Triethylamine → 4-[1-(2-aminopyrimidin-4-yl)-2-(2-hydroxyethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-fluoropyridin-2-yl)but-3-yn-2-ol

Participants

Reaction Steps

A mixture of 2-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]ethan-1-ol (200 mg, 0.57 mmol), 2-(5-fluoropyridin-2-yl)but-3-yn-2-ol (940 mg, 5.69 mmol), bis(triphenylphosphine)palladium(II) dichloride (200 mg, 0.28 mmol) and triethylamine (0.5 mL) in dimethylsulfoxide (1 mL) was irradiated with microwave radiation under nitrogen for 1 hr at 120° C. The reaction mixture was cooled to room temperature then filtered through a frit filter to remove the catalyst. The filtrate was concentrated under vacuum and the crude product (80 mg) was purified by preparative HPLC to give 3.7 mg (1%) of 4-[1-(2-aminopyrimidin-4-yl)-2-(2-hydroxyethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-fluoropyridin-2-yl)but-3-yn-2-ol as a light yellow solid: 1H NMR (300 MHz, DMSO) delta 8.54 (d, J=2.7 Hz, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.15 (d, J=1.2, 1H), 7.84 (q, 1H), 7.78-7.72 (m, 1H), 7.43 (d, J=8.1 Hz, 1H), 7.24 (q, 1H), 7.10-7.04 (m, 3H), 6.37 (s, 1H), 5.03 (s, 1H), 4.60 (t, J=4.5 Hz, 2H), 3.81 (d, J=4.5 Hz, 2H), 1.82 (s, 3H); LC-MS: m/z=+435 (M+H)+.

Provenance & Evidence