Diisopropylethylamine → N-(1-Azabicyclo[2.2.2]oct-3-ylmethyl)-5-trifluoromethoxy-1H-indazole-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(trifluoromethoxy)-1H-indazole-3-carboxylic acid (0.40 mmol) in tetrahydrofuran (5.0 mL) and N,N-dimethylformamide (5.0 mL) was added 1-(1-azabicyclo[2.2.2]oct-3-yl)methanamine dihydrochloride (0.40 mmol) and HATU (0.40 mmol). N,N-Diisopropylethylamine (10.0 mmol) was added and the reaction mixture was maintained for 16 h. The reaction mixture was heated at 60° C. for 1 h, and was filtered and concentrated. The residue was redissolved in methanol and loaded on a 5 g SCX column. The column was washed with methanol and the product was eluted with methanoudimethylethylamine (9/1) and concentrated. The residue was purified by preparative HPLC to produce the desired product in 20% yield. 1H NMR (CDCl3) δ 8.47 (s, 1 H), 8.10 (s, 1 H), 7.67 (d, J=9.1, 1H), 7.36 (d, J=9.1, 1H), 3.63-3.52 (m, 3 H), 3.48-3.23 (m, 4 H), 3.08-3.01 (m, 1 H), 2.66-2.44 (m, 1 H), 2.32-2.22 (m, 1 H), 2.14-2.08 (m, 1 H), 2.06-1.85 (m, 3 H); LC/MS (EI) tR 4.8 min, m/z 369 (M++1).

Provenance & Evidence