Phosgene → 1-(5-tert-butyl-2-methoxy-phenyl)-3-[4-(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-naphthalen-1-yl)-urea

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Reaction Steps

To 4-tert-butyl-o-anisidine (0.035 g, 0.198 mmol) in 2 mL dichloromethane and 2 mL saturated aqueous NaHCO3 at 0° C., phosgene (˜2 M in toluene, 0.21 mL, 0.40 mmol) was added via syringe to the organic layer in one portion, while not stirring. The resulting mixture was stirred vigorously for 10 min, then the organic layer was separated and dried (MgSO4), filtered and concentrated in vacuo. To the resulting isocyanate solution was added a solution of 7-(4-amino-naphthalen-1-yl)-1H-pyrido[2,3-b][1,4]oxazin-2-one hydrochloride (Example 7) (72 mg, 0.220 mmol) and diisopropyl ethylamine (42 uL, 0.242 mmol) in 2 mL anhydrous THF. This mixture was stirred overnight, then diluted with EtOAc, washed with water and brine, dried (MgSO4), filtered and the solvents removed in vacuo. The residue was purified by preparative HPLC to afford 12 mg of the title compound, m.p.>200° C.

Provenance & Evidence