4-(Tri-n-butylstannyl)thiazole → 3-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-6-{[6-(1,3-thiazol-4-yl)pyridine-3-yl]methyl}benzo[h]quinazolin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (Example 1, 0.100 g, 0.237 mmol) in 1 mL of DMF under an atmosphere of nitrogen was added 4-(tributylstannyl)-1,3-thiazole (0.111 g, 0.296 mmol), tetrakis(triphenylphosphine)palladium(0) (0.055 g, 0.047 mmol), and copper(I) iodide (0.018 g, 0.095 mmol). The reaction was heated at 50° C. for 15 h, and then at 140° C. for an additional 6 h. The mixture was cooled to rt, diluted with ethyl acetate, and washed with brine and water. The solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 471.1478 for [M+H]+ [Calc'd for C26H23N4O3S, [M+H]+=471.1485]: 1H NMR (400 MHz, CD3OD) δ 9.18 (s, 1H), 9.01 (d, J=8.1 Hz, 1H), 8.62 (s, 1H), 8.58 (s, 1H), 8.54 (s, 1H), 8.39 (d, J=8.4 Hz, 1H), 8.32-8.30 (m, 1H), 8.08 (d, J=8.1 Hz, 1H), 7.98 (s, 1H), 7.76-7.68 (m, 2H), 4.72 (s, 2H), 4.72-4.66 (m, 1H), 4.36-4.24 (m, 1H), 4.09-3.99 (m, 2H), 3.53 (t, J=10.1 Hz, 1H), 3.23 (t, J=10.2 Hz, 1H), 2.36-2.34 (m, 1H), 2.00-1.95 (m, 1H).

Provenance & Evidence