1-(4-fluorophenyl)sulfonylazetidine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (60.0 mg, 0.139 mmol) synthesized in Example (38d) and 1-[(4-fluorophenyl)sulfonyl]azetidine (60.0 mg, 0.279 mmol) synthesized in Example (55a) were dissolved in N-methylpyrrolidone (5.0 mL), and sodium hydride (60%, 24 mg, 0.60 mmol) was added, followed by stirring at 100° C. for 6 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (20 mL) was added, and extraction was carried out with ethyl acetate (30 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-35%) to afford the desired compound (42 mg, yield 57%) as a white solid. The reaction solution was cooled to room temperature extraction The organic layer was washed with saturated brine subsequently dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-35%)

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

実験手順: Commercially available 4-fluorophenylsulfonylchloride (225 mg, 1.15 mmol) was suspended in water (8 mL), and azetidine hydrochloride (90.0 mg, 0.96 mmol) and potassium carbonate (293 mg, 2.12 mmol) were added, followed by stirring at room temperature for 16 hours. To the reaction solution, water (15 mL) was added, followed by extraction twice with diethyl ether (15 mL), and washing was carried out with saturated brine (15 mL), followed by drying over sodium sulfate. The solvent was distilled off under reduced pressure, followed by vacuum drying, to afford the desired compound (170 mg, yield 82%) as a white solid. followed by extraction twice with diethyl ether (15 mL) washing by drying over sodium sulfate The solvent was distilled off under reduced pressure drying

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

実験手順: Azetidine (0.25 g, 4.35 mmol) was added to a solution of sodium hexamethyldisilylazide (0.85 g, 4.6 mmol) in THF (10 mL) at 0° C. and reaction mixture stirred for 10 minutes. 4-fluorobenzenesulfonyl chloride (0.85 g, 4.35 mmol) was subsequently added and the reaction mixture was allowed to warm up to ambient temperature overnight. The reaction mixture was concentrated in vacuo and the residue taken up in ethyl acetate and water. The organic layer was separated and then dried (MgSO4), filtered and evaporated to give a waxy, yellow solid (75 mg). reaction mixture The reaction mixture was concentrated in vacuo The organic layer was separated dried (MgSO4) filtered evaporated

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

実験手順: Azetidine (0.25 g, 4.35 mmol) was added to a solution of sodium hexamethyldisilylazide (0.85 g, 4.6 mmol) in THF (10 mL) at 0° C. and reaction mixture stirred for 10 minutes. 4-fluorobenzenesulfonyl chloride (0.85 g, 4.35 mmol) was subsequently added and the reaction mixture was allowed to warm up to ambient temperature overnight. The reaction mixture was concentrated in vacuo and the residue taken up in ethyl acetate and water. The organic layer was separated and then dried (MgSO4), filtered and evaporated to give a waxy, yellow solid (75 mg). reaction mixture The reaction mixture was concentrated in vacuo The organic layer was separated dried (MgSO4) filtered evaporated

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (60.0 mg, 0.139 mmol) synthesized in Example (38d) and 1-[(4-fluorophenyl)sulfonyl]azetidine (60.0 mg, 0.279 mmol) synthesized in Example (55a) were dissolved in N-methylpyrrolidone (5.0 mL), and sodium hydride (60%, 24 mg, 0.60 mmol) was added, followed by stirring at 100° C. for 6 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (20 mL) was added, and extraction was carried out with ethyl acetate (30 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-35%) to afford the desired compound (42 mg, yield 57%) as a white solid. The reaction solution was cooled to room temperature extraction The organic layer was washed with saturated brine subsequently dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-35%)

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

実験手順: Commercially available 4-fluorophenylsulfonylchloride (225 mg, 1.15 mmol) was suspended in water (8 mL), and azetidine hydrochloride (90.0 mg, 0.96 mmol) and potassium carbonate (293 mg, 2.12 mmol) were added, followed by stirring at room temperature for 16 hours. To the reaction solution, water (15 mL) was added, followed by extraction twice with diethyl ether (15 mL), and washing was carried out with saturated brine (15 mL), followed by drying over sodium sulfate. The solvent was distilled off under reduced pressure, followed by vacuum drying, to afford the desired compound (170 mg, yield 82%) as a white solid. followed by extraction twice with diethyl ether (15 mL) washing by drying over sodium sulfate The solvent was distilled off under reduced pressure drying

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (60.0 mg, 0.139 mmol) synthesized in Example (38d) and 1-[(4-fluorophenyl)sulfonyl]azetidine (60.0 mg, 0.279 mmol) synthesized in Example (55a) were dissolved in N-methylpyrrolidone (5.0 mL), and sodium hydride (60%, 24 mg, 0.60 mmol) was added, followed by stirring at 100° C. for 6 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (20 mL) was added, and extraction was carried out with ethyl acetate (30 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-35%) to afford the desired compound (42 mg, yield 57%) as a white solid. The reaction solution was cooled to room temperature extraction The organic layer was washed with saturated brine subsequently dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-35%)

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

実験手順: Commercially available 4-fluorophenylsulfonylchloride (225 mg, 1.15 mmol) was suspended in water (8 mL), and azetidine hydrochloride (90.0 mg, 0.96 mmol) and potassium carbonate (293 mg, 2.12 mmol) were added, followed by stirring at room temperature for 16 hours. To the reaction solution, water (15 mL) was added, followed by extraction twice with diethyl ether (15 mL), and washing was carried out with saturated brine (15 mL), followed by drying over sodium sulfate. The solvent was distilled off under reduced pressure, followed by vacuum drying, to afford the desired compound (170 mg, yield 82%) as a white solid. followed by extraction twice with diethyl ether (15 mL) washing by drying over sodium sulfate The solvent was distilled off under reduced pressure drying

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

実験手順: Azetidine (0.25 g, 4.35 mmol) was added to a solution of sodium hexamethyldisilylazide (0.85 g, 4.6 mmol) in THF (10 mL) at 0° C. and reaction mixture stirred for 10 minutes. 4-fluorobenzenesulfonyl chloride (0.85 g, 4.35 mmol) was subsequently added and the reaction mixture was allowed to warm up to ambient temperature overnight. The reaction mixture was concentrated in vacuo and the residue taken up in ethyl acetate and water. The organic layer was separated and then dried (MgSO4), filtered and evaporated to give a waxy, yellow solid (75 mg). reaction mixture The reaction mixture was concentrated in vacuo The organic layer was separated dried (MgSO4) filtered evaporated