). The aqueous phase was extracted with ethyl acetate (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (7:3 to 5:5) as eluent. After precipitation in DCM/Et2O and triturations in acetone, the title product was obtained as a white solid (10 mg, 17%). The aqueous phase was extracted with ethyl acetate (2×40 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×40 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel After precipitation in DCM/Et2O

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

実験手順: 3-Butoxyazetidine hydrochloride (100 mg, 0.6 mmol), EDCI (113 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 mmol) were successively added to a solution of (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-acrylic acid hydrochloride (100 mg, 0.4 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight and then partioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was separated and extracted successively with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (99:1 to 97:3) as eluent. The title product was obtained as a grey solid (30 mg, 23%). The aqueous layer was separated extracted successively with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel