Reaction Steps
To a stirred solution of N-(4-(1-(4-methoxybenzyl)-3-vinyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.357 g, 0.60 mmol) in THF (5 mL) was added a 0.5 M solution of 9-BBN (3.60 mL, 1.80 mmol) in THF. The reaction was stirred for 18 hours at room temperature. The reaction was cooled in an ice bath, and then was quenched by addition of 2N aqueous NaOH (3 mL). After stirring for 10 minutes in the ice bath, 30% aqueous hydrogen peroxide (0.577 mL, 6.00 mmol) was added. The reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL). The phases were separated, and the aqueous phase was re-extracted with EtOAc (2×10 mL). The combined organic phases were washed with brine (20 mL), dried (Na2SO4), filtered, and concentrated. The crude was partially purified by Biotage Flash 40, eluting with 30% EtOAc/hexanes, 1:1 EtOAc/hexanes, 2:1 EtOAc/hexanes, then neat EtOAc. The resulting solid was further purified by preparative TLC, eluting with 5% MeOH (containing 7N NH3) in DCM. The product was obtained as a waxy, white solid (179 mg, 48%). 1H NMR (400 MHz, CDCl3) δ 10.18 (s, 1H), 8.49 (s, 1H), 8.28 (d, J=6 Hz, 1H), 7.75 (m, 1H), 7.46 (m, 2H), 7.32 (d, J=9 Hz, 2H), 7.27 (m, 1H, overlaps chloroform), 7.18 (t, J=9 Hz, 1H), 7.06 (t, J=9 Hz, 2H), 6.83 (d, J=9 Hz, 2H), 6.17 (d, J=6 Hz, 1H), 5.57 (s, 2H), 4.09 (m, 2H), 3.76 (s, 3H), 3.36 (t, J=6 Hz, 2H), 2.76 (s, 1H), 1.80 (m, 2H), 1.63 (m, 2H).
