Synthesis
1. Methyl 5-nitro-1H-indole-3-carboxylate (206 mg, 0.940 mmol) was dissolved in methanol (40 mL) and 5% palladium carbon (40 mg) was added. The reaction mixture was stirred under hydrogen atmosphere at 1 atmosphere for 5 hours. Upon completion of the reaction, the catalyst was removed by diatomaceous earth filtration and the filtrate was evaporated to give the brown solid product methyl 5-amino-1H-indole-3-carboxylate (173 mg, 97% yield) which did not require further purification.TLC showed a single spot (Rf = 0.64, unfolding agent: ethyl acetate).
2. 3-Chloro-2-methylbenzenesulfonyl chloride (124 mg, 0.552 mmol) was dissolved in dichloromethane (4 mL) and pyridine (100 μL, 1.3 mmol) was added. The mixture was stirred under nitrogen protection for 5 min, then methyl 5-amino-1H-indole-3-carboxylate (100 mg, 0.526 mmol) was added. Stirring was continued at room temperature for 1.5 h. When the reaction was complete, saturated sodium bicarbonate solution (15 mL) was added and extracted with ethyl acetate (20 mL). The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product. Purification by fast column chromatography afforded a white solid target compound (129 mg, 65% yield).TLC showed a single spot (Rf = 0.84, unfolding agent: ethyl acetate). Melting point: 216.8-219.3 °C. HPLC purity ≥ 99% (mobile phase: 10% water-acetonitrile, retention time: 2.07 min).
References
[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 22, p. 9875 - 9890
[2] Patent: WO2004/37251, 2004, A1. Location in patent: Page/Page column 111; 112
