反应详情

温度

80 °C

A mixture of N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-5-(3-hydroxyphenyl)thiophene-2-carboxamide (Example 144, 80 mg, 0.20 mmol), (R)-(−)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-toluenesulfonate (70 mg, 0.24 mmol) and K2CO3 (84 mg, 0.61 mmol) in DMF (0.3 mL) was stirred and heated at 80° C. for 17 h. After cooling to rt, the mixture was diluted with water (˜5 mL) and extracted with EtOAc (3×10 mL) and the combined extracts were washed with brine, dried over anhyd. Na2SO4, filtered, and concentrated under vacuum to afford a brown oil. This material was purified by reverse-phase Prep HPLC to isolate the major product which was dissolved in MeOH (˜3 mL) and 2 N aq HCl (0.3 mL) was added. The solution was warmed to 65° C. for 45 min then cooled to rt and concentrated under vacuum to remove most of the MeOH. The resulting heterogeneous mixture was diluted with water (˜2-3 mL) and stirred for 1 h. The resulting solid was collected by vacuum filtration, rinsed with water (˜5 mL), and air dried in funnel then under vacuum to afford 29 mg (30%) of an off-white solid as the title compound (Example 193). HPLC Ret. Time=2.90 min, LCMS [M+H]+ 467.29.

1. temperatureAfter cooling to rt
2. extractionextracted with EtOAc (3×10 mL)
3. washthe combined extracts were washed with brine
4. customdried over anhyd
5. filtrationNa2SO4, filtered
6. concentrationconcentrated under vacuum
7. customto afford a brown oil
8. customThis material was purified by reverse-phase Prep HPLC
9. customto isolate the major product which
10. temperatureThe solution was warmed to 65° C. for 45 min
11. temperaturethen cooled to rt
12. concentrationconcentrated under vacuum
13. customto remove most of the MeOH
14. additionThe resulting heterogeneous mixture was diluted with water (˜2-3 mL)
15. stirringstirred for 1 h
16. filtrationThe resulting solid was collected by vacuum filtration
17. washrinsed with water (˜5 mL), and air
18. customdried in funnel