ethyl 5-aminopentanoate;hydrochloride

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

実験手順: 13 g of sodium azide and 59 ml of triethyl orthoformate are added to a solution of 13.4 g of 5-amino-valeric acid ethyl ester hydrochloride in 89 ml of acetic acid and the whole is stirred for 6 hours at 100°. The reaction mixture is cooled and partitioned betwen ethyl acetate and water. The organic phase is washed several times with saturated sodium bicarbonate solution and once with brine and, after drying over sodium sulphate, is concentrated. After purification by chromatography over silica gel (eluant: toluene/ethyl acetate 4:1 to 7:3), the pure title compound is obtained. Rf (toluene/ethyl acetate 1:1); 0.32. The reaction mixture is cooled partitioned betwen ethyl acetate and water The organic phase is washed several times with saturated sodium bicarbonate solution once with brine and, after drying over sodium sulphate is concentrated After purification by chromatography over silica gel (eluant: toluene/ethyl acetate 4:1 to 7:3)

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

実験手順: 1.4 ml of triethylamine are added to 1.8 g of 5-aminovaleric acid ethyl ester hydrochloride in 40 ml of formic acid ethyl ester and the whole is then heated under reflux for 2 hours. The precipitate is filtered off, washed with a small quantity of formic acid ethyl ester and concentrated by evaporation under reduced pressure in a rotary evaporator. The residue is partitioned between methylene chloride and sodium bicarbonate solution, and the organic phase is then washed with brine, dried and concentrated by evaporation. The title compound is obtained in the form of an oil. the whole is then heated under reflux for 2 hours The precipitate is filtered off washed with a small quantity of formic acid ethyl ester concentrated by evaporation under reduced pressure in a rotary evaporator The residue is partitioned between methylene chloride and sodium bicarbonate solution the organic phase is then washed with brine dried concentrated by evaporation

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

実験手順: Potassium carbonate (66.23 g, 0.479 mol), triethylamine (167 mL, 1.20 mol), and ethyl 5-aminovalerate hydrochloride (104 g, 0.575 mol) were added to a mixture of 4-chloro-3-nitroquinoline (100 g, 0.470 mol) in chloroform (1 L). The reaction mixture was stirred at room temperature for 4 hours, then water (200 mL) was added. The mixture was transferred to a separatory funnel and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford 151 g of ethyl 5-[(3-nitroquinolin-4-yl)amino]pentanoate. The mixture was transferred to a separatory funnel the layers were separated The organic layer was washed with saturated aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered concentrated under reduced pressure

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

実験手順: 13 g of sodium azide and 59 ml of triethyl orthoformate are added to a solution of 13.4 g of 5-amino-valeric acid ethyl ester hydrochloride in 89 ml of acetic acid and the whole is stirred for 6 hours at 100°. The reaction mixture is cooled and partitioned betwen ethyl acetate and water. The organic phase is washed several times with saturated sodium bicarbonate solution and once with brine and, after drying over sodium sulphate, is concentrated. After purification by chromatography over silica gel (eluant: toluene/ethyl acetate 4:1 to 7:3), the pure title compound is obtained. Rf (toluene/ethyl acetate 1:1); 0.32. The reaction mixture is cooled partitioned betwen ethyl acetate and water The organic phase is washed several times with saturated sodium bicarbonate solution once with brine and, after drying over sodium sulphate is concentrated After purification by chromatography over silica gel (eluant: toluene/ethyl acetate 4:1 to 7:3)

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

実験手順: 1.4 ml of triethylamine are added to 1.8 g of 5-aminovaleric acid ethyl ester hydrochloride in 40 ml of formic acid ethyl ester and the whole is then heated under reflux for 2 hours. The precipitate is filtered off, washed with a small quantity of formic acid ethyl ester and concentrated by evaporation under reduced pressure in a rotary evaporator. The residue is partitioned between methylene chloride and sodium bicarbonate solution, and the organic phase is then washed with brine, dried and concentrated by evaporation. The title compound is obtained in the form of an oil. the whole is then heated under reflux for 2 hours The precipitate is filtered off washed with a small quantity of formic acid ethyl ester concentrated by evaporation under reduced pressure in a rotary evaporator The residue is partitioned between methylene chloride and sodium bicarbonate solution the organic phase is then washed with brine dried concentrated by evaporation

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

実験手順: 1.4 ml of triethylamine are added to 1.8 g of 5-aminovaleric acid ethyl ester hydrochloride in 40 ml of formic acid ethyl ester and the whole is then heated under reflux for 2 hours. The precipitate is filtered off, washed with a small quantity of formic acid ethyl ester and concentrated by evaporation under reduced pressure in a rotary evaporator. The residue is partitioned between methylene chloride and sodium bicarbonate solution, and the organic phase is then washed with brine, dried and concentrated by evaporation. The title compound is obtained in the form of an oil. the whole is then heated under reflux for 2 hours The precipitate is filtered off washed with a small quantity of formic acid ethyl ester concentrated by evaporation under reduced pressure in a rotary evaporator The residue is partitioned between methylene chloride and sodium bicarbonate solution the organic phase is then washed with brine dried concentrated by evaporation

