4-Amino-2-substituted thieno pyrimidines

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... 

Chloroacetylation of the amino group provides an intermediate that can be cyclized to 2-substituted-4-amino thieno[2,3- pyrimidines upon treatment with KSCN <1996JPR206>. 

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. 

Virtually all of the syntheses of thieno[2,3-synthetic strategy. Thus, thiophenes with a 2-amino- (or (substituted)amino-) function, and either a carboalkoxy, carboxamido, or a cyano group at 03 are the preferred starting points. Typically, when the thiophene has a carbonyl function at 03 (268 R = OEt or NH2) cyclization affords the 4-oxothienopyrimidines (269) (Equation (93)). 

A number of densely substituted 3-aminothiophene derivatives, including several fused systems, have been obtained by cyclization reactions of suitable acrylonitriles or similar precursors with ethyl mercaptopyruvate in the presence of a base, as illustrated by the conversion of the pyridine-1-oxide 4 into the pyridothiophene 5 <05JHC661>. Similar annulations involving 2-amino-4,6-dichloropyrimidine-5-carboxaldehyde and methyl mercaptoacetate leading to thieno[2,3-t/]pyrimidine derivatives have also been reported <05JHC1305>. 

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