反应详情

A flask was charged with ethyl 2-cyano-3-methylbutanoate (3b, 20.72 g, 133.5 mmol), ethyl urea (3a, 12.35 g, 140.2 mmol) and MeOH (97.2 mL). To the slurry at room temperature was added sodium methoxide in methanol (25% w/w soln, 36.8 mL), mild exotherm detected. The heterogeneous reaction mixture was then heated to reflux. The reaction was refluxed for 4-12 h. Upon reaction completion, as determined by TLC analysis, the reaction mixture was concentrated and solvent exchanged to acetonitrile (ACN) through 3×50 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 3 to 4, (by pH paper) white slurry resulted. This slurry was aged for 0.5 to 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 to 50° C. giving 18.63 g (60%) of 1-ethyl-5-isopropyl-6-amino uracil 2 (HCl salt).

1. temperatureThe heterogeneous reaction mixture was then heated to reflux
2. temperatureThe reaction was refluxed for 4-12 h
3. customUpon reaction completion
4. concentrationthe reaction mixture was concentrated
5. customleaving a basic 1-2 vol. solution in ACN
6. customwhite to off-with solids began 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 to 50° C.