反应详情

温度

80 °C

A solution of maleic acid (0.66 g) in IMS (10 ml) was added to 4-(3-chloro-2-fluoroanilino)-6-[1-(hydroxyacetyl)piperidin-4-yloxy]-7-methoxyquinazoline (2.5 g) in IMS (25 ml) at 80° C. Water (3 ml) was added. After stirring at 80° C. for 5 minutes, the solution was cooled to ambient temperature over 1 hour. At approximately 50° C., a solid crystallised. The mixture was stirred at ambient temperature for 30 minutes before cooling to 0–5° C. The solid was filtered and washed with IMS (2×7.5 ml). The solid was dried at 50° C. under vacuum to constant weight. The solid was then heated in 10% aqueous IPA at 82–85° C. for 1 hour before cooling to ambient temperature over 1 hour. The solid was filtered and washed with IPA (2×5 ml). The solid was dried at 50° C. under vacuum to constant weight to give the title product (1.63 g; 52.3% yield); NMR Spectrum: (DMSO d6) 1.63–1.82 (m, 2H); 2.00–2.10 (m, 2H); 3.28–3.45 (m, 2H); 3.59–3.67 (m, 1H); 3.83–3.90 (m, 1H); 3.98 (s, 3H); 4.14 (s, 2H); 4.79 (m, 1H); 6.19 (s, 2H); 7.25 (s, 1H); 7.33 (t, 1H); 7.52–7.59 (m, 2H); 7.95 (s, 1H); 8.54 (s, 1H) 10.14 (bs, 1H); Melting Point: Onset 165.4° C., peak 169.7° C.

1. temperaturethe solution was cooled to ambient temperature over 1 hour
2. customAt approximately 50° C., a solid crystallised
3. stirringThe mixture was stirred at ambient temperature for 30 minutes
4. temperaturebefore cooling to 0–5° C
5. filtrationThe solid was filtered
6. washwashed with IMS (2×7.5 ml)
7. customThe solid was dried at 50° C. under vacuum to constant weight
8. temperatureThe solid was then heated in 10% aqueous IPA at 82–85° C. for 1 hour
9. temperaturebefore cooling to ambient temperature over 1 hour
10. filtrationThe solid was filtered
11. washwashed with IPA (2×5 ml)
12. customThe solid was dried at 50° C. under vacuum to constant weight