反应详情

384 mg (2.0 mmol) of EDC, 306 μl (1.8 mmol) of DIPEA and 135 mg (1.0 mmol) of HOBt were added to a solution of 275 mg (1.0 mmol) of 4-oxo-4-(3-(trifluoromethyl)benzylamino)butyric acid (intermediate VVV01) in DCM (13 ml) and the mixture was stirred for 5 min at RT. Then 268 mg (1.2 mmol) of 4-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline were added and the mixture was stirred for a further 2 h at RT. It was then diluted with DCM and washed successively with a 10% aqueous hydrochloric acid, a saturated aqueous Na2CO3 solution, a saturated aqueous NH4Cl solution and brine. The organic phase was dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (hexane/EE 7:3) of the residue produced 346 mg (0.72 mmol, 72%) of 4-(4-methyl-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-N-[[3-(trifluoromethyl)phenyl]methyl]butyric acid amide. MS: m/z 481.2 [M+H]+.

1. stirringthe mixture was stirred for a further 2 h at RT
2. washwashed successively with a 10% aqueous hydrochloric acid
3. dry with materialThe organic phase was dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated to small volume under vacuum