Sodium Bicarbonate → 1-(4-(5-Isopropyl-6a-methyl-6-oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)-3-methylurea

Participants

Reaction Conditions

Reaction Steps

2-Chloro-5-isopropyl-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (98 mg, 0.330 mmol) was mixed with PdCl2(dppf) (48.3 mg), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (100 mg, 0.363 mmol) and saturated sodium bicarbonate solution (2 mL, sat.) in 1,4-dioxane (4 mL). The suspension was heated by microwave irradiation at 100° C. for 30 minutes. The suspension was filtered, the solids washed with methanol then DMSO and the filtrate evaporated in vacuo. The resulting solid was purified by mass triggered preparative HPLC eluted with 20-35% of ACN (containing 0.035% TFA) in water (containing 0.05% TFA) on a Phenomenex Gemini 5 μm C18, 75×30 mm column) to give the title compound (30 mg 22% yield) as a pale yellow solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.55 (m, 6H) 1.62 (s, 3H) 2.80 (s, 3H) 3.50 (td, J=12, 4 Hz, 1H) 3.68 (td, J=12, 4 Hz, 1H) 3.79 (d, J=12 Hz, 1H) 4.14 (m, 1H) 4.62 (dd, J=12, 4 Hz, 1H) 4.66 (m, 1 H) 7.62 (d, J=8 Hz, 2H) 8.10 (d, J=8 Hz, 2H) 8.13 (s, 1H). MS [M+H] Found 411.

Provenance & Evidence