反应详情

A stirred solution of 1-tert-butyloxycarbonyl-trans-3-amino-4-(2-pyridyl)pyrrolidine from step 7 above (2.5 g, 9.5 mmol), 3-bromo-1-ethoxycarbonylmethylpyrazinone (2.5 g, 9.5 mmol), and DIEA (1.9 mL, 11 mmol) in toluene (30 mL) was heated to reflux for 24 h. The mixture was cooled to ambient temperature, diluted with EtOAc, and washed with aqueous NaHCO3. The organic phase was separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography using a gradient elution of 60-85% EtOAc:hexanes to give the title compound as an amorphous solid (3.4 g; TLC Rf=0.5, 4:1 EtOAc:hexanes; HPLC RT=5.92 min, method A).

1. temperatureto reflux for 24 h
2. washwashed with aqueous NaHCO3
3. customThe organic phase was separated
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash column chromatography
8. washa gradient elution of 60-85% EtOAc