1,4-Dioxane → methyl(1S,4R)-4-(5-{3-cyclopropyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate

Participants

Reaction Steps

A reaction mixture containing N-[3-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-methylpyrimidin-2-amine (60 mg, 0.171 mmol), methyl (1S,4R)-4-(5-bromo-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (62.5 mg, 0.179 mmol), PdCl2(dppf)-CH2Cl2 adduct (27.9 mg, 0.034 mmol), 1,4-dioxane (1.2 mL), water (0.1 mL), and aqueous sodium bicarbonate solution (2 M, 0.171 mL, 0.342 mmol) was irradiated in the microwave for 15 minutes at 160° C. The reaction mixture was partitioned between ethyl acetate (30 mL) and saturated aqueous sodium bicarbonate solution (15 mL). The layers were separated and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel flash column chromatography (25-50% ethyl acetate/hexanes) to afford methyl (1S,4R)-4-(5-{3-cyclopropyl-5-[(4-methyl-pyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (41.3 mg, 0.084 mmol, 49% yield) as an off-white solid.

Provenance & Evidence