(2-bromophenyl)methanamine;hydrochloride

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

実験手順: 15.0 g of 2-Bromobenzylamine hydrochloride was dissolved in 100 ml of tetrahydrofuran, and a solution of 13 g of t-butyl dicarbonate in tetrahydrofuran (25 ml) was added thereto. The mixture was stirred at room temperature for 1 hour, and then the solvent was evaporated. The residue was dissolved in ethyl acetate, and washed successively with 1N hydrochloric acid and brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated, to give 16.0 g of the title compound. the solvent was evaporated The residue was dissolved in ethyl acetate washed successively with 1N hydrochloric acid and brine The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated

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

実験手順: 15.0 g of 2-Bromobenzylamine hydrochloride was dissolved in 100 ml of tetrahydrofuran, and a solution of 13 g of t-butyl dicarbonate in tetrahydrofuran (25 ml) was added thereto. The mixture was stirred at room temperature for 1 hour, and then the solvent was evaporated. The residue was dissolved in ethyl acetate, and washed successively with 1N hydrochloric acid and brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated, to give 16.0 g of the title compound. the solvent was evaporated The residue was dissolved in ethyl acetate washed successively with 1N hydrochloric acid and brine The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated

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

実験手順: To a solution of commercially available 1-(2-bromophenyl)methanamine hydrochloride salt (1 eq.) in CH2Cl2 (0.3M) at room temperature was added triethylamine (2.1 eq) then acetic anhydride (1.1 eq.). The mixture was stirred at room temperature for 6 h, poured in aqueous HCl (0.5N) and extracted with CH2Cl2. The organic extract was dried over MgSO4 filtered and concentrated to afford the desired compound as a white solid. extracted with CH2Cl2 The organic extract was dried over MgSO4 filtered concentrated

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

実験手順: 2-Chloro-5-nitro-4-thiocyanatopyrimidine (100 mg, 0.46 mmol) was suspended in 1 mL absolute EtOH. o-Bromobenzylamine hydrochloride (103 mg, 0.46 mmol) was dissolved in 1 mL absolute EtOH and added to the reaction quickly at ambient temperature. Then triethylamine (129 μL, 0.92 mmol) was added dropwise via syringe. The reaction was stirred 16 h at ambient temperature. The resulting precipitate was filtered providing 136 mg of the desired (2-bromo-benzyl)-(5-nitro-4-thiocyanato-pyrimidin-2-yl)-amine as a white solid. added to the reaction quickly at ambient temperature The resulting precipitate was filtered

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

実験手順: To a stirring solution of 2-bromobenzylamine hydrochloride (80.7 mg, 95%, 0.345 mmol) in anhydrous DMF (5 ml) was added triethylamine (51.8 ul. 0.345 mmol), After 5 min, 2-[1,6]naphthyridinecarboxylic acid (40 mg, 0.229 mmol), 1-hydroxybenzotriazole hydrate (34.2 mg, 0.253 mmol) and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (48.5 mg, 0.253 mmol) was sequentially added. The resulting mixture was allowed to stir at room temperature for 4 h and it was found to be clear. The solvent was removed under vacuum and the resulting residue was redissolved in CH2Cl2 (100 ml). The organic layer was washed with aqueous NaHCO3, dried over anhydrous MgSO4, and concentrated to give the crude mixture. Chromatography of the crude (Hex:EtOAc=1:1 to pure EtOAc) afforded desired product as white solid (70 mg, 89%): m.p. 129-130° C. The solvent was removed under vacuum the resulting residue was redissolved in CH2Cl2 (100 ml) The organic layer was washed with aqueous NaHCO3 dried over anhydrous MgSO4 concentrated to give the crude mixture

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

実験手順: To a solution of 2-bromobenzylamine hydrochloride (5.00 g) and di-tert-butoxycarbonyl (5.39 g) in ethyl acetate (30 ml) was added saturated sodium bicarbonate solution (30 ml), and stirred at room temperature for 16 hours. The obtained reaction mixture was diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried with magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography to give the title compound as a colorless liquid (6.48 g, 95%). The obtained reaction mixture extracted with ethyl acetate The organic layer was washed with saturated brine dried with magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography

