反应详情

温度

80 °C

A solution of L-tartaric acid (0.85 g) in water (5 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. After stirring at 80° C. for 5 minutes, the solution was cooled to ambient temperature over 1 hour. At around 45° 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 to give the title product (3.13 g; 89.3% yield). NMR Spectrum: (DMSO d6) 1.63–1.81 (m, 2H); 1.98–2.11 (m, 2H); 3.28–3.45 (m, 2H); 3.59–3.67 (m, 1H); 3.83–3.90 (m, 1H); 3.95 (s, 3H); 4.14 (s, 2H); 4.32 (s, 2H); 4.55 (bs, 1H), 4.77 (m, 1H); 7.24 (s, 1H); 7.29 (t, 1H); 7.47–7.56 (m, 2H); 7.89 (s, 1H); 8.39 (s, 1H) 9.62 (bs, 1H); Melting Point: Onset 128.8° C., peak 137.4° C.

1. temperaturethe solution was cooled to ambient temperature over 1 hour
2. customAt around 45° 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