反应详情

In a 10 mL microwave reaction vessel were placed compound 4 (40 mg, 158 μmol), 1-(6-chloro-pyridin-3-ylmethyl)piperidin-4-ol (36 mg, 158 μmol), tris(dibenzylideneacetone)dipalladium (0) (7.2 mg, 7.9 μmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (11 mg, 20 μmol), and cesium carbonate (25 μl, 316 μmol) followed by 1,4-dioxane (3 mL). The vessel was purged with N2 for 5 min, then capped and subjected to microwave condition (1.5 h at 120° C.). After the volatiles were removed, the residue was purified by combi-flash column chromatography followed by reverse phase preparative HPLC (acetonitrile/H2O containing 0.1% TFA each, 40 min from 10 to 40%). Lyophilization provided compound 342 (10 mg) as an off-white solid (TFA salt). 1H NMR (500 MHz, DMSO-d6) δ ppm 10.00 (1 H, s), 9.32 (1 H, s), 9.03 (1 H, s), 8.46 (1 H, d, J=5.1 Hz), 8.32 (1 H, d, J=8.3 Hz), 8.19 (1 H, d, J=1.7 Hz), 8.04-8.10 (1 H, m), 7.72 (1 H, dd, J=8.6, 2.0 Hz), 5.39 (1 H, quin, J=8.8 Hz), 4.54 (1 H, d, J=3.9 Hz), 3.43 (3 H, s), 2.64-2.72 (2 H, m), 2.37-2.45 (2 H, m), 2.00-2.17 (6 H, m), 1.65-1.84 (4 H, m), 1.39 (2 H, t, J=9.9 Hz). LCMS-ESI (POS), M/Z, M+1: Found 444.2.

1. customIn a 10 mL microwave reaction vessel were placed
2. customThe vessel was purged with N2 for 5 min
3. customcapped
4. customsubjected to microwave condition (1.5 h at 120° C.)
5. customAfter the volatiles were removed
6. customthe residue was purified by combi-flash column chromatography
7. custom40 min