Synthesis of Pyridyl-Pyridone Compound

Example 93

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To a solution of compound 101-1 (50.0 mg, 0.15 mmol, 1.0 eq), compound 101-1a (23.1 mg, 0.18 mmol, 1.2 eq) and DIPEA (40.7 mg, 0.31 mmol, 2.0 eq) in DCM (3 mL) was added HATU (89.9 mg, 0.23 mmol, 1.5 eq). The reaction mixture was stirred at 25° C. for 1 hour. LC-MS showed starting material was consumed completely and one main peak with desired MS was detected. The reaction mixture was concentrated under reduced pressure. The mixture was diluted with water (10 mL) and the resultant mixture was extracted with EA (20 mL*3). 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 (27.8 mg, 41% yield) as a white solid. LCMS (ESI): RT=0.841 min, mass calcd. for C₂₄H₁₈F₃N₃O 421.14 m/z found 422.1 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ 9.42 (d, J=2.3 Hz, 1H), 8.78 (d, J=2.3 Hz, 1H), 8.60 (d, J=4.5 Hz, 1H), 8.22 (br d, J=6.8 Hz, 1H), 8.02 (dd, J=1.3, 8.0 Hz, 1H), 7.87-7.82 (m, 3H), 7.81-7.77 (m, 2H), 7.77-7.69 (m, 2H), 7.35 (d, J=7.8 Hz, 1H), 7.28-7.25 (m, 1H), 5.41 (quin, J=6.8 Hz, 1H), 1.67 (s, 3H).