[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1.Cl.[CH:14]12[O:21][CH:18]([CH2:19][CH2:20]1)[CH2:17][NH:16][CH2:15]2.C(N(CC)CC)C>C(OCC)C.C(O)C>[Cl:1][C:2]1[N:7]=[C:6]([N:16]2[CH2:15][CH:14]3[O:21][CH:18]([CH2:19][CH2:20]3)[CH2:17]2)[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1A solution of crude 2,4-dichloro-6-(trifluoromethyl)pyrimidine (62, 6.7 mmol) in diethyl ether (10 mL) was diluted with ethanol (25 mL) and cooled in an ice-water bath. 8-Oxa-3-azabicyclo[3.2.1]octane hydrochloride (2, 3.4 mmol) was added, followed by triethylamine (2 mL). Two additional portions of 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (2, 100 mg each) were added, the mixture was slowly warmed to room temperature and stirred overnight. Additional triethylamine (4 mL) was added to the mixture, which was then concentrated to dryness under reduced pressure. The residue was purified via flash silica gel chromatography (40% ethyl acetate/hexanes) to provide the title compound as a light colored solid (1.2 g, 61%). MS (ES+): 294.2 (M+H)+.
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