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

実験手順: To 100 ml of absolute ethanol, stirred under a dry nitrogen atmosphere and cooled in an ice bath, was added 12.0 ml (167 mmole) of thionyl chloride, followed by 10.0 gm (85.3 mmole) of 5-aminopentanoic acid. The mixture was heated at reflux for 18 hours, cooled and concentrated in vacuo to a sticky solid. The crude ester was triturated with 150 ml of diethyl ether, and the resultant fluffy white solid was collected, washed thoroughly with diethyl ether, and dried in vacuo over potassium hydroxide to give 14.3 gm (78.7 mmole) of ethyl 5-aminopentanoate hydrochloride. The ester was sufficiently pure according to nmr spectroscopy (in (CD3)2SO) for subsequent use without further purification. cooled in an ice bath The mixture was heated at reflux for 18 hours cooled concentrated in vacuo to a sticky solid The crude ester was triturated with 150 ml of diethyl ether the resultant fluffy white solid was collected washed thoroughly with diethyl ether dried in vacuo over potassium hydroxide

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

実験手順: Potassium carbonate (66.23 g, 0.479 mol), triethylamine (167 mL, 1.20 mol), and ethyl 5-aminovalerate hydrochloride (104 g, 0.575 mol) were added to a mixture of 4-chloro-3-nitroquinoline (100 g, 0.470 mol) in chloroform (1 L). The reaction mixture was stirred at room temperature for 4 hours, then water (200 mL) was added. The mixture was transferred to a separatory funnel and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford 151 g of ethyl 5-[(3-nitroquinolin-4-yl)amino]pentanoate. The mixture was transferred to a separatory funnel the layers were separated The organic layer was washed with saturated aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered concentrated under reduced pressure

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

実験手順: Potassium carbonate (66.23 g, 479.3 mmol), triethylamine (167 mL, 1.20 mol), and ethyl 5-aminovalerate hydrochloride (104.4 g, 575.2 mmol) were added to a solution of 4-chloro-3-nitroquinoline (100.0 g, 479.3 mmol) in chloroform (1000 mL) according to the method described in Part B of Example 6. The reaction was run for four hours and provided 151 g of ethyl 5-(3-nitroquinolin-4-ylamino)pentanoate.

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

実験手順: Potassium carbonate (66.23 g, 0.479 mol), triethylamine (167 mL, 1.20 mol), and ethyl 5-aminovalerate hydrochloride (104 g, 0.575 mol) were added to a mixture of 4-chloro-3-nitroquinoline (100 g, 0.470 mol) in chloroform (1 L). The reaction mixture was stirred at room temperature for 4 hours, then water (200 mL) was added. The mixture was transferred to a separatory funnel and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford 151 g of ethyl 5-[(3-nitroquinolin-4-yl)amino]pentanoate. The mixture was transferred to a separatory funnel the layers were separated The organic layer was washed with saturated aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered concentrated under reduced pressure

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

実験手順: Potassium carbonate (66.23 g, 0.479 mol), triethylamine (167 mL, 1.20 mol), and ethyl 5-aminovalerate hydrochloride (104 g, 0.575 mol) were added to a mixture of 4-chloro-3-nitroquinoline (100 g, 0.470 mol) in chloroform (1 L). The reaction mixture was stirred at room temperature for 4 hours, then water (200 mL) was added. The mixture was transferred to a separatory funnel and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford 151 g of ethyl 5-[(3-nitroquinolin-4-yl)amino]pentanoate. The mixture was transferred to a separatory funnel the layers were separated The organic layer was washed with saturated aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered concentrated under reduced pressure

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

実験手順: 5-Benzoyl-6-(bromomethyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (Intermediate C) (1.38 g, 4.09 mmol), ethyl 5-aminovalerate hydrochloride (1.109 g, 6.14 mmol) and triethylamine (1.711 mL, 12.28 mmol) were combined in ethanol (20 mL) and the mixture heated at reflux for 40 mins. The reaction mixture was cooled to room temperature and evaporated under vacuum. The residue was partitioned between water and DCM and the phases separated. The organic phase was passed through a hydrophobic frit and evaporated onto silica. The silica was deposited onto a 25 g silica cartridge and the system eluted with 20% EtOAc/hexane, 40% EtOAc/hexane, 60% EtOAc/hexane and 80% EtOAc/hexane. The product fractions were combined and concentrated under reduced pressure to afford the title compound; the mixture heated at reflux for 40 mins evaporated under vacuum The residue was partitioned between water and DCM the phases separated evaporated onto silica the system eluted with 20% EtOAc/hexane, 40% EtOAc/hexane, 60% EtOAc/hexane and 80% EtOAc/hexane concentrated under reduced pressure