BOC-DL-3-氨基异丁酸

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

实验步骤: Benzyl (S)-3-(1-t-butoxyformamido)succinamate was deprotected using trifluoroacetic acid and then coupled with DL-N-(t-butoxycarbonyl)-2-methyl-β-alanine to yield t-Butyl [(RS)-2-[[(S)-2-[(benzyloxy)carbonyl]-1-carbamoylethyl]-carbamoyl]propyl]carbamate, m.p. 135°-136° C.

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

实验步骤: To a solution of N-Boc-α-(R,S)-methyl-β-alanine (1.33 g, 6.5 mmol) in THF (80 ml)was added pentane washed sodium hydride(1.2 g, 60% in oil dispersion) followed by methyl iodide (2 ml, exess). The reaction mixture was stirred overnight and then poured into an iced solution of citric acid (0.5N). The aqueous THF solution was extracted into ethyl acetate. Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions. The organic extracts were dried (MgSO4) and evaporated to afford the title compound. (1.00 g, 71%), Anal: C10H19NO4.0.3H2O, Calc: C, 53.94; H, 8.87; N, 6.29. Found, C, 54.02; H, 8.56; N, 6.63. washed sodium hydride(1.2 g, 60% in oil dispersion) poured into an iced solution of citric acid (0.5N) The aqueous THF solution was extracted into ethyl acetate Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions The organic extracts were dried (MgSO4) evaporated

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

实验步骤: To a solution of N-Boc-α-(R,S)-methyl-β-alanine (1.33g, 6.5 mmol) in THF (80 ml) was added pentane washed sodium hydride(1.2 g, 60% in oil dispersion) followed by methyl iodide (2 ml, exess). The reaction mixture was stirred overnight and then poured into an iced solution of citric acid (0.5 N). The aqueous THF solution was extracted into ethyl acetate. Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions. The organic extracts were dried (MgSO4) and evaporated to afford the title compound. (1.00 g, 71%), Anal: C10H19NO4.0.3H2O, Calc: C, 53.94; H, 8.87; N, 6.29. Found, C, 54.02; H, 8.56; N, 6.63. washed sodium hydride(1.2 g, 60% in oil dispersion) poured into an iced solution of citric acid (0.5 N) The aqueous THF solution was extracted into ethyl acetate Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions The organic extracts were dried (MgSO4) evaporated

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

实验步骤: To a solution of N-Boc-α-(R,S)-methyl-β-alanine (1.33g, 6.5 mmol) in THF (80 ml) was added pentane washed sodium hydride(1.2 g, 60% in oil dispersion) followed by methyl iodide (2 ml, exess). The reaction mixture was stirred overnight and then poured into an iced solution of citric acid (0.5 N). The aqueous THF solution was extracted into ethyl acetate. Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions. The organic extracts were dried (MgSO4) and evaporated to afford the title compound. (1.00 g, 71%), Anal: C10H19NO4.0.3H2O, Calc: C, 53.94; H, 8.87; N, 6.29. Found, C, 54.02; H, 8.56; N, 6.63. washed sodium hydride(1.2 g, 60% in oil dispersion) poured into an iced solution of citric acid (0.5 N) The aqueous THF solution was extracted into ethyl acetate Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions The organic extracts were dried (MgSO4) evaporated

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

实验步骤: To a solution of N-Boc-α-(R,S)-methyl-β-alanine (1.33 g, 6.5 mmol) in THF (80 ml)was added pentane washed sodium hydride(1.2 g, 60% in oil dispersion) followed by methyl iodide (2 ml, exess). The reaction mixture was stirred overnight and then poured into an iced solution of citric acid (0.5N). The aqueous THF solution was extracted into ethyl acetate. Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions. The organic extracts were dried (MgSO4) and evaporated to afford the title compound. (1.00 g, 71%), Anal: C10H19NO4.0.3H2O, Calc: C, 53.94; H, 8.87; N, 6.29. Found, C, 54.02; H, 8.56; N, 6.63. washed sodium hydride(1.2 g, 60% in oil dispersion) poured into an iced solution of citric acid (0.5N) The aqueous THF solution was extracted into ethyl acetate Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions The organic extracts were dried (MgSO4) evaporated

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

实验步骤: To a solution of N-Boc-α-(R,S)-methyl-β-alanine (1.33 g, 6.5 mmol) in THF (80 ml)was added pentane washed sodium hydride(1.2 g, 60% in oil dispersion) followed by methyl iodide (2 ml, exess). The reaction mixture was stirred overnight and then poured into an iced solution of citric acid (0.5N). The aqueous THF solution was extracted into ethyl acetate. Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions. The organic extracts were dried (MgSO4) and evaporated to afford the title compound. (1.00 g, 71%), Anal: C10H19NO4.0.3H2O, Calc: C, 53.94; H, 8.87; N, 6.29. Found, C, 54.02; H, 8.56; N, 6.63. washed sodium hydride(1.2 g, 60% in oil dispersion) poured into an iced solution of citric acid (0.5N) The aqueous THF solution was extracted into ethyl acetate Then the required acid was back extracted between ethyl acetate, sodium hydrogen carbonate and potassium hydrogen sulphate solutions The organic extracts were dried (MgSO4) evaporated

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

实验步骤: 50 mg of (±)-1-(3,4-dihydro-2H-1,5-benzodioxepine-7-yl)-4-methylpentan-3-ylamine was mixed with of (±)-2-Methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid (25 mg), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (53 mg), and DMAP (33 mg) in dichloromethane (5 ml) and stirred overnight. Water (5 ml) was added, and the reaction mixture was extracted with ethyl acetate (5 ml three times). The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography on silica (20% ethyl acetate in hexane) yielded a resin: MS (m+1)=435.6. the reaction mixture was extracted with ethyl acetate (5 ml three times) The organic layer was washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure Purification by flash chromatography on silica (20% ethyl acetate in hexane) yielded a resin

