2-Amino-5-methylpyridine → HCID 66755653, compound

Participants

Reaction Steps

Dimethylaluminum chloride (15.5 mmol, 15.5 ml of 1M in hexanes) was added to a solution of 2-amino-5-picoline (1.67g, 15.5 mmol) in dichloroethane (10 ml) at 0 C. The mixture was allowed to warm to room temperature, held 30 minutes at room temperature, then recooled to 0° C. and treated with 4-(4-methanesulfonyl-phenoxy)-benzo[b]thiophene-6-carboxylic acid ethyl ester (0.58 g, crude product from previous step) in dichloroethane (5 ml). The mixture is allowed to warm to room temperature and held at room temperature for 8 h. The reaction was quenched by the drop wise addition of MeOH (2 mL) at 0 C, followed by 1M aqueous pH6 phosphate buffer (10 ml), then ethyl acetate (50 ml). Separation of the organic layer followed by evaporation yielded crude product (1.1 g). This was purified by silica gel chromatography (0-20% MeOH/CHCl3) to yield 0.35 g (59%) of 4-(4-methanesulfonyl-phenoxy)-benzo[b]thiophene-6-carboxylic acid (5-methyl-pyridin-2-yl)-amide. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.85(s, 1H), 8.69 (s, 1H), 8.22(d, J=8.8, 2H), 8.10 (d, J=8.6, 1H), 8.03 (d, J=5.5, 1H), 7.94 (d, J=8.8, 2H), 7.76 (d, J=1.3, 1H), 7.67 (dd, J=9.0, 2.0, 1H), 7.38 (d, J=5.5, 1H), 7.26 (d, J=8.8, 2H), 3.21 (s, 3H0, 2.28 (s, 3H). LRMS for C22H18N2O4S2 m/z 439 (M+H)+. Anal. Calcd. for C22H18N2O4S2 C, 60.26;H, 4.14; N, 6.39; Found: C, 60.58; H, 4.23; N, 6.22.

Provenance & Evidence