反应详情

In a 50 mL round-bottomed flask was added 2-chloro-N-(3-chloro-4-fluorophenyl)-6-iodoquinazolin-4-amine (200 mg, 0.46 mmol), N,N-dimethylpropargylamine (99 mL, 0.92 mmol), NEt3 (0.26 mL, 1.84 mmol), CuI (0.88 mg, 4.6 mmol) and PdCl2(PPh3)2 (6.5 mg, 9.2 mmol) in DMF (3 mL) to give a light yellow suspension. The mixture was stirred at room temperature overnight under an argon atmosphere. The reaction mixture was diluted with water (10 mL) and ethyl acetate (10 mL) and then a precipitate formed. The resulting precipitate was removed by filtration through Celite. The filtrate was extracted with ethyl acetate (2×10 mL). The combined organic layer was washed with water (1×15 mL) and brine (1×15 mL) and was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with CH2Cl2/MeOH 1:0 to 9:1). The desired product was washed with CH2Cl2 to give 61 mg of 2-chloro-N-(3-chloro-4-fluorophenyl)-6-(3-(dimethylamino)prop-1-ynyl)quinazolin-4-amine, as pale yellow solid in a 34% yield. LCMS m/z=389 (M+1) (Method C) (retention time=2.2.4 min). 1H NMR (300 MHz, DMSO) δ 10.30 (s, 1H), 8.68 (s, 1H), 8.07 (dd, J=2.7, 6.9 Hz, 1H), 7.86 (dd, J=1.8, 8.7 Hz, 1H), 7.81-7.70 (m, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.49 (t, J=9.2 Hz, 1H), 3.52 (s, 2H), 2.28 (s, 6H).

1. customto give a light yellow suspension
2. customa precipitate formed
3. customThe resulting precipitate was removed by filtration through Celite
4. extractionThe filtrate was extracted with ethyl acetate (2×10 mL)
5. washThe combined organic layer was washed with water (1×15 mL) and brine (1×15 mL)
6. dry with materialwas dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by column chromatography on silica gel (eluted with CH2Cl2/MeOH 1:0 to 9:1)
10. washThe desired product was washed with CH2Cl2