1-amino-3,3-dimethylbutan-2-one

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:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 6.8 g of aminomethyl-(1,1-dimethylethyl)ketone, as the hydrochloride salt, in 30 ml of water were added portionwise 5.0 g of cyanamide. The pH of the reaction mixture was adjusted to 6.0 with 1N sodium hydroxide, and then the mixture was heated to 90° C. and stirred for fifty-five minutes. The reaction mixture was next cooled to room temperature, diluted with 100 ml. of water, and extracted several times with diethyl ether. The aqueous layer was made alkaline with ammonium hydroxide, and again extracted several times with diethylether. The extracts from the alkaline mixture were combined and concentrated to dryness to provide a solid residue. The residue thus obtained was dissolved in 20 m of 6N hydrochloric acid and heated at reflux for sixteen hours. The reaction mixture was cooled, concentrated to an oil by evaporation of the solvent, and the oil was dissolved in water and made alkaline to pH 8.5. The alkaline mixture was extracted several times with diethyl ether. The etheral extracts were combined, washed with water, dried, and the solvent was removed by evaporation under reduced pressure to provide 0.5 g of 5-(1,1-dimethylethyl)-2-aminoimidazole. The reaction mixture was next cooled to room temperature diluted with 100 ml of water, and extracted several times with diethyl ether concentrated to dryness to provide a solid residue The residue thus obtained heated at reflux for sixteen hours The reaction mixture was cooled concentrated to an oil by evaporation of the solvent the oil was dissolved in water The alkaline mixture was extracted several times with diethyl ether washed with water dried the solvent was removed by evaporation under reduced pressure

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

実験手順: To a solution of benzyl 2-(4-(4-(5-aminopyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (150 mg, 0.350 mmol) in DCM (6 ml) at room temperature was added 1,1′-thiocarbonyldi-2(1H)-pyridone (85 mg, 0.368 mmol) and the reaction was stirred at room temperature for 0.5 hr. To the mixture was added 1-amino-3,3-dimethylbutan-2-one (80 mg, 0.525 mmol) and DIPEA (0.110 ml, 0.630 mmol) and the mixture was stirred at 40° C. or until the reaction was completed. To the mixture was added EDC.HCl (268 mg, 1.400 mmol) and the reaction was stirred at 40° C. overnight. The reaction mixture was concentrated and purified by flash chromatography (10 to 50% EtOAc/Heptane) to give the title compound (100 mg, 51.8% yield). LC/MS, ESI-MS(+) m/z 552.1, RT: 1.73 (Condition R). the mixture was stirred at 40° C. or until the reaction the reaction was stirred at 40° C. overnight The reaction mixture was concentrated purified by flash chromatography (10 to 50% EtOAc/Heptane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The compound was synthesized as hydrochloride salt by the following procedure. Phenyl chloroformate (0.98 mL, 7.8 mmol) was dissolved in CH2Cl2, cooled down to 0° C. and 5-aminobenzimidazole (0.865 g, 6.5 mmol) was added slowly. The mixture was kept at 0° C. for 30 min and then the mixture was allowed to adapt ambient temperature. The mixture was stirred at ambient temperature for 2 h. The resulting solid was withdrawn by suction, dried and taken up in a small amount of DMF. To the solution, 1-amino-3,3-dimethylbutan-2-one (0.986, 6.5 mmol) and TEA (2.73 mL, 19.5 mmol) were added. The mixture was kept at 40° C. for 2 h. The solvent was removed and purified by means of preparative HPLC. The remains were re-dissolved in MeOH and a small amount of HCl was added (1-2%). The solution was subjected to hydrogenation (PdC, 10% on charcoal, 4 bar, 60° C.) for 4 h. The catalyst was removed by filtration through a pad of CELITE® and the residue was washed with water. The organic layer was dried, filtrated and the solvent was removed to result in the final product. to adapt ambient temperature The resulting solid was withdrawn by suction dried The mixture was kept at 40° C. for 2 h The solvent was removed purified by means of preparative HPLC The remains were re-dissolved in MeOH a small amount of HCl was added (1-2%) The solution was subjected to hydrogenation (PdC, 10% on charcoal, 4 bar, 60° C.) for 4 h The catalyst was removed by filtration through a pad of CELITE® the residue was washed with water The organic layer was dried filtrated the solvent was removed

