Formaldehyde → (+/-)-6-[4-(1-Methyl-piperidin-3-yl)-phenoxy]-nicotinamide

Participants

Reaction Steps

Combine 6-(4-piperidin-3-yl-phenoxy)-nicotinamide (free base of compound of example 322) (0.95 mL of 0.12 M stock solution in methanol, 0.0341 g, 0.115 mmol) and formaldehyde (37% w/w in water, 0.014 mL, 0.156 mmol) and stir overnight. Add sodium borohydride (0.0128 g, 0.338 mmol) and stir. After 4.5 h concentrate the reaction mixture and purify by silica gel chromatography (20:1 ethyl acetate:methanol→2 M ammonia/methanol), then ion exchange chromatography (SCX resin, methanol→2 M ammonia (2M in methanol) to provide 0.02215 g (600%) of the title compound as a white solid: high resolution mass spectrum (electrospray): m/z calc for C18H22N3O2 312.1712, found 312.1718; 1H NMR (methanol-d4): 8.66 (d, 1H, J=2.4 Hz), 8.29 (dd, 1H, J=2.4, 8.8 Hz), 7.40-7.35 (m, 2H), 7.16-7.11 (m, 2H), 7.02 (d, 1H, J=8.8 Hz), 3.10-3.02 (m, 2H), 2.92 (tt, 1H, J=3.4, 11.7 Hz), 2.43 (s, 3H), 2.27-2.15 (m, 2H), 2.02-1.88 (m, 2H), 1.81 (qt, 1H, J=3.9, 12.7 Hz), 1.57 (dq, 1H, J=3.9, 12.2 Hz).

Provenance & Evidence