Reaction Steps
A solution of the bisallylamine 269c (1.15 g, 2.04 mmol), N,N′-dimethylbarbituric acid (NDMBA, 637 mg, 4.08 mmol), and Pd(PPh3)4 (110 mg, 0.096 mmol) in CH2Cl2 (20 mL) was degassed by bubbling argon for 10 min. The reaction was stirred at 23° C. over the week-end (3 d), concentrated, diluted with DMF (12 mL), and treated with salicylic acid (290 mg, 2.10 mmol), 1-hydroxybenzotriazole (HOBt, 283 mg, 2.10 mmol), and N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide (EDC, 402 mg, 2.10 mmol) for 24 h at 23° C. Dilution with EtOAc, washing (H2O, NaHCO3 sat., brine), drying (MgSO4), and evaporation afforded the crude 3-hydroxybenzamide. Purification by reverse-phase prep. HPLC (C8, H2O:CH3CN 60:40→0:100 over 40 min, r.t=23 min) and freeze-drying afforded 466 mg (38% from 269c) of the title 3-hydroxybenzamide as a white powder: NMR (DMSO-d6) δ 12.1 (s, 1H), 9.48 (t, J=5.9 Hz, 1H), 7.86 (dd, 7.9, 1.5 Hz, 1H), 7.50 (d, J=3.8 Hz, 1H), 7.45 (t, J=8.1 Hz, 1H), 7.41 (dd, J=8.9, 1.5 Hz, 1H), 7.21 (d, J=3.8 Hz, 1H), 7.18-7.10 (m, 3H), 6.93 (d, J=83 Hz, 1H), 6.91 (td, J=8.4, 1.1 Hz, 1H), 6.52 (d, J=7.7 Hz, 1H), 4.73 (d, J=5.8 Hz, 2H), 3.57-3.47 (br. d, 12.1, 2H), 3.52-3.35 (br. m., 1H), 2.62 (t, J=10.4 Hz, 2H), 2.07 (s, 1.2H, residual CH3CN), 2.02-1.92 (br. d, J=10.4 Hz, 2H), 1.47 (qd, 11.2, 3.6 Hz, 2H). 13C NMR (DMSO-d6) δ167.52 (s, C═O), 158.36 (s), 148.98 (s), 147.85 (s), 132.83 (d), 132.74 (s), 131.47 (d), 130.00 (d), 128.98 (s), 127.09 (d), 125.52 (d), 124.83 (s), 118.92 (q, residual CH3CN), 11834 (q, J=326 Hz, CF3), 117.75 (d), 116.24 (d), 115.23 (d), 114.19 (q), 111.33 (d), 45.93 (d), 43.66 (t), 36.66 (t), 29.18 (t), 0.00 (s, residual CH3CN). M/Z APCI: 604 (M+1), 602 (M−1). Anal. HPLC: R.t=6.60 min (method a). C24H24F3N3O6S3. 0.3 CH3CN 1.0 H2O Calc.: C, 47.53%. H, 4.36%. N, 7.44%. Found: C, 47.41%, H, 4.09%, N, 7.49%.
