1,4-Dioxane → HCID 51352113, compound

Participants

Reaction Conditions

Reaction Steps

To a microwave vial containing (R)-2-chloro-5-(cyclopropylmethyl)-6a,9-dimethyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (about 0.4 mmol) was added 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.133 g, 0.48 mmol), Pd(dppf)Cl2-dichloromethane, 1,4-dioxane (1.2 mL) and NaHCO3 (sat., 0.6 mL). It was heated in a microwave at 100° C. for 1 hour 45 minutes and then conventionally at 100° C. (bath temperature) for 3 hours. The mixture was diluted with MeOH, passed through a microfilter. The filtrate was purified on the HPLC (40-60% of AcCN in water containing 10 mM NH4HCO3, Phenomenex Gemini 5 μm C18, 75×30 mm column) to give a mixture containing the title product, which was further purified and resolved on a ChiralPak AD-H (5 μm, 10×250 mm, 25-25% of MeOH in liquid CO2) to give the title compound as a white solid (2.1 mg) and having a retention time of 5.20 minutes on ChiralPak AD-H column (5 μm, 2.1×150 mm, 26% of MeOH in liquid CO2). 1H NMR (400 MHz, METHANOL-d6) δ ppm 0.4-0.56 (m, 4 H) 1.22 (m, 1 H) 1.34 (d, J=4 Hz, 3 H) 1.44 (s, 3 H) 2.79 (s, 3 H) 2.95 (dd, J=16, 12 Hz, 1 H) 3.73 (m, 1 H) 3.82 (m, 2 H) 3.95 (m, 1 H) 4.12 (d, J=12 Hz, 1 H) 4.35 (dd, J=12, 4 Hz, 1 H) 7.46 (d, J=8 Hz, 2 H) 8.19 m (s, 1 H) 8.20 (d, J=8 Hz, 2 H). MS [M+H] found 437.4.

Provenance & Evidence