Bromine → 3-Bromo-1,5-naphthyridine

Temperature

80 °C

To a stirred mixture of 1,5-naphthyridine (C-1) (50.0 g, 384 mmol, 1.0 eq) and sodium acetate (62.9 g, 768 mmol, 2.0 eq) in acetic acid (300 mL) at 80° C., a solution of bromine (67.5 g, 422 mmol, 1.1 eq) in acetic acid (80 mL) was added dropwise while keeping the reaction temperature at 80° C. to 90° C. After stirring for 2 h at 80° C., the reaction was complete based on TLC analysis. The resulting mixture was cooled to RT and then filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (0-30% ethyl acetate-petroether) to afford the desired product 3-bromo-1,5-naphthyridine (C-2) (36.5 g, 45% yield) as a pale yellow solid. 1H NMR (300 MHz, CDCl3-d6) δ: 8.97 (m, 2H), 8.57 (s, 1H), 8.37 (d, J=8.4 Hz, 1H), 7.65 (m, 1H); ESI-MS m/z: 208.96 [M+H]+.

1. customat 80° C. to 90° C
2. temperatureThe resulting mixture was cooled to RT
3. filtrationfiltered
4. concentrationThe filtrate was concentrated in vacuo
5. customthe residue was purified by flash column chromatography on silica gel (0-30% ethyl acetate-petroether)

ORD record

ord-82d587a211524095aeecaf53f5dbfb11

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09359352B2