Cesium carbonate → 1-[5-(3-Chloro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol

Participants

Reaction Steps

The product of Step 3 (460 mg, 1.720 mmol), 2-chloro-4-(trifluoromethyl)pyrimidine (314 mg, 1.638 mmol), Xantphos (284 mg, 0.492 mmol), palladium (II) acetate (73.6 mg, 0.328 mmol), cesium carbonate (1.068 g, 3.28 mmol) and dioxane (12.3 mL) were heated at 90° C. for 90 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and dried over Na2SO4. Filtration and solvent evaporation gave a residue which was further purified by column chromatography on silica gel, eluting with 40% ethyl acetate in hexane to afford 1-[5-(3-chloro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol as a brown solid (390 mg, 55.8%). 1H NMR (500 MHz, CDCl3): δ 8.71 (d, J=4.7 Hz, 1H); 7.92 (s, 1H); 7.85 (s, 1H); 7.78 (s, 1H); 7.69 (s, 1H); 7.25 (s, 1H); 7.13 (d, J=4.8 Hz, 1H); 3.81 (s, 1H); 2.73 (s, 2H); 2.58-2.47 (m, 2H); 2.13-1.97 (m, 2H) MS APCI: [M+H]+ m/z 427.1. rhSYK activity=++

Provenance & Evidence