反应详情

To a stirred suspension of 7-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridine-2-carboxylic acid (Compound F1) (100 mg, 0.23 mmol) in 10 ml of anhydrous acetonitrile were added HATU (95 mg, 0.25 mmol) and N,N-diisopropylethylamine (89 mg, 0.69 mmol). The mixture was stirred at room temperature for 20 minutes, followed by addition of 3-(1H-tetrazol-5-yl)propan-1-amine hydrochloride (57 mg, 0.35 mmol). The mixture was stirred at room temperature for another 40 minutes and poured into 100 ml of water with vigorous stirring. 1M HCl was added dropwise until pH=5. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 8˜12% methanol in chloroform containing 0.5% of triethylamine to give 7-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]-N-[3-(2H-tetrazol-5-yl)propyl]thieno[3,2-b]pyridine-2-carboxamide as white solid. Yield: 50 mg, 40%.

1. stirringThe mixture was stirred at room temperature for another 40 minutes
2. filtrationThe precipitates were filtered
3. washwashed with water
4. customdried in vacuo
5. customto give the crude, which
6. customwas purified by silica gel chromatography
7. washeluting with 8˜12% methanol in chloroform containing 0.5% of triethylamine