Synthesis of Fluorinated Benzoxazole Compound

Example 274

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To a solution of compound 274-1 (30 mg, 93 umol, 1.0 eq), compound 274-1a (21.2 mg, 0.11 mmol, 1.2 eq) and Na₂CO₃ (29.6 mg, 0.28 mmol, 3.0 eq) in Dioxane (2 mL) and H₂O (0.4 mL) was added Pd(dppf)Cl₂ (3.4 mg, 4.6 umol, 0.05 eq) under N₂. The reaction mixture was stirred at 90° C. for 16 hours. LC-MS showed starting material was consumed completely and one main peak with desired MS was detected. The reaction mixture was adjusted with HCl (1M) to pH=6, and then the suspension was extracted with EA (10 mL*2). The combined organic layers were dried over Na₂SO₄, filtered and concentrated to dryness under reduced pressure. The residue was purified by prep-HPLC to give the title compound (14.63 mg, 37% yield, HCl) as a white solid. LCMS (ESI): RT=1.002 min, mass calcd. for C₂₀H₁₄F₃NO₃ 373.09, m/z found 373.9 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ 9.14 (d, J=2.3 Hz, 1H), 8.97 (d, J=2.3 Hz, 1H), 7.93 (d, J=2.8 Hz, 1H), 7.90-7.82 (m, 4H), 7.60 (d, J=2.8 Hz, 1H), 4.10-4.03 (m, 1H), 0.96-0.89 (m, 2H), 0.82-0.76 (m, 2H).