5-Ethyl-2-methylpyridine, from pyrimidines

Seidel28 cyclized compounds (32) derived from the amides (31) with dimethylformamide dimethyl acetal to the 3-substituted 2-oxo-2H-pyrido-[l,2- ]pyrimidines (33) by heating in acetic anhydride. On this basis he corrected the conclusion of Antaki,29 who had assumed that by reacting 2-amino-4-methylpyridine and ethyl ethoxymethylenecyanoacetate, the 2-oxo-2//-pyrido[l,2-a]pyrimidine (33 R = 8-Me, R1 = OEt) was produced. The product was in fact the 4-oxo isomer (36 R = 8-Me, R1 = H, R2 = COOEt). 

Shur and Israelstam41 applied polyphosphoric acid to cause ring closure. Although the crotonates (39) and the crotonic amides (40) cyclized almost quantitatively to 4-oxo-4H-pyrido[l,2- ] pyrimidines (41), cyclization of the 2-acetylacetamidopyridines (38) could only be achieved in less than 50% yield. When one additional equivalent of 2-aminopyridine was included in the reaction mixture of 38, the yield of 41 increased to over 80%. When the ring closure was carried out from crotonic amides (40) containing different 2-aminopyridine moieties, the resulting 4-oxo-4//-pyrido[l,2-a]pyrimidines bore the substituent of the pyridine of the enamine part of the crotonic amide. The authors proposed that the 4-oxo-4H-pyrido[l,2-a]pyrimidines (41) may arise from 2-aminopyridines and ethyl acetoacetate in polyphosphoric acid via two pathways (see Scheme 1). 2-Amino-3-methylpyridine and 2-amino-3,5-dibromopyridine react via pathway A and 2-aminopyridine, 2-amino-4-, -5-, and -6-methylpyridines react via pathway B, whereas 2-amino-5-chloro- and 5-bromopyridines may react via both pathways. 

Mendel44 found that reaction of 2-aminopyridine-3-carboxylic acid with ethyl acetoacetate or ethyl benzoylacetate gave rise to a decarboxylated product (36 R1 = Me, Ph R = R2 = H), whereas with ethyl 4,4,4-tri-fluoroacetoacetate, the product was ethyl 2-aminopyridine-3-carboxylate. Yale51 obtained 3-benzoyl-2-hydroxy-4-oxo-4ff-pyrido[ 1,2-a] pyrimidine in 4- 5%, yield from 2-amino-3-methylpyridine and ethyl benzoylacetate in diethylbenzene. 

From 2-amino-6-methylpyridine and ethyl 3-aminocrotonate the expected 2,6-dimethyl-4-oxo-4//-pyrido[l,2-a]pyrimidine was not obtained, but instead a urea derivative is formed.36 Ethyl acetoacetate has also been replaced... 

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