反应详情

温度

100 °C

To a solution of crude 1-(1-methyl-1H-pyrazol-4-yl)guanidine (17.5 g, crude) and ethyl 2-cyano-4,4-diethoxybutanoate (13.08 g, 0.06 mol) in EtOH (50 mL) was added CH3ONa/CH3OH (150 mL, 0.06 mol) at 20° C., and the reaction mixture was stirred at 100° C. for 20 hrs. The pH was adjusted to 2 by HCl (6 M) and stirred for 30 min. Then pH was adjusted to 7-8 by aqueous NaOH (1 M). The reaction mixture was filtered and the filter cake was dried in vacuo to afford a first batch of pure product. The filtrate was concentrated in vacuo and the residue was purified by column chromatography eluted with CH2Cl2:MeOH=13:1 to afford the title compound (combined batches yielded 5 g, 43.5% yield over two steps). 1H NMR: (400 MHz, DMSO) δ ppm 11.21 (s, 1H), 10.28 (s, 1H), 8.44 (s, 1H), 7.88 (s, 1H), 7.50 (s, 1H), 6.67-6.68 (m, 1H), 6.22-6.24 (m, 1H), 3.79 (s, 3H).

1. stirringstirred for 30 min
2. filtrationThe reaction mixture was filtered
3. customthe filter cake was dried in vacuo
4. customto afford a first batch of pure product
5. concentrationThe filtrate was concentrated in vacuo
6. customthe residue was purified by column chromatography
7. washeluted with CH2Cl2