反应详情

A solution of 5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylic acid (1.00 g, 3.09 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.77 g, 4.02 mmol), and 1-hydroxy-7-azabenzotriazole (0.55 g, 4.02 mmol) in degassed dry DMP (20 mL) was aged for 30 minutes to preform the activated ester. Triethylamine (0.47 mL, 3.40 mmol) and {4-fluoro-2-[(methylamino)carbonyl]phenyl}-methanaminium chloride (0.74 g, 3.40 mmol) were added and the reaction stirred for 30 minutes. The reaction was poured into water, the pH was adjusted to 10 using 1N NaOH, and resulting solution was extracted several times with CHCl3. The combined organic extracts were dried over Na2SO4′, filtered, and concentrated to dryness in vacuo. The residue was partitioned between basic water (pH=10 using 1N NaOH) and ether. The layers were separated and the aqueous layer was extracted twice more with ether. The aqueous layer was then acidified to pH=4 using 1N HCl and extracted several times with CHCl3. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to a brown oil. Methanol was added to the flask and the flask was sonicated for 5 minutes. Solids crashed out of the solution upon sonication and were collected by vacuum filtration to afford the title compound as a whitish solid.

1. customdry DMP (20 mL)
2. customresulting solution
3. extractionwas extracted several times with CHCl3
4. dry with materialThe combined organic extracts were dried over Na2SO4′
5. filtrationfiltered
6. concentrationconcentrated to dryness in vacuo
7. customThe residue was partitioned between basic water (pH=10 using 1N NaOH) and ether
8. customThe layers were separated
9. extractionthe aqueous layer was extracted twice more with ether
10. extractionextracted several times with CHCl3
11. dry with materialThe combined organic extracts were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated to a brown oil
14. additionMethanol was added to the flask
15. customthe flask was sonicated for 5 minutes
16. customSolids crashed out of the solution upon sonication
17. filtrationwere collected by vacuum filtration