反应详情

To a stirred solution of 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-9-(4-fluorophenyl)-8,9-dihydro-5H-[1,2,4]triazolo[1,5-a]azepin-7(6H)-one (200 mg, 0.428 mmol, from example 137) in MeOH (2 mL) was added trimethyl orthoformate (0.469 mL, 4.28 mmol) followed by Ts-OH (8.15 mg, 0.043 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction was concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (AcCN/water/ammonium acetate) to afford the titled compound (104 mg, 46% yield). LC-MS (M+H)+ 513.3. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.51 (1 H, d, J=1.5 Hz), 7.40 (1 H, d, J=2.4 Hz), 7.31-7.35 (2 H, m), 7.06-7.14 (3 H, m), 7.02 (1 H, d, J=1.5 Hz), 6.78 (1 H, dd, J=8.5, 2.4 Hz), 6.59 (1 H, s), 4.39 (1 H, ddd, J=14.7, 5.9, 2.3 Hz), 4.20-4.28 (1 H, m), 4.11-4.17 (1 H, m), 3.76 (3 H, s), 3.29 (3 H, s), 3.26 (3 H, s), 2.35-2.43 (2 H, m), 2.05-2.12 (1 H, m), 1.89 (1 H, ddd, J=14.5, 11.9, 2.3 Hz).

1. concentrationThe reaction was concentrated in vacuo
2. customThe crude product was purified