Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:7](=[O:17])[C:6]3([CH3:22])[CH2:18][O:19][CH2:20][CH2:21][N:5]3[C:4]=2[N:3]=1.[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1.C([O-])(O)=O.[Na+]>O1CCOCC1.C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:23]1([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:7](=[O:17])[C:6]5([CH3:22])[CH2:18][O:19][CH2:20][CH2:21][N:5]5[C:4]=4[N:3]=3)=[CH:32][CH:31]=2)=[O:28])[CH2:25][CH2:24]1A mixture of 2-chloro-6a-methyl-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (292 mg, 0.868 mmol), 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (446 mg, 1.48 mmol), saturated aqueous NaHCO3 (2 ml) and PdCl2(dppf) (56.7 mg, 0.069 mmol) in 1,4-dioxane (4 ml) was irradiated in 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 THF). The filtrate was purified by preparative HPLC (eluting with a gradient of 25-50% 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 (THF was added to dissolve the precipitate). The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound (206 mg, 0.432 mmol, 50% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 0.37-0.45 (m, 2 H) 0.59-0.69 (m, 2 H) 1.37 (s, 3 H) 2.51-2.60 (m, 1 H) 3.22-3.33 (m, 1 H) 3.55-3.73 (m, 2 H) 3.98-4.11 (m, 2 H) 4.15-4.24 (m, 1 H) 4.80-4.94 (m, 1 H) 4.94-5.11 (m, 1 H) 6.43-6.50 (m, 1 H) 7.46-7.54 (m, 2 H) 8.15-8.23 (m, 2 H) 8.47 (s, 1 H) 8.56 (s, 1 H). MS [M+H] found 477.
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