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

온도

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 기록

ord-5a59d5b0626646c18126fd14b79e86af

출처 데이터셋

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09340555B2