反应详情

A flask was charged with ethyl 2-cyano-3-methylbutanoate (3b, 10.0 g, 64.4 mmol), ethyl urea (3a, 5.96 g, 67.6 mmol) and EtOH (129 mL). To the slurry at room temperature was added sodium ethoxide in ethanol (21% w/w soln, 28.8 mL), mild exotherm detected. The heterogeneous reaction mixture was then heated to reflux. The reaction was refluxed for 4 to 12 h. Upon reaction completion, as determined by TLC analysis, the reaction mixture was concentrated and solvent exchanged to acetonitrile (ACN) through 3×20 mL co-evaporations leaving a basic 1-2 vol. solution in ACN. To the reaction mixture was added 1-2 vol. of water followed by a pH adjustment with 2N HCl (aq.). As the pH approached 10 white to off-with solids began forming and as the pH was further reduced to 9 (by pH paper) white slurry resulted. This slurry was aged for 0.5-24 h and then filtered. The resulting solids were washed with 1 vol. of water and 2×2 vol. MTBE. The white to off-white solids were then dried in a vacuum oven at 40-50° C. giving 4.99 g (39%) of 1-ethyl-5-isopropyl-6-amino uracil 2:

1. temperatureThe heterogeneous reaction mixture was then heated to reflux
2. temperatureThe reaction was refluxed for 4 to 12 h
3. customUpon reaction completion
4. concentrationthe reaction mixture was concentrated
5. customleaving a basic 1-2 vol. solution in ACN
6. custombegan forming and as the pH
7. customresulted
8. filtrationfiltered
9. washThe resulting solids were washed with 1 vol. of water and 2×2 vol. MTBE
10. customThe white to off-white solids were then dried in a vacuum oven at 40-50° C.