N-CBZ-N-甲基乙二胺

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

实验步骤: To a solution of compound B (˜311 mmol) in MeOH (1.2 L) was added a solution of LiOH (14.9 g, 622 mmol) in water (120 mL). The reaction mixture was stirred at ambient temperature for 3 h. Solvents were evaporated to 75% of the initial volume followed by dilution with water (400 mL). The solution was extracted with EtOAc (2×300 mL). The organic layer was washed with brine (200 mL), dried over MgSO4 and evaporated in vacuo. The residue was dissolved in ether (300 mL) and treated with 2 N HCl/ether (200 mL). Formed precipitate was filtrated, washed with ether and dried in vacuo to provide the hydrochloric salt of compound C (67.8 g, 89%) as a white solid. LC-MS [M+H] 209.0 (C11H16N2O2+H, calc: 209.3). Compound C was used directly in the next reaction without purification as a DMF solution. Solvents were evaporated to 75% of the initial volume The solution was extracted with EtOAc (2×300 mL) The organic layer was washed with brine (200 mL) dried over MgSO4 evaporated in vacuo The residue was dissolved in ether (300 mL) treated with 2 N HCl/ether (200 mL) Formed precipitate was filtrated washed with ether dried in vacuo

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

实验步骤: To a solution of compound B (˜311 mmol) in MeOH (1.2 L) was added a solution of LiOH (14.9 g, 622 mmol) in water (120 mL). The reaction mixture was stirred at ambient temperature for 3 h. Solvents were evaporated to 75% of the initial volume followed by dilution with water (400 mL). The solution was extracted with EtOAc (2×300 mL). The organic layer was washed with brine (200 mL), dried over MgSO4 and evaporated in vacuo. The residue was dissolved in ether (300 mL) and treated with 2 N HCl/ether (200 mL). Formed precipitate was filtrated, washed with ether and dried in vacuo to provide the hydrochloric salt of compound C (67.8 g, 89%) as a white solid. LC-MS [M+H] 209.0 (C11H16N2O2+H, calc: 209.3). Compound C was used directly in the next reaction without purification as a DMF solution. Solvents were evaporated to 75% of the initial volume The solution was extracted with EtOAc (2×300 mL) The organic layer was washed with brine (200 mL) dried over MgSO4 evaporated in vacuo The residue was dissolved in ether (300 mL) treated with 2 N HCl/ether (200 mL) Formed precipitate was filtrated washed with ether dried in vacuo

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

实验步骤: To a solution of compound Y (103.0 g, 340.7 mmol) in MeOH (1200 mL) was added a solution of LiOH (16.4 g, 681.4 mmol) in water (120 mL). The reaction mixture was stirred at room temperature for 3 h. Solvents were evaporated to ¾ of initial volume followed by dilution with water (400 mL). Solution was extracted with EtOAc (2×300 mL). The organic layer was washed with brine (200 mL), dried over MgSO4 and evaporated in vacuo. The resultant residue was dissolved in ether (300 mL) and treated with 2 N HCl/ether (200 mL). The formed precipitate was filtered, washed with ether and dried in vacuo to provide hydrochloric salt of compound Z (54.5 g, 261.2 mmol) as white solid. LC-MS [M+H] 209.5 (C11H16N2O2+H, calc: 209.3). Solvents were evaporated Solution was extracted with EtOAc (2×300 mL) The organic layer was washed with brine (200 mL) dried over MgSO4 evaporated in vacuo The resultant residue was dissolved in ether (300 mL) treated with 2 N HCl/ether (200 mL) The formed precipitate was filtered washed with ether dried in vacuo

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

实验步骤: To a solution of compound Y (103.0 g, 340.7 mmol) in MeOH (1200 mL) was added a solution of LiOH (16.4 g, 681.4 mmol) in water (120 mL). The reaction mixture was stirred at room temperature for 3 h. Solvents were evaporated to ¾ of initial volume followed by dilution with water (400 mL). Solution was extracted with EtOAc (2×300 mL). The organic layer was washed with brine (200 mL), dried over MgSO4 and evaporated in vacuo. The resultant residue was dissolved in ether (300 mL) and treated with 2 N HCl/ether (200 mL). The formed precipitate was filtered, washed with ether and dried in vacuo to provide hydrochloric salt of compound Z (54.5 g, 261.2 mmol) as white solid. LC-MS [M+H] 209.5 (C11H16N2O2+H, calc: 209.3). Solvents were evaporated Solution was extracted with EtOAc (2×300 mL) The organic layer was washed with brine (200 mL) dried over MgSO4 evaporated in vacuo The resultant residue was dissolved in ether (300 mL) treated with 2 N HCl/ether (200 mL) The formed precipitate was filtered washed with ether dried in vacuo

