反应详情

A solution of 5-bromo-2-ethoxypyridin-3-amine (53 mg, 0.25 mmol) and diisopropylethylamine (96 uL, 0.55 mmol) in dichloromethane (1 mL) was cooled to 0° C. and methanesulfonyl chloride (39 uL, 0.5 mmol) was added. The mixture was allowed to warm to rt over 15 h, and then water was added. The resulting mixture was extracted with dichloromethane. The organic extract was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in methanol (500 uL) and dioxane (500 uL), and then sodium hydroxide (2 M, 190 uL, 0.38 mmol) was added. The mixture was heated to 60° C. and 3 drops of aqueous sodium hydroxide (50%) were added. After stirring a further 30 min, the mixture was cooled to rt. Dilution with water was followed by acidification with aqueous citric acid (10%) and then two extractions with ethyl acetate. The combined organic extracts were washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (gradient 100% hexanes to 70% hexanes:30% ethyl acetate) to provide N-(5-bromo-2-ethoxypyridin-3-yl)methanesulfonamide (32.1 mg, 0.11 mmol, 43% yield) as a colorless film. 1H NMR (400 MHz, CDCl3) δ 7.95 (d, 1H), 7.89 (d, 1H), 6.75 (br s, 1H), 4.42 (q, 2H), 3.05 (s, 3H), 1.41 (t, 3H); MS (EI) for C8H11BrN2O3S: 295, 297 (Br isotopes, MH+).

1. extractionThe resulting mixture was extracted with dichloromethane
2. extractionThe organic extract
3. dry with materialwas dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in methanol (500 uL)
7. temperatureThe mixture was heated to 60° C.
8. temperaturethe mixture was cooled to rt
9. extractiontwo extractions with ethyl acetate
10. washThe combined organic extracts were washed with water
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customThe residue was purified by flash chromatography (gradient 100% hexanes to 70% hexanes:30% ethyl acetate)