2-Tolyl isocyanate → 1-[[(o-Tolylamino)carbonyl]amino]-1,4-dihydro-2,3-quinoxalinedione

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Reaction Conditions

Reaction Steps

The procedure of Leeson, P. D. et al., J. Med. Chem 35:1954-68 (1992) was adapted. A suspension of 1-amino-1,4-dihydro-2,3-quinoxalinedione (37 mg, 0.21 mMol) in pyridine (2.5 mL) was stirred at 70° C. until dissolving was completed. To the solution was then added o-tolyl isocyanate (27.8 mg, 0.21 mMol, Aldrich), which was stirred at 60° C. for 2 h, then overnight at room temperature. The solvent was evaporated under reduced pressure, the residue was washed by ether (2×2 mL) to give 59 mg of crude 1-[[(o-tolylamino)carbonyl]amino]-1,4-dihydro-2,3-quinoxalinedione (66% product; 30% tolyl-byproduct; 4% 1-amino-1,4-dihydro-2,3-quinoxalinedione by 1H NMR). Separated by chromatograph with silica gel (2 g) column, eluted with 100% benzene (20 mL) and benzene:acetone=1:1 (20 mL) and 100% acetone (20 mL) to remove most of impurity. The residue (43 mg of 1-[[(o-tolylamino)carbonyl]amino]-1,4-dihydro-2,3-quinoxalinedione) was washed with ethanol (2×2 mL) and ether (2×1 mL) to give 38 mg of pure 1-[[(o-tolylamino)carbonyl]amino]-1,4-dihydro-2,3-quinoxalinedione as a white powder (60%). Mp:decomposed from 265° C. IR (KBr, cm-1): 3375; 3237; 1718; 1693; 1675. NMR (1H, DMSO-d6) δ2.161 (s, 3H); 6.996-7.380 (m, 8H); 8.530 (s, 1H), 9.343 (s, 1H); 12.155(s, 1H).

Provenance & Evidence