Water → 2-(5-chloro-2-fluoro-phenyl)-4-{5-[1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyridin-3-yl}-[1,8]naphthyridine formate

Participants

Reaction Conditions

Reaction Steps

To a solution of 59.7 mg (0.144 mmol) 4-(5-bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine and 55.3 mg (0.190 mmol) 1-methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine 67.2 mg (0.316 mmol) tri-potassiumphosphate trihydrate were added. The mixture was heated to 80° C. under nitrogen. Then 5.5 mg (0.008 mmol) bis(triphenylphosphine)palladium(II)-chloride were added. The reaction mixture was stirred for 4 hours at 80° C. The reaction mixture was cooled to room temperature and water was added. The resulting precipitate was filtered off, washed with water and air-dried. The residue was purified by preparative HPLC yielding 2-(5-chloro-2-fluoro-phenyl)-4-{5-[1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyridin-3-yl}-[1,8]naphthyridine formate as colourless crystals; HPLC-MS: 1.29 min, [M+H] 292. 1H NMR (400 MHz, DMSO) δ=9.22 (dd, J=4.1, 1.9, 1H), 9.07 (d, J=2.1, 1H), 8.63 (d, J=2.1, 1H), 8.50 (s, 1H), 8.38 (dd, J=8.4, 1.9, 1H), 8.30 (t, J=2.1, 1H), 8.18 (m, 2H), 8.11 (d, J=0.5, 1H), 8.10 (d, J=2.0, 1H), 7.70 (m, 2H), 7.53 (dd, J=10.7, 8.9, 1H), 4.15 (m, 1H), 3.4 (m, 2H), 2.88 (d, J=11.7, 2H), 2.23 (s, 3H), 2.03 (m, 4H).

Provenance & Evidence