Potassium Phosphate, Tribasic → 2-chloro-5-((R)-1-(4-chlorophenyl)ethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Participants

Reaction Conditions

Reaction Steps

To an oven dried vial were added 4-(5-bromo-2-chloropyrimidin-4-yl)-N-((R)-1-(4-chlorophenyl)ethyl)morpholine-3-carboxamide (PREPARATION x31, 574 mg, 1.247 mmol), Xantphos (54.1 mg, 0.094 mmol), potassium phosphate tribasic (265 mg, 1.247 mmol) and palladium(II) acetate (14.00 mg, 0.062 mmol) in dioxane (5 mL) and tert-butanol (1 mL). The reaction mixture was degassed for 5 minutes with N2. The vial was then sealed and heated to 105° C. and the contents were stirred for 72 hours to give a brown suspension. The reaction mixture was subsequently diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×5 mL) and brine (3×5 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give a crude product which was loaded onto an ISCO® silica gel cartridge (40 g) and eluted using an ethyl acetatehexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a white solid (58 mg, 12%). 1H NMR (400 MHz, DMSO-d6) δ 1.68-1.80 (m, 3 H), 2.91-3.02 (m, 1 H), 3.46-3.64 (m, 1 H), 3.64-3.76 (m, 1 H), 3.88-4.01 (m, 1 H), 4.13-4.27 (m, 2 H), 4.41-4.60 (m, 1 H), 5.99-6.24 (m, 1 H), 7.27-7.49 (m, 4 H), 7.50-7.57 (m, 1 H). ESI-MS m/z [M+H]+ calc'd for C17H16Cl2N4O2, 379.07; found 379.3.

Provenance & Evidence