反应详情

Mix 2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (128 mg, 0.48 mmol), toluene-4-sulfonic acid 4-bromo-2-methoxy-phenyl ester (218 mg, 0.61 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (17.2 mg, 0.030 mmol), Cs2CO3 (0.123 mg, 0.377 mmol) in dioxane (13 mL). Purge the solution with nitrogen for 30 min and then add tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (6.7 mg, 0.0073 mmol). Stir the mixture at reflux overnight, then cool to room temperature. Dilute the mixture with EtOAc (50 mL) and wash with water (2×30 mL) and brine (30 mL). Dry, filter and concentrate the organic solution and purify the residue by flash chromatography, using a linear gradient of 100% hexanes to 80% EtoAc/hexanes as eluent, to give the title compound as a light brown solid (155 mg, 60%). MS (ES+) 541.0 (M+1)+. 1H NMR (CDCl3): δ 7.92 (d, 2H, J=8.4 Hz), 7.78 (d, 2H, J=8.4 Hz), 7.44 (d, 2H, J=8.8 Hz), 7.31 (d, 2H, J=8.4 Hz), 7.17 (d, 1H, J=8.8 Hz), 6.96 (d, 1H, J=2.6 Hz), 6.82 (dd, 1H, J=8.6, 2.4 Hz), 4.11 (t, 2H, J=6.8 Hz), 3.57 (s, 3H), 3.28 (t, 2H, J=6.8 Hz), 2.44 (s, 3H).

1. customPurge the solution with nitrogen for 30 min
2. temperatureat reflux overnight
3. washwash with water (2×30 mL) and brine (30 mL)
4. customDry
5. filtrationfilter
6. concentrationconcentrate the organic solution
7. custompurify the residue by flash chromatography