Formaldehyde → Trifluoroacetic acid

Participants

Reaction Steps

To 6-(4-(2-(4-fluoropiperidin-4-yl)ethoxy)-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile (TFA salt, 100 mg) in acetonitrile/THF (2 ml, 1:1) was added formaldehyde (37%, 140 ul), acetic acid (0.3 ml), followed by sodium cyanoborohydride (100 mg). The mixture was stirred at room temperature for 2 hours, and then poured to aqueous sodium bicarbonate (10 ml). The mixture was then extracted with ethyl acetate (20 ml+10 ml×4). Combined organic layer was then dried over sodium sulphate. After removal of solvent under reduced pressure, the residue was purified by HPLC to give 6-(4-(2-(4-fluoro-1-methyl-piperidin-4-yl)ethoxy)-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile as a TFA salt. 1H NMR (CD3OD) δ: 8.45 (s, 1H), 8.38 (s, 2H), 8.35 (d, 1H), 7.35 (d, 1H), 4.39 (t, 2H), 4.02 (s, 3H), 3.50 (m, 2H), 3.3 (m, 2H), 2.93 (s, 3H), 2.25-2.4 (m, 4H), 2.0-2.25 (m, 2H). MS m/z 462 (M+H).

Provenance & Evidence