Sodium Iodide → 4-Iodo-1,5-naphthyridine

Temperature

100 °C

4-bromo-1,5-naphthyridine (99 mg, 0.47 mmol), copper(I) iodide (4.5 mg, 0.024 mmol) and sodium iodide (142 mg, 0.947 mmol) were combined into one vial fitted with a Teflon septum. The vial was flushed with nitrogen and 1,4-dioxane (4 ml) was added. After sparging with nitrogen for 5 minutes, rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (7.5 μl, 0.047 mmol) was added and the reaction was heated to 100° C. for 12 hours. The mixture was cooled to ambient temperature, and saturated aqueous ammonium chloride (2 ml) was added to quench the reaction. After stirring for 10 minutes, the mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was separated, and the aqueous layer was back extracted with ethyl acetate one more time. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (methanol/dichloromethane gradient) to afford 4-iodo-1,5-naphthyridine.

1. customThe vial was flushed with nitrogen and 1,4-dioxane (4 ml)
2. additionwas added
3. customAfter sparging with nitrogen for 5 minutes
4. temperatureThe mixture was cooled to ambient temperature
5. customto quench
6. customthe reaction
7. washwashed with saturated aqueous sodium bicarbonate
8. customThe organic layer was separated
9. extractionthe aqueous layer was back extracted with ethyl acetate one more time
10. dry with materialThe combined organic layers were dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customThe residue was purified by column chromatography on silica gel (methanol/dichloromethane gradient)

ORD record

ord-a0409396fff64d59adad9814eea6ddc1

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455477B2