2-Substituted thieno 2,3-<7 pyrimidin-4 ones

Thieno[2,3-d]pyrimidines can also be synthesized by cyclic transformations from other ring systems. Thieno[2,3-d]oxazin-4-ones 123 were transformed into 3-substituted thieno[2,3-d]pyrimidin-4-ones 19a-d by treat-... 

To synthesize 2-methyl-3-substituted thienopyrimidin-4-ones 178, a two-step reaction was applied. o-Aminoesters 189 (Y = Me) were reacted with acetic anhydride in the presence of 4-dimethylaminopyridine to give methyl 3-acetylaminothiophene-2-carboxylates 196. These were then cyclized by heating with primary amines to the thieno[3,2-d]pyrimidin-4-ones 197 (91GEP295381 92PHA577). 

Cycloaddition and cyclization routes were used to access certain 1,3-diazines. The 4+2 cycloaddition reaction of 4-(N-allyl-N-aryl)amino-l,3-diaza-l,3-butadienes with vinyl-, isopropenyl-, and chloroketene led to pyrimidinone-fused pyrimidinones <97T13841>. Cis-cyclopenta[d]pyrimidines were derived from cis-2-amino-l-cyclopentanecarboxylates by cyclization with KOCN and KSCN <97JHC1211>. 2-Thioxopyrido[3, 2 4,5]thieno[3,2-r/]pyrimidin-4(3//)-ones 19 were prepared by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-/)]pyridines and isothiocyanates <97JHC937>. Thiazolyl-benzimidazoles derived from 2-cyanomethyl-l//-benzimidazole and 2,3-dihydrothiazole-2-(3//)-thiones were cyclized to the corresponding thiazolo[4,5-r/]pyrimidines <97PHA346>. Reductive cyclization of 6-cyanomethyl-5-nitropyrimidines afforded 7-alkyl-5//-pyrrolo[3,2-r/]pyrimidines and 6-amino-7,7-dialkyl-7//-pyrrolo[3,2-rf]pyrimidines <97T391>. 7-Methyl-5-alkyl-2-vinyl-pyrazolo[3,4-r/]pyrimidine-4,6(5//,7//)-diones arose from cyclization and alkylation of... 

Surprisingly, only one example of the synthesis of thieno[3,4-,7 pyrimidines has been described starting from a pyrimidine ring. In CHEC-II(1996) <1996CHEC-II(7)229>, substituted 5-cyanouracils, upon reaction with elemental sulfur, led to the formation of compounds in this class. Now the use of a 5-cyanopyrimidino-2-thione 419 under similar conditions (Equation 156) leads to the thienopyrimidine 420 <1997HC0151>. 

Electrophilic substitution reactions of thieno[3,2-cf pyridine occur at position 7 (equation 38). With dimethyl sulfate in an alkaline medium, thieno[3,2-cf pyrimidin-4-one (347) yields an N-methyl derivative. 

Strong heating of 2-substituted 5-propargylsulfanyl-3-aryl-3//-pyrimidin-4-ones, and their 5-allylsulfanyl derivatives, has been shown to lead to 2-substituted 3-aryl-6-methyl-3//-thieno[3,2-d]pyrimidin-4-ones and their 6,7-dihydro derivatives. The proposed mechanism in both cases is a [3,3]-sigmatropic thia-Claisen rearrangement followed by tautomerization and a 5-exodig or 5-exo-trig cyclization.38... 

Starting from 2-amino-3-cyano-4,5-dihydrothiophenes 60 the derived 2-benzamido derivatives 61 were treated with cyclohexylamine, morpholine, piperidine, or pyrrolidine to yield the respective 5,6-dihydro-2-phenyl 4-substituted aminothieno[2,3-d]pyrimidines 62a-d (83CPB401). In the presence of tin(IV) chloride, benzamides 61 reacted with acetic (or propionic) anhydride to give the corresponding 3-acetyl(or propionyl)thieno[2,3-[Pg.206]

Ring chlorination of 2-amino(or substituted amino)thieno[3,4-d]pyrim-idin-4(3//)-ones 370 (90EUP404356) and 5,7-dihydro-2-(2-methylanilino) thieno[3,4-c/]pyrimidin-4(3//)-one 372 (91MIP1) in boiling phosphoryl chloride gave the respective 4-chloro compounds 371 (90EUP404356) and 373 (91MIP1). The displacement of chlorine from both these compounds by a variety of nucleophiles was also reported. 

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