Phosphorus oxychloride → 7-Bromo-2-chloro-1,5-naphthyridine

7-bromo-1,5-naphthyridin-2(1H)-one (C-4) (3.1 g, 13.78 mmol, 1.0 eq) was dissolved in POCl3 (20 mL) and the resulting mixture was stirred at reflux for 1 h. The reaction was complete based on TLC analysis. The mixture was concentrated in vacuo to remove POCl3. The residue was poured into ice water (30 mL) and neutralized with saturated aqueous Na2CO3 solution to adjust the pH value to 7-8 while keeping the temperature below 10° C. The resulting mixture was extracted with ethyl acetate (3×30 mL), the combined organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford the desired product 7-bromo-2-chloro-1,5-naphthyridine (F-31) (2.11 g, 62.9% yield). ESI-MS m/z: 242.9 [M+H]+.

1. temperatureat reflux for 1 h
2. concentrationThe mixture was concentrated in vacuo
3. customto remove POCl3
4. additionThe residue was poured into ice water (30 mL)
5. customthe temperature below 10° C
6. extractionThe resulting mixture was extracted with ethyl acetate (3×30 mL)
7. washthe combined organic layer was washed with brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-13252f3726cc4bc0a5426d0333668d69

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09359352B2