Potassium Phosphate, Tribasic → 2-(2,2-Difluoropropyl)-N-(4-methyl-3-(5-methylpyridin-2-yl)phenyl)-1,2,3,4-tetrahydroisoquinolin-5-amine

Participants

Reaction Conditions

Reaction Steps

To a reaction tube under argon containing 5-bromo-2-(2,2-difluoropropyl)-1,2,3,4-tetrahydroisoquinoline (29 mg, 0.1 mmol), 4-methyl-3-(5-methylpyridin-2-yl)aniline (20 mg, 0.1 mmol), Pd2(dba)3 (10 mg, 0.01 mmol), xantphos (17 mg, 0.02 mmol), potassium phosphate (60 mg, 0.3 mmol) is added anhydrous dioxane (0.5 ml). The mixture is stirred at 96° C. under argon for 18 hours, cooled to room temperature and filtered through a celite pad. The filtrate is concentrated and preparative HPLC is used to isolate 2-(2,2-Difluoropropyl)-N-(4-methyl-3-(5-methylpyridin-2-yl)phenyl)-1,2,3,4-tetrahydroisoquinolin-5-amine as a white solid. LC-MS m/z: 408.2 (M+1); 1H NMR 400 MHz (CDCl3) δ 8.48 (s, 1H), 7.52 (dd, 2H, J=1.6, 8 Hz), 7.28 (d, 1H, J=8.0 Hz), 7.14 (d, 1H, J=8.0 Hz), 7.07-7.00 (m, 2H), 6.95 (dd, 1H, J=2.4, 8.0 Hz), 6.62 (d, 1H, J=6.8 Hz), 5.30 (s, 1H), 3.77 (s, 2H), 2.92 (t, 2H, J=6.0 Hz), 2.83 (t, 2H, J=13.6 Hz), 2.66 (t, 2H, J=6.0 Hz), 2.36 (s, 3H), 2.27 (s, 3H), 1.66 (t, 3H, J=18.8 Hz).

Provenance & Evidence