4-Aminophenol → Methyl 7-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)-phenoxy]thieno[3,2-b]pyridine-2-carboxylate

温度

70 °C

To a stirred solution of methyl 7-bromothieno[3,2-b]pyridine-2-carboxylate (200 mg, 0.74 mmol) in 8 ml of DMSO, were added CuBr (10 mg, 0.074 mmol), ethyl 2-cyclohexanonecarboxylate (26 mg, 0.15 mmol), cesium carbonate (500 mg, 1.54 mmol) and 4-aminophenol (96 mg, 0.88 mmol). The mixture was purged with nitrogen for 10 minutes, and then heated at 70° C. under N2 for 3 hours. The reaction was cooled to room temperature and poured into 100 ml of water. The precipitates were filtered, washed with water and dried to give the crude aniline intermediate as a pale green solid (˜140 mg). This crude material was dissolved in 10 ml of THF, and 2-fluoro-5-methylphenyl isocyanate (70 mg, 0.46 mmol) was added. The mixture was stirred at room temperature for 5 hours, and poured into 100 ml of water. The brown precipitates were filtered, washed with water and dried to give the crude product, which was purified by silica gel chromatography, eluting with 2-3% MeOH/CHCl3 to give methyl 7-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]thieno[3,2-b]pyridine-2-carboxylate as light brown solid. Yield: 90 mg, 27%.

1. customThe mixture was purged with nitrogen for 10 minutes
2. temperatureThe reaction was cooled to room temperature
3. additionpoured into 100 ml of water
4. filtrationThe precipitates were filtered
5. washwashed with water
6. customdried
7. customto give the crude aniline intermediate as a pale green solid (˜140 mg)
8. customThe brown precipitates
9. filtrationwere filtered
10. washwashed with water
11. customdried
12. customto give the crude product, which
13. customwas purified by silica gel chromatography
14. washeluting with 2-3% MeOH/CHCl3

ORDレコード

ord-25b1b78abb0242b2bd2e39f1b1274a31

出典データセット

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08809534B2