反应详情

温度

60 °C

A mixture of 3-cyano-5,7-difluoro-4-hydroxyquinoline (4.12 g), 1-methylpiperidin-4-ol (2.6 g) and potassium tert-butoxide (6.72 g) in anhydrous tetrahydrofuran (250 ml) was stirred and heated at 60° C. for 2 hours. Acetic acid was added until pH6 was reached and then the solution was evaporated to dryness. The residue was dissolved in a mixture of dichloromethane and methanol (2:1) and the solution added to powdered silica gel (15 g). The suspension was evaporated to dryness and powder was packed into a preload cartridge. This was then chromatographed with an Isco Combiflash system and a Biotage 40M silica cartridge using a gradient elution of 0.6% to 30% ammonia (7.0M in methanol) in dichloromethane. The fractions containing the product were combined and evaporated. This gave the title compound as a white foam (3.55 g, 59%); NMR spectrum: (DMSOd6) 1.77 (m, 2H), 1.92 (m, 2H), 2.30 (s, 3H), 2.43 (m, 2H), 2.81 (m, 2H), 4.55 (m, 1H), 6.81 (m, 2H), 8.40 (s, 1H), Mass spectrum: M+H+ 302.

1. customthe solution was evaporated to dryness
2. dissolutionThe residue was dissolved in a mixture of dichloromethane and methanol (2:1)
3. additionthe solution added to powdered silica gel (15 g)
4. customThe suspension was evaporated to dryness and powder
5. customThis was then chromatographed with an Isco Combiflash system
6. washa gradient elution of 0.6% to 30% ammonia (7.0M in methanol) in dichloromethane
7. additionThe fractions containing the product
8. customevaporated