A mixture of 1-(1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (200 mg, 0.56 mmol), (S)-tert-butyl 2-(bromomethyl)pyrrolidine-1-carboxylate (GRA-B-188) (298 mg, 1.12 mmol), and cesium carbonate (732 mg, 2.25 mmol) in methyl sulfoxide (5 mL) was stirred overnight at ambient temperature. The reaction mixture was diluted with water (20 mL) and extracted with dichloromethane (2×30 mL). The combined organic extracts were washed with brine (20 mL), dried (Na2SO4), and concentrated under reduced pressure. Isolation of the desired regioisomer was performed by column chromatography (silica gel, Et2O to 9:1 Et2O/90:9:1 Et2O/MeOH/concd NH4OH). To the desired regioisomer (100 mg, 0.18 mmol) was added dichloromethane (10 mL) and trifluoroacetic acid (2 mL). After stirring at ambient temperature for 2 h, the reaction was brought to pH=9 with 1N NaOH. The organic layer was washed with brine (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The dried residue (87 mg, 0.20 mmol) was dissolved in dichloromethane (10 mL) and HCl (1.25 M solution in methanol, 0.22 mL, 0.17 mmol) was added. The mixture was concentrated under reduced pressure and then triturated with dichloromethane/hexanes and the obtained solid was triturated with diethyl ether. The solid was dried to afford the title compound (43 mg, 16%) as an off-white solid: mp 241-245° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.05 (br s, 2H), 8.28 (s, 1H), 8.03-7.85 (m, 7H), 7.51 (d, J=8.5 Hz, 1H), 6.89 (s, 1H), 6.75 (d. J=7.0 Hz, 1H), 4.80 (d, J=6.0 Hz, 2H), 3.99-3.95 (m, 1H), 3.30-3.23 (m, 1H), 3.16-3.10 (m, 1H), 2.08-2.03 (m, 1H), 1.99-1.96 (m, 1H), 1.91-1.85 (m, 1H), 1.74-1.70 (m, 1H); ESI MS m/z 439 [M+H]+; HPLC (Method B) 98.7% (AUC), tR=15.5 min; [α]23D +20.5° (c 0.13, Methanol).
