General procedure for the synthesis of 3,7-dibromo-1,5-naphthyridine from 1,5-naphthyridine:
1. 1,5-naphthyridine (30.80 g, 236.7 mmol) and sodium acetate (38.83 g, 473.3 mmol) were dissolved in acetic acid (236.7 mL) and heated to 60°C. The mixture was then heated to 60°C. The mixture was then heated to 60°C.
2. a solution of bromine (25.6 mL, 496.9 mmol) in acetic acid (35 mL) was added slowly and dropwise over 30 minutes.
3. the reaction mixture is stirred continuously at 60°C for 22 hours.
4. After completion of the reaction, it was cooled to room temperature, diluted with water (250 mL) and alkalized with 4N aqueous NaOH (300 mL), at which time a beige precipitate was produced.
5. The precipitate was collected by filtration and washed with water, methanol and acetone.
6. The resulting solid (54.7 g) was recrystallized from chloroform (1.36 L) to afford a pure cream colored solid 3,7-dibromo-1,5-naphthyridine (30 g, 44% yield).
Product characterization: 1H NMR (400 MHz, CDCl3) δ 9.08-8.95 (m, 2H), 8.62 (dd, J = 2.2, 0.7 Hz, 1H), 8.46-8.35 (m, 1H), 8.23 (d, J = 8.8 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.69 (dd, J = 8.5, 4.3 Hz, 1H). [M + H]+ = 286.9.
