A 1-L three-neck round-bottomed flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (56 mL), 37 (3.00 g, 11.7 mmol),4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (1.29 g, 7.12 mmol) and cesium carbonate (5.09 g, 15.6 mmol). After bubbling nitrogen through the resulting solution for 30 min, Xantphos (350 mg, 0.605 mmol) and tris(dibenzylideneacetone)-dipalladium(0) (326 mg, 0.365 mmol) were added and the reaction mixture was heated at reflux for 2 h. After this time the reaction was cooled to room temperature and filtered through a pad of Celite 521. The filter cake was washed with methylene chloride (50 mL). The filtrate was concentrated under reduced pressure and the resulting residue was purified by column chromatography using 500 cc of silica and eluting with 5% EtOAc/hexanes to afford a 37% yield of 38 (940 mg) a white solid: Rf=0.55 (20% ethyl acetate in hexanes); 1H NMR (500 MHz, CDCl3) δ7.80 (bs, 1H), 7.38 (m, 1H), 7.37 (s, 1H), 7.32 (dd, 1H, J=3.0, 8.0 Hz), 2.81 (t, 2H, J=6.5 Hz), 2.64 (t, 2H, J=6.0 Hz), 1.85 (m, 4H); MS (ESI+) m/z 355.1 (M+H) and N-(6-bromo-5-fluoropyridin-2-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide in 34% yield as a white solid: Rf=0.85 (20% ethyl acetate in hexanes); 1H NMR (500 MHz, CDCl3) δ 8.29 (dd, 1H, J=3.5, 9.0 Hz), 8.24 (bs, 1H), 7.47 (dd, 1H, m), 7.33 (s, 1H), 2.81 (t, 2H, J=6.5 Hz), 2.64 (t, 2H, J=6.0 Hz), 1.85 (m, 4H); MS (ESI+) m/z 355.1 (M+H).
