反应详情

温度

80 °C

To a solution of 6-butyl-8-(4-piperidinyloxy)quinoline (for example, as prepared for Intermediate 4) (0.15 g, 0.53 mmol) in THF (5 ml) was added 2,3-dihydrothiophene 1,1-dioxide (commercially available, for example, from AKOS) (0.150 g, 1.27 mmol). The solution was heated to 80° C. for 2.5 h. To the solution at ambient temperature was added a further amount of 2,3-dihydrothiophene 1,1-dioxide (0.150 g, 1.27 mmol) and the solution stirred overnight at ambient temperature. The solution was heated to reflux for 2 h and then at ambient temperature for 7 days. The reaction was applied to an SCX-2 cartridge (20 g), preconditioned with methanol, and the cartridge washed with methanol (2 column volumes). The cartridge was eluted with 10% 0.880 s.g. ammonia in methanol (2 column volumes) and the basic fractions concentrated in vacuo. The residue was purified by MDAP and the appropriate fractions combined and evaporated. The combined fractions were applied to an SCX-2 cartridge (20 g), preconditioned with methanol, and the cartridge washed with methanol. The cartridge was eluted with 10% 0.88 s.g. ammonia in methanol (2 column volumes) and the basic fractions concentrated in vacuo to give the title compound (17 mg, 8%). LCMS RT=2.59 min, ES+ve m/z 403 (M+H)+.

1. temperatureThe solution was heated
2. temperatureto reflux for 2 h
3. waitat ambient temperature for 7 days
4. washthe cartridge washed with methanol (2 column volumes)
5. washThe cartridge was eluted with 10% 0.880 s
6. concentrationammonia in methanol (2 column volumes) and the basic fractions concentrated in vacuo
7. customThe residue was purified by MDAP
8. customevaporated
9. washthe cartridge washed with methanol
10. washThe cartridge was eluted with 10% 0.88 s
11. concentrationammonia in methanol (2 column volumes) and the basic fractions concentrated in vacuo