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

実験手順: 2-Bromobenzenesulfonyl chloride [(X), 5.9 g, 23.5 mmol] was added dropwise to a stirred 0° C. suspension of 2-bromobenzylamine hydrochloride [(II), R=(4-bromophenyl)methyl, 4.79 g, 19.6 mmol], pyridine (7.9 mL, 97.9 mmol) and 4-dimethylaminopyridine (0.23 g, 1.96 mmol) in dichloromethane (10 mL). The reaction mixture was then stirred at room temperature for 1 hour, then triethylamine (2.73 mL, 19.6 mmol) was then added at 0° C. After stirring overnight at room temperature, the reaction was diluted with dichloromethane (100 mL) then washed with water (50 mL), 0.5N HCl (2×50 mL), water (50 mL), saturated aq. NaHCO3 (2×50 mL) and water (50 mL). The dichloromethane solution was dried (brine, MgSO4) and silica gel (80 mL) was added. The solution was concentrated and the adsorbate was flash chromatographed (4:1 petroleum ether:ethyl acetate) to provide the title compound as a white solid (5.92 g, 75%): mp 108°-110° C.; NMR (CDCl3, 300 MHz): d 8.08 (m, 1H, ArH), 7.70 (m, 1H, ArH), 7.55-7.30 (m, 4H, ArH), 7.08 (d, 2H, ArH), 5.42 (t, 1H, NH), 4.07 (d, 2H, CH2); Anal. (C13H11Br2NO2S) C, H, N. After stirring overnight at room temperature then washed with water (50 mL), 0.5N HCl (2×50 mL), water (50 mL), saturated aq. NaHCO3 (2×50 mL) and water (50 mL) The dichloromethane solution was dried (brine, MgSO4) and silica gel (80 mL) was added The solution was concentrated chromatographed (4:1 petroleum ether:ethyl acetate)

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

実験手順: To a stirring solution of 2-bromobenzylamine hydrochloride (80.7 mg, 95%, 0.345 mmol) in anhy. DMF (5 ml) was added triethylamine (51.8 ul. 0.345 mmol). After 5 min, 2-[1,6]naphthyridinecarboxylic acid (40 mg, 0.229 mmol), 1-hydroxybenzotriazole hydrate (34.2 mg, 0.253 mmol) and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (48.5 mg, 0.253 mmol) was sequentially added. The resulting mixture was allowed to stir at room temperature for 4 h and it was found to be clear. The solvent was removed under vacuum and the resulting residue was redissolved in CH2Cl2 (100 ml). The organic layer was washed with aq. NaHCO3, dried over anhy. MgSO4, and concentrated to give the crude mixture Chromatography of the crude (Hex:EtOAc=1:1, pure EtOAc) afforded desired product as white solid (70 mg, 89% 129-130° C. The solvent was removed under vacuum the resulting residue was redissolved in CH2Cl2 (100 ml) The organic layer was washed with aq. NaHCO3 dried over anhy MgSO4, and concentrated to give the crude mixture Chromatography of the crude (Hex:EtOAc=1:1, pure EtOAc)

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

実験手順: To a stirring solution of 2-bromobenzylamine hydrochloride (80.7 mg, 95%, 0.345 mmol) in anhydrous DMF (5 ml) was added triethylamine (51.8 ul. 0.345 mmol). After 5 min, 2-[1,6]naphthyridinecarboxylic acid (40 mg, 0.229 mmol), 1-hydroxybenzotriazole hydrate (34.2 mg, 0.253 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (48.5 mg, 0.253 mmol) was sequentially added. The resulting mixture was allowed to stir at room temperature for 4 h and it was found to be clear. The solvent was removed under vacuum and the resulting residue was redissolved in CH2Cl2 (100 ml). The organic layer was washed with aqueous NaHCO3, dried over anhydrous MgSO4, and concentrated to give the crude mixture. Chromatography of the crude (Hex:EtOAc=1:1 to pure EtOAc) afforded desired product as white solid (70 mg, 89%): m.p. 129-130° C. The solvent was removed under vacuum the resulting residue was redissolved in CH2Cl2 (100 ml) The organic layer was washed with aqueous NaHCO3 dried over anhydrous MgSO4 concentrated to give the crude mixture