To a solution of 4-[6-ethynyl-2-(2-fluoroethoxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (30 mg, 0.10 mmol) in tetrahydrofuran (0.5 mL) under a nitrogen atmosphere at −78° C. was added a lithium diisopropylamide solution (0.3 mL, 3.00 equiv) dropwise with stirring. The reaction mixture was stirred at −78° C. for 15 min. A solution of 1-(pyrimidin-2-yl)ethan-1-one (48.8 mg, 0.40 mmol) in tetrahydrofuran (0.5 mL) was then added and the mixture was stirred at −78° C. for another 20 min. The resulting solution was then stirred at room temperature for 13 h. The reaction was then quenched by the addition of saturated ammonium chloride solution (1 mL) and the mixture was extracted with 10 mL of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column (ethyl acetate/petroleum ether, 1:3) to give 3.7 mg (9%) of 4-[1-(2-aminopyrimidin-4-yl)-2-(2-fluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol as an off-white solid: 1H NMR (400 MHz, DMSO) delta 8.89 (d, J=4.8 Hz, 2H), 8.40 (d, J=5.6 Hz, 1H), 8.13 (d, J=1.2 Hz, 1H), 7.51-7.44 (m, 2H), 7.25-7.22 (m, 1H), 7.10 (s, 1H), 6.96 (d, J=5.2 Hz, 1H), 6.12 (s, 1H), 4.93-4.88 (m, 2H), 4.80 (s, 2H), 1.88 (s, 3H); LC-MS: m/z=+420 (M+H)+.
