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

Participants

Reaction Conditions

Reaction Steps

2-Chloro-5-fluoro-4-methylpyrimidine (500 mg, 3.41 mmol), 3-methyl-5-(1,3-thiazol-5-yl)aniline (649 mg, 3.41 mmol), PdOAc2 (77 mg, 0.341 mmol), Xantphos (296 mg, 0.512 mmol), and cesium carbonate (2223 mg, 6.82 mmol) were combined in a flask and degassed with Argon. Dioxane (12 mL) was added and the solution was degassed with Argon for 5 min. The mixture was heated to 100° C. for 2 h and then allowed to cool to room temperature. The mixture was diluted with Brine and EtOAc. The layers were separated and the aqueous portion was re-extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. Purification via silica gel flash chromatography (0-40% EtOAc:CH2Cl2) afforded 5-fluoro-4-methyl-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (588 mg, 57%) as a beige solid. MS ESI: [M+H]+ m/z 301. 1H NMR (500 MHz, CDCl3) δ 8.75 (s, 1H), 8.33 (s, 2H), 8.09 (s, 1H), 7.74 (s, 1H), 7.33 (s, 1H), 7.08 (s, 1H), 2.40 (s, 3H). rhSYK activity=+++.

Provenance & Evidence