X bridge 150 25 5 μm column

Example 98

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To a solution of 5-(2-furyl)isoxazole-3-carboxylic acid (140 mg, 0.78 mmol) and N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (356 mg, 0.94 mmol) in N,N′-dimethylformamide (3 mL) was added diisopropylethylamine (303 mg, 2.34 mmol) and 3-phenylazetidine hydrochloride (146 mg, 0.86 mmol). The mixture was stirred at 15° C. for 2 h. The mixture was purified by prep-HPLC (Waters X bridge 150×25 5 μM column; 35-70% acetonitrile in a 10 mM ammonium acetate solution in water, 10 min gradient) to afford [5-(2-furyl)isoxazol-3-yl]-(3-phenylazetidin-1-yl)methanone (0.086 g, 0.29 mmol, 37%) as a brown solid. ¹H NMR (400 MHz, Chloroform-d) δ 7.59 (s, 1H), 7.41-7.35 (m, 4H), 7.31 (br. d, J=7.0 Hz, 1H), 6.95 (d, J=3.5 Hz, 1H), 6.89 (s, 1H), 6.56 (dd, J=1.8, 3.5 Hz, 1H), 5.02 (t, J=9.6 Hz, 1H), 4.68-4.61 (m, 2H), 4.32-4.26 (m, 1H), 4.01-3.92 (m, 1H); LCMS (ESI) m/z: 295.0 [M+H]⁺.

Example 103

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To a solution of 5-(2-furyl)isoxazole-3-carboxylic acid (0.100 g, 0.56 mmol) and N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (0.254 g, 0.67 mmol) in N,N′-dimethylformamide (3 mL) was added diisopropylethylamine (0.216 g, 1.67 mmol) and 3-benzylazetidine hydrochloride (0.113 g, 0.61 mmol). The mixture was stirred at 15° C. for 1 h and then directly purified by prep-HPLC (Waters X bridge 150×25 5 μM column; 35-75% acetonitrile in a 10 mM ammonium acetate solution in water, 10 min gradient) to give (3-benzylazetidin-1-yl)-[5-(2-furyl)isoxazol-3-yl]methanone (0.062 g, 0.20 mmol, 36%) as a yellow solid. ¹H NMR (400 MHz, Chloroform-d) δ 7.57 (s, 1H), 7.31 (d, J=7.6 Hz, 2H), 7.26-7.22 (m, 1H), 7.18 (d, J=7.2 Hz, 2H), 6.94 (d, J=3.4 Hz, 1H), 6.85 (s, 1H), 6.56 (dd, J=1.7, 3.3 Hz, 1H), 4.68-4.62 (m, 1H), 4.33-4.26 (m, 2H), 3.95 (dd, J=4.7, 10.8 Hz, 1H), 3.05-2.97 (m, 3H); LCMS (ESI) m/z: 309.0 [M+H]⁺.