Cesium carbonate → N-[3-fluoro-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

The product of Step 2 (0.93 g, 4.79 mmol), 2-chloro-4-(trifluoromethyl)pyrimidine (0.874 g, 4.79 mmol), palladium(II) acetate (0.107 g, 0.479 mmol), xantphos (0.416 g, 0.718 mmol), and cesium carbonate (3.12 g, 9.58 mmol) were added to a dry flask. The flask was degassed with argon, and then dioxane (20 ml) was added. The reaction mixture was degassed with argon for five minutes, and then heated to 90° C. After 2 hours, the reaction mixture was cooled, diluted with ethyl acetate, filtered through celite, and concentrated. The residue was purified by column chromatography on silica gel (EtOAc/hexane gradient) to afford solids. The solids were dissolved in hot ethyl acetate (25 mL) and then triturated with hexanes (50 mL) while cooling. After 2 hours, the mixture was filtered to afford N-[3-fluoro-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (1.18 g, 3.47 mmol, 72% yield). MS ESI: [M+H]+ m/z 341.1. 1H NMR (500 MHz, DMSO-d6) δ 10.52 (s, 1H); 9.10 (s, 1H); 8.87 (d, J=4.0 Hz, 1H); 8.31 (s, 1H); 7.93 (s, 1H); 7.66-7.62 (m, 1H); 7.35 (d, J=4.5 Hz, 1H); 7.28 (dt, J=8.0 Hz, 1.5 Hz, 1H).

Provenance & Evidence