3- Formyl-2-hydroxy-8- -4//-pyrido

Vilsmeier-Haack formylation of 2-(4-methyl-l-piperazinyl)-4//-pyrido-[l,2-n]pyrimidin-4-one with a mixture of POCI3 and DMF at 95°C gave a 3-formyl derivative (93FES1225) while ethyl 4-oxo-6,7,8, 9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-2-acetate at 50 °C yielded a 9-dimethylaminomethylene-3-formyl derivative (01MI4). 3-Formyl-2-hydroxy-8-[2-(4-isopropyl-l,3-thiazol-2-yl)-l-ethenyl]-4//-pyrido[l,2-n]pyri-midin-4-one was obtained from the 3-unsubstituted derivative with oxalyl chloride-DMF reagent in CH2CI2 at room temperature for 3h (OlMIPl). 

The 3-formyl group of 8-substituted 3-formyl-2-hydroxy-4//-pyrido[l,2-n]pyrimidin-4-one was reacted with (cyanomethyl)- and (terr-butoxycarbo-nylmethylene)triphenylphosphorane in THF, and with 5-aminotetrazole in boiling MeOH for 9h to yield ( )-3-propenenitrile, terr-butyl ( )-3-propenoate and 3-[(2//-tetrazol-5-yl)imino]methyl derivatives, respectively (OlMIPl). 

Reduction of 2,3,6,7-tetrahydro-177,5i/-pyrido[3,2,l-//]quinazoline-l,3,7-trione and 7-chloro-6-formyl-2,3-dihydro-177,5i/-pyrido[3,2,1 -(/]quinazo-line-l,3-dione with NaBH4 in THF in the presence of 60% aqueous solution of NaOH gave 7-hydroxy and 7-chloro-6-hydroxymethyl derivatives, respectively (01MI28). 

Vilsmeyer-Haack formylation of 7-hydroxy-2,3,6,7-tetrahydro-l//,5//-pyrido[3,2,l-y]quinazoline-l,3-dione with POCI3/DMF gave 7-chloro-6-formyl-2,3-dihydro-l//,5// derivative. Boiling a toluene solution of the aforementioned 7-hydroxy derivative in the presence of pTSA yielded dehydrated 2,3-dihydro derivative (01MI28). 

Reduction of 3-benzyl-8-chloro-4-oxo-4//-pyrido[l,2- ]pyrimidine-2-carboxylate <2004W004/064741> and 2-methyl-4-oxo-4//-pyrido[l,2-tf]pyrimidine-3-carboxylate <2003T4123> with DIBAL-H afforded 2- and 3-formyl derivatives, respectively. Reduction of /V-(4-fluorobenzyl)-3-hydroxy-8-[methoxy(methyl)amino]-4-oxo-6,7,8,9-tetra-hydro-4//-pyrido[l,2- ]pyrimidine-2-carboxamide with Zn-dust in aqueous AcOH afforded the 8-methylamino derivative, which was acylated with AcOH in the presence of Hiinig s base, HOBt, and l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide-HCl <2004W004/058756>. 3-(Perhydropyrido[l,2- ]pyrimidin-2-yl)propylamine was obtained by catalytic hydrogenation of 2-(perhydropyrido[l,2- ]pyrimidin-2-yl)propionitrile over a Pt02 catalyst <2003FRP1275647>. 

Formyl-1,3,6-trimethyluracil is transformed by a [l,5-//]-shift into a 5-hydroxy-methylene-6-methyleneuracil intermediate, an o-quinodimeth-anes that is capable of [4 + 2]-cycloadditions with aldimines of the same uracil to afford pyrido[3,4-step preparation. Accordingly, maleimide leads to pyrrolo[3,4-g]quinazolines (88JHC205 89PC1) (Scheme 165). 

The 2-amino group of 4-oxo-4//-pyrido[l,2-(/]pyrimidines can be transformed to a hydroxy group by sodium nitrite in concentrated sulfuric acid at 0 The 2-hydroxy group can be formed from the 2-mercapto group by treatment with 3" hydrogen peroxide in I N potassium hydroxide. The hydrazino group of 2-hydrazino-4-oxo-4H-pyrido[l,2-a]pyrimidine was alkylated at N-2 with 6-chloronebularine, formylated at N-2 by heating in formic acid, and transformed to a Schiff s base by reaction with benzaldehyde. " ... 

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