7-Cyano-3-ethyl-2-methyl-4/7-pyrido

When 6-aminopyridine-3-carboxamide was reacted with ethyl 2-ethyl-acetoacetate in a mixture of phosphoryl chloride-polyphosphoric acid, 7-cyano-3-ethyl-2-methyl-4//-pyrido[l,2-a]pyrimidin-4-one 94 was obtained... 

Heating ethyl 5-fluoro-4-[cyano(ethoxycarbonyl)methyl]-2,3-dihydro-l-methyl-7-oxo-l//,7//-pyrido[3,2,l-i7]cinnoline-8-carboxylate (83, R = COOEt) in a mixture of cone. HCl and acetic acid gave the 8-carboxy-4-acetic acid derivative (92EUP470578). The acetic acid group was decarboxylated by heating in boiling ethanol in the presence of NEts to give the 4-methyl derivative. When the 4-[cyano(tert-butoxycarbonyl)methyl]-8-carboxylate 83 (R = COOrBu) was treated with trifluoroacetic acid in methylene chloride at room temperature, the 4-cyanomethyl-8-carboxylate 83 (R = H) was obtained. 

Aminopyridine and ethyl a-ethoxyethylidenecyanoacetate heated at 150 in an oil bath until the reaction mass solidifies 3-cyano-2-methyl-4H-pyrido-[l,2-a]pyrimidin-4-one. Y 74%.—The ease of this ring closure is due to hyperconjugation. F. e. s. H. Antaki, J. Org. Ghem. 27, 1371 (1962). 

Reaction of 2-aminopyridine with ethyl 2-cyano-3-ethoxy-3-methyl-, -3-ethyl-, -3-phenylacrylates and ethyl 2-ethoxycarbonyl-3-ethoxy-3-methyl-, -3-phenylacrylates in boiling xylene yielded 2-substituted 4/f-pyrido[l,2-u]pyrimidine-3-carbonitriles and -3-carboxylates (99MI7). Similar reactions of 2-aminopyridine with 2-cyano-3-ethoxyacrylonitrile and its 3-methyl, 3-ethyl, -3-phenyl derivatives in boiling MeCN afforded 4-imino-4//-pyrido[l,2-u]-pyrimidine-3-carbonitrile and its 2-substituted derivatives. 

Alkylation of l-aryl-4-cyano-l-trifluoromethyl-2,3-dihydro-lH-pyrido [l,2-c]pyrimidine-3-thiones with benzyl bromides, ethyl 2-broroacetate, and 2-chloroacetamides in the presence of K2C03 in DMF at ambient temperature gave 3-[(substituted methyl)thio)]-lH-pyrido[l,2-c]pyrimi-dines in 51-87% yields (07MI1). 

Aluminum chloride (3.51 g, 0.0263 mole) was added to cold (-30°C) tetrahydrofuran (180 ml). Sodium azide (5.12 g, 0.0788 mole) was added and the mixture heated under reflux for 30 min. The mixture was cooled to 5°C. Ethyl 2-cyano-3-(3-methyl-2-pyridylamino)acrylate (5.0 g, 0.0216 mole) was added and the mixture heated under reflux for 18 h. The tetrahydrofuran was removed under reduced pressure. The residue was treated with ice water (100 ml) and acidified to pH 3 with 6 N hydrochloric acid. The mixture was filtered and the collected solid recrystallized from N,N-dimethylformamide to give the 9-methyl-3-(lH-tetrazol-5-yl)-4H-pyrido[l,2-a]pyrimidin-4-one (2.5 g,... 

The 3-imino group of 4-cyano-2-ethyl-3-imino-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidine-l-thione was acylated with phenyl isocyanate (78MI1). The imino group of l-imino-4-cyano-3-methylthio-l//-pyrido[l,2-cjpyrimidine was alkylated and acylated with methyl iodide and acetic anhydride (75YZ13). Reaction of 3-amino-4-phenyl-4-[2-(A, N-di-n-pro-pylamino)ethyl-4,4 a,5,6,7,8-hexahydro-l //-pyrido[l, 2-c ]pyri midin-l-one with acetic anhydride in pyridine and with sodium nitrite in aqueous acetic acid afforded 3-acetamido and perhydro-l,3-dioxo derivatives, respectively (87USP4680295). 

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