反应详情

3-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-phenyl-imidazolidine-4-carboxylic acid methyl ester (51 mg, 0.14 mmol) was dissolved in THF (1.2 mL) and MeOH (0.8 mL). An aqueous solution of LiOH (6.0 mg, 0.14 mmol) was added and stirring at room temperature was continued. After the hydrolysis was complete, the reaction was neutralized with aqueous HCl (1M). The organic solvents were removed in vacuo and the aqueous suspension was frozen and lyophilized. The crude material was used in the next step without further purification. The crude material was dissolved in DMF (1.5 mL) and HATU (54.3 mg, 0.14 mmol) and DIEA (36.9 mg, 0.28 mmol) were added. The reaction was stirred at room temperature for five minutes, after which the amino-(4′bromo) acetophenone hydrochloride salt (35.7 mg, 0.14 mmol) was added. Stirring at room temperature was continued. After 10 minutes, all volatiles were removed in vacuo and the crude material was purified via silica gel chromatography (eluent: EtOAc/hexanes) to yield the slightly impure product (95 mg): LCMS-ESI+: calc'd for C25H29BrN4O5: 545.4 (M+). Found: 545.2/547.4 (M+H+).

1. customThe organic solvents were removed in vacuo
2. temperaturethe aqueous suspension was frozen
3. customThe crude material was used in the next step without further purification
4. dissolutionThe crude material was dissolved in DMF (1.5 mL)
5. stirringThe reaction was stirred at room temperature for five minutes
6. stirringStirring at room temperature
7. customall volatiles were removed in vacuo
8. customthe crude material was purified via silica gel chromatography (eluent: EtOAc/hexanes)