Reaction Steps
A solution of the crude NMDBA salt of 18d (3.2 g, “5.1 mmol”), salicylic acid (987 mg, 7.14 mmol), HOBt (966 mg, 7.14 mmol), and EDC (1.37 g, 7.14 mmol) in DMF (69 ml) was stirred for 1 h at 23° C. The mixture was diluted with EtOAc (700 ml) and washed (3×H2O; brine). The aqueous layers were back-extracted with EtOAc (250 ml). The combined organic layers were concentrated and chromatographed (EtOAc:cyclohexane 1:1→2:1) to give 2.18 g (73%) of the title 3-hydroxybenzamide, which was further purified by preparative reverse-phase HPLC(H2O:CH3CN 70:40 →25:75 over 35 min, Rt=31 min) to give 1.50 g (50%) of a white powder: m.p. 174.5-175.5° C. 1H NMR (DMSO-d6) δ10.03 (s, 1H), 9.75-9.65 (br. d, 1H), 9.15 (t, J=6.0 Hz, 1H), 8.33-8.29 (br. s, 1H), 7.93 (d, J=2.0 Hz, 1H), 7.42 (d, J=3.8 Hz, 1H), 7.27-21 (m, 4H), 7.01 (d, J=3.8 Hz, 1H), 6.91 (dt, J=7.1, 2.2 Hz), 4.59 (d, J=5.8 Hz, 2H), 2.69 (q, J=7.0 Hz, 2H), 2.04 (t, J=6.9 Hz, 2H), 1.67 (quint, J=7.1 Hz, 2H). 13C NMR (DMSO-d6) δ169.65, 167.57, 158.49, 154.79, 149.06, 142.54 (q, J=4 Hz, C—C—CF3), 136.39, 132.80, 131.61, 126.91, 124.82, 122.93 (q, J=271 Hz, CF3), 117.66, 116.22, 114.01, 112.91, 112.01 (q, J=33 Hz, C—CF3), 39.19, 36.62, 29.42, 23.35. 19F NMR (DMSO-d6) δ-59.52 (s). M/Z APCI: 592 (M+1), 590 (M−1). Anal. HPLC: Rt=6.22 min (method a). C24H23F3N4O7S3 Calc.: C: 44.63%. H, 3.8%. N, 11.83%. Found: C, 44.68%, H, 3.59%, N: 11.90%.
