反应详情

4-Fluoro-N2-isopropylbenzene-1,2-diamine (0.7 g, 5.07 mmol) was dissolved in DCM (10 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.06 g, 5.58 mmol) added. To the resultant dark red solution was added HOAt (0.76 g, 5.58 mmol), followed by N-methyl morpholine (1.23 mL, 11.15 mmol) and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.07 g, 5.58 mmol). The resultant blue/black solution was stirred at RT overnight, under an atmosphere of nitrogen. The mixture was diluted with DCM (40 mL) and washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organic fraction was dried (MgSO4), filtered and concentrated in vacuo to afford a dark red oil. This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which solidified on standing. This was dissolved in acetic acid (20 mL) and heated at 70° C. overnight. The resultant mixture was allowed to cool to RT and was concentrated in vacuo to afford the title compound as a dark red gum (1.0 g, 88%). This material was used in the next step without any purification. LCMS (Method B): RT 2.78 min [M+H]+ 322.2

1. washwashed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL)
2. dry with materialThe organic fraction was dried (MgSO4)
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customto afford a dark red oil
6. customThis was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM)
7. customto afford a red oil which
8. temperatureheated at 70° C. overnight
9. temperatureto cool to RT
10. concentrationwas concentrated in vacuo