Cesium carbonate → (R)-2-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

Participants

Reaction Conditions

Reaction Steps

A mixture of (R)-2-chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x10 50 mg, 0.127 mmol), 2-(difluoromethyl)-1H-benzo[d]imidazole (21.29 mg, 0.127 mmol), cesium carbonate (61.9 mg, 0.190 mmol), tris(dibenzylideneacetone)dipalladium(0) (4.64 mg, 5.06 μmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (4.83 mg, 10.13 μmol) in DMF 253 μL was heated to 130° C. in a microwave for 40 minutes. Additional tris(dibenzylideneacetone)dipalladium(0) (4.64 mg, 5.06 μmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (4.83 mg, 10.13 μmol) were added, and the reaction mixture was heated to 130° C. in a microwave for 1 hour. EtOAc and water were added and the mixture was filtered through Celite and extracted with EtOAc (2×). The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2—NH2, 30-100% EtOAc/hexane gradient) to afford the title compound as a yellow solid (14.3 mg, 21.4%). 1H NMR (400 MHz, CDCl3) δ 3.08 (s, 3 H), 3.19-3.38 (m, 4 H), 3.68 (td, J=12.00, 2.78 Hz, 1 H), 3.83-3.92 (m, 1 H), 3.94-4.02 (m, 1 H), 4.11-4.20 (m, 1 H), 4.44-4.63 (m, 3 H), 7.36-7.75 (m, 6 H), 7.93-8.01 (m, 3 H), 8.17-8.23 (m, 1 H). ESI-MS m/z [M+H]+ calc'd for C25H24F2N6O3S, 527.16; found 527.3.

Provenance & Evidence