Reaction Steps
In a nitrogen blanketed flask was dissolved 5.17 g (15.70 mmol) of the intermediate of Example 5 in 30 mL of ethanol. To this stirring solution was added 1.75 g (19.7 mmol) of methyl semicarbazide. The mixture was heated to reflux to dissolve the solids and then 5 drops of conc. HCl was added. Over 1 h at reflux, yellow solids precipitated out of solution. After 1 h, HPLC analysis indicated complete reaction, 38.2% and 55.4% of 2 product isomers and no remaining starting material. The yellow slurry was slowly cooled to ambient temperature to stir for 1 h and then stirred for 30 min. in an ice water bath. The mixture was filtered through coarse glass. The solids were washed with ethanol and dried under vacuum at 50° C. to afford 5.08 g (81.2%) of the title compound as a yellow solid, mp=238° C. HPLC assay indicated two isomers, 46.2%+53.1%. MS (FD+)=400. IR: 1692, 1345 cm-1. 1H NMR (DMSO): δ0.90 (t, 3, J=6); 2.22 (m, 2); 2.72 (d, 3, J=5); 3.63 (m, 1); 4.42 (d, 1/2, J=6); 4.58 (d, 1/2, J =6); 6.10 (s,2); 6.69 (d, 1, J=8); 7.05 (d, 1, J=10); 7.32 (br. t, 1, J=4); 7.85 (d, 2, J=9); 8.18 (d, 2, J=9); 8.62 (d, 1, J=8). 13C NMR (DMSO): δ24.27, 24.51, 27.18, 43.30, 43.73, 67.09, 67.47, 102.45, 108.95, 109.19, 111.50, 111.54, 112.41, 112.45, 124.40, 124.48, 124.69, 128.35, 133.47, 133.69, 144.55, 144.61, 144.68, 144.79, 147.71, 147.76, 148.06, 149.39, 149.54, 156.11, 156.23. Anal. Calcd for: C19H20N4O6 : C, 57.00; H, 5.03; N, 13.99; Found: C, 57.72; H, 5.01; N, 13.99.
