Acetic Acid → methyl 1-(2-(quinuclidin-4-ylmethylamino)ethyl)-1H-indazole-7-carboxylate

Participants

Reaction Steps

To a stirred solution of quinuclidin-4-ylmethanamine dihydrochloride (894 mg, 4.2 mmol) in methanol (12 mL) at room temperature was added sodium methoxide (25 wt % in MeOH, 1.8 mL, 8.4 mmol) dropwise. The reaction was stirred at room temperature for 1 h and then glacial acetic acid (0.6 mL, 9.7 mmol) was added to neutralize the basicity of the mixture. Sodium cyanoborohydride (528 mg, 8.4 mmol) was added, followed by a solution of methyl 1-(2-oxoethyl)-1H-indazole-7-carboxylate (920 mg, 4.2 mmol) from Step E above in methanol (10 mL). The mixture was stirred at room temperature until the reaction was complete by TLC (1-2 h). The reaction mixture was concentrated, absorbed onto silica gel, and purified by column chromatography (80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide) to afford methyl 1-(2-(quinuclidin-4-ylmethylamino)ethyl)-1H-indazole-7-carboxylate as a yellow oil (563 mg, 39%): 1H NMR (300 MHz, CD3OD) δ 8.26 (s, 1H), 8.09-8.03 (m, 2H), 7.27 (t, J=7.2 Hz, 1H), 4.95 (t, J=5.7 Hz, 2H), 4.01 (s, 3H), 3.50-3.44 (m, 2H), 3.39 (t, J=7.8 Hz, 6H), 2.93 (s, 2H), 1.85 (t, J=8.1 Hz, 6H).

Provenance & Evidence