Reaction Steps
To a 2 mL microwave vial were added 2-chloro-5-((S)-1-(4-chlorophenyl)ethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x51, 100 mg, 0.264 mmol), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (146 mg, 0.527 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (10.85 mg, 0.013 mmol). After the vial was sealed, dioxane (1.5 mL) and aqueous saturated NaHCO3 (0.38 mL) were added, and the mixture was degassed by bubbling nitrogen through a syringe needle for 10 minutes. The mixture was then heated in a microwave to 120° C. for 30 minutes. The reaction mixture was partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by normal phase column chromatography (SiO2, 50-100% EtOAc/hexanes in 20 minutes) to give the title compound (single diastereomer, 21 mg, 16%). 1H NMR (400 MHz, DMSO-d6) δ 1.75 (d, J=7.1 Hz, 1H), 1.83 (d, J=7.1 Hz, 3H), 2.65 (d, J=4.5 Hz, 3H), 2.95-3.07 (m, 1H), 3.55-3.73 (m, 2H), 4.02 (dd, J=11.6, 3.0 Hz, 1H), 4.25 (dd, J=11.2, 3.7 Hz, 1H), 4.40 (dd, J=10.6, 3.8 Hz, 1H), 4.45-4.54 (m, 1H), 6.02-6.09 (m, 1H), 6.14 (d, J=7.1 Hz, 1H), 7.33-7.50 (m, 7H), 7.60 (s, 1H), 7.76 (s, 1H), 8.07-8.16 (m, 2H), 8.70 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C25H25ClN6O3, 493.17; found 493.4.
