[Synthesis]
A mixture of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (20.00 g), K2CO3 (10.37 g), KI (1.04 g), 1-bromo-3-chloropropane (7.50 mL), and DMF (150 mL) was stirred and reacted for 6 hours at 40 °C. After completion of the reaction, the reaction mixture was poured into water and the solid was collected by filtration. The filtrate was purified by silica gel column chromatography (eluent: ethyl acetate) to afford the target compound, N-(3-chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine, as a light yellow liquid (22.05 g, 89.00% yield). The structure of the compound was confirmed by the following spectral data: mass spectrum (ESI, positive ion mode) m/z: 396.1 ([M+H]+); 1H NMR (400 MHz, CDCl3) δ: 2.01 (m, 2H), 3.68 (t, J=4.2 Hz, 2H), 4.00 (s, 3H), 4.10 (t, J=4.2 Hz, 2H). 6.80 (s, 1H), 7.16 (s, 1H), 7.26 (s, 1H), 7.30 (s, 1H), 7.47 (s, 1H), 8.64 (s, 1H) ppm. |
[References]
[1] Patent: WO2013/71697, 2013, A1. Location in patent: Paragraph 00197
[2] Patent: US2014/228361, 2014, A1. Location in patent: Paragraph 0277-0278
[3] Patent: US2014/206664, 2014, A1. Location in patent: Paragraph 0225; 0229
[4] Patent: EP2796451, 2014, A1. Location in patent: Paragraph 0082 |