Acetic Anhydride → 6-amino-1-(2,4-dichlorophenyl)-3-methyl-2,4(1H,3H)-pyrimidinedione

Participants

Reaction Conditions

Reaction Steps

A solution of N-(2,4-dichlorophenyl)-N′-methyl-urea (12.0 g, 54.8 mmol) in acetic anhydride (100 mL) was treated with cyanoacetic acid (5.6 g, 65.8 mmol). The reaction mixture was heated at 85° C. for 2.5 h. Additional cyanoacetic acid (0.90 g, 11.0 mmol) was added and the reaction mixture was stirred for 45 min. A third portion of cyanoacetic acid (0.45 g, 5.5 mmol) was added and the reaction mixture was stirred for 30 min. Excess acetic anhydride was distilled off under reduced pressure at a temperature not higher than 70° C. The residue was treated with 20% aqueous sodium hydroxide (95 mL) in portions. During the addition a spontaneous increase in temperature (65-70° C.) occurred. The reaction mixture was heated at 60° C. for 1 h during which time the product precipitated. The reaction mixture was then cooled to 0° C. The precipitate was collected on a Buchner funnel, washed with cold water, and dried at 55° C. under vacuum. The crude product was triturated in hot toluene (stirred for 1 h at 110° C.), and the solid was immediately collected on a Buchner funnel then dried under vacuum to afford a pale yellow solid (8.46 g, 54% yield): mp 249-251° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.89 (d, J=1.8 Hz, 1H), 7.59 (d, J=1.8 Hz, 2H), 6.44 (s br, 1H), 4.79 (s, 1H), 3.09 (s, 3H); LRMS (APCI) m/e 286.0 [(M+H)+, calcd for C11H10N3O2Cl2 286.0].

Provenance & Evidence