反应详情

A solution of 200 mg (0.61 mmol) of 4-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyric acid (intermediate VVV04) and 88.0 μl (0.61 mmol) of 3-trifluoromethyl benzylamine in DCM (15 ml) was cooled to 0° C. and then 8.3 mg (0.06 mmol) of HOAt and 129 mg (0.67 mmol) of EDC were added in succession. The mixture was then stirred for 16 h at room temperature. The reaction solution was poured into water (75 ml) and extracted with DCM (2×75 ml). The combined organic phases were washed with a 1M aqueous NaOH solution (100 ml) and brine, dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (heptane/EE 1:1+2% 7N NH3 in MeOH) of the residue produced 240 mg (0.50 mmol, 81%) of 4-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxo-N-(3-(trifluoromethyl)benzyl)butyric acid amide. MS: m/z 485.2 [M+H]+.

1. extractionextracted with DCM (2×75 ml)
2. washThe combined organic phases were washed with a 1M aqueous NaOH solution (100 ml) and brine
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated to small volume under vacuum