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

实验步骤: 50 mg of (±)-1-(3,4-dihydro-2H-1,5-benzodioxepine-7-yl)-4-methylpentan-3-ylamine was mixed with of (±)-2-Methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid (25 mg), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (53 mg), and DMAP (33 mg) in dichloromethane (5 ml) and stirred overnight. Water (5 ml) was added, and the reaction mixture was extracted with ethyl acetate (5 ml three times). The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography on silica (20% ethyl acetate in hexane) yielded a resin: MS (m+1)=435.6. the reaction mixture was extracted with ethyl acetate (5 ml three times) The organic layer was washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure Purification by flash chromatography on silica (20% ethyl acetate in hexane) yielded a resin

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

实验步骤: The mixture of N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-2-methylpropan-1-amine (600 mg), (±)-2-Methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid (200 mg), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (475 mg) and of dimethyl aminopyridine (284 mg) in DCM (30 ml) was stirred overnight. The reaction mixture was partitioned between ethyl acetate and water (30 mL each). The aqueous layer was extracted with EtOAc (30 mL×2). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica (33% ethyl acetate in hexane) to give (±)-2-Methyl-3-(methylpropan-2-yl)oxycarbonylamino-N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-N-isobutylpropanamide as a resin: MS (m+1)=455.5. The reaction mixture was partitioned between ethyl acetate and water (30 mL each) The aqueous layer was extracted with EtOAc (30 mL×2) The combined organic layer was washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by flash chromatography on silica (33% ethyl acetate in hexane)

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

实验步骤: 3-[(tert-Butoxycarbonyl)amino]-2-methylpropanoic acid (2.0 g, 9.9 mmol) was dissolved in acetonitrile (50 mL). To this solution was added HOBT (1.6 g, 11.85 mmol) and EDC (2.0 g, 10.4 mmol). The reaction was stirred at room temperature for 2 hr, and then treated with triethylamine (2.8 mL, 20 mmol) and N,O-dimethylhydroxyamine hydrochloride (2.0 g, 20 mmol). The reaction mixture was stirred at room temperature overnight. The reaction was quenched with water and extracted with ethyl acetate (3×). The combined organic extract was washed sequentially with 0.5N hydrochloric acid, 1N aqueous sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on a Biotage® system (silica, 40-100% ethyl acetate in hexanes) to yield tert-butyl {3-[methoxy(methyl)amino]-2-methyl-3-oxopropyl}carbamate as white solid. MS (M+1−Boc): 147. The reaction mixture was stirred at room temperature overnight The reaction was quenched with water extracted with ethyl acetate (3×) The combined organic extract was washed sequentially with 0.5N hydrochloric acid, 1N aqueous sodium bicarbonate solution and brine dried over sodium sulfate filtered evaporated The crude product was purified by flash chromatography on a Biotage® system (silica, 40-100% ethyl acetate in hexanes)

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

实验步骤: 3-[(tert-Butoxycarbonyl)amino]-2-methylpropanoic acid (2.0 g, 9.9 mmol) was dissolved in acetonitrile (50 mL). To this solution was added HOBT (1.6 g, 11.85 mmol) and EDC (2.0 g, 10.4 mmol). The reaction was stirred at room temperature for 2 hr, and then treated with triethylamine (2.8 mL, 20 mmol) and N,O-dimethylhydroxyamine hydrochloride (2.0 g, 20 mmol). The reaction mixture was stirred at room temperature overnight. The reaction was quenched with water and extracted with ethyl acetate (3×). The combined organic extract was washed sequentially with 0.5N hydrochloric acid, 1N aqueous sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on a Biotage® system (silica, 40-100% ethyl acetate in hexanes) to yield tert-butyl {3-[methoxy(methyl)amino]-2-methyl-3-oxopropyl}carbamate as white solid. MS (M+1−Boc): 147. The reaction mixture was stirred at room temperature overnight The reaction was quenched with water extracted with ethyl acetate (3×) The combined organic extract was washed sequentially with 0.5N hydrochloric acid, 1N aqueous sodium bicarbonate solution and brine dried over sodium sulfate filtered evaporated The crude product was purified by flash chromatography on a Biotage® system (silica, 40-100% ethyl acetate in hexanes)

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

实验步骤: The 3-[(tert-butoxycarbonyl)amino]-2-methylpropanoic acid (3.0 g, 14.76 mmol) was dissolved in CH2Cl2 (73.8 ml), cooled to 0° C. and treated with 2,2-dimethyl-1,3-dioxane-4,6-dione (2.55 g, 17.71 mmol) and DMAP (2.71 g, 22.14 mmol) and EDC (3.40 g, 17.71 mmol) and allowed to stir at room temperature for 18 hrs. The reaction mixture was diluted with CH2Cl2, washed with 5% KHSO4 (×3), dried (Na2SO4), filtered and evaporated in vacuo to give the title compound: 1H NMR (400 MHz, CDCl3) δ 4.78 (bs, 1H), 4.23 (bs, 1H), 3.42 (m, 2H), 1.75 (s, 6H), 1.41 (s, 9H), 1.23 (d, J=6.8 Hz, 3H). washed with 5% KHSO4 (×3) dried (Na2SO4) filtered evaporated in vacuo