Cesium carbonate → (S)-1-(4-(benzo[d]oxazol-2-yl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

A mixture of (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (0.040 g, 0.135 mmol), 2-chlorobenzo[d]oxazole (0.031 mL, 0.270 mmol), tris(dibenzylideneacetone)dipalladium (0.012 g, 0.013 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (0.016 g, 0.027 mmol), and cesium carbonate (0.088 g, 0.270 mmol) in t-butanol (2.0 mL) was heated in the microwave at 80° C. for 1.5 h. Additional portions of Xantphos (0.016 g, 0.027 mmol), tris(dibenzylideneacetone)dipalladium (0.012 g, 0.013 mmol), and 2-chlorobenzo[d]oxazole (0.031 ml, 0.270 mmol) were added, and the mixture stirred at 100° C. for 2.5 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 50-100% ethyl acetate-hexane) to afford (S)-1-(4-(benzo[d]oxazol-2-yl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (0.049 g, 88%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.89-1.03 (m, 2 H), 1.03-1.11 (m, 5 H), 2.18 (s, 3 H), 3.76 (tt, J=7.44, 3.85 Hz, 1 H), 4.01 (br d, J=10.26 Hz, 1 H), 4.07-4.19 (m, 1 H), 5.08 (br s, 1 H), 7.13-7.37 (m, 3 H), 7.53 (dd, J=18.03, 7.48 Hz, 3 H), 7.85 (s, 1 H), 8.24 (s, 1 H), 8.38 (d, J=2.05 Hz, 1H). MS (ESI, pos. ion) m/z 414 [M+1]+.

Provenance & Evidence