Acetic Acid → HCID 66899017, compound

Participants

Reaction Steps

(S)-Quinuclidin-3-amine dihydrochloride (355 mg, 1.8 mmol) was stirred in MeOH (5 mL) at room temperature while sodium methoxide (25 wt % in MeOH, 0.8 mL, 3.6 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1 h. Glacial acetic acid (0.2 mL, 4.1 mmol) was added to neutralize the basicity of the mixture. Sodium cyanoborohydride (224 mg, 3.6 mmol) was added, followed by methyl 5-chloro-1-(2-oxoethyl)-1H-indazole-7-carboxylate (472 mg, 1.9 mmol) from Step C above in MeOH (8 mL). The mixture was stirred at room temperature until the reaction was complete by TLC (1-2 h). The reaction mixture was concentrated and absorbed onto silica gel and purified by column chromatography (80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide) to afford (S)-methyl 5-chloro-1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indazole-7-carboxylate as a light yellow solid (525 mg, 77%): 1H NMR (500 MHz, CD3OD) δ 8.17 (s, 1H), 8.03 (s, 1H), 7.92 (s, 1H), 4.80 (t, J=6.5 Hz, 2H), 4.02 (s, 3H), 3.50-3.38 (m, 1H), 3.25-3.05 (m, 4H), 3.05-2.90 (m, 3H), 2.65-2.55 (m, 1H), 2.10-2.00 (m, 1H), 2.00-1.90 (m, 2H), 1.90-1.75 (m, 2H), 1.65-1.55 (m, 1H); MS (ESI+) m/z 363 (M+H).

Provenance & Evidence