反应详情

温度

50 °C

To a solution of methyl 2-chloro-6-(methylamino)isonicotinate (2.00 g, 9.97 mmol) in 3:1 CH2Cl2:pyridine (100 mL total) was added 3-pyridine sulfonyl chloride hydrochloride (6.40 g, 29.9 mmol) and dimethylaminopyridine (0.609 g, 4.98 mmol). Reaction heated to reflux at 50° C. After 36 h, reaction cooled to rt. Reaction diluted with CH2Cl2 (200 mL) and washed with 1N HCl (150 mL) solution. The aqueous solution was extracted with CH2Cl2 (100 mL×2). The combined organics were washed with brine (100 mL), dried over Mg2SO4, filtered, and concentrated in vacuo. Purification by normal-phase chromatography (20->40% EtOAc/hexanes) yielded 3.12 g (92%) of methyl 2-chloro-6-[methyl(pyridin-3-ylsulfonyl)amino]isonicotinate as a yellow residue. 1H NMR (CDCl3, 400 MHz) 8.95 (d, J=0.64 Hz, 1H); 8.82 (m, 1H); 8.03 (m, 2H); 7.67 (m, 1H); 7.45 (m, 1H); 3.99 (s, 3H); 3.39 (s, 3H); LC/MS [M+H]+=341.9.

1. customReaction
2. temperatureheated
3. customreaction
4. temperaturecooled to rt
5. customReaction
6. washwashed with 1N HCl (150 mL) solution
7. extractionThe aqueous solution was extracted with CH2Cl2 (100 mL×2)
8. washThe combined organics were washed with brine (100 mL)
9. dry with materialdried over Mg2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customPurification by normal-phase chromatography (20->40% EtOAc/hexanes)