1,4-Dioxane → HCID 68194840, compound

Participants

Reaction Conditions

Reaction Steps

To a 5 mL microwave vial were added 2-chloro-5-(tetrahydro-2H-pyran-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x55, 190 mg, 0.585 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (404 mg, 1.463 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (24.07 mg, 0.029 mmol). After the vial was sealed, dioxane (2 mL) and aqueous saturated NaHCO3 (0.500 mL) were added, and the mixture was degassed by bubbling nitrogen through a syringe needle for 10 minutes. The mixture was heated in a microwave to 120° C. for 60 minutes. Since the reaction was not complete, another 0.025 equivalents of palladium catalyst were added, and the mixture was heated in the microwave to 130° C. for another 60 minutes. DMF (1 mL) was added and the mixture was filtered by syringe filter. The crude product was purified by preparatory HPLC using a gradient of 15-25% CH3CN (with 0.035% TFA) in H2O (with 0.05% TFA). Lyophilization of the collected fractions gave the title compound as a white powder (21 mg, 8.2%). 1H NMR (400 MHz, DMSO-d6) δ 1.56-1.74 (m, 2H), 2.58-2.69 (m, 4H), 2.97 (td, J=12.8, 3.8 Hz, 1H), 3.41 (t, J=10.9 Hz, 1H), 3.47-3.63 (m, 3H), 3.88-4.05 (m, 3H), 4.14-4.24 (m, 2H), 4.39 (d, J=11.9 Hz, 2H), 6.05-6.15 (m, 1H), 7.45-7.55 (m, 2H), 8.15-8.23 (m, 2H), 8.46 (s, 1H), 8.75 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C22H26N6O4, 439.2; found 439.5.

Provenance & Evidence