Thieno pyrimidines, bromination

Electrophilic and nucleophilic reactions of 2-(2-thienyl)thieno[2,3-cf pyrimidine (346), prepared as shown in Scheme 99, permits a conclusion concerning the reactivity compared with that of thiophene bearing an electron deficient substituent in position 2. Both nitration and bromination primarily occur in the thiophene moiety whereas lithium organic reagents (methyllithium, butyllithium) add at carbon atom 4 (77BSF676). Bromination of (324) yields the 5- (or 6-) bromo derivative (68CR(C)(267)697). 

Russian workers (82KGS118) reported the synthesis of 5,6-dihydro-thieno[2,3-d]pyrimidine 122 by brominating 5-allylpyrimidine-4(3//)-thione 121. 

PHA457). Thieno[2,3-d]pyrimidine 89c was brominated, nitrated, and formylated at position 6 to give the 6-bromo, 6-nitro, and 6-formyl derivatives 89d, respectively (90JHC717). 

Potent antiviral activity was found for 2,6-diethylthieno[2,3-rf]pyrimidin-4(3//)-one 180 (81KFZ40). The antiviral activity of some brominated thieno[2,3-d]pyrimidines has also been studied (87KFZ197). 

Chlorothieno[3,2-<7]pyrimidin-4(3//)-one 190a (R2 = Cl, R3 = H) was converted to the 8-bromo derivative 285 by heating at 80°C in a mixture of bromine and acetic acid (88USP4725599). Thieno[3,2-d]pyrimidinedione 270 (R = 2 - F, R1 = 4 - Br, R2 = R3 = H) was chlorinated at position 6 by heating at 60°C with sulfuryl chloride in carbon tetrachloride. The reaction worked equally well with N-chlorosuccinimide instead of sulfuryl chloride (93MI1). 

Bromination of 5-allyl-6-methyl-2-methylthio(phenyl)pyrimidine-4-thiols (144) in chloroform afforded 6-bromomethyl-4-methyl-2-melhylthio(phenyl)-5,6-di-hydrothieno[2,3-<7]pyrimidines 145. The latter were transformed into 4,6-dimethyl-2-methylthio(phenyl)thieno[2,3-<7]pyrimidines 146 by refluxing with ethanolic sodium ethoxide (1999KZA60). 

Thiazolo[3,2-a]tiiieno[2 aiid wOlpyrimidlnes [C3NS-C4S-C4N2].—An attempt to prepare thiazolo[3,2-fl]thieno[3,2-t/]pyrimidines containing basic side-chains by the reaction of a 5-allyl-6-mercapto-thienopyrimidine with bromine followed by base led to the formation of the 2-methyl compound (114). > Subsequent... 

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