Potassium Carbonate → Isopropyl 4-(3-(2-fluoropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

Participants

Reaction Steps

Isopropyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate (4 g, 10.86 mmol), 2-fluoropyridine-3-boronic acid hydrate (3.44 g, 21.7 mmol), potassium carbonate (4.5 g, 32.6 mmol), Pd(OAc)2 (24 mg, 0.1086 mmol), and x-Phos (146 mg, 0.217 mmol) were taken up in dioxane and water under nitrogen and stirred at 80° C. for 2 hours. Reaction then cooled to room temperature, filtered through celited plug with ethyl acetate. Reduced in vacuo and run through an isco silica column with hexane:ethyl acetate 75-100%. Product plus desbromo co elute, reduced in vacuo. Product recrystallized 3 times from IPAC, washed with heptanes dried to get 889 mg product. 1H NMR (400 MHz, DMSO-d6) δ 8.95 (t, J=2.15 Hz, 1 H), 8.78 (d, J=7.83 Hz, 1 H), 8.29 (d, J=4.29 Hz, 1 H), 8.00 (d, J=4.80 Hz, 1 H), 7.43 (dt, J=2.40, 4.99 Hz, 1 H), 6.85 (d, J=7.83 Hz, 1 H), 4.78-4.87 (m, 1 H), 3.73-3.83 (m, 4 H), 3.48-3.58 (m, 4 H), 3.31 (s, 1 H), 1.22 (d, J=6.06 Hz, 6 H) LRMS (ESI) m/z 385 [(M+H)]+, calc'd for C19H21FN6O2: 384.42.

Provenance & Evidence