反应详情

温度

25 °C

DMF (100 mL) was added to methyl 2-((S)-1-amino-2-methylpropyl)-5-(7-bromo-1H-indol-3-yl)oxazole-4-carboxylate hydrobromide (9.16 g, 19.4 mmol), HOBt (3.17 g, 23.5 mmol), and Cbz-Tyr-OH (6.44 g, 20.4 mmol) in a round-bottom flask. N,N-Diisopropylethylamine (4.22 mL, 3.13 g, 129 mmol) was added, followed by EDC (4.15 g, 21.6 mmol). After stirring for 24 h at 25° C., the solution was diluted with EtOAc (500 mL) and the mixture was washed with 1 N aqueous HCl (250 mL), saturated aqueous NaHCO3 (250 mL), and saturated aqueous NaCl (250 mL). The solution was dried (Na2SO4), decanted, and evaporated to give a tan solid. This material was dissolved in 2-PrOH (180 mL) at 90° C. Hexanes (85 mL) were added and the solution was allowed to cool to RT. After standing overnight, the mixture was cooled to 5° C. for 4 h. The solid was separated by filtration and washed with 1:1 2-PrOH/hexanes (140 mL). This material, which at this point held residual solvent, was dried on a vacuum manifold to give methyl 2-((S)-1-((S)-2-(benzyloxycarbonylamino)-3-(4-hydroxyphenyl)propanamido)-2-methylpropyl)-5-(7-bromo-1H-indol-3-yl)oxazole-4-carboxylate (11.58 g, 87% yield). 1H NMR (300 MHz, DMSO-d6): consistent with proposed structure. MS: m/z=689.0 (M+1).

1. washthe mixture was washed with 1 N aqueous HCl (250 mL), saturated aqueous NaHCO3 (250 mL), and saturated aqueous NaCl (250 mL)
2. dry with materialThe solution was dried (Na2SO4)
3. customdecanted
4. customevaporated
5. customto give a tan solid
6. temperatureto cool to RT
7. waitAfter standing overnight
8. temperaturethe mixture was cooled to 5° C. for 4 h
9. customThe solid was separated by filtration
10. washwashed with 1:1 2-PrOH/hexanes (140 mL)
11. customwas dried on a vacuum manifold