A mixture of 2-chloro-5-(2-hydroxy-2-methylpropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (84.9 mg, 0.260 mmol), 1-methyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenyl]-urea (143 mg, 0.520 mmol), saturated aqueous NaHCO3 (1 ml) and PdCl2(dppf) (17.0 mg, 0.021 mmol) in 1,4-dioxane (2 ml) was irradiated in the microwave at 110° C. for 30 minutes The reaction mixture was diluted with THF and passed through 0.45 μM PTFE syringe filter (washed with small amount of MeOH). The filtrate was purified by preparative HPLC (eluting with a gradient of 20-20% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column). The fractions containing the desired product were combined and were evaporated under reduced pressure. Then NaHCO3 aqueous solution was added (in order to adjust the pH to basic) and extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo to afford a crude solid. The solid was triturated with hexane/ethyl acetate (3:1), collected by filtration, rinsed with hexane/ethyl acetate (3:1) and dried to afford the title compound (21.1 mg, 0.048 mmol, 18.4% yield) as a pale beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (s, 3 H) 1.15 (s, 3 H) 1.35 (s, 3 H) 2.66 (d, J=4.55 Hz, 3 H) 3.19-3.33 (m, 1 H) 3.52-3.80 (m, 3 H) 3.94-4.11 (m, 3 H) 4.12-4.22 (m, 1 H) 4.67 (s, 1 H) 6.00-6.10 (m, 1 H) 7.48 (d, J=8.84 Hz, 2 H) 8.17 (d, J=8.84 Hz, 2 H) 8.58 (s, 1 H) 8.68 (s, 1 H). MS [M+H] found 441.
