2-Methylthio-4-oxo-477-pyrido

Methylthio-4//-pyrido[l,2-u]pyrimidin-4-one was prepared by FVT of 2-methylthio-4-oxo-4//-pyrido[l, 2-u]pyrimidine-3-carboxylic acid at 650 °C at 8 X 10 -nbar for 4h (99JCS(P2)1087). 

Cyclocondensation of 3-cyano-2-methylthio-4//-pyrido[l, 2-u]pyrimidin-4-ones and ethyl mercaptoacetate in boiling EtOH in the presence of NaOEt afforded 4//-pyrido[l,2-u]thieno[2,3-r/ pyrimidin-4-ones 210 (00HC571). 2-Methylthio-4-oxo-4//-pyrido[l,2-u]pyrimidine-3-carboxylates 211 and mercaptoacetates afforded tricyclic derivatives 212 (93MIP1). Cyclocondensation of 2-methylthio-4-oxo-4//-pyrido[l, 2-u]pyrimidin-3-car-bonitriles 213 with H2NNH2 H2O and with guanidine HCl afforded tricyclic derivatives 214 and 215, respectively (96FES781). 

The cyclocondensation of 2-aminopyridine and diethyl bis(methylthio)-malonate at 150°C for 24 hours, then at 180°C for another 6 hours afforded ethyl 2-methylthio-4-oxo-4//-pyrido[l, 2-a]pyrimidine-3-carboxylate 183 in 20% yield (88CP1232904). 

Cyclocondensation of 2-aminopyridine and its 3-, 4-, and 5-methyl derivatives with ethyl 2-(bismethylthiomethylene)cyanoacetate in boiling BuOH for 5 h afforded 2-methylthio-4-oxo-4 -pyrido[l,2-a]pyrimidine-3-carbonitriles in 55-87% yields (96FES781). 

Another way to prepare 2-amino derivatives is by the reaction of 2-methylthio-4-oxo-4// derivatives with amines.268,288 The 2-methylthio-4-imino derivative reacted differently (see Section III,C,8). 2-Ainino-4-oxo-4//-pyrido[l,2-a]pyrimidine could have also been prepared by reducing the 2-hydrazino derivative with hydrogen sulfide.289... 

Cyclocondensation of ethyl 2-methylthio-4-oxo-4/f-pyrido[l,2-a]py-rimidine-3-carboxylate 459 and ethyl mercaptoacetate in acetonitrile in the presence of potassium carbonate at 60°C for 2 hours, then at room temperature for 16 hours gave pyrido[l,2-a]thieno[2,3-t/]pyrimidine-2-carboxylate 460 (88CP1232904). 

Aminopyridine and isopropylidene (methylthio)methylenemalonates 184 were reacted in refluxing ethanol to give 2-substituted 4-oxo-4H-pyridof 1,2-a]pyrimidine-3-carboxylic acids 185 (89S317). 2-Methylthio-4-oxo-47/-pyrido[ 1,2-a]pyrimidine-3-nitrile was formed in the reaction of 2-aminopyridine and ethyl bis(methylthio)methylenecyanoacetate (91MI17). 

Reaction of 1,3-propanediamine and 3-cyano-4-methyl-6-methylthio-l-phenyl-2-oxo-l,2-dihydropyridine-5-carboxylate 385 yielded 7-cyano-8-methy 1-6-oxo-1,2,3,4-tetrahydro-6//-pyrido[l, 2-a]py rimidine-9-carboxylate (386) (94JHC393). 

Treatment of ethyl 10-methylthio-9-fluoro-3-methyl-2,3-dihydro-7-oxo-7//-pyrido[l,2,3- 7e]-l,4-benzoxazine-6-carboxylate with oxone in aqueous MeOH at 0°C afforded 10-methylsulfonyl derivative (99H(51)1563). Methylthio group in a 7-(4-methylthiophenyl)-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- 7e]-l,4-benzoxazine-3-carboxamide was oxidized to a sulfoxide and a sulfone group (OOMIPl). 

The reaction of 2-aminothiazole and isopropylidene bis(methylthio)-methylenemalonate (459, R2 = R3 = SMe) or 1-methylthioalkylidenema-lonates (459, R2 = Me, Et, Ph R3 = SMe) in boiling ethanol for 2.5 hr or in dimethylformamide at 120-130°C for 4-5 hr, gave 2-substituted 5-oxo-5//-thiazolo[3,2-a]pyrimidine-6-carboxylates (462) in good yields (89S-317). Similarly, in boiling ethanol, 2-substituted 4-oxo-4//-pyrido[l,2-a]-pyrimidine-3-carboxylic acids (463) were obtained in 80-85% yields. When anilines were reacted with isopropylidene bis(methylthio)methy-lenemalonate (459, R2 = R3 = MeS), (methylthio)(arylamino)methylene-malonates (464) were obtained 61-88% yields. 

With carbon disulfide and ethanolic potassium hydroxide, ethyl 6-methyl-4-oxo-6,7,8,9-tetrahydro-4ii-pyrido[l,2-tt]pyrimidine gave the dipotassium salt (247), which was methylated with dimethyl sulfate to the 9-methylthio-thiocarbonyl compound (248) and alkylated with 1,2-dibromoethane to the... 

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