but-2-yn-1-amine;hydrochloride

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

Procedure: A mixture of 5-(2-chlorophenyl)-1,3-cyclohexanedione (1.1 g), 1-amino-2-butyne hydrochloride (0.5 g), molecular sieve 4A (2 g) and tetrahydrofuran (20 ml) was combined with triethylamine (0.48 g), stirred at room temperature for 1 hour, and then heated under reflux for 12 hours. After cooling, insolubles were filtered off, and the solvent was distilled off under reduced pressure. The residue was stirred at 220° C. for 4 hours. Ethyl acetate and aqueous sodium hydrogen carbonate were added, and the organic layer was washed successively with water and saturated brine, and then dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was subjected to a column chromatography on a silica gel (EtOAc/hexane) to obtain a crystal which was then recrystallized from ethyl acetate-hexane to obtain 7-(2-chlorophenyl)-4-methyl-5,6,7,8-tetrahydroquinoline-5-one (0.20 g) as a colorless crystal. heated under reflux for 12 hours After cooling insolubles were filtered off the solvent was distilled off under reduced pressure The residue was stirred at 220° C. for 4 hours Ethyl acetate and aqueous sodium hydrogen carbonate were added the organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate After concentrating under reduced pressure to obtain a crystal which was then recrystallized from ethyl acetate-hexane

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

Procedure: A mixture of 5-(2-chlorophenyl)-1,3-cyclohexanedione (1.1 g), 1-amino-2-butyne hydrochloride (0.5 g), molecular sieve 4A (2 g) and tetrahydrofuran (20 ml) was combined with triethylamine (0.48 g), stirred at room temperature for 1 hour, and then heated under reflux for 12 hours. After cooling, insolubles were filtered off, and the solvent was distilled off under reduced pressure. The residue was stirred at 220° C. for 4 hours. Ethyl acetate and aqueous sodium hydrogen carbonate were added, and the organic layer was washed successively with water and saturated brine, and then dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was subjected to a column chromatography on a silica gel (EtOAc/hexane) to obtain a crystal which was then recrystallized from ethyl acetate-hexane to obtain 7-(2-chlorophenyl)-4-methyl-5,6,7,8-tetrahydroquinoline-5-one (0.20 g) as a colorless crystal. heated under reflux for 12 hours After cooling insolubles were filtered off the solvent was distilled off under reduced pressure The residue was stirred at 220° C. for 4 hours Ethyl acetate and aqueous sodium hydrogen carbonate were added the organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate After concentrating under reduced pressure to obtain a crystal which was then recrystallized from ethyl acetate-hexane

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

Procedure: The title compound was synthesized in the same manner as in Example 1 (2), (3) and (4), and Examples 2 and 5.

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

Procedure: Sodiummethoxide (150 mg, 2.78 mmol) was added to a methanol (8 ml) suspension of 5-[6-amino-8-(2-furyl)-9H-9-purinyl]-1,2-dihydro-2-pyridinone (400 mg, 1.36 mmol) synthesized in the same method as in Example 1 (2), (3) and (4) and Example 2, and the mixture was stirred in a nitrogen atmosphere at room temperature. After 15 minutes, iodomethane (0.26 ml, 4.18 mmol) was added thereto and further stirred for 16.5 hours. The reaction solution was concentrated, and the residue was subjected to silica gel column chromatography (eluting solvent: hexane, hexane/ethyl acetate=40:1,20:1,10:1). The crude product was suspended in ethanol, and the solid was collected by filtration and washed with ethanol and diethyl ether, to give the title compound in free form (337 mg). The resulting free compound was dissolved in methanol-4N hydrochloric acid/ethyl acetate (0.4 ml) and concentrated. The residue was crystallized from methanol/ethyl acetate/diethyl ether, and the solid was collected by filtration and washed with diethyl ether, to give the title compound (270 mg, 58%) as a pale brown solid. further stirred for 16.5 hours The reaction solution was concentrated the residue was subjected to silica gel column chromatography (eluting solvent: hexane, hexane/ethyl acetate=40:1,20:1,10:1) the solid was collected by filtration washed with ethanol and diethyl ether

