Reaction Steps
tert-Butyl 4-(((1,5-dimethyl-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate and tert-Butyl 4-(((2,5-dimethyl-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate. To a solution of tert-butyl 4-(((5-methyl-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (38 mg, 0.087 mmol) in dimethylformamide (1 mL) at 0° C. was added sodium hydride (60% in mineral oil, 7.0 mg, 0.174 mmol). After 5 min, the reaction was treated with iodomethane (11 μL, 0.174 mmol). After 30 min, the reaction was quenched by addition of saturated ammonium chloride and poured into diethyl ether. The organics were washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→75% EtOAc/Hex) gave two fractions. The faster eluting fraction was concentrated to give tert-butyl 4-(((1,5-dimethyl-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (24 mg, 61%). Concentration of the second fraction gave tert-butyl 4-(((2,5-dimethyl-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (8 mg, 20%). tert-Butyl 4-(((1,5-dimethyl-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate: 1H-NMR (CDCl3, 500 MHz) δ 7.81 (s, 1H), 7.39 (s, 1H), 7.15-7.30 (m, 5H), 6.92 (s, 1H), 4.63 (s, 2H), 3.90 (s, 3H), 3.65 (bs, 2H), 3.41 (s, 2H), 3.00 (m, 2H), 2.39 (s, 3H), 2.10 (m, 2H), 1.79 (m, 2H), 1.41 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.1, 142.9, 137.3, 132.1, 130.8, 129.3, 128.5, 127.2, 126.4, 126.0, 120.6, 119.8, 79.4, 78.7, 71.3, 41.5, 40.1 (br), 38.0, 32.1, 28.6, 21.0. tert-Butyl 4-(((2,5-dimethyl-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate: 1H-NMR (CDCl3, 500 MHz) δ 7.72 (s, 1H), 7.30-7.43 (m, 4H), 7.22 (m, 2H), 6.84 (s, 1H), 4.81 (s, 2H), 4.15 (s, 3H), 3.71 (bs, 2H), 3.53 (s, 2H), 3.06 (m, 2H), 2.32 (s, 3H), 2.17 (m, 2H), 1.97 (m, 2H), 1.43 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.1, 146.3, 143.3, 131.0, 128.5, 127.4, 127.1, 126.3, 125.7, 122.9, 122.5, 117.0, 79.4, 79.3, 69.1, 41.9, 40.3, 40.2 (br), 32.0, 28.6, 21.9.
