反应详情

温度

100 °C

N-(9-Bromomethyl-1,2-dihydro-1-oxobenzo[f]quinazolin-3-yl)pivalamide (0.97 g, 2.5 mmole) and 4-fluoroaniline (0.56 g, 5 mmole) (Aldrich) were dissolved in dimethylformamide (15 ml). The reaction was stirred for 30 minutes at 100° C., sodium bicarbonate (0.42 g, 5mmole) added and the suspension stirred for a further 30 minutes. The dimethyl-formamide was removed in vacuo, the residue washed with methylene chloride and filtered. The filtrate was evaporated, and the residue was subjected to chromatography on a Waters Prep 500 instrument (silica cartridge, elution with ethyl acetate/methylene chloride (1:19)). Fractions containing product were concentrated in vacuo, the residue dissolved in a minimum amount of ethyl acetate, and the solution diluted with hexane until precipitate formed. The solid was collected by filtration and dried under high vacuum to give the title compound as a beige solid (0.305 g,29%). 1H NMR (DMSO-d6, 200 MHz) δ: 1.25 (s, 9H, t-butyl); 4.42 (d, J=6 Hz,2H, CH2); 6.33 (t,J=6 Hz, 1H, NH); 6.53-6.60 (m, 2H, Ar); 6.85 (t, J=8 Hz, 2H, Ar); 7.50 (d, J=10 Hz, 1H, Ar); 7.60 (dd, J=8, 2 Hz, 1H, Ar); 7.96 (d, J=8 Hz, 1H, Ar); 8.19 (d, J=8 Hz, 1H, Ar); 9.72 (s, 1H, Ar); 11.23 (s, 1H, NH); 12.28 (s, 1H, NH).

1. stirringthe suspension stirred for a further 30 minutes
2. customThe dimethyl-formamide was removed in vacuo
3. washthe residue washed with methylene chloride
4. filtrationfiltered
5. customThe filtrate was evaporated
6. washthe residue was subjected to chromatography on a Waters Prep 500 instrument (silica cartridge, elution with ethyl acetate/methylene chloride (1:19))
7. additionFractions containing product
8. concentrationwere concentrated in vacuo
9. dissolutionthe residue dissolved in a minimum amount of ethyl acetate
10. additionthe solution diluted with hexane until precipitate
11. customformed
12. filtrationThe solid was collected by filtration
13. customdried under high vacuum