Conditions: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5-(4-fluorophenyl)cyclohexane-1, 3-dione (0.98 g), 1-amino-2-butyne hydrochloride (0.5 g), molecular sieves 4A (2 g) and tetrahydrofuran (20 ml) was added triethylamine (0.48 g), and the mixture was refluxed for 14 hours and cooled. Insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and the residue was stirred for 6 hours at 220° C. and cooled, to which were added ethyl acetate and sodium hydrogen carbonate solution. The organic layer was washed with water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure, and the residue was purified with silica gel column chromatography (EtoAc/hexane) to give oil of 7-(4-fluorophenyl)-4methyl-5,6,7,8-tetrahydroquinolin-5-one (0.35 g). the mixture was refluxed for 14 hours cooled Insoluble materials were filtered off Under reduced pressure, the solvent was evaporated cooled, to which were added ethyl acetate and sodium hydrogen carbonate solution The organic layer was washed with water and saturated brine dried with magnesium sulfate concentrated under reduced pressure the residue was purified with silica gel column chromatography (EtoAc/hexane)

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

Procedure: To a mixture of 5-(4-pyridyl)cyclohexane-1,3-dione (0.90 g), 1-amino-2-butyne hydrochloride (0.5 g), molecular sieves 4A (2 g) and tetrahydrofuran (20 ml) was added triethylamine (0.48 g), and the mixture was stirred at room temperature for 1 hour, refluxed for 15 hours and cooled, insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and the residue was stirred for 3.5 hours at 220° C. and cooled, to which were added ethyl acetate and sodium hydrogen carbonate solution. The organic layer was washed with water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure, and the residue was purified with silica gel column chromatography (EtOAc/MeOH) to give oil of 4-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydroquinolin-5-one (0.1 g). refluxed for 15 hours cooled insoluble materials were filtered off Under reduced pressure, the solvent was evaporated the residue was stirred for 3.5 hours at 220° C. cooled, to which were added ethyl acetate and sodium hydrogen carbonate solution The organic layer was washed with water and saturated brine dried with magnesium sulfate concentrated under reduced pressure the residue was purified with silica gel column chromatography (EtOAc/MeOH)

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

Procedure: To a mixture of 5-(2-pyridyl)cyclohexane-1,3-dione (2.0 g), 1-amino-2-butyne hydrochloride (0.1.1 g), molecular sieves 4A (2 g), tetrahydrofuran (30 ml) and ethanol (10 ml) was added triethylamine (2.1 g), and the mixture was stirred at room temperature for 1 hour, refluxed for 4 hours and cooled. Insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (EtOAc/MeOH) to give solid. The solid was stirred for 10 hours at 220° C., to which were added ethyl acetate and sodium hydrogen carbonate solution. The organic layer was washed with water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure, and the residue was purified with silica gel column chromatography (EtOAc/hexane) to give oil of 4-methyl-7-(2-pyridyl)-5,6,7,8-tetrahydroquinolin-5-one (0.28 g). refluxed for 4 hours cooled Insoluble materials were filtered off Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column chromatography (EtOAc/MeOH) to give solid The solid was stirred for 10 hours at 220° C., to which The organic layer was washed with water and saturated brine dried with magnesium sulfate concentrated under reduced pressure the residue was purified with silica gel column chromatography (EtOAc/hexane)

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

Procedure: To a mixture of 5-(5-chloro-2-thienyl)cyclohexane-1,3-dione (2.2 g), 1-amino-2-butyne hydrochloride (1.0 g) and tetrahydrofuran (40 ml) was added triethylamine (0.96 g), and the mixture was stirred at room temperature for 1 hour, refluxed for 12 hours and cooled. Insoluble materials were filtered off, and under reduced pressure, the solvent was evaporated. The residue was stirred at 250° C. for 3.5 hours, cooled and purified with silica gel column chromatography (EtOAc/hexane) to give oil of 7-(5-chloro-2-thienyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one (0.79 g). refluxed for 12 hours cooled Insoluble materials were filtered off under reduced pressure, the solvent was evaporated The residue was stirred at 250° C. for 3.5 hours cooled purified with silica gel column chromatography (EtOAc/hexane)

