Fused pyrimidine derivatives R 0515Chemoselective Cyclocondensation of α-Acylacetamidines with 2-Methylsulfanyl-4,6-dichloropyrimidine-5-carbaldehyde. -(RYAZANOV, S. G.; SELIVANOV, S. I.; DAR'IN, D. V.; LOBANOV, P. S.; POTEKHIN, A. A.; Russ. J. Org. Chem. 44 (2008) 2, 288-291; St. Petersburg State Univ., St. Petersburg 198904, Russia; Eng.) -A. Forchert 01-169

The cyclocondensation of α-acylacetamidines with esters of 2-fluoro-5-nitrobenzoic and 4-chloro-2-methyl-5-pyrimidinecarboxylic acids leads to condensed azines. The reaction proceeds chemoselectively such that the α-carbon atom of the amidine replaces the halogen atom in the aromatic ring, while the amino group reacts with the ester group.In a continuation of our study of the reactivity of α-acylacetamidines with aromatic dielectrophiles [1, 2], we investigated the reactions of amidines 1a-c with esters 2 and 4. α-Acylacetamidines 1a-c exist in DMSO-d 6 solution in the enediamine tautomeric form, which accounts for their C,N-dinucleophilic properties upon reaction with dielectrophiles.α-Acylacetamidines 1a-c act as C,N-dinucleophiles in their reactions with ester 2 and selectively give the corresponding isoquinolines 3 in good yield. The reactions with amidines 1a and 1b were carried out at room temperature. The reaction with benzoylacetamidine 1c proceeds more slowly and required heating to 50°C.We should note that our proposed method for the synthesis of isoquinolines 3 complements a recently reported method for the synthesis of analogous 3-aminoisoquinolines from amides of 2-chloro-5-nitrobenzoic acid and aryl and hetaryl acetonitriles [3,4].The reaction of amidines 1a and 1b with ester 4 proceeds smoothly at room temperature over 60-100 h and pyrido[4,3-d]pyrimidines 5a and 5b are formed in high yield. The reaction with amidine 1c proved rather slow as in the case of ester 2 but significant tar formation occurred upon attempting to carry out this reaction with heating. On the other hand, carrying out this reaction at room temperature required 60 days. The major product was also pyrido[4,3-d]pyrimidine 6c, which was isolated chromatographically as a mixture of E-and Zisomers as indicated by the double set of signals in the 1 H and 13 C NMR spectra.

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