反应详情

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid 10b (22 mg, 0.057 mmol) is dissolved in DMF (1 mL) and HOBt (9 mg, 0.063 mmol) followed by triethyl amine (18 μl, 0.132 mmol) is added. Cyclopropyl methyl hydroxylamine hydrochloride (8 mg, 0.062 mmol) is added following by EDCl (14 mg, 0.074 mmol). After 16 hours, the reaction mixture is diluted with ethyl acetate and water and the layers separated. The organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine. The organic layer is dried (MgSO4) and concentrated under reduced pressure to give 23 mg (80%) pure desired product. MS APCI (+) m/z 455, 453 (M+ Br pattern) detected; MS APCI (−) m/z 453, 451 (M− Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 11.69 (broad s, 1 H), 8.43 (s, 1H), 7.62 (d, 1H), 7.28 (dd, 1H), 6.42 (m, 1H), 3.63 (d, 2H), 1.03 (m, 1H), 0.48 (m, 2H), 0.19 (m, 2H); 19F NMR (376 MHz, DMSO−d6)−132.95 (s).

1. additionis added
2. customthe layers separated
3. washThe organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine
4. dry with materialThe organic layer is dried (MgSO4)
5. concentrationconcentrated under reduced pressure