Aminoacids in the synthesis of heterocyclic systems. The synthesis of methyl 2-acetylamino-3-dimethylaminopropenoate and 2-(N-methyl-N-trifluoroacetyl)amino-3-dimethylaminopropenoate and their application in the synthesis of heterocyclic compounds

Methyl (Z)-2-acetylamino-3-dimethylaminopropenoate (3) was prepared from N-acetylglycine (1), which was converted with N,N-dimethylformamide and phosphorus oxychloride into 4-dimethylaminomethylene-2-methyl-5(4H)-oxazolone (2), followed by treatment with methanol in the presence of potassium carbonate, into 3. The compound 3 was shown to be a versatile reagent in the synthesis of various heterocyclic systems. With N-nucleophiles, such as heterocyclic amines 4, either methyl 2-acetylamino-3-heteroarylaminopropenoates 5 or fused pyrimidinones 6 were formed, dependent on the reaction conditions and/or heterocyclic substituents: C-nucleophiles with an active or potentially active methylene group, such as 1,3-dicarbonyl compounds 7,8 and 9, substituted phenols 10a,b, naphthols If, 12a-c, and substituted coumarin 13a, afforded substituted pyranones 20 and 22, and fused pyranones 21, 23-26. The nitrogen containing heterocycles 14-19 produced pyranoazines 27-31 and pyranoazole 32. In all of these systems the acetylamino group is attached at position 3 of the newly formed pyranone ring. The orientation around the double bond for methyl (Z)-2-(N-methyl-N-trifluoroacetyl)-3-dimethylaminopropenoate (36) was established by X-ray analysis.