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

实验步骤: A solution of Boc-Arg(Pbf)-OH (3.33 g, 6.32 mmol), HATU (2.88 g, 7.58 mmol) and DIEA (7.4 ml, 31.6 mmol) in DMF (40 ml) was maintained at room temperature for 20 min, followed by the addition of compound C hydrochloride (1.45 g, 6.95 mmol). Stirring was continued for additional 1 h. The reaction mixture was diluted with EtOAc (500 ml) and extracted with water (3×75 ml) and brine (75 ml). The organic layer was dried over MgSO4 and then evaporated to provide compound D (4.14 g, 5.77 mmol) as yellowish amorphous solid. LC-MS [M+H] 717.6 (C35H52N6O8S+H, calc: 717.9). extracted with water (3×75 ml) and brine (75 ml) The organic layer was dried over 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 compound B (103.0 g, 340.7 mmol) in MeOH (1200 ml) was added a solution of LiOH (16.4 g, 681.4 mmol) in water (120 ml). The reaction mixture was stirred at room temperature for 3 h. Solvents were evaporated to ¾ of initial volume followed by dilution with water (400 ml). Solution was extracted with EtOAc (2×300 ml). The organic layer was washed with brine (200 ml), dried over MgSO4 and evaporated in vacuo. The resultant residue was dissolved in ether (300 ml) and treated with 2 N HCl/ether (200 ml). The formed precipitate was filtered, washed with ether and dried in vacuo to provide hydrochloric salt of compound C (54.5 g, 261.2 mmol) as white solid. LC-MS [M+H] 209.5 (C11H16N2O2+H, calc: 209.3). Solvents were evaporated Solution was extracted with EtOAc (2×300 ml) The organic layer was washed with brine (200 ml) dried over MgSO4 evaporated in vacuo The resultant residue was dissolved in ether (300 ml) treated with 2 N HCl/ether (200 ml) The formed precipitate was filtered washed with ether dried in vacuo

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

实验步骤: To a solution of compound B (103.0 g, 340.7 mmol) in MeOH (1200 ml) was added a solution of LiOH (16.4 g, 681.4 mmol) in water (120 ml). The reaction mixture was stirred at room temperature for 3 h. Solvents were evaporated to ¾ of initial volume followed by dilution with water (400 ml). Solution was extracted with EtOAc (2×300 ml). The organic layer was washed with brine (200 ml), dried over MgSO4 and evaporated in vacuo. The resultant residue was dissolved in ether (300 ml) and treated with 2 N HCl/ether (200 ml). The formed precipitate was filtered, washed with ether and dried in vacuo to provide hydrochloric salt of compound C (54.5 g, 261.2 mmol) as white solid. LC-MS [M+H] 209.5 (C11H16N2O2+H, calc: 209.3). Solvents were evaporated Solution was extracted with EtOAc (2×300 ml) The organic layer was washed with brine (200 ml) dried over MgSO4 evaporated in vacuo The resultant residue was dissolved in ether (300 ml) treated with 2 N HCl/ether (200 ml) The formed precipitate was filtered washed with ether dried in vacuo

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

实验步骤: To a solution of compound B (103.0 g, 340.7 mmol) in MeOH (1200 ml) was added a solution of LiOH (16.4 g, 681.4 mmol) in water (120 ml). The reaction mixture was stirred at room temperature for 3 h. Solvents were evaporated to ¾ of initial volume followed by dilution with water (400 ml). Solution was extracted with EtOAc (2×300 ml). The organic layer was washed with brine (200 ml), dried over MgSO4 and evaporated in vacuo. The resultant residue was dissolved in ether (300 ml) and treated with 2 N HCl/ether (200 ml). The formed precipitate was filtered, washed with ether and dried in vacuo to provide hydrochloric salt of compound C (54.5 g, 261.2 mmol) as white solid. LC-MS [M+H] 209.5 (C11H16N2O2+H, calc: 209.3). Solvents were evaporated Solution was extracted with EtOAc (2×300 ml) The organic layer was washed with brine (200 ml) dried over MgSO4 evaporated in vacuo The resultant residue was dissolved in ether (300 ml) treated with 2 N HCl/ether (200 ml) The formed precipitate was filtered washed with ether dried in vacuo

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

实验步骤: To a solution of compound B (˜311 mmol) in MeOH (1.2 L) was added a solution of LiOH (14.9 g, 622 mmol) in water (120 mL). The reaction mixture was stirred at ambient temperature for 3 h. Solvents were evaporated to 75% of the initial volume followed by dilution with water (400 mL). The solution was extracted with EtOAc (2×300 mL). The organic layer was washed with brine (200 mL), dried over MgSO4 and evaporated in vacuo. The residue was dissolved in ether (300 mL) and treated with 2 N HCl/ether (200 mL). Formed precipitate was filtrated, washed with ether and dried in vacuo to provide the hydrochloric salt of compound C (67.8 g, 89%) as a white solid. LC-MS [M+H] 209.0 (C11H16N2O2+H, calc: 209.3). Compound C was used directly in the next reaction without purification as a DMF solution. Solvents were evaporated to 75% of the initial volume The solution was extracted with EtOAc (2×300 mL) The organic layer was washed with brine (200 mL) dried over MgSO4 evaporated in vacuo The residue was dissolved in ether (300 mL) treated with 2 N HCl/ether (200 mL) Formed precipitate was filtrated washed with ether dried in vacuo

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

实验步骤: To a solution of compound Y (103.0 g, 340.7 mmol) in MeOH (1200 mL) was added a solution of LiOH (16.4 g, 681.4 mmol) in water (120 mL). The reaction mixture was stirred at room temperature for 3 h. Solvents were evaporated to ¾ of initial volume followed by dilution with water (400 mL). Solution was extracted with EtOAc (2×300 mL). The organic layer was washed with brine (200 mL), dried over MgSO4 and evaporated in vacuo. The resultant residue was dissolved in ether (300 mL) and treated with 2 N HCl/ether (200 mL). The formed precipitate was filtered, washed with ether and dried in vacuo to provide hydrochloric salt of compound Z (54.5 g, 261.2 mmol) as white solid. LC-MS [M+H] 209.5 (C11H16N2O2+H, calc: 209.3). Solvents were evaporated Solution was extracted with EtOAc (2×300 mL) The organic layer was washed with brine (200 mL) dried over MgSO4 evaporated in vacuo The resultant residue was dissolved in ether (300 mL) treated with 2 N HCl/ether (200 mL) The formed precipitate was filtered washed with ether dried in vacuo