反应详情

A solution of 5-fluoro-1-[(4-methyl-2-pyridin-2-yl-pyrimidine-5-carbonyl)-amino]-1H-indole-3-carboxylic acid methyl ester (2.6 mmol) in MeOH (10 mL) is treated with an aqueous solution of KOH (500 mg, 8.9 mmol) in H2O (200 mL) and heated at reflux for 2 h. The mixture is diluted with EtOAc (50 mL) and extracted with 1% aqueous KOH (3×50 mL). The combined aqueous layer is neutralized with HCl (conc.), and the precipitate is collected by filtration and dried in vacuo to afford 5-fluoro-1-[(4-methyl-2-pyridin-2-yl-pyrimidine-5-carbonyl)-amino]-1H-indole-3-carboxylic acid (195 mg, 19%, 3 steps). MS: 392 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 12.44 (s, OH, 1H), 12.31 (s, NH, 1H), 9.31 (s, 1H), 8.81 (d, 1H), 8.48 (d, 1H), 8.35 (s, 1H), 8.03 (m, 1H), 7.77 (m, 1H), 7.62 (m, 2H), 7.19 (m, 1H), 2.79 (s, 3H).

1. temperatureheated
2. temperatureat reflux for 2 h
3. extractionextracted with 1% aqueous KOH (3×50 mL)
4. filtrationthe precipitate is collected by filtration
5. customdried in vacuo