反应详情

A solution of 4-methyl-3-thiosemicarbazide (902 mg, 8.58 mmol), nicotinic acid (960 mg, 7.80), EDCI (1.64 g, 8.58 mmol), HOBt (1.16 g, 8.58 mmol) in DMF (10 ml) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (100 ml), successively washed with hydrochloric acid (50 ml, 10% aqueous), water (50 ml), saturated sodium carbonate (50 ml, aqueous), water (50 ml) and brine (50 ml). The organic phase was dried (sodium sulfate), filtered and concentrated in-vacuo. The residue was stirred in sodium hydroxide (53.4 ml, 66.7 mmol, 5% aqueous) at 60° C. overnight. The reaction mixture was cooled to room temperature, then carefully brought to pH about 6 using hydrochloric acid (1 N water). The aqueous phase was saturated with solid sodium chloride, then extracted with ethyl acetate (4×50 ml). The combined organic phase was washed with brine (100 ml), dried (sodium sulfate), filtered and concentrated in-vacuo (180 mg, off-white solid). 1H NMR (CDCl3), δ (ppm): 11.6 (bs, 1H), 8.94 (s, 1H), 8.83 (dd, 1H), 7.98 (m, 1H), 7.51 (dd, 1H), 3.69 (s, 3H).

1. washsuccessively washed with hydrochloric acid (50 ml, 10% aqueous), water (50 ml), saturated sodium carbonate (50 ml, aqueous), water (50 ml) and brine (50 ml)
2. dry with materialThe organic phase was dried (sodium sulfate)
3. filtrationfiltered
4. concentrationconcentrated in-vacuo
5. extractionextracted with ethyl acetate (4×50 ml)
6. washThe combined organic phase was washed with brine (100 ml)
7. dry with materialdried (sodium sulfate)
8. filtrationfiltered
9. concentrationconcentrated in-vacuo (180 mg, off-white solid)