反应详情

To a dry 50 ml round bottom flask equipped with magnetic stirrer, nitrogen inlet, bleach scrubber, thermometer, and addition funnel, was charged methyl pyridine-3-carbodithioate (2.0 g, 11.82 mmol), methyl 2-aminoacetate hydrochloride (1.48 g; 11.82 mmol) and 20 ml of methanol. Triethylamine (1.20 g, 11.82 mmol) in methanol (5 mls) was added, dropwise. The mixture was stirred at ambient temperature for 16 hours. The reaction mixture was poured into 200 ml of water, and the aqueous mixture was extracted with 3×50 ml of ethyl acetate. The combined organic extracts were washed with water and brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure on a rotary evaporator. The crude product was then dissolved in dichloromethane and chromatographed on silica gel (80 g ISCO cartridge) with a gradient of 100% hexanes to 100% ethyl acetate over 20 minutes. The pure fractions were combined and then solvent evaporated under vacuum to afford the title compound as a thick yellow oil (1.6 g, 64%): 1H NMR (400 MHz, CDCl3) δ 8.96 (dd, J=2.4, 0.8 Hz, 1H), 8.68 (dd, J=4.8, 1.7 Hz, 1H), 8.47 (bs, 1H), 8.16 (ddd, J=8.0, 2.4, 1.7 Hz, 1H), 7.35 (ddd, J=8.0, 4.8, 0.9 Hz, 1H), 4.59 (d, J=4.7 Hz, 2H), 3.86 (s, 3H); ESIMS m/z 209.17 ([M-H]−). Step 2: Preparation of N-ethyl-2-(pyridin-3-carbothioamido)acetamide:

1. customTo a dry 50 ml round bottom flask equipped with magnetic stirrer, nitrogen inlet
2. additionbleach scrubber, thermometer, and addition funnel
3. extractionthe aqueous mixture was extracted with 3×50 ml of ethyl acetate
4. washThe combined organic extracts were washed with water and brine
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure on a rotary evaporator
8. dissolutionThe crude product was then dissolved in dichloromethane
9. customchromatographed on silica gel (80 g ISCO cartridge) with a gradient of 100% hexanes to 100% ethyl acetate over 20 minutes
10. customsolvent evaporated under vacuum