2-苄氧基-1-乙胺盐酸盐

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under a nitrogen atmosphere, triethylamine (40.4 mL, 290 mmol) was added to a solution of 2,4-dichloro-6-methyl-3-nitropyridine (12.0 g, 58.0 mmol), prepared according to the general method of Part A of Example 1 using 2,4-dihydroxy-6-methyl-3-nitropyridine in lieu of 2,4-dihydroxy-5,6-dimethyl-3-nitropyridine, in anhydrous N,N-dimethylformamide (DMF) (200 mL). To the resulting dark brown solution was added 2-(benzyloxy)ethylamine hydrochloride (11.97 g, 63.76 mmol), and the mixture was stirred at room temperature for 23 hours. The volatiles were then removed under reduced pressure, and the residue was mixed with water and ethyl acetate. The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a brown oil. The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane:ethyl acetate. The resulting crystals were isolated by filtration and dried to provide 4.7 g of [2-(benzyloxy)ethyl]-(2-chloro-6-methyl-3-nitropyridin-4-yl)amine as a yellow solid. prepared The volatiles were then removed under reduced pressure the residue was mixed with water and ethyl acetate The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide a brown oil The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane The resulting crystals were isolated by filtration dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethanolamine hydrochloride (20 g, 0.21 mol) in toluene (100 mL) was treated with sodium metal (pellets washed with hexane) (10.14 g, 0.44 mL). The reaction was refluxed until the sodium metal was no longer present. The mixture was cooled and benzyl chloride (24.17 mL, 0.21 mol) was added, the reaction was stirred at room temperature overnight. The reaction mixture was filtered and the solid washed with toluene. The filtrate was cooled to 0° C. and HCl gas was bubbled in for 10 minutes. A white precipitate was obtained and filtered. The solid was recrystallized using 70 mL of isopropyl alcohol (10.4 g, 0.056 mol); MS-CI 188 (m+1). The mixture was cooled The reaction mixture was filtered the solid washed with toluene The filtrate was cooled to 0° C. HCl gas was bubbled in for 10 minutes A white precipitate was obtained filtered The solid was recrystallized

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethanolamine hydrochloride (20 g, 0.21 mol) in toluene (100 mL) was treated with sodium metal (pellets washed with hexane) (10.14 g, 0.44 mL). The reaction was refluxed until the sodium metal was no longer present. The mixture was cooled and benzyl chloride (24.17 mL, 0.21 mmol) was added, the reaction was stirred at room temperature overnight. The reaction mixture was filtered and the solid washed with toluene. The filtrate was cooled to 0° C. and HCl gas was bubbled in for 10 minutes. A white precipitate was obtained and filtered. The solid was recrystallized using 70 mL of isopropyl alcohol (10.4 g, 0.056 mol); MS-CI 188 (m+1). The mixture was cooled The reaction mixture was filtered the solid washed with toluene The filtrate was cooled to 0° C. HCl gas was bubbled in for 10 minutes A white precipitate was obtained filtered The solid was recrystallized

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared by reacting 2-(phenylmethoxy)ethylamine hydrochloride (0.51 g, 2.7 mmol) with 9-(2,3,5-tri- O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.43 g, 2.25 mmol), followed by debenzoylation of the purified product using methanolic ammonia to provide the title 2-chloro- N-[2-(phenylmethoxy)ethyl]adenosine (0.38 g, 44%)(after column chromatography) as a solid, mp 115°-124° C., 1H NMR (DMSO-d6)δ 3.50-3.58 (1H, m, H-5'a), 3.60-3.70 (4H, m, H-5'b, --CH2 -- and --CH--), 3.95 (1H, q, H-4'), 4.04-4.16 (2H, m, H-3' and --CH--), 4.52 (1H, br s, H-2' and --CH2 --), 5.07 (1H, t, 5'-0H), 5.21, 5.50 (2H, 2d, 2'- and 3'-OH), 5.84 (1H, d, H-1'), 7.22-7.36 (5H, m, Ar--H), 8.25-8.40 (2H, m, H-8 and N--H). The title compound was prepared

