反应详情

To a solution of Fmoc-Arg(Pbf)-OH 1 (25.0 g, 38.5 mmol) in DMF (200 mL) at room temperature was added DIEA (13.41 mL, 77.1 mmol). After stirring at room temperature for 10 min, the reaction mixture was cooled to ˜5° C. To the reaction mixture was added HATU (16.11 g, 42.4 mmol) in portions and stirred for 20 min and a solution of tert-butyl-1-piperazine carboxylate (7.18 g, 38.5 mmol) in DMF (50 mL) was added dropwise. The reaction mixture was stirred at ˜5° C. for 5 min The mixture reaction was then allowed to warm to room temperature and stirred for 2 h. Solvent was removed in vacuo and the residue was dissolved in EtOAc (500 mL), washed with water (2×750 mL), 1% H2SO4 (300 mL) and brine (750 mL). The organic layer was separated, dried over Na2SO4 and solvent removed in vacuo to a total volume of 100 mL. Compound T was taken to the next step as EtOAc solution (100 mL). LC-MS [M+H] 817.5 (C43H56N6O8S+H, calc: 817.4).

1. temperaturethe reaction mixture was cooled to ˜5° C
2. stirringstirred for 20 min
3. stirringThe reaction mixture was stirred at ˜5° C. for 5 min
4. customThe mixture reaction
5. temperatureto warm to room temperature
6. stirringstirred for 2 h
7. customSolvent was removed in vacuo
8. dissolutionthe residue was dissolved in EtOAc (500 mL)
9. washwashed with water (2×750 mL), 1% H2SO4 (300 mL) and brine (750 mL)
10. customThe organic layer was separated
11. dry with materialdried over Na2SO4 and solvent
12. customremoved in vacuo to a total volume of 100 mL