BrCC1C=C2C(=CC=1)C1=N[O:11][C:12](C3C([C:18]([F:21])([F:20])[F:19])=C(C4C=CC=CC=4)ON=3)=C1CC2.N1CC[O:34]CC1CO.C(N(CC)CC)C.CN([CH:49]=[O:50])C>C(OCC)(=O)C>[OH:34][C:49]([C:18]([F:21])([F:20])[F:19])=[O:50].[CH3:12][OH:11]A mixture of 7-(bromomethyl)-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (6C, 0.025 g, 0.053 mmol), morpholin-3-ylmethanol (6.16 mg, 0.053 mmol) and triethylamine (7.33 mL, 0.053 mmol) in DMF (3.0 mL) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with water (3×1.0 mL). The ethyl acetate extract was concentrated, and the residue was chromatographed using reverse-phase preparative HPLC (Column: LUNA 5 u C18, 21×100 mm:Solvent MeOH(B)—H2O(A), 0.1% TFA: 0% B-100% B, Gradient Time 12 min, Stop Time 20 min, Flow Rate 20 ml/min, Wavelength 220 Nm) to give 4-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)morpholino-3-yl)methanol TFA [0.013 g, 0.500 mmol, 50%] as a viscous tan film. The product had an HPLC ret. time=4.02 min. (condition B). LC/MS M+1=512.1. 1H NMR (400 MHz, CD3OD) δ ppm 7.97-8.14 (1H, m), 7.78 (2H, d, J=7.48 Hz), 7.44-7.73 (5H, m), 4.20 (2H, br. s.), 3.76 (6H, br. s.), and 2.96-3.25 (7H, m).
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