反应详情

温度

118 °C

In a dried sealable pressure tube flushed with argon was placed methyl 5-bromo-8-{[(4-methylphenyl)sulfonyl]oxy}-1,6-naphthyridine-7-carboxylate (2.0 g, 4.57 mmol), prepared as described in Example 2, Step 2), N-methylethanesulfonamide (1.13 g, 9.15 mmol), dry DMF (4 mL) and copper(I) oxide (785 mg, 5.49 mmol) and 2,2′ bipyridyl (857 mg, 5.49 mmol). The tube was capped and heated to 118° C. for 2 hours. The reaction was cooled and filtered through a glass fiber filter, washing with chloroform. The filtrate was diluted with chloroform (about 100 mL total volume) and stirred with an EDTA solution (5 g EDTA in 100 mL water) for two hours or until the aqueous layer became aqua in color and the organic layer became yellow. The layers were separated and the aqueous layer was extracted twice more with chloroform. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was redissolved in 2 mL of DMSO and purified by preparative HPLC (Gilson semi preparative HPLC system using a Waters Nova pak column (10×40 mm I.D. cartridges, C18, 6 μM pore size) eluting with 95-5% water (0.025% TfEA)/acetonitrile (0.025% TFA) at 35 mLjmin) and the desired fractions were freeze dried to give the product as a yellow powder.

1. customIn a dried sealable pressure tube flushed with argon
2. customprepared
3. customThe tube was capped
4. temperatureThe reaction was cooled
5. filtrationfiltered through a glass fiber
6. filtrationfilter
7. washwashing with chloroform
8. additionThe filtrate was diluted with chloroform (about 100 mL total volume)
9. customThe layers were separated
10. extractionthe aqueous layer was extracted twice more with chloroform
11. dry with materialThe combined organic extracts were dried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. dissolutionThe residue was redissolved in 2 mL of DMSO
15. custompurified by preparative HPLC (Gilson semi preparative HPLC system
16. washeluting with 95-5% water (0.025% TfEA)/acetonitrile (0.025% TFA) at 35 mLjmin) and the desired fractions
17. customdried