Sodium hydride → HCID 66772970, compound

Participants

Reaction Steps

To a stirred suspension of (R)-(+)-3-aminoquinuclidine dihydrochloride (360 mg, 1.8 mmol) in dichloromethane (15 mL) was added sodium hydride (144 mg, 3.6 mmol) in portions and the mixture was stirred for 1 h. Acetic acid (0.15 mL) was added dropwise. Then methyl 1-(4-fluorophenyl)-3-formyl-1H-indazole-4-carboxylate (454 mg, 1.5 mmol) from Step A above was added and the mixture continued to stir at room temperature for an additional 4 h. Sodium triacetoxyborohydride (1.3 g, 6.0 mmol) was added in one portion and stirring was continued overnight at room temperature. The solvent was removed under reduced pressure and the crude material was purified by column chromatography (silica gel, 90:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (R)-methyl 1-(4-fluorophenyl)-3-((quinuclidin-3-ylamino)methyl)-1H-indazole-4-carboxylate as a light yellow oil (492 mg, 80%): 1H NMR (500 MHz, CDCl3) δ 7.89 (d, J=7.3 Hz, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.63-7.60 (m, 2H), 7.46 (t, J=7.9 Hz, 1H), 7.27-7.24 (m, 2H), 4.37 (d, J=14.1 Hz, 1H), 4.27 (d, J=14.1 Hz, 1H), 4.00 (s, 3H), 3.39-3.34 (m, 1H), 3.22-3.01 (m, 5H), 2.81 (dd, J=13.4, 2.3 Hz, 1H), 2.30-2.25 (m, 1H), 2.20-2.17 (m, 1H), 1.92-1.86 (m, 1H), 1.75-1.69 (m, 1H) 1.63-1.59 (m, 1H); MS (ESI+) m/z 409 (M+H).

Provenance & Evidence