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

Procedure: To a mixture of 5-(2-thienyl)cyclohexane-1,3-dione (1.5 g), 1-amino-2-butyne hydrochloride (0.82 g), molecular sieves 4A (3 g) and tetrahydrofuran (30 ml) was added triethylamine (0.78 g). The mixture was stirred at room temperature for 1 hour, refluxed for refluxed for 12 hours and cooled, and insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and to the residue was added diphenylether (80 ml), and the mixture was stirred at 250° C. for 6 hours. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in ethyl acetate. The solution was washed with water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure, and the residue was purified with silica gel column chromatography (EtOAc/hexane) to give colorless crystals of 4-methyl-7-(2-thienyl)-5,6,7,8-tetrahydroquinolin-5-one (0.67 g). refluxed for refluxed for 12 hours cooled insoluble materials were filtered off Under reduced pressure, the solvent was evaporated to the residue was added diphenylether (80 ml) the mixture was stirred at 250° C. for 6 hours Under reduced pressure, the solvent was evaporated the residue was dissolved in ethyl acetate The solution was washed with water and saturated brine dried with magnesium sulfate concentrated under reduced pressure the residue was purified with silica gel column chromatography (EtOAc/hexane)

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

Procedure: To a mixture of 5-(2-methoxyphenyl)-1,3-cyclohexanedione (1.0 g), 1-amino-2-butyne hydrochloride (0.5 g), molecular sieves 4A (2 g) and tetrahydrofuran (20 ml) was added triethylamine (0.48 g). The mixture was stirred at room temperature for 1 hour, refluxed for 12 hours and cooled, and insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and the residue was stirred for 4 hours at 220° C. and cooled, to which was added ethyl acetate and sodium hydrogen carbonate solution. The organic layer was washed with water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure, and the residue was purified with silica gel column chromatography (EtOAc/hexane) to give oil of 7-(2-methoxyphenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one (0.4 g). refluxed for 12 hours cooled insoluble materials were filtered off Under reduced pressure, the solvent was evaporated the residue was stirred for 4 hours at 220° C. cooled, to which was added ethyl acetate and sodium hydrogen carbonate solution The organic layer was washed with water and saturated brine dried with magnesium sulfate concentrated under reduced pressure the residue was purified with silica gel column chromatography (EtOAc/hexane)

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

Procedure: To a mixture of 5-(2-bromophenyl)cyclohexane-1,3-dione (1.5 g), 1-amino-2-butyne hydrochloride (0.59 g) and tetrahydrofuran (30 ml) was added triethylamine (0.57 g). The mixture was stirred at room temperature for 1 hour, refluxed for 13 hours and cooled, and insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and to the residue was added diphenylether. The mixture was stirred at 250° C. for 12 hours and cooled, and to the mixture was added diethylether. The mixture was extracted with 1N hydrochloric acid, and the aqueous layer was washed with diethylether, neutralized with 1N sodium hydroxide and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure to give crystals of 7-(2-bromophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one (0.52 g). refluxed for 13 hours cooled insoluble materials were filtered off Under reduced pressure, the solvent was evaporated to the residue was added diphenylether The mixture was stirred at 250° C. for 12 hours cooled to the mixture was added diethylether The mixture was extracted with 1N hydrochloric acid the aqueous layer was washed with diethylether extracted with ethyl acetate The organic layer was washed with water and saturated brine dried with magnesium sulfate concentrated under reduced pressure

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

Procedure: To a mixture of 5-(2-chlorophenyl)-1,3-cyclohexanedione (1.1 g), 1-amino-2-butyne hydrochloride (0.5 g), molecular sieves 4A (2 g) and tetrahydrofuran (20 ml) was added triethylamine (0.48 g), and the mixture was stirred at room temperature for 1 hour and then refluxed for 12 hours and cooled. Insoluble materials were filtered, and under reduced pressure, the solvent was evaporated. The residue was stirred for 4 hours at 220° C., to which were added ethyl acetate and sodium hydrogen carbonate solution. The organic layer was washed with water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the mixture was concentrated, and the residue was subjected to silica gel column chromatography (EtOAc/hexane) to give crystals, which were recrystallized from ethyl acetate-hexane to give colorless crystals of 7-(2-chlorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one (0.20 g) refluxed for 12 hours cooled Insoluble materials were filtered under reduced pressure, the solvent was evaporated The residue was stirred for 4 hours at 220° C., to which were added ethyl acetate and sodium hydrogen carbonate solution The organic layer was washed with water and saturated brine dried with magnesium sulfate Under reduced pressure, the mixture was concentrated to give crystals, which were recrystallized from ethyl acetate-hexane