Synthesis of novel dihydrothiazolo[3,2‐ a ]pyrimidinone derivatives

Condensation of 2‐amino‐4‐hydroxy‐2‐mercaptopyrimidine (2) hydrate and ethyl 4‐bromocrotonate gave a mixture of ethyl 7‐amino‐2,3‐dihydro‐5‐oxo‐5 H ‐thiazolo[3,2‐ a ]pyrimidine‐3‐acetate (4) and 2a,3‐dihydro‐1‐thia‐5,8,8b‐triazaacenaphthylene‐4,7(2 H )‐dione (5) whereas reaction of 2 with 4‐bromocrotononitrile afforded only 7‐amino‐2,3‐dihydro‐5‐oxo‐5 H ‐thiazolo[3,2‐ a ] pyrimidine‐3‐acetonitrile. Reaction of the tricycle 5 (which was isolated as a hemihydrate) with excess methyl iodide/potassium carbonate in dimethylformamide resulted in both ring hydrolysis and methylation to give 3,4‐dihydro‐1,7‐dimethyl‐4‐ [(methylthio)methyl]‐2 H ‐pyrimido[1,6‐ a ]pyrimidine‐2,6,8(1 H ,7 H )‐trione (10). Methylating 5 with excess methyl iodide/sodium methoxide in methanol also resulted in ring fragmentation and methylation but instead afforded methyl 7‐methyl‐amino‐2,3‐dihydro‐5‐oxo‐7 H ‐thiazolo[3,2‐ a ]pyrimidine‐3‐acetate. The mechanistic aspects of these reactions are discussed.