反应详情

温度

100 °C

Methyl 3-(6-bromo-4-oxoquinazolin-3(4H)-yl)-4-methylbenzoate (2 g), Cs2CO3 (4.4 g), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.67 g), palladium acetate (0.12 g) in anhydrous toluene (20 ml) at ambient temperature was added N-boc piperazine (2.5 g). The mixture was heated to 100° C. and stirred for 16 hours. Inorganic solids were removed via a hot filtration and the filtrate concentrated to give an oil. The oil was resuspended in MeOH (16 ml), 4N HCl in dioxane (10 ml) was added and the reaction mixture stirred at 50° C. for 1 hour when additional 4N HCl in dioxane (2 ml) was added and heating continued for a further 30 minutes. The reaction mixture was cooled to room temperature and the solid collected by filteration, washed with ethyl acetate (×2) and ether and dried. The resultant solid was suspended in saturated K2CO3 solution and extracted with ethyl acetate (×5). The organic layers combined, dried (magnesium sulphate) and concentrated to yield methyl 4-methyl-3-(4-oxo-6-piperazin-1-ylquinazolin-3(4H)-yl)benzoate as a yellow foam (1.41 g); NMR Spectrum: (DMSOd6) 2.17 (s, 3H), 2.31 (m, 1H), 2.87 (m, 4H), 3.19 (m, 4H), 3.87 (s, 3H), 7.46 (s, 1H), 7.61 (m, 3H), 7.97 (s, 1H), 8.02 (d, 1H), 8.08 (s, 1H); Mass Spectrum: M+H+ 379.

1. customInorganic solids were removed via a hot filtration
2. concentrationthe filtrate concentrated
3. customto give an oil
4. additionwas added
5. temperatureheating
6. waitcontinued for a further 30 minutes
7. temperatureThe reaction mixture was cooled to room temperature
8. customthe solid collected by filteration
9. washwashed with ethyl acetate (×2) and ether
10. customdried
11. extractionextracted with ethyl acetate (×5)
12. dry with materialdried (magnesium sulphate)
13. concentrationconcentrated