[Synthesis]
The general procedure for the synthesis of N-[2-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-quinazolinyl]amino]-3-methylphenyl]-2-acrylamide from the compound (CAS: 1538605-10-5) and acryloyl chloride was performed as follows: the N'-[6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl]- 6-methylbenzene-1,2-diamine (5.16 g, 11.33 mmol) was dissolved in dichloromethane (DCM, 100 mL) and cooled to 0 °C. Subsequently, N,N-diisopropylethylamine (DIEA, 1.781 mL, 10.20 mmol) and acryloyl chloride (1.013 mL, 12.47 mmol) were sequentially added at 0 °C and the reaction mixture was stirred for 2 h at this temperature. After completion of the reaction, the mixture was directly sampled onto a silica gel column and purified by fast column chromatography using 0-100% ethyl acetate (EtOAc)/hexane gradient elution. Finally, the target product N-[2-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-quinazolinyl]amino]-3-methylphenyl]-2-propenamide was obtained as an off-white solid (3.5 g, 61% yield). The mass spectrum (electrospray positive ion mode, ES+) showed the molecular ion peak m/z 509 [M+H]+, which is consistent with the calculated value of the molecular formula C26H22Cl2N4O3.1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 9.23 (s, 1H), 8.68 (s, 1H), 7.82-7.65 (m, 2H) , 7.51 (s, 2H), 7.21 (m, 1H), 7.12 (d, J = 6.8 Hz, 1H), 7.01 (s, 1H), 6.49 (dd, J = 17.0, 10.2 Hz, 1H), 6.28-6.15 (m, 1H), 5.68 (dd, J = 10.2, 2.0 Hz, 1H), 3.97 (s, 6H) , 2.19 (s, 3H). |