反应详情

温度

93 °C

(6-Aminopyridin-3-yl)(morpholino)methanone (58 g, 280 mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (63.66 g, 285 mmol, Eq: 1.02) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.86 g, 8.4 mmol, Eq: 0.03) were dissolved in DMF (1.1 l) under heating. Cesium carbonate (274 g, 840 mmol, Eq: 3) was added. Finally Pd2 (dba)3 (3.84 g, 4.2 mmol, Eq: 0.015) was added under an argon atmosphere. The reaction mixture was heated to 93° C. (internal temperature) for 3 hr. The warm reaction mixture was poured into water/ice (10 l). A beige precipitate was collected by filtration and washed with water (2 l). The resulting solid was taken up in DCM (51) and filtered. The filtrate was concentrated in vacuo to give a solid, which was triturated with isopropanol (700 ml), filtered and dried under vacuum to afford the desired product (70.24 g) as a beige solid. (M+H)+=350 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.56-3.79 (m, 8 H) 3.83 (s, 3 H) 6.96 (d, J=8.31 Hz, 1 H) 7.77 (dd, J=8.31, 2.27 Hz, 1 H) 8.34-8.42 (m, 2 H) 8.47 (d, J=2.27 Hz, 1 H).

1. temperatureunder heating
2. customThe warm reaction mixture
3. filtrationA beige precipitate was collected by filtration
4. washwashed with water (2 l)
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo
7. customto give a solid, which
8. customwas triturated with isopropanol (700 ml)
9. filtrationfiltered
10. customdried under vacuum