1,4-Dioxane → 1-methyl-3-(4-(6a-methyl-5-((1-methyl-1H-pyrazol-3-yl)methyl)-6-oxo-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl)urea

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-6a-methyl-5-((1-methyl-1H-pyrazol-3-yl)methyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (118 mg), PdCl2(dppf) (43.6 mg), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (124 mg, 0.447 mmol), saturated sodium bicarbonate solution (1.5 mL), and 1,4-dioxane (3 mL) was heated by microwave irradiation at 100° C. for 45 minutes. The reaction mixture was diluted with 2 mL of methanol, filtered then purified by mass-triggered preparative HPLC eluted with 20-30% 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 (36 mg) as a pale yellow solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.72 (s, 3H) 2.80 (s, 3H) 3.57 (m, 1H) 3.70 (m, 1H) 3.85 (s, 3 H) 3.89 (d, J=12 Hz, 1H) 4.15 (dd, J=12, 4 Hz, 1H) 4.19 (d, J=12 Hz, 1H) 4.71 (m, 1H) 4.95 (d, J=12 Hz, 1H) 5.30 (d, J=12 Hz, 1H) 6.24 (d, J=4 Hz, 1H) 7.55 (d, J=4 Hz, 1H) 7.63 (d, J=8 Hz, 2H) 8.07 (d, J=8 Hz, 2H) 8.12 (s, 1H). MS [M+H] Found 463.

Provenance & Evidence