89% |
With aluminum oxide; potassium fluoride In N,N-dimethyl acetamide for 2h; Sonication; |
A13 Example A13
A mixture of Example C5 (2.191 g, 7.94 mmol), Example B1 (1.538 g, 8.33 mmol) and KF on alumina (40 wt %) (9.22 g, 63.5 mmol) in DMA (40 mL) was sonicated for 2 h. The mixture was filtered through a shallow bed of silica gel and rinsed well with EtOAc. The filtrate was washed with satd. NaHCO3 (1*), 5% LiCl (2*), then brine (1*), dried (MgSO4), and concentrated to dryness to afford 3-(5-amino-2-bromo-4-fluorophenyl)-7-chloro-1-ethyl-1,6-naphthyridin-2(1H)-one (2.793 g, 89% yield) as a brown solid. 1H NMR (400 MHz, DMSO-d6): δ 8.77 (s, 1H), 8.00 (s, 1H), 7.74 (s, 1H), 7.37 (d, 1H), 6.77 (d, 1H), 5.45 (s, 2H), 4.27 (q, 2H), 1.20 (t, 3H); MS (ESI) m/z: 398.0 [M+H]+. |
89% |
With 40% potassium fluoride/alumina In N,N-dimethyl acetamide for 2h; Sonication; |
A13
Example A13: A mixture of Example CS (2.191 g, 7.94 mmol), Example B1(1.538 g, 8.33 mmol) and KF on alumina (40 wt%) (9.22 g, 63.5 mmol) in DMA (40 mL)was sonicated for 2 h. The mixture was filtered through a shallow bed of silica gel and rinsedwell with EtOAc. The filtrate was washed with satd. NaHC03 (1x), 5% LiCl (2x), then brine(1x), dried (MgS04), and concentrated to dryness to afford 3-(5-amino-2-bromo-4-fluorophenyl)-7 -chloro-1-ethyl-1 ,6-naphthyridin-2(1H)-one (2. 793 g, 89% yield) as a brownsolid. 1H NMR (400 MHz, DMSO-d6): 8 8.77 (s, 1 H), 8.00 (s, 1 H), 7.74 (s, 1 H), 7.37 (d, 1H), 6.77 (d, 1 H), 5.45 (s, 2 H), 4.27 (q, 2 H), 1.20 (t, 3 H); MS (ESI) m/z: 398.0 [M+Ht. |