反应详情

To an solution of 2-bromo-6-chloromethylpyridine (1.88 g, 1.11 mmol) obtained in Step 1 of Example 1 in ethanol (20 ml), 3-(1-thiocarbamoylpiperidin-4-yl)propionic acid methyl ester (2.10 g, 9.12 mmol) obtained in Step 1 was added and the mixture was heated at reflux overnight. The reaction solution was cooled to room temperature, dimethylformamide dimethylacetal (1.8 ml, 14 mmol) and triethylamine (3.8 ml, 27 mmol) were added, and heated at reflux for 1 hour. After the reaction solution was concentrated, water was added, and it was extracted with ethyl acetate and washed with a saturated brine. The organic layer was dried over magnesium sulfate and the residue obtained by vacuum concentration was purified by chromatography on silica gel (n-hexane:ethyl acetate=50:50 to 0:100) and the title compound (748 mg, 20%) was obtained.

1. temperaturethe mixture was heated
2. temperatureat reflux overnight
3. temperatureheated
4. temperatureat reflux for 1 hour
5. concentrationAfter the reaction solution was concentrated
6. additionwater was added
7. extractionit was extracted with ethyl acetate
8. washwashed with a saturated brine
9. dry with materialThe organic layer was dried over magnesium sulfate
10. customthe residue obtained by vacuum concentration
11. customwas purified by chromatography on silica gel (n-hexane:ethyl acetate=50:50 to 0:100)