Hydrochloric Acid → HCID 178524075, compound

Participants

Reaction Conditions

Reaction Steps

To a sealed tube containing a solution of crude lithium (R)-6-bromo-3-((quinuclidin-3-ylamino)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-4-carboxylate 0.40 g, 0.90 mmol) in 2-propanol (40 mL) was added 6N HCl (4 mL). The reaction mixture was flushed with argon, sealed and heated to 140° C. for 30 min, cooled to ambient temperature and concentrated under reduced pressure. The residue was concentrated and purified by reverse phase semi-preparative HPLC (5-20% acetonitrile in water—both eluents contained 0.05% trifluoroacetic acid as modifier). The solvents were removed in vacuo and the desired product trifluoracetate salt was purified further by preparative TLC (6:3:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (R)-6-bromo-3-((quinuclidin-3-ylamino)methyl)-1H-indazole-4-carboxylic acid (119 mg, 40%) as an amorphous white solid: 1H NMR (500 MHz, d4-MeOH) δ, 7.74 (d, J=1.5 Hz, 1H), 7.66 (d, J=1.5 Hz, 1H), 4.40-4.28 (m, 2H), 3.60-3.30 (m, 3H), 3.22-3.00 (m, 5H), 2.26-2.20 (m, 1H), 2.19-2.02 (m, 1H), 2.00-1.90 (m, 1H) 1.88-1.68 (m, 2H).

Provenance & Evidence