Acetic Acid → N-(4-bromophenyl)-N'-[4-ethoxy-6-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl]-N-methylurea

Participants

Reaction Conditions

Reaction Steps

To a suspension of NaH (320 mg, 8.0 mmol, 60% dispersion in mineral oil) in anhydrous DMF (5 mL) under an N2 atmosphere was added anhydrous EtOH (583 μL, 10 mmol). To this solution was added a solution of N-(4-bromophenyl)-N′-[4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl]-N-methylurea (1.0 g, 2.0 mmol), prepared in a manner similar to 7, in anhydrous DMF (3 mL). The resulting solution was heated (ca. 60° C.) for 2 h, the heat was removed and the solution cooled to room temperature. The solution was diluted with EtOAc (100 mL) and extracted with 2 N HCl (2×50 mL). The organics were dried over MgSO4, filtered and concentrated to afford a brown oil. The brown oil was eluted through a plug of silica using a mixture of hexane and EtOAc and the resulting organic solution concentrated to afford a yellow oil. The yellow oil was further purified by reverse phase chromatography (HPLC grade acetonitrile and water, both with 0.1% acetic acid) to afford 103 as a yellow tacky oil (186 mg, 41% yield): 1H NMR (CDCl3) δ 7.64 (d, 2H, J=8.8 Hz), 7.24 (d, 2H, J=8.8 Hz), 6.84 (s, 1H), 4.81-4.72 (q, 2H, J=8.5 Hz), 4.33-4.26 (q, 2H J=7.1 Hz), 1.39-1.37 (t, 3H, J=7.1 Hz); ESI/MS 449, 451 (M+H), 447, 449 (M−H).

Provenance & Evidence