反应详情

A mixture of 6-(2-(benzo[d]isothiazol-3-ylamino)ethylcarbamoyl)nicotinic acid (62 mg, 0.13 mmol), diethyl cyanophosphonate (21 μL, 0.14 mmol), methylamine (2.0M soln in THF, 15 μL, 0.14 mmol) and triethylamine (20 μL, 0.14 mmol) in dichloromethane (5 mL) was allowed to stir at room temperature overnight. The solution was washed with water, then dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with a mixture of 30% ethyl acetate in hexanes, and selected fractions were combined and concentrated under reduced pressure to yield N2-(2-(benzo[d]isothiazol-3-ylamino)ethyl)-N5-methylpyridine-2,5-dicarboxamide as a white solid, (50 mg). 1H NMR (300 MHz, DMSO-d6): 9.16 (broad s, 1H), 8.99 (s, 1H), 8.79 (m, 1H), 8.37 (d, 1H), 8.23 (t, 2H), 7.91 (d, 1H), 7.58 (s, 1H), 7.49 (t, 1H), 7.39 (t, 1H), 3.61 (m, 3H), 3.34 ppm (m, 4H). MW=355 confirmed by LC-MS, tr=2.98 min (Method B) MH+=356.

1. washThe solution was washed with water
2. dry with materialdried over anhydrous sodium sulfate
3. filtrationfiltered
4. concentrationthe filtrate concentrated under reduced pressure
5. customPurification by column chromatography
6. washon silica gel, eluting with a mixture of 30% ethyl acetate in hexanes
7. concentrationconcentrated under reduced pressure