Phosphorus oxychloride → 2-Chloro-7-iodo-1,5-naphthyridine

7-iodo-1,5-naphthyridin-2(1H)-one (D-16) (740 mg, 2.72 mmol, 1.0 eq) was dissolved in POCl3 (10 mL), and then heated at reflux for 1 h. The reaction was complete based on TLC analysis. The reaction mixture was concentrated in vacuo, poured into ice-water (30 mL), and neutralized with saturated sodium carbonate solution (about 30 mL) to adjust pH value to 8-9. The mixture was extracted with ethyl acetate (3×30 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo. The resultant residue was purified by silica gel column chromatography (5-10% ethyl acetate/petroether) to afford the desired product, 2-chloro-7-iodo-1,5-naphthyridine (D-17) (715 mg, 90.5%) as a solid. 1H NMR (400 MHz, CDCl3-d6) δ: 9.13 (d, J=2.0 Hz, 1H), 8.74 (d, J=1.6 Hz, 1H), 8.33 (d, J=8.8 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H); ESI-MS m/z: 290.93 [M+H]+.

1. temperatureheated
2. temperatureat reflux for 1 h
3. concentrationThe reaction mixture was concentrated in vacuo
4. additionpoured into ice-water (30 mL)
5. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
6. washThe combined organic layer was washed with brine (50 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationThe filtrate was concentrated in vacuo
10. customThe resultant residue was purified by silica gel column chromatography (5-10% ethyl acetate/petroether)

ORD record

ord-16811ec33c7046f0ae11c53a2e6dc268

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09359352B2