Ethyl 6-methoxy-1H-indole-2-carboxylate (5.0 g) was dissolved in tetrahydrofuran (90 mL), lithium hydroxide (2.33 g) and water (30 mL) were added and the reaction was stirred for 16 hours at room temperature. After completion of the reaction, the reaction mixture was acidified with 10% hydrochloric acid solution, diluted with water and subsequently extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 6-methoxy-1H-indole-2-carboxylic acid (4.60 g). The resulting carboxylic acid (4.64 g) was dissolved with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.60 g) in dichloromethane (200 mL), N-methylpiperazine (3.23 mL) was added, and the reaction was stirred for 16 hours at room temperature. The reaction mixture was diluted with dichloromethane (200 mL), washed sequentially with water, saturated sodium bicarbonate solution and brine, the organic phase was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 0-10% 2M ammonia in methanol solution/dichloromethane) to give (6-methoxy-1H-indol-2-yl)-(4-methylpiperazin-1-yl)-methanone (6.60 g). The product (0.16 g) was dissolved in dichloromethane (10 mL) and 1M boron tribromide solution (1.5 mL) was added slowly and dropwise at room temperature, followed by heating the reaction mixture to reflux overnight. After cooling, the reaction was quenched with saturated sodium bicarbonate solution and extracted with dichloromethane. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 0-10% 2M ammonia in methanol solution/dichloromethane) to give 6-methoxyindole-2-carboxylic acid as final product.
