Reaction Steps
(R)-3,5-Dibromo-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole (77 mg, 0.15 mmol) was dissolved in acetonitrile (1 mL) and treated with formalin (50 μL) and sodium cyanoborohydride (9.5 mg, 0.15 mmol) and one drop of acetic acid. The reaction was stirred at room temperature for 1 h. The reaction was poured into water and extracted with diethyl ether. The aqueous was made basic by addition of 4 M sodium hydroxide and extracted with diethyl ether. The ethereal was combined, washed with brine, dried over magnesium sulfate, and concentrated. The resulting residue was dissolved in 20% trifluoroacetic acid in dichloromethane and stirred at room temperature for 5 min. The solution was concentrated, loaded onto a strong cation exchange cartridge in methanol, and the cartridge washed with several volumes of methanol which were discarded. The product was eluted with 2M ammonia in methanol and concentrated to give 41 mg (52%). 1H-NMR (CDCl3, 500 MHz) δ 10.09 (bs, 1H), 7.62 (d, J=1.5 Hz, 1H), 7.24 (dd, J=8.9 Hz, 5.2, 2H), 7.13 (d, J=1.5 Hz, 1H), 7.05 (dd, J=8.9, 8.5 Hz, 2H), 4.49 (q, J=6.7 Hz, 1H), 3.39 (d, J=8.9 Hz, 1H), 3.25 (d, J=8.9 Hz, 1H), 2.59 (m, 2H), 1.85-2.30 (m, 9H), 1.40 (d, J=6.7 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 161.6 (d, J=246 Hz), 137.2, 128.7, 128.63, 128.57, 127.68, 125.3, 121.7, 121.6, 115.7, 115.5, 114.3, 78.9, 77.9, 51.9, 51.7, 46.1, 40.3, 32.6, 32.3, 22.1.
