606144-04-1

606144-02-9

606144-04-1

General procedure for the synthesis of 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylic acid methyl ester: 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylic acid methyl ester (2 g, from Example 4) was dissolved in tetrahydrofuran (20 mL), deionized water (10 mL) was added. and [d]imidazole-6-carboxylic acid methyl ester (2 g, from Example 4) was dissolved in tetrahydrofuran (20 mL), deionized water (10 mL) was added, and the reaction temperature was maintained at 25°C to 30°C. A solution of sodium hydroxide (0.74 g) in deionized water (4 mL) was added slowly and dropwise to the reaction mixture over 10 minutes at the same temperature. The reaction mixture was stirred continuously for 3 hours, maintaining the temperature at 25°C to 30°C. Upon completion of the reaction (monitored by TLC), tetrahydrofuran was removed by distillation under reduced pressure at 40 °C to 45 °C and deionized water (20 mL) was added. The aqueous phase was extracted with dichloromethane (2 x 20 mL). The aqueous phase was cooled to 5 °C to 10 °C, the pH was adjusted to 1.3 with 50% aqueous hydrochloric acid, and stirring was continued at 5 °C to 10 °C for 30 min. The precipitated solid was collected by filtration and washed with deionized water (2 x 20 mL). The wet solid was dried under reduced pressure at 35 °C to 40 °C for 14 h to afford the target product 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-1 -methyl-1H-benzo[d]imidazole-6-carboxylic acid in 88.5% yield.1H NMR (d6-DMSO, 400 MHz): δ 3.92 (s, 3H), 6.48-6.51 (m, 1H), 7.30-7.32 (m, 1H), 7.64-7.65 (d, 1H), 8.10 (s, 1H), 8.44 (s, 1H), 8.52 (s, 1H). Mass (m/z): 400.1 [M+2].