tert-butyl N-[(2S)-1-(dimethylamino)-3-methyl-1-oxobutan-2-yl]carbamate

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.85 g of 2(S)-tert-butoxycarbonylamino-3-methylbutanoic acid (N,N-dimethyl)amide is dissolved in 10 ml of 4N hydrochloric acid in dioxane at 0° C. and stirred for 7 hours at 0° C. The reaction mixture is lyophilised and the title compound is obtained: Rf (ethyl acetate/methanol/conc. ammonia=80:15:5)=0.23.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.85 g of 2(S)-tert-butoxycarbonylamino-3-methylbutanoic acid (N,N-dimethyl)amide is dissolved in 10 ml of 4N hydrochloric acid in dioxane at 0° C. and stirred for 7 hours at 0° C. The reaction mixture is lyophilised and the title compound is obtained: Rf (ethyl acetate/methanol/conc. ammonia=80:15:5)=0.23.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.85 g of 2(S)-tert-butoxycarbonylamino-3-methylbutanoic acid (N,N-dimethyl)amide is dissolved in 10 ml of 4N hydrochloric acid in dioxane at 0° C. and stirred for 7 hours at 0° C. The reaction mixture is lyophilised and the title compound is obtained: Rf (ethyl acetate/methanol/conc. ammonia=80:15:5)=0.23.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.85 g of 2(S)-tert-butoxycarbonylamino-3-methylbutanoic acid (N,N-dimethyl)amide is dissolved in 10 ml of 4N hydrochloric acid in dioxane at 0° C. and stirred for 7 hours at 0° C. The reaction mixture is lyophilised and the title compound is obtained: Rf (ethyl acetate/methanol/conc. ammonia=80:15:5)=0.23.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.85 g of 2(S)-tert-butoxycarbonylamino-3-methylbutanoic acid (N,N-dimethyl)amide is dissolved in 10 ml of 4N hydrochloric acid in dioxane at 0° C. and stirred for 7 hours at 0° C. The reaction mixture is lyophilised and the title compound is obtained: Rf (ethyl acetate/methanol/conc. ammonia=80:15:5)=0.23.

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

实验步骤: In a 100 mL round bottom flask, (S)-tert-butyl(1-(dimethylamino)-3-methyl-1-oxobutan-2-yl)carbamate S2 (4.65 g, 19.3 mmol, 1.00 equiv.) is allowed to stir with a 4.0 M solution of hydrochloric acid in dioxane (28.9 mL, 116 mmol, 6.00 equiv.) for 1.5 h at 22° C. under air, after which the solution is purged with nitrogen for 30 min (removal of HCl gas) and the solvent is removed under reduced pressure to yield (S)-2-amino-N,N,3-trimethylbutanamide as HCl salt S3, which is used without purification in the subsequent condensation. after which the solution is purged with nitrogen for 30 min (removal of HCl gas) the solvent is removed under reduced pressure

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

实验步骤: EDC.HCl (4.22 g, 22.0 mmol), reagent grade CH2Cl2 (80 mL), HOBt.H2O (3.36 g, 22.0 mmol), and Boc-Val-OH (4.34 g, 20.0 mmol) are added successively at 22° C. under air to a 250 mL round bottom flask equipped with a stir bar. The light yellow solution is allowed to stir for five minutes and dimethylamine (40 wt % in H2O, 5.3 mL, 50 mmol) is added drop-wise over one minute. The flask with the resulting light yellow solution is sealed with a rubber septum and allowed to stir for 12 h at 22° C. An aqueous solution of citric acid (10 wt %, 80 mL) is then added and the mixture is allowed to stir for 0.5 h during which time a white precipitate is formed. The precipitate is removed by filtration and the resulting two layers are separated. The organic layer is washed sequentially with an aqueous solution of citric acid (10 wt %, 80 mL), a saturated aqueous solution of NaHCO3 (80 mL), and brine (80 mL) and is dried over Na2SO4 to give (S)-tert-butyl(1-(dimethylamino)-3-methyl-1-oxobutan-2-yl)carbamate (S2) as pale yellow oil, which is employed without purification in the subsequent deprotection. equipped with a stir bar The flask with the resulting light yellow solution is sealed with a rubber septum to stir for 12 h at 22° C to stir for 0.5 h during which time a white precipitate is formed The precipitate is removed by filtration the resulting two layers are separated The organic layer is washed sequentially with an aqueous solution of citric acid (10 wt %, 80 mL) a saturated aqueous solution of NaHCO3 (80 mL), and brine (80 mL) and is dried over Na2SO4

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

实验步骤: tert-Butyl (1S)-1-[(dimethylamino)carbonyl]-2-methylpropylcarbamate (131 mg) was treated with 4M of hydrogen chloride in 1,4-dioxane (1.0 mL) at RT for 2 h. The solvent was evaporated under reduced pressure. The residue was dried to give the desired product (96 mg). The solvent was evaporated under reduced pressure The residue was dried

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

实验步骤: N,N-Diisopropylethylamine (1.0 mL, 5.74 mmol) was added to a mixture of (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoic acid (0.217 g, 1.0 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.211 g, 1.1 mmol) and dimethylamine in THF (2M, 1.0 mL) in methylene chloride (10 mL). The mixture was stirred overnight at RT. The mixture was washed with water, saturated NaHCO3 solution, brine, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on silica gel to give the desired product (131 mg, 53.6%). The mixture was washed with water, saturated NaHCO3 solution, brine dried over Na2SO4 filtered concentrated The residue was chromatographed on silica gel

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

实验步骤: N,N-Diisopropylethylamine (1.0 mL, 5.74 mmol) was added to a mixture of (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoic acid (0.217 g, 1.0 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.211 g, 1.1 mmol) and dimethylamine in THF (2M, 1.0 mL) in methylene chloride (10 mL). The mixture was stirred overnight at RT. The mixture was washed with water, saturated NaHCO3 solution, brine, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on silica gel to give the desired product (131 mg, 53.6%). The mixture was washed with water, saturated NaHCO3 solution, brine dried over Na2SO4 filtered concentrated The residue was chromatographed on silica gel

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.85 g of 2(S)-tert-butoxycarbonylamino-3-methylbutanoic acid (N,N-dimethyl)amide is dissolved in 10 ml of 4N hydrochloric acid in dioxane at 0° C. and stirred for 7 hours at 0° C. The reaction mixture is lyophilised and the title compound is obtained: Rf (ethyl acetate/methanol/conc. ammonia=80:15:5)=0.23.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.85 g of 2(S)-tert-butoxycarbonylamino-3-methylbutanoic acid (N,N-dimethyl)amide is dissolved in 10 ml of 4N hydrochloric acid in dioxane at 0° C. and stirred for 7 hours at 0° C. The reaction mixture is lyophilised and the title compound is obtained: Rf (ethyl acetate/methanol/conc. ammonia=80:15:5)=0.23.