Cesium carbonate → 2-[3-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenylamino]-isonicotinic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Combine 1-[4-(3-amino-benzyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone (500 mg, 1.67 mmol), 2-chloro-isonicotinic acid methyl ester (287 mg, 1.67 mmol) and cesium carbonate (762 mg, 2.34 mmol) in toluene (25 mL) and stir. Purge reaction vessel with argon. Add 2-(bicyclohexylphosphino)biphenyl (234 mg, 0.668 mmol), and tris(dibenzylideneacetone)dipalladium (153 mg, 0.167 mmol). Purge reaction vessel with argon. Heat to 110° C. After 18 hours, cool to ambient temperature. Add diethyl ether (25 mL) and filter. Concentrate filtrate under reduced pressure to dryness. Purify the resulting residue by flash chromatography eluting with ethyl acetate:hexanes to yield the title compound as a yellow solid (282 mg, 39%): 1H NMR (DMSO-d6) δ 0.86 (t, 3H), 1.52 (sextet, 2H), 2.57 (s, 3H), 2.63 (t, 2H), 3.88 (s, 3H), 5.25 (bs, 2H), 6.72 (d, 1H), 6.99 (d, 1H), 7.14 (d, 1H), 7.31 (t, 1H), 7.39 (s, 1H), 7.58 (d, 1H), 7.80 (d, 1H), 7.91 (s, 1H), 8.29 (d, 1H), 9.43 (s, 1H), 12.85 (s, 1H).

Provenance & Evidence