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The compound was synthesized as hydrochloride salt by the following procedure. Phenyl chloroformate (0.98 mL, 7.8 mmol) was dissolved in CH2Cl2, cooled down to 0° C. and 5-aminobenzimidazole (0.865 g, 6.5 mmol) was added slowly. The mixture was kept at 0° C. for 30 min and then the mixture was allowed to adapt ambient temperature. The mixture was stirred at ambient temperature for 2 h. The resulting solid was withdrawn by suction, dried and taken up in a small amount of DMF. To the solution, 1-amino-3,3-dimethylbutan-2-one (0.986, 6.5 mmol) and TEA (2.73 mL, 19.5 mmol) were added. The mixture was kept at 40° C. for 2 h. The solvent was removed and purified by means of preparative HPLC. The remains were re-dissolved in MeOH and a small amount of HCl was added (1-2%). The solution was subjected to hydrogenation (PdC, 10% on charcoal, 4 bar, 60° C.) for 4 h. The catalyst was removed by filtration through a pad of CELITE® and the residue was washed with water. The organic layer was dried, filtrated and the solvent was removed to result in the final product. to adapt ambient temperature The resulting solid was withdrawn by suction dried The mixture was kept at 40° C. for 2 h The solvent was removed purified by means of preparative HPLC The remains were re-dissolved in MeOH a small amount of HCl was added (1-2%) The solution was subjected to hydrogenation (PdC, 10% on charcoal, 4 bar, 60° C.) for 4 h The catalyst was removed by filtration through a pad of CELITE® the residue was washed with water The organic layer was dried filtrated the solvent was removed

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 6.8 g of aminomethyl-(1,1-dimethylethyl)ketone, as the hydrochloride salt, in 30 ml of water were added portionwise 5.0 g of cyanamide. The pH of the reaction mixture was adjusted to 6.0 with 1N sodium hydroxide, and then the mixture was heated to 90° C. and stirred for fifty-five minutes. The reaction mixture was next cooled to room temperature, diluted with 100 ml. of water, and extracted several times with diethyl ether. The aqueous layer was made alkaline with ammonium hydroxide, and again extracted several times with diethylether. The extracts from the alkaline mixture were combined and concentrated to dryness to provide a solid residue. The residue thus obtained was dissolved in 20 ml of 6N hydrochloric acid and heated at reflux for sixteen hours. The reaction mixture was cooled, concentrated to an oil by evaporation of the solvent, and the oil was dissolved in water and made alkaline to pH 8.5. The alkaline mixture was extracted several times with diethyl ether. The etheral extracts were combined, washed with water, dried, and the solvent was removed by evaporation under reduced pressure to provide 0.5 g of 5-(1,1-dimethylethyl)-2-aminoimidazole. The reaction mixture was next cooled to room temperature diluted with 100 ml of water, and extracted several times with diethyl ether concentrated to dryness to provide a solid residue The residue thus obtained heated at reflux for sixteen hours The reaction mixture was cooled concentrated to an oil by evaporation of the solvent the oil was dissolved in water The alkaline mixture was extracted several times with diethyl ether washed with water dried the solvent was removed by evaporation under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Phenyl chloroformate (0.98 mL, 7.8 mmol) was dissolved in CH2Cl2, cooled down to 0° C. and 5-aminobenzimidazole (0.865 g, 6.5 mmol) was added slowly. The mixture was kept at 0° C. for 30 min and then the mixture was allowed to adapt ambient temperature. The mixture was stirred at ambient temperature for 2 h. The resulting solid was withdrawn by suction, dried and taken up in a small amount of DMF. To the solution, 1-amino-3,3-dimethylbutan-2-one (0.986, 6.5 mmol) and TEA (2.73 mL, 19.5 mmol) were added. The mixture was kept at 40° C. for 2 h. The solvent was removed and purified by means of preparative HPLC. The remains were re-dissolved in MeOH and a small amount of HCl was added (1-2%). The solution was subjected to hydrogenation (PdC, 10% on charcoal, 4 bar, 60° C.) for 4 h. The catalyst was removed by filtration through a pad of CELITE® and the residue was washed with water. The organic layer was dried, filtrated and the solvent was removed to result in the final product. Yield: 0.087 g (6.3%); MS m/z 259.4 (M+H)+; 1H NMR (DMSO, 400 MHz): δ 0.72 (s, 9H); 3.23-3.27 (m, H); 3.46-3.50 (m, H); 4.37-4.41 (m, H); 6.84 (bs, H); 7.56 (dd, H, 3J=9.1 Hz, 4J=1.7 Hz); 7.70 (d, H, J=9.1 Hz); 7.81 (d, H, 4J=1.7 Hz); 9.27 (s, H), HPLC (λ=214 nm, [B]: rt 6.83 min (99%). to adapt ambient temperature The resulting solid was withdrawn by suction dried The mixture was kept at 40° C. for 2 h The solvent was removed purified by means of preparative HPLC The remains were re-dissolved in MeOH a small amount of HCl was added (1-2%) The solution was subjected to hydrogenation (PdC, 10% on charcoal, 4 bar, 60° C.) for 4 h The catalyst was removed by filtration through a pad of CELITE® the residue was washed with water The organic layer was dried filtrated the solvent was removed

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:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 6.8 g of aminomethyl-(1,1-dimethylethyl)ketone, as the hydrochloride salt, in 30 ml of water were added portionwise 5.0 g of cyanamide. The pH of the reaction mixture was adjusted to 6.0 with 1N sodium hydroxide, and then the mixture was heated to 90° C. and stirred for fifty-five minutes. The reaction mixture was next cooled to room temperature, diluted with 100 ml. of water, and extracted several times with diethyl ether. The aqueous layer was made alkaline with ammonium hydroxide, and again extracted several times with diethylether. The extracts from the alkaline mixture were combined and concentrated to dryness to provide a solid residue. The residue thus obtained was dissolved in 20 ml of 6N hydrochloric acid and heated at reflux for sixteen hours. The reaction mixture was cooled, concentrated to an oil by evaporation of the solvent, and the oil was dissolved in water and made alkaline to pH 8.5. The alkaline mixture was extracted several times with diethyl ether. The etheral extracts were combined, washed with water, dried, and the solvent was removed by evaporation under reduced pressure to provide 0.5 g of 5-(1,1-dimethylethyl)-2-aminoimidazole. The reaction mixture was next cooled to room temperature diluted with 100 ml of water, and extracted several times with diethyl ether concentrated to dryness to provide a solid residue The residue thus obtained heated at reflux for sixteen hours The reaction mixture was cooled concentrated to an oil by evaporation of the solvent the oil was dissolved in water The alkaline mixture was extracted several times with diethyl ether washed with water dried the solvent was removed by evaporation under reduced pressure

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 6.8 g of aminomethyl-(1,1-dimethylethyl)ketone, as the hydrochloride salt, in 30 ml of water were added portionwise 5.0 g of cyanamide. The pH of the reaction mixture was adjusted to 6.0 with 1N sodium hydroxide, and then the mixture was heated to 90° C. and stirred for fifty-five minutes. The reaction mixture was next cooled to room temperature, diluted with 100 ml. of water, and extracted several times with diethyl ether. The aqueous layer was made alkaline with ammonium hydroxide, and again extracted several times with diethylether. The extracts from the alkaline mixture were combined and concentrated to dryness to provide a solid residue. The residue thus obtained was dissolved in 20 ml of 6N hydrochloric acid and heated at reflux for sixteen hours. The reaction mixture was cooled, concentrated to an oil by evaporation of the solvent, and the oil was dissolved in water and made alkaline to pH 8.5. The alkaline mixture was extracted several times with diethyl ether. The etheral extracts were combined, washed with water, dried, and the solvent was removed by evaporation under reduced pressure to provide 0.5 g of 5-(1,1-dimethylethyl)-2-aminoimidazole. The reaction mixture was next cooled to room temperature diluted with 100 ml of water, and extracted several times with diethyl ether concentrated to dryness to provide a solid residue The residue thus obtained heated at reflux for sixteen hours The reaction mixture was cooled concentrated to an oil by evaporation of the solvent the oil was dissolved in water The alkaline mixture was extracted several times with diethyl ether washed with water dried the solvent was removed by evaporation under reduced pressure