(S)-(+)-2-氨基-1-丁醇

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

实验步骤: As described for example 191, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.65 mmol) was converted, using (S)-(+)-2-amino-1-butanol instead of 2-aminoethyl isopropylether, to the title compound (210 mg, 85%) which was obtained as a white solid. MS: m/e=380.2 [M−H]−.

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

实验步骤: As described for example 191, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.65 mmol) was converted, using (S)-(+)-2-amino-1-butanol instead of 2-aminoethyl isopropylether, to the title compound (210 mg, 85%) which was obtained as a white solid. MS: m/e=380.2 [M−H]−.

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

实验步骤: Triethylamine (0.94 ml, 6.74 mmol) was added to a solution of 400 mg (4.49 mmol) of (S)-2-aminobutan-1-ol in tetrahydrofuran (5 ml), and the mixture was stirred at room temperature for 10 min. 2-Nitrobenzenesulfonyl chloride (995.1 mg, 4.49 mmol) was added to the solution, and the mixture was stirred at room temperature for 15 min. A saturated aqueous sodium hydrogencarbonate solution was added thereto to stop the reaction, and the reaction solution was then extracted with ethyl acetate, was dried over anhydrous sodium sulfate, and was filtered. The filtrate was concentrated under the reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give 1.22 g (yield 99%) of the title compound. the mixture was stirred at room temperature for 15 min the reaction the reaction solution was then extracted with ethyl acetate was dried over anhydrous sodium sulfate was filtered The filtrate was concentrated under the reduced pressure the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1)

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

实验步骤: Triethylamine (0.94 ml, 6.74 mmol) was added to a solution of 400 mg (4.49 mmol) of (S)-2-aminobutan-1-ol in tetrahydrofuran (5 ml), and the mixture was stirred at room temperature for 10 min. 2-Nitrobenzenesulfonyl chloride (995.1 mg, 4.49 mmol) was added to the solution, and the mixture was stirred at room temperature for 15 min. A saturated aqueous sodium hydrogencarbonate solution was added thereto to stop the reaction, and the reaction solution was then extracted with ethyl acetate, was dried over anhydrous sodium sulfate, and was filtered. The filtrate was concentrated under the reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give 1.22 g (yield 99%) of the title compound. the mixture was stirred at room temperature for 15 min the reaction the reaction solution was then extracted with ethyl acetate was dried over anhydrous sodium sulfate was filtered The filtrate was concentrated under the reduced pressure the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1)

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

实验步骤: A mixture of (S)-2-aminobutan-1-ol (14.5 g, 0.163 mmol), 1-hydroxypropan-2-one (13.3 mL, 0.195 mmol) and platinum(IV) oxide (100 mg, 0.440 mol) were stirred under a hydrogen atmosphere (1 atm). After 30.5 h, the reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The residue was purified by distillation to give (S)-2-(1-hydroxypropan-2-ylamino)butan-1-ol (17.5 g, 74%) as a colorless oil. 1H NMR consistent. the reaction mixture was filtered through diatomaceous earth the filtrate was concentrated under reduced pressure The residue was purified by distillation

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

实验步骤: A mixture of (S)-2-aminobutan-1-ol (14.5 g, 0.163 mmol), 1-hydroxypropan-2-one (13.3 mL, 0.195 mmol) and platinum(IV) oxide (100 mg, 0.440 mol) were stirred under a hydrogen atmosphere (1 atm). After 30.5 h, the reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The residue was purified by distillation to give (S)-2-(1-hydroxypropan-2-ylamino)butan-1-ol (17.5 g, 74%) as a colorless oil. 1H NMR consistent. the reaction mixture was filtered through diatomaceous earth the filtrate was concentrated under reduced pressure The residue was purified by distillation

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

实验步骤: To an ice cold, stirred suspension of NaH(60% in oil, 1.6 g, 39.0 mmol) in toluene (50 mL) was added dropwise a solution of (S)-2-aminobutan-1-ol (1.5 g, 17.0 mmol) in toluene (36 mL). After the addition was completed, the reaction mixture was warmed to room temperature and a solution of ethyl chloroacetate (2.3 g, 19.0 mmol) in toluene (9 mL) was added in a dropwise manner. The resulting mixture was then stirred at reflux for 20 h, cooled to room temperature, and solid NH4Cl (2.0 g, 38.7 mmol) was added to the reaction. The mixture was stirred for 20 min and then concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 95:5 methylene chloride/CH3OH) to give (S)-5-ethylmorpholine-3-one (1.9 g, 88%) as an off-white semi-solid: 1H NMR and MS consistent. After the addition at reflux for 20 h cooled to room temperature The mixture was stirred for 20 min concentrated under reduced pressure The crude material was purified by column chromatography (silica gel, 95:5 methylene chloride/CH3OH)

