反应详情

温度

100 °C

1-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (40 mg, 0.22 mmol), 3-methoxybenzylamine (48 mg, 0.35 mmol), palladium(II) acetate (2 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (7 mg, 0.02 mmol), and sodium tert-butoxide (67 mg, 0.69 mmol) were suspended in dioxane (2 mL), and stirred overnight at 100° C. The reaction mixture was concentrated, partitioned between H2O/EtOAc, and filtered. The precipitate was washed with H2O/EtOAc, and suspended in MeOH. 2M HCl/ether was added and the resulting mixture was filtered. The precipitate (Pd salts) was washed with MeOH, and the filtrate was concentrated. The crude product was purified via prep-LC-MS. The purified product was converted to the HCl salt via dissolving in MeOH, addition of 2 M HCl, and evaporation. The resulting precipitate was triturated from CH2Cl2, filtered, and dried under vacuum to provide 97 (10 mg, 16% yield) as a yellow solid. LC-MS (M+H=332, obsd.=332). 1H NMR (400 MHz, d6-DMSO): δ 9.10 (s, 1H), 8.63 (d, 1H), 8.38 (d, 1H), 8.08 (d, 1H), 7.98 (t, 1H), 7.71 (m, 2H), 7.29 (t, 1H), 7.05 (m, 2H), 6.87 (dd, 1H), 6.74 (d, 1H), 4.76 (d, 2H), 3.72 (s, 3H).

1. concentrationThe reaction mixture was concentrated
2. custompartitioned between H2O/EtOAc
3. filtrationfiltered
4. washThe precipitate was washed with H2O/EtOAc
5. addition2M HCl/ether was added
6. filtrationthe resulting mixture was filtered
7. washThe precipitate (Pd salts) was washed with MeOH
8. concentrationthe filtrate was concentrated
9. customThe crude product was purified via prep-LC-MS
10. dissolutionvia dissolving in MeOH
11. additionaddition of 2 M HCl, and evaporation
12. customThe resulting precipitate was triturated from CH2Cl2
13. filtrationfiltered
14. customdried under vacuum