反应详情

To a solution of the crude of 2-[2-hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-7-methyl-3H-benzoimidazole-5-carboxylic acid (estimated 0.4 mmol), 4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamine (88 mg, 0.4 mmol) and HATU (167 mg, 0.44 mmol) in DMF (5 mL) was added DIEA (0.5 mL, 371 mg, 2.87 mmol). The reaction mixture was stirred at room temperature for 2 h and heated at 60° C. for 15 h, and then evaporated to dry under reduced pressure. The residue was diluted with DMSO (1.5 mL), filtered and then purified with using HPLC (TFA/H2O/CH3CN) to afford the title compound (34.5 mg, 11% from two steps from 3,4-diamino-5-methyl-benzoic acid). 1H NMR (MeOH-d4) δ 2.77 (s, 3H), 2.90 (s, 3H), 2.97-3.43 (12H), 3.97 (s, 3H), 7.09 (m, 1H), 7.22 (d, J=9 Hz, 1H), 7.31 (d, J=9 Hz, 2H), 7.70 (d, J=9 Hz, 2H), 7.82-7.84 (2H), 7.91 (s, 1H), 8.17 (m, 1H), 8.20 (s, 1H), 8.31 (s, 1H). ESI-MS m/z 577.5 (MH+).

1. temperatureheated at 60° C. for 15 h
2. customevaporated
3. customto dry under reduced pressure
4. additionThe residue was diluted with DMSO (1.5 mL)
5. filtrationfiltered
6. custompurified with using HPLC (TFA/H2O/CH3CN)