反应详情

温度

150 °C

To a solution of 6-butyl-8-[(3R)-3-pyrrolidinyloxy]quinoline (for example, as prepared for Intermediate 10) (0.130 g, 0.481 mmol), in DMF (3 ml) was added a mixture of 3-bromopropyl 1,1-dimethylethyl sulfone and 3-chloropropyl 1,1-dimethylethyl sulfone (for example, as prepared for Intermediate 17) (1:1, 0.215 g, 0.96 mmol), sodium iodide (0.144 g, 0.96 mmol), then potassium carbonate (0.133 g, 0.96 mmol). The suspension was heated to 150° C. for 15 min in a Smith Creator™ microwave oven with fixed hold time on. The mixture 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% 0.88 s.g. ammonia in methanol (2 column volumes) and the basic fraction concentrated in vacuo. The residue (0.2 g) was purified by MDAP and the appropriate fractions combined and concentrated in vacuo. The residue (0.113 g) was further purified by Flashmaster II chromatography (50 g cartridge) eluting with 0-25% methanol in DCM over 40 min. The appropriate fractions were combined and the solvent removed in vacuo (70 mg, 33%). To a portion of this material (29 mg, 0.067 mmol) in methanol (0.5 ml) was added 1.25 M hydrogen chloride in methanol (0.3 ml). The solvent was removed using a stream of nitrogen to leave the title compound as white solid (34 mg). LCMS RT=2.97 min, ES+ve m/z 433 (M+H)+.

1. washthe cartridge washed with methanol (2 column volumes)
2. washThe cartridge was eluted with 10% 0.88 s
3. concentrationammonia in methanol (2 column volumes) and the basic fraction concentrated in vacuo
4. customThe residue (0.2 g) was purified by MDAP
5. concentrationconcentrated in vacuo
6. customThe residue (0.113 g) was further purified by Flashmaster II chromatography (50 g cartridge)
7. washeluting with 0-25% methanol in DCM over 40 min
8. customthe solvent removed in vacuo (70 mg, 33%)
9. customThe solvent was removed