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under a nitrogen atmosphere, triethylamine (40.4 mL, 290 mmol) was added to a solution of 2,4-dichloro-6-methyl-3-nitropyridine (12.0 g, 58.0 mmol), prepared according to the general method of Part A of Example 1 using 2,4-dihydroxy-6-methyl-3-nitropyridine in lieu of 2,4-dihydroxy-5,6-dimethyl-3-nitropyridine, in anhydrous N,N-dimethylformamide (DMF) (200 mL). To the resulting dark brown solution was added 2-(benzyloxy)ethylamine hydrochloride (11.97 g, 63.76 mmol), and the mixture was stirred at room temperature for 23 hours. The volatiles were then removed under reduced pressure, and the residue was mixed with water and ethyl acetate. The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a brown oil. The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane:ethyl acetate. The resulting crystals were isolated by filtration and dried to provide 4.7 g of [2-(benzyloxy)ethyl]-(2-chloro-6-methyl-3-nitropyridin-4-yl)amine as a yellow solid. prepared The volatiles were then removed under reduced pressure the residue was mixed with water and ethyl acetate The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide a brown oil The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane The resulting crystals were isolated by filtration dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under a nitrogen atmosphere, triethylamine (40.4 mL, 290 mmol) was added to a solution of 2,4-dichloro-6-methyl-3-nitropyridine (12.0 g, 58.0 mmol), prepared according to the general method of Part A of Example 1 using 2,4-dihydroxy-6-methyl-3-nitropyridine in lieu of 2,4-dihydroxy-5,6-dimethyl-3-nitropyridine, in anhydrous N,N-dimethylformamide (DMF) (200 mL). To the resulting dark brown solution was added 2-(benzyloxy)ethylamine hydrochloride (11.97 g, 63.76 mmol), and the mixture was stirred at room temperature for 23 hours. The volatiles were then removed under reduced pressure, and the residue was mixed with water and ethyl acetate. The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a brown oil. The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane:ethyl acetate. The resulting crystals were isolated by filtration and dried to provide 4.7 g of [2-(benzyloxy)ethyl]-(2-chloro-6-methyl-3-nitropyridin-4-yl)amine as a yellow solid. prepared The volatiles were then removed under reduced pressure the residue was mixed with water and ethyl acetate The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide a brown oil The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane The resulting crystals were isolated by filtration dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under a nitrogen atmosphere, triethylamine (40.4 mL, 290 mmol) was added to a solution of 2,4-dichloro-6-methyl-3-nitropyridine (12.0 g, 58.0 mmol), prepared according to the general method of Part A of Example 1 using 2,4-dihydroxy-6-methyl-3-nitropyridine in lieu of 2,4-dihydroxy-5,6-dimethyl-3-nitropyridine, in anhydrous N,N-dimethylformamide (DMF) (200 mL). To the resulting dark brown solution was added 2-(benzyloxy)ethylamine hydrochloride (11.97 g, 63.76 mmol), and the mixture was stirred at room temperature for 23 hours. The volatiles were then removed under reduced pressure, and the residue was mixed with water and ethyl acetate. The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a brown oil. The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane:ethyl acetate. The resulting crystals were isolated by filtration and dried to provide 4.7 g of [2-(benzyloxy)ethyl]-(2-chloro-6-methyl-3-nitropyridin-4-yl)amine as a yellow solid. prepared The volatiles were then removed under reduced pressure the residue was mixed with water and ethyl acetate The organic layer was washed with water (3×200 mL), aqueous sodium bicarbonate (2×200 mL), and brine (3×250 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide a brown oil The crude product (18.1 g) was purified by column chromatography on silica gel (700 g, eluting with 80:20 hexane:ethyl acetate) to provide an oil which was triturated with 80:20 hexane The resulting crystals were isolated by filtration dried