To a stirred solution of (S)-(−)-3-aminoquinuclidine dihydrochloride (0.3 g, 1.3 mmol) in THF (13 mL) was added sodium hydride (0.1 g, 2.7 mmol) and the mixture was stirred for 1.5 h. Acetic acid (0.5 mL) and sodium triacetoxyborohydride (380 mg, 1.8 mmol) were added and stirred for 0.5 h. A solution of methyl 1-(2-oxoethyl)-1H-indazole-7-carboxylate (0.3 g, 1.3 mmol) from Step E above in THF (13 mL) was added dropwise, and the resulting suspension was stirred overnight at ambient temperature. The solvent was removed under reduced pressure, and the crude material was purified by preparative thin layer chromatography (90:9:1 methylene chloride/methanol/concentrated ammonium hydroxide) to afford (S)-methyl 1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indazole-7-carboxylate: 1H NMR (500 MHz, DMSO-d6) δ 8.25 (s, 1H), 8.03 (dd, J=8.0, 1.0 Hz, 1H), 7.85 (dd, J=7.0, 1.0 Hz, 1H), 7.22 (t, J=7.5 Hz, 1H), 4.68-4.65 (m, 2H), 3.94 (s, 3H), 2.84-2.70 (m, 3H), 2.64-2.45 (m, 2H), 2.03-1.99 (m, 2H), 1.86-1.75 (m, 2H), 1.58-1.51 (m, 3H), 1.45-1.32 (m, 1H), 1.08-1.01 (m, 1H); MS (ESI+) m/z 329 (M+H).
