2-iodoethyl benzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-ol (73 mg, 0.16 mmol) produced in Example 31-B(i), (2-iodoethyl)benzoate (88 mg, 0.32 mmol), potassium carbonate (44 mg, 0.32 mmol) and N,N-dimethylformamide (3 mL) was stirred at 60° C. for 4 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0). The obtained solution was concentrated under reduced pressure. 1N Hydrochloric acid (2 mL), methanol (2 mL) and tetrahydrofuran (2 mL) were added to the obtained residue, and the mixture was stirred at 60° C. for 1 hr. To the reaction mixture were added methanol (1 mL) and tetrahydrofuran (1 mL), and the mixture was stirred at 60° C. for 2 hr. To the reaction mixture was added 2N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was washed with diisopropyl ether to give the title compound (54 mg, 81%) as a colorless solid. the mixture was extracted with ethyl acetate The collected organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the insoluble material was filtered off The filtrate was concentrated under reduced pressure the obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0) The obtained solution was concentrated under reduced pressure 1N Hydrochloric acid (2 mL), methanol (2 mL) and tetrahydrofuran (2 mL) were added to the obtained residue the mixture was stirred at 60° C. for 1 hr To the reaction mixture were added methanol (1 mL) and tetrahydrofuran (1 mL) the mixture was stirred at 60° C. for 2 hr To the reaction mixture was added 2N aqueous sodium hydroxide solution (2 mL) the mixture was stirred at room temperature for 1 hr To the reaction mixture was added water the mixture was extracted with ethyl acetate The collected organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the insoluble material was filtered off The filtrate was concentrated under reduced pressure the obtained residue was washed with diisopropyl ether

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-ol (73 mg, 0.16 mmol) produced in Example 31-B(i), (2-iodoethyl)benzoate (88 mg, 0.32 mmol), potassium carbonate (44 mg, 0.32 mmol) and N,N-dimethylformamide (3 mL) was stirred at 60° C. for 4 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0). The obtained solution was concentrated under reduced pressure. 1N Hydrochloric acid (2 mL), methanol (2 mL) and tetrahydrofuran (2 mL) were added to the obtained residue, and the mixture was stirred at 60° C. for 1 hr. To the reaction mixture were added methanol (1 mL) and tetrahydrofuran (1 mL), and the mixture was stirred at 60° C. for 2 hr. To the reaction mixture was added 2N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was washed with diisopropyl ether to give the title compound (54 mg, 81%) as a colorless solid. the mixture was extracted with ethyl acetate The collected organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the insoluble material was filtered off The filtrate was concentrated under reduced pressure the obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0) The obtained solution was concentrated under reduced pressure 1N Hydrochloric acid (2 mL), methanol (2 mL) and tetrahydrofuran (2 mL) were added to the obtained residue the mixture was stirred at 60° C. for 1 hr To the reaction mixture were added methanol (1 mL) and tetrahydrofuran (1 mL) the mixture was stirred at 60° C. for 2 hr To the reaction mixture was added 2N aqueous sodium hydroxide solution (2 mL) the mixture was stirred at room temperature for 1 hr To the reaction mixture was added water the mixture was extracted with ethyl acetate The collected organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the insoluble material was filtered off The filtrate was concentrated under reduced pressure the obtained residue was washed with diisopropyl ether

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-ol (73 mg, 0.16 mmol) produced in Example 31-B(i), (2-iodoethyl)benzoate (88 mg, 0.32 mmol), potassium carbonate (44 mg, 0.32 mmol) and N,N-dimethylformamide (3 mL) was stirred at 60° C. for 4 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0). The obtained solution was concentrated under reduced pressure. 1N Hydrochloric acid (2 mL), methanol (2 mL) and tetrahydrofuran (2 mL) were added to the obtained residue, and the mixture was stirred at 60° C. for 1 hr. To the reaction mixture were added methanol (1 mL) and tetrahydrofuran (1 mL), and the mixture was stirred at 60° C. for 2 hr. To the reaction mixture was added 2N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was washed with diisopropyl ether to give the title compound (54 mg, 81%) as a colorless solid. the mixture was extracted with ethyl acetate The collected organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the insoluble material was filtered off The filtrate was concentrated under reduced pressure the obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0) The obtained solution was concentrated under reduced pressure 1N Hydrochloric acid (2 mL), methanol (2 mL) and tetrahydrofuran (2 mL) were added to the obtained residue the mixture was stirred at 60° C. for 1 hr To the reaction mixture were added methanol (1 mL) and tetrahydrofuran (1 mL) the mixture was stirred at 60° C. for 2 hr To the reaction mixture was added 2N aqueous sodium hydroxide solution (2 mL) the mixture was stirred at room temperature for 1 hr To the reaction mixture was added water the mixture was extracted with ethyl acetate The collected organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the insoluble material was filtered off The filtrate was concentrated under reduced pressure the obtained residue was washed with diisopropyl ether

