反应详情

5-(Methoxycarbonyl)picolinic acid (390 mg, 2.2 mmol), was dissolved in anhydrous dichloromethane. Several drops of dimethylformamide were added, followed by oxalyl chloride (0.23 mL, 1.2 mmol). After 1.5 h at room temperature the reaction mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane (10 mL) and added to a solution of N1-(benzo[d]isothiazol-3-yl)ethane-1,2-diamine (300 mg, 1.6 mmol) in anhydrous dichloromethane with triethylamine (420 μL, 3.0 mmol). After 4 h, the reaction was diluted with dichloromethane and washed with saturated sodium bicarbonate solution, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by flash column chromatography, on silica gel, eluting with a mixture of 2% methanol in dichloromethane and selected fractions were combined and concentrated under reduced pressure. Trituration with boiling dichloromethane and methanol removed impurities and gave methyl 6-(2-(benzo[d]isothiazol-3-ylamino)ethylcarbamoyl)nicotinate (255 mg) as a pale yellow solid. 1H NMR (300 MHz, CDCl3): 9.11 (m, 1H), 8.55 (broad s, 1H), 8.40 (m, 1H), 8.24 (d, 1H), 7.68-7.76 (m, 2H), 7.42 (t, 1H), 7.32 (t, 1H), 3.98 (s, 3H), 3.88 ppm (m, 4H). MW=356 confirmed by LC-MS, tr=12.06 min (Method Y) MH+=357.

1. concentrationAfter 1.5 h at room temperature the reaction mixture was concentrated under reduced pressure
2. dissolutionThe residue was dissolved in dichloromethane (10 mL)
3. washwashed with saturated sodium bicarbonate solution
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe crude product was purified by flash column chromatography, on silica gel
7. washeluting with a mixture of 2% methanol in dichloromethane
8. concentrationconcentrated under reduced pressure