Triethylamine → N-[(4-fluorophenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

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Reaction Conditions

Reaction Steps

Additional procedure. Ethyl 3-hydroxy-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate (50 g, 0.186 mol) and ethanol SDA3A (500 mL) was added to a 1 L round bottom flask equipped with a mechanical stirrer, nitrogen inlet-outlet, temperature probe, and condenser. Triethylamine (18.86 g, 0.186 mol) was added to the slurry. The resulting solution was heated to 35° C. followed by slow addition of 4-fluorobenzylamine (35.0 g, 0.279 mol). The thick slurry was heated at 78° C. with stirring for 6 h. The reaction mixture was polish filtered and the filtrate reheated to 70° C. The pH was adjusted to about 1.0 by slow addition of 1N HCl (405 mL). The thick slurry was cooled to 20–25° C., the solids filtered off, washed twice with ethanol SDA 3A (each 250 mL) and twice with water (each 500 mL). The white solid was dried in vacuo at 50–55° C. to afford N-[(4-fluorophenyl)methyl]-4,6,7,9-tetrahydro-3-hydroxy-9,9-dimethyl-4-oxo-pyrimido[2,1-c][1,4]oxazine-2-carboxamide (58.9 g).

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