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

実験手順: A solution of 2-mercaptoethanol (1.52 mL), 2-iodoethyl benzoate (6.00 g) and ethyldiisopropylamine (4.53 mL) in N,N-dimethylformamide (60 mL) was stirred at 40° C. for 3 days. Water was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, hexane:ethyl acetate=4:1→3:7) to give the title compound (3.77 g) as an orange oil. the mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate concentrated under reduced pressure The residue was separated purified by silica gel column chromatography (eluent, hexane:ethyl acetate=4:1→3:7)

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

実験手順: To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (141 mg) in N,N-dimethylformamide (2.5 mL) was added cesium carbonate (358 mg) under ice-cooling, and the reaction mixture was stirred while warming to room temperature for 15 min. To the reaction mixture was added 2-iodoethyl benzoate (298 mg), and the mixture was stirred at room temperature for 15 hrs. The reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (50 mL), and extracted with ethyl acetate (50 mL×3). The organic layer was washed successively with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel chromatography (eluent:hexane/ethyl acetate=95/5→60/40). The object fraction was concentrated under reduced pressure and dried to give 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl benzoate (205 mg) as a colorless transparent oil. cooling the mixture was stirred at room temperature for 15 hrs extracted with ethyl acetate (50 mL×3) The organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The object fraction was concentrated under reduced pressure dried

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidine (300 mg) and 2-iodoethyl benzoate (548 mg) in N,N-dimethylformamide (10 mL) was added potassium carbonate (374 mg), and the mixture was stirred at 60° C. for 1 hr. After the completion of the reaction, water was added to the reaction mixture. The mixture was diluted with ethyl acetate and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:2) to give 2-[7-(methylthio)-1H-pyrazolo[4,3-d]pyrimidin-1-yl]ethyl benzoate (266 mg) and 2-[7-(methylthio)-2H-pyrazolo[4,3-d]pyrimidin-2-yl]ethyl benzoate (191 mg) both as pale-yellow solids. was added to the reaction mixture washed with water and saturated brine The organic layer was dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:2)

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

実験手順: A solution of 2-mercaptoethanol (1.52 mL), 2-iodoethyl benzoate (6.00 g) and ethyldiisopropylamine (4.53 mL) in N,N-dimethylformamide (60 mL) was stirred at 40° C. for 3 days. Water was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, hexane:ethyl acetate=4:1→3:7) to give the title compound (3.77 g) as an orange oil. the mixture was extracted with ethyl acetate The organic layer washed with saturated brine dried over magnesium sulfate concentrated under reduced pressure The residue was separated purified by silica gel column chromatography (eluent, hexane:ethyl acetate=4:1→3:7)

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

実験手順: To a suspension of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (141 mg) in N,N-dimethylformamide (2.5 mL) was added cesium carbonate (358 mg) under ice-cooling, and the reaction mixture was stirred while warming to room temperature for 15 min. To the reaction mixture was added 2-iodoethyl benzoate (298 mg), and the mixture was stirred at room temperature for 15 hrs. The reaction mixture was poured into 5% aqueous sodium hydrogen carbonate solution (50 mL), and extracted with ethyl acetate (50 mL×3). The organic layer washed successively with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel chromatography (eluent:hexane/ethyl acetate=95/5→60/40). The object fraction was concentrated under reduced pressure and dried to give 2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl benzoate (205 mg) as a colorless transparent oil. cooling the mixture was stirred at room temperature for 15 hrs extracted with ethyl acetate (50 mL×3) The organic layer washed successively with water and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The object fraction was concentrated under reduced pressure dried