Thieno pyrimidin-4 -ones chlorination

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). 

The hydroxy group of l-(2-hydroxyethyl)thieno[3,4-d]pyrimidine-2,4(3//)-dione 344 was chlorinated with thionyl chloride in a mixture of pyridine and chloroform, or mesylated with methanesulfonyl chloride in pyridine. No ring chlorination was observed under these conditions. The resulting l-(2-chloro or 2-methanesulfonylethyl) derivative 365 was cyclized to l,2-dihydrooxazolo[2,3-6]thieno[3,4-d]pyrimidin-5-one 366 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (89H985). A similar transformation of 3-(2-hydroxyethyl)thieno[3,4-d]pyrimidine-2(l//),4-diones 333a,b into the 3-(2-chloroethyl) derivatives 367 with thionyl chloride occurred in chlo-... 

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. 

In the case of Y = C02Et, the reaction affords 5-hydroxy thienopyrimidines, which exist predominantly as the oxo form (118). Pyrimidines 119 starting compounds can be prepared by two methods. One of them involves substitution of the mercaptoacetic acid residue for the chlorine atom in 4-chloro-5-ethoxycarbonylpy-rimidines 120. Pyrimidines 119 are then cyclized in the presence of bases to thieno[2,3-<7]pyrimidin-5-ones 118 (1988JHC959, 1993INP13664). 

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