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

实验步骤: To an ice cold, stirred suspension of NaH(60% in oil, 1.6 g, 39.0 mmol) in toluene (50 mL) was added dropwise a solution of (S)-2-aminobutan-1-ol (1.5 g, 17.0 mmol) in toluene (36 mL). After the addition was completed, the reaction mixture was warmed to room temperature and a solution of ethyl chloroacetate (2.3 g, 19.0 mmol) in toluene (9 mL) was added in a dropwise manner. The resulting mixture was then stirred at reflux for 20 h, cooled to room temperature, and solid NH4Cl (2.0 g, 38.7 mmol) was added to the reaction. The mixture was stirred for 20 min and then concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 95:5 methylene chloride/CH3OH) to give (S)-5-ethylmorpholine-3-one (1.9 g, 88%) as an off-white semi-solid: 1H NMR and MS consistent. After the addition at reflux for 20 h cooled to room temperature The mixture was stirred for 20 min concentrated under reduced pressure The crude material was purified by column chromatography (silica gel, 95:5 methylene chloride/CH3OH)

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

实验步骤: To an ice cold, stirred suspension of sodium hydride (60% in oil, 1.6 g, 39.0 mmol) in toluene (50 mL) was added dropwise a solution of (S)-2-aminobutan-1-ol (1.5 g, 17.0 mmol) in toluene (36 mL). After the addition was completed, the reaction mixture was warmed to room temperature and a solution of ethyl chloroacetate (2.3 g, 19.0 mmol) in toluene (9 mL) was added in a dropwise manner. The resulting mixture was then stirred at reflux for 20 h, cooled to room temperature, and solid ammonium chloride (2.0 g, 38.7 mmol) added to the reaction. The mixture was stirred for 20 min and then concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 95:5 CH2Cl2/CH3OH) to give (S)-5-ethylmorpholine-3-one (1.9 g, 88%) as an off-white semi-solid. 1H NMR consistent. After the addition at reflux for 20 h cooled to room temperature The mixture was stirred for 20 min concentrated under reduced pressure The crude material was purified by column chromatography (silica gel, 95:5 CH2Cl2/CH3OH)

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

实验步骤: To an ice cold, stirred suspension of sodium hydride (60% in oil, 1.6 g, 39.0 mmol) in toluene (50 mL) was added dropwise a solution of (S)-2-aminobutan-1-ol (1.5 g, 17.0 mmol) in toluene (36 mL). After the addition was completed, the reaction mixture was warmed to room temperature and a solution of ethyl chloroacetate (2.3 g, 19.0 mmol) in toluene (9 mL) was added in a dropwise manner. The resulting mixture was then stirred at reflux for 20 h, cooled to room temperature, and solid ammonium chloride (2.0 g, 38.7 mmol) added to the reaction. The mixture was stirred for 20 min and then concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 95:5 CH2Cl2/CH3OH) to give (S)-5-ethylmorpholine-3-one (1.9 g, 88%) as an off-white semi-solid. 1H NMR consistent. After the addition at reflux for 20 h cooled to room temperature The mixture was stirred for 20 min concentrated under reduced pressure The crude material was purified by column chromatography (silica gel, 95:5 CH2Cl2/CH3OH)

反应条件: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-chloro-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine (300 mg, 1 mmol), (S)-2-amino-1-butanol (107 mg, 1.2 mmol) and phenol (188 mg, 2 mmol) was heated in 190° C. oil bath for 15 hours. The mixture was cooled, quenched with 2 N sodium hydroxide and extracted with chloroform. The organic layer was separated and neutralized with 2 N hydrochloride and water. The organic layer was dried and concentrated to give an oil residue. The residue was purified through silica gel column chromatography using chloroform as eluent to give 157 mg of starting material, and 52 mg of 3,6-dimethyl-4-phenoxy-1-(2,4,6-trimethylphenyl)-1H-pyrazolo-[3,4-b]pyridine as beige crystals. 1H NMR (CDCl3): 7.1-7.45 (m, 5H), 6.95 (s, 2H), 6.06 (s, 1H), 2.71 (s, 3H), 2.38 (s, 3H), 2.29 (S, 3H), 1.94 (s, 6H) ppm; and 30 mg of 2-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1-H-pyrazolo[3,4-b]pyridin4-ylamino]-butan-1-olasa yellow glass. The mixture was cooled quenched with 2 N sodium hydroxide extracted with chloroform The organic layer was separated The organic layer was dried concentrated to give an oil residue The residue was purified through silica gel column chromatography

反应条件: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-chloro-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine (300 mg, 1 mmol), (S)-2-amino-1-butanol (107 mg, 1.2 mmol) and phenol (188 mg, 2 mmol) was heated in 190° C. oil bath for 15 hours. The mixture was cooled, quenched with 2 N sodium hydroxide and extracted with chloroform. The organic layer was separated and neutralized with 2 N hydrochloride and water. The organic layer was dried and concentrated to give an oil residue. The residue was purified through silica gel column chromatography using chloroform as eluent to give 157 mg of starting material, and 52 mg of 3,6-dimethyl-4-phenoxy-1-(2,4,6-trimethylphenyl)-1H-pyrazolo-[3,4-b]pyridine as beige crystals. 1H NMR (CDCl3): 7.1-7.45 (m, 5H), 6.95 (s, 2H), 6.06 (s, 1H), 2.71 (s, 3H), 2.38 (s, 3H), 2.29 (S, 3H), 1.94 (s, 6H) ppm; and 30 mg of 2-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1-H-pyrazolo[3,4-b]pyridin4-ylamino]-butan-1-olasa yellow glass. The mixture was cooled quenched with 2 N sodium hydroxide extracted with chloroform The organic layer was separated The organic layer was dried concentrated to give an oil residue The residue was purified through silica gel column chromatography