反应详情

To a suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide (1.75 g, 6.75 mmol) in 8.2 mL of iso-propanol was added triethylorthoformate (1.5 g, 10.1 mmol). The mixture was heated to reflux. After 20 minutes, 4-methoxy-3-[3-(4-methyl-piperazin-1-yl)-propoxy]-phenylamine in 20 mLs of iso-propanol was added dropwise so as to maintain reflux. After 26 hours, the reaction was cooled to room temperature and the suspended solids were filtered. The solids were rinsed with iso-propanol until effluent was colorless. The yellow solid was dried in vacuo to give 3.45 g (93%) of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-{4-methoxy-3-[3-(4-methylpiperazin-1-yl)-propoxy]-phenylamino}-acrylamide as a mixture of isomers. 1H NMR (300 MHz, CDCl3) δ 11.35 (br d, 1H), 8.17 (m, 2H), 7.76 (d, 1H), 7.41 (s, 1H), 6.88 (m, 1H) 6.69 (m, 2H), 4.10 (t, J=7 Hz, 2H), 3.96 (s, 3H), 3.87 (s, 3), 2.55 (t, J=7 Hz, 2H), 2.48 (m, 8H), 2.29 (s, 3H), 2.06 (m, 2H); MS (ES) m/z548.1 (M+)

1. temperatureThe mixture was heated to reflux
2. temperatureto maintain
3. temperaturereflux
4. waitAfter 26 hours
5. filtrationthe suspended solids were filtered
6. washThe solids were rinsed with iso-propanol until effluent
7. customThe yellow